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He S, Lu JJ, Wu JJ, Zheng MX, Ma J, Hua XY, Xu JG. Altered cerebellar activity and cognitive deficits in Type 2 diabetes: Insights from resting-state fMRI. Brain Res 2025; 1856:149586. [PMID: 40113193 DOI: 10.1016/j.brainres.2025.149586] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Revised: 02/13/2025] [Accepted: 03/18/2025] [Indexed: 03/22/2025]
Abstract
OBJECTIVE To investigate alterations in brain activity in patients with Type 2 Diabetes and explore the relationship between altered regions and neuropsychological performances. METHODS A total of 36 patients with Type 2 Diabetes and 40 age- and education-matched healthy controls were recruited for this case-control study. All participants underwent resting-state functional magnetic resonance imaging (Resting-state fMRI) and neuropsychological tests. The neuropsychological scales included the Auditory Verbal Learning Test (AVLT), Shape Trajectory Test B (STT-B), Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), and Boston Naming Test (BNT), Symbol Digit Modality Test (SDMT), Regional homogeneity (ReHo) and the amplitude of low-frequency fluctuations (ALFF) were used to assess differences in spontaneous regional brain activity. For functional connectivity (FC) analyses, the differences identified among the groups were selected as seed regions. Then, the correlations between neuropsychological scale scores (AVLT, HAMA, HAMD, STT-B, BNT, and SDMT) and ALFF/ReHo values were specifically analyzed in the focal regions that exhibited significant alterations between the T2DM and control groups, as detailed in Tables 2 and 3. RESULTS Patients with Type 2 Diabetes exhibited significantly higher ALFF values in the superior lobe of the cerebellum, specifically in the left cerebellar crus I (Cerebellum_Crus I_L), left cerebellar lobule VI (Cerebellum_6_L), and left cerebellar lobule IV-V (Cerebellum_4_5_L). Additionally, they exhibited elevated ReHo values in the Cerebellum_Crus I_L and Cerebellum_6_L. The findings were statistically significant with a family-wise error-corrected, cluster-level p-value of less than 0.05. However, the FC analysis was not significant. AVLT scores were significantly lower in the diabetes group. The correlation analysis demonstrated a negative association between ALFF values of the Cerebellum_6_L and AVLT scores (R2 = 0.1375, P < 0.001). The ReHo values within the Cerebellum_6_L also exhibited a negative association with AVLT scores (R2 = 0.0937, P = 0.007). CONCLUSION Patients with Type 2 Diabetes showed abnormal neural activities in diverse cerebellar regions mainly related to cognitive functions. This provides supplementary information to deepen our insight into the neural mechanisms by which Type 2 Diabetes affects the functional activity of the brain's posterior circulation, as well as the potential association of these changes with cognitive impairment.
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Affiliation(s)
- Shuang He
- Department of Orthopaedics, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200021, China
| | - Juan-Juan Lu
- Center of Rehabilitation Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China; School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Jia-Jia Wu
- Center of Rehabilitation Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China
| | - Mou-Xiong Zheng
- Department of Orthopaedics, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200021, China; Engineering Research Center of Traditional Chinese Medicine Intelligent Rehabilitation, Ministry of Education, Shanghai, China
| | - Jie Ma
- Center of Rehabilitation Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China; School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
| | - Xu-Yun Hua
- Department of Orthopaedics, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200021, China; Engineering Research Center of Traditional Chinese Medicine Intelligent Rehabilitation, Ministry of Education, Shanghai, China.
| | - Jian-Guang Xu
- Center of Rehabilitation Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China; School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Engineering Research Center of Traditional Chinese Medicine Intelligent Rehabilitation, Ministry of Education, Shanghai, China.
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Janssen EPJ, Spauwen PJJ, Rijnen SJM, Ponds RWHM. Eye movement desensitization and reprocessing for posttraumatic stress disorder following acquired brain injury: A multiple baseline single case experimental design study across four cases. Neuropsychol Rehabil 2025:1-29. [PMID: 40036114 DOI: 10.1080/09602011.2024.2444999] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Accepted: 12/10/2024] [Indexed: 03/06/2025]
Abstract
Posttraumatic stress disorder (PTSD) is prevalent in individuals with acquired brain injury (ABI). This study investigated the effectiveness and applicability of Eye Movement Desensitization and Reprocessing (EMDR) for PTSD in individuals with ABI. Data were collected using a non-concurrent multiple baseline single case experimental design (SCED), with a baseline, treatment, maintenance, and 3-month follow-up phase, across four cases. EMDR treatment was provided using a manualized standard EMDR protocol. The primary outcome was PTSD symptoms. Secondary outcomes were general mental health and cognitive functions. Visual analyses, TAU-U analyses, and analyses using the Reliable Change Index were performed. All four participants (two with TBI, two with stroke) showed a significant decrease in PTSD symptoms, which continued in maintenance and was retained at follow-up. The participants no longer fulfilled criteria for PTSD classification and showed reliable improvement in PTSD severity score post-treatment and at follow-up. No adverse events occurred and no adjustments in EMDR protocol were necessary. There was no consistent improvement in general mental health nor a consistent improvement in cognitive functioning. This study provided empirical support for the effectiveness and applicability of EMDR for PTSD in four participants with stroke or TBI.
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Affiliation(s)
- Ellen P J Janssen
- Centre of Excellence for Brain Injury and Neuropsychiatry, GGZ Oost Brabant, Boekel, The Netherlands
- School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands
- Limburg Brain Injury Centre, Maastricht, The Netherlands
| | - Peggy J J Spauwen
- Centre of Excellence for Brain Injury and Neuropsychiatry, GGZ Oost Brabant, Boekel, The Netherlands
- Clinical Center of Excellence for Personality Disorders in Older Adults, Mondriaan Mental Health Center, Heerlen-Maastricht, The Netherlands
| | - Sophie J M Rijnen
- Centre of Excellence for Brain Injury and Neuropsychiatry, GGZ Oost Brabant, Boekel, The Netherlands
- Limburg Brain Injury Centre, Maastricht, The Netherlands
| | - Rudolf W H M Ponds
- School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands
- Limburg Brain Injury Centre, Maastricht, The Netherlands
- Department of Medical Psychology, Amsterdam University Medical Center, Amsterdam, The Netherlands
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De Longis E, Kassis A, Rémond-Derbez N, Thota R, Darimont C, Donato-Capel L, Hudry J. Cognitive benefits of sleep: a narrative review to explore the relevance of glucose regulation. SLEEP ADVANCES : A JOURNAL OF THE SLEEP RESEARCH SOCIETY 2024; 6:zpae095. [PMID: 39850251 PMCID: PMC11756301 DOI: 10.1093/sleepadvances/zpae095] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Revised: 11/16/2024] [Indexed: 01/25/2025]
Abstract
Sleep is essential for maintaining optimal health. Both sleep duration and quality have been linked to various physiological functions and physical and mental health outcomes. Nutrition has been shown to impact sleep parameters, from the nutrient composition of foods, such as tryptophan levels, to the physiological response to foods, such as the glucose response. However, the relationship between glycemic control and sleep, and its impact on next-day benefits, particularly on cognitive performance, remains complex and is not fully understood. This narrative review aims to explore the relationship between glycemia and sleep, and how it may affect cognitive performance the following day. The review includes data from observational and interventional studies, discussing mechanisms of action that may explain the modulating effect of glycemia on sleep and cognition. The evidence suggests that lower postprandial glucose and low variation of nocturnal glucose are associated with better sleep quality and shorter sleep onset latency. Good sleep quality, in turn, is positively associated with cognitive processes such as sustained attention and memory consolidation measured the next day after sleep. Future research opportunities lie in investigating the effects of modulating the glycemic and insulinemic responses through evening meals on sleep quality and next-day cognitive performance. Well-designed clinical trials involving healthy individuals are necessary to establish the effects of these interventions. Controlling glycemic and insulinemic profiles through the evening meal may have significant implications for improving sleep quality and cognitive performance, with potential impact on individual mental health, productivity, and overall well-being.
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Affiliation(s)
- Evelina De Longis
- Nestlé Institute of Health Sciences, Société des Produits Nestlé S.A., Lausanne, Switzerland
| | | | - Noëla Rémond-Derbez
- Nestlé Institute of Health Sciences, Société des Produits Nestlé S.A., Lausanne, Switzerland
| | - Rohith Thota
- Nestlé Institute of Health Sciences, Société des Produits Nestlé S.A., Lausanne, Switzerland
| | - Christian Darimont
- Nestlé Institute of Health Sciences, Société des Produits Nestlé S.A., Lausanne, Switzerland
| | | | - Julie Hudry
- Nestlé Institute of Health Sciences, Société des Produits Nestlé S.A., Lausanne, Switzerland
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Zhang S, Wang F, Xie L, Xu J, Song X, Tao J, Chen J, Ma D, Yu X, Shi X, Yang Y. Sodium-glucose cotransporter 2 inhibition through henagliflozin ameliorates cognitive impairment in patients with type 2 diabetes. J Diabetes Investig 2024; 15:1596-1603. [PMID: 39254788 PMCID: PMC11527823 DOI: 10.1111/jdi.14306] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Revised: 08/12/2024] [Accepted: 08/22/2024] [Indexed: 09/11/2024] Open
Abstract
AIMS/INTRODUCTION To assess whether the sodium-glucose cotransporter 2 inhibitor, henagliflozin, improves cognitive impairment in patients with type 2 diabetes. MATERIALS AND METHODS We carried out a prospective study on 290 patients with type 2 diabetes and cognitive impairment. Montreal Cognitive Assessment scores and plasma phosphorylated tau181 levels were used to assess cognition. The association between henagliflozin use and changes in cognition was examined using multivariable logistic regression analysis. RESULTS Montreal Cognitive Assessment scores at enrollment and after 6 months were 21 (interquartile range [IQR]19-23) versus 22 (IQR 20-25; P < 0.0001) in all patients, 21 (IQR 19-23) versus 24 (IQR 22-26; P < 0.0001) in the henagliflozin group and 21 (IQR 19-22) versus 21 (IQR 19-23; P > 0.05) in the non-sodium-glucose cotransporter 2 inhibitor group. Logistic regression analysis showed that henagliflozin treatment was associated with Montreal Cognitive Assessment score improvement independent of potential confounders (odds ratio [OR] 3.670, 95% confidence interval [CI] 2.224-6.056, P < 0.0001). Additionally, plasma phosphorylated tau181 levels significantly decreased at 6-month follow up in all patients (OR 11.5, 95% CI 9.9-13.7 vs OR 10.1, 95% CI 7.8-12.9, P < 0.0001) and in the henagliflozin group (OR 11.5, 95% CI 10.3-13.0 vs OR 9.2, 95% CI 7.1-10.7, P < 0.0001), but not in the non-sodium-glucose cotransporter 2 inhibitor group. Henagliflozin treatment was independently associated with decreased phosphorylated tau181 levels (OR 3.670, 95% CI 1.598-4.213, P < 0.0001). CONCLUSIONS Henagliflozin treatment was independently associated with improvements in Montreal Cognitive Assessment scores and plasma phosphorylated tau181 levels, indicating significant beneficial effects on cognitive impairment in patients with type 2 diabetes.
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Affiliation(s)
- Shujun Zhang
- Department of Endocrinology, Tongji Medical College, Tongji HospitalHuazhong University of Science and TechnologyWuhanHubei ProvinceChina
- Branch of National Clinical Research Center for Metabolic DiseaseWuhanHubei ProvinceChina
| | - Fen Wang
- Department of Endocrinology, Tongji Medical College, Tongji HospitalHuazhong University of Science and TechnologyWuhanHubei ProvinceChina
- Branch of National Clinical Research Center for Metabolic DiseaseWuhanHubei ProvinceChina
| | - Lei Xie
- Department of Endocrinology, Tongji Medical College, Tongji HospitalHuazhong University of Science and TechnologyWuhanHubei ProvinceChina
- Branch of National Clinical Research Center for Metabolic DiseaseWuhanHubei ProvinceChina
| | - Jialu Xu
- Department of Endocrinology, Tongji Medical College, Tongji HospitalHuazhong University of Science and TechnologyWuhanHubei ProvinceChina
- Branch of National Clinical Research Center for Metabolic DiseaseWuhanHubei ProvinceChina
| | - Xiaoqing Song
- Department of Endocrinology, Tongji Medical College, Tongji HospitalHuazhong University of Science and TechnologyWuhanHubei ProvinceChina
- Branch of National Clinical Research Center for Metabolic DiseaseWuhanHubei ProvinceChina
| | - Jing Tao
- Department of Endocrinology, Tongji Medical College, Tongji HospitalHuazhong University of Science and TechnologyWuhanHubei ProvinceChina
- Branch of National Clinical Research Center for Metabolic DiseaseWuhanHubei ProvinceChina
| | - Juan Chen
- Department of Neurosurgery, Tongji Medical College, Tongji HospitalHuazhong University of Science and TechnologyWuhanHubei ProvinceChina
| | - Delin Ma
- Department of Endocrinology, Tongji Medical College, Tongji HospitalHuazhong University of Science and TechnologyWuhanHubei ProvinceChina
- Branch of National Clinical Research Center for Metabolic DiseaseWuhanHubei ProvinceChina
| | - Xuefeng Yu
- Department of Endocrinology, Tongji Medical College, Tongji HospitalHuazhong University of Science and TechnologyWuhanHubei ProvinceChina
- Branch of National Clinical Research Center for Metabolic DiseaseWuhanHubei ProvinceChina
| | - Xiaoli Shi
- Department of Endocrinology, Tongji Medical College, Tongji HospitalHuazhong University of Science and TechnologyWuhanHubei ProvinceChina
- Branch of National Clinical Research Center for Metabolic DiseaseWuhanHubei ProvinceChina
| | - Yan Yang
- Department of Endocrinology, Tongji Medical College, Tongji HospitalHuazhong University of Science and TechnologyWuhanHubei ProvinceChina
- Branch of National Clinical Research Center for Metabolic DiseaseWuhanHubei ProvinceChina
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Cui J, Robert C, Teh CM, Jun Yi EC, Chong JR, Tan BY, Venketasubramanian N, Lai MKP, Chen C, Hilal S. Interactive effect of diabetes mellitus and subclinical MRI markers of cerebrovascular disease on cognitive decline and incident dementia: a memory-clinic study. Alzheimers Res Ther 2024; 16:214. [PMID: 39363381 PMCID: PMC11448036 DOI: 10.1186/s13195-024-01577-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2024] [Accepted: 09/14/2024] [Indexed: 10/05/2024]
Abstract
BACKGROUND Cognitive impairment is an increasingly recognized comorbidity of diabetes, yet the mechanisms underlying this association remain poorly understood. This knowledge gap has contributed to conflicting findings regarding the impact of diabetes on long-term cognitive outcomes in older adults. The presence of cerebrovascular disease (CeVD) may potentially modify this relationship. However, interactive effect between diabetes and subclinical MRI markers of CeVD on cognitive trajectories and incident dementia remains unexplored. METHODS A total of 654 participants underwent brain MRI at baseline, from whom 614 with at least one follow-up were selected for longitudinal analysis. Cognitive tests were performed annually up to 5 years. CeVD markers of interest were lacunes, white matter hyperintensities (WMHs), cerebral microbleeds (CMBs), cortical microinfarcts (CMIs), intracranial stenosis (ICS), and cortical infarcts. Blood-based Alzheimer biomarkers, including p-tau181 and p-tau181/Aβ42 ratio, were used as indicators of Alzheimer pathology. RESULTS At baseline, diabetes was associated with lower cognitive performance and higher burden of CeVD, but not p-tau181 or p-tau181/Aβ42 ratio. Longitudinally, we found an interactive effect of diabetes and WMHs, rather than an independent effect of diabetes, on cognitive decline and dementia risk. Subgroup analyses showed association of diabetes with cognitive outcomes was stronger in participants with high WMHs load but non-significant in those with low WMHs load. Moreover, these associations remained unchanged after adjusting for blood-based Alzheimer biomarkers. CONCLUSIONS The effect of diabetes on cognitive decline is contingent upon the presence of WMHs and independent of Alzheimer's pathology. This finding raises the possibility of utilizing WMHs as an imaging biomarker to identify diabetic subgroup at greater risk of developing cognitive impairment. Furthermore, therapeutic interventions targeting WMHs may prevent cognitive deterioration in older adults with diabetes.
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Affiliation(s)
- Jiangbo Cui
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Memory Aging and Cognition Centre, National University Health System, Singapore, Singapore
| | - Caroline Robert
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Memory Aging and Cognition Centre, National University Health System, Singapore, Singapore
| | - Chia May Teh
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Memory Aging and Cognition Centre, National University Health System, Singapore, Singapore
| | - Eddie Chong Jun Yi
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Memory Aging and Cognition Centre, National University Health System, Singapore, Singapore
| | - Joyce R Chong
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Memory Aging and Cognition Centre, National University Health System, Singapore, Singapore
| | | | | | - Mitchell K P Lai
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Memory Aging and Cognition Centre, National University Health System, Singapore, Singapore
| | - Christopher Chen
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Memory Aging and Cognition Centre, National University Health System, Singapore, Singapore
| | - Saima Hilal
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
- Memory Aging and Cognition Centre, National University Health System, Singapore, Singapore.
- Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.
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Liu Y, He B, Du K, Zheng J, Ke D, Mo W, Li Y, Jiang T, Xiong R, Sun F, Zhao S, Wei W, Xu Z, Zhang S, Li S, Wang X, Zhou Q, Ye J, Liang Y, Lin H, Liu Y, Chen L, Zhang H, Zhang Y, Gao Y, Wang JZ. Periphery Biomarkers Predicting Conversion of Type 2 Diabetes to Pre-Alzheimer-Like Cognitive Decline: A Multicenter Follow-Up Study. J Alzheimers Dis 2024; 100:S115-S129. [PMID: 39058442 DOI: 10.3233/jad-240455] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/28/2024]
Abstract
Background The prevalence of Alzheimer's disease (AD) is increasing, therefore, identifying biomarkers to predict those vulnerable to AD is imperative. Type 2 diabetes (T2D) serves as an independent risk factor for AD. Early prediction of T2D patients who may be more susceptible to AD, so as to achieve early intervention, is of great significance to reduce the prevalence of AD. Objective To establish periphery biomarkers that could predict conversion of T2D into pre-AD-like cognitive decline. Methods A follow-up study was carried out from 159 T2D patients at baseline. The correlations of cognitive states (by MMSE score) with multi-periphery biomarkers, including APOE genotype, plasma amyloid-β level, platelet GSK-3β activity, and olfactory score were analyzed by logistic regression. ROC curve was used for establishing the prediction model. Additionally, MRI acquired from 38 T2D patients for analyzing the correlation among cognitive function, biomarkers and brain structure. Results Compared with the patients who maintained normal cognitive functions during the follow-up period, the patients who developed MCI showed worse olfactory function, higher platelet GSK-3β activity, and higher plasma Aβ42/Aβ40 ratio. We conducted a predictive model which T2D patients had more chance of suffering from pre-AD-like cognitive decline. The MRI data revealed MMSE scores were positively correlated with brain structures. However, platelet GSK-3β activity was negatively correlated with brain structures. Conclusions Elevated platelet GSK-3β activity and plasma Aβ42/Aβ40 ratio with reduced olfactory function are correlated with pre-AD-like cognitive decline in T2D patients, which used for predicting which T2D patients will convert into pre-AD-like cognitive decline in very early stage.
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Affiliation(s)
- Yanchao Liu
- Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Department of Pathophysiology, School of Basic Medicine, Ministry of Education Key Laboratory for Neurological Disorders, Hubei Key Laboratory for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Benrong He
- Department of Pathophysiology, School of Basic Medicine, Ministry of Education Key Laboratory for Neurological Disorders, Hubei Key Laboratory for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Department of Emergency of General Hospital of Central Theater Command, Wuhan, China
| | - Kai Du
- Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing, China
- National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, China
| | - Jie Zheng
- Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University. Key Laboratory for Neuroscience, Ministry of Education/National Health Commission, Peking University, Beijing, China
| | - Dan Ke
- Department of Pathophysiology, School of Basic Medicine, Ministry of Education Key Laboratory for Neurological Disorders, Hubei Key Laboratory for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Wen Mo
- Health Service Center of Jianghan District, Wuhan, China
| | - Yanni Li
- Health Service Center of Jianghan District, Wuhan, China
| | - Tao Jiang
- Department of Pathophysiology, School of Basic Medicine, Ministry of Education Key Laboratory for Neurological Disorders, Hubei Key Laboratory for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Rui Xiong
- Department of Pathophysiology, School of Basic Medicine, Ministry of Education Key Laboratory for Neurological Disorders, Hubei Key Laboratory for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Fei Sun
- Department of Pathophysiology, School of Basic Medicine, Ministry of Education Key Laboratory for Neurological Disorders, Hubei Key Laboratory for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Shi Zhao
- Department of Endocrinology, the Central Hospital of Wuhan, Wuhan, China
| | - Wei Wei
- Department of Endocrinology, the Central Hospital of Wuhan, Wuhan, China
| | - Zhipeng Xu
- Department of Neurology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Shujuan Zhang
- Department of Pathophysiology, School of Basic Medicine, Ministry of Education Key Laboratory for Neurological Disorders, Hubei Key Laboratory for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Shihong Li
- Department of Pathophysiology, School of Basic Medicine, Ministry of Education Key Laboratory for Neurological Disorders, Hubei Key Laboratory for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xin Wang
- Department of Pathophysiology, School of Basic Medicine, Ministry of Education Key Laboratory for Neurological Disorders, Hubei Key Laboratory for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Qiuzhi Zhou
- Department of Pathophysiology, School of Basic Medicine, Ministry of Education Key Laboratory for Neurological Disorders, Hubei Key Laboratory for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jinwang Ye
- Department of Pathophysiology, School of Basic Medicine, Ministry of Education Key Laboratory for Neurological Disorders, Hubei Key Laboratory for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yi Liang
- Department of Radiology, Wuhan Brain Hospital, Wuhan, China
| | - Hao Lin
- Department of Radiology, Wuhan Brain Hospital, Wuhan, China
| | - Yong Liu
- Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing, China
- National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, China
| | - Liangkai Chen
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Huaqiu Zhang
- Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yao Zhang
- Li-Yuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yang Gao
- Department of Pathophysiology, School of Basic Medicine, Ministry of Education Key Laboratory for Neurological Disorders, Hubei Key Laboratory for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Jian-Zhi Wang
- Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Department of Pathophysiology, School of Basic Medicine, Ministry of Education Key Laboratory for Neurological Disorders, Hubei Key Laboratory for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China
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Ottomana AM, Presta M, O'Leary A, Sullivan M, Pisa E, Laviola G, Glennon JC, Zoratto F, Slattery DA, Macrì S. A systematic review of preclinical studies exploring the role of insulin signalling in executive function and memory. Neurosci Biobehav Rev 2023; 155:105435. [PMID: 37913873 DOI: 10.1016/j.neubiorev.2023.105435] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Revised: 10/04/2023] [Accepted: 10/23/2023] [Indexed: 11/03/2023]
Abstract
Beside its involvement in somatic dysfunctions, altered insulin signalling constitutes a risk factor for the development of mental disorders like Alzheimer's disease and obsessive-compulsive disorder. While insulin-related somatic and mental disorders are often comorbid, the fundamental mechanisms underlying this association are still elusive. Studies conducted in rodent models appear well suited to help decipher these mechanisms. Specifically, these models are apt to prospective studies in which causative mechanisms can be manipulated via multiple tools (e.g., genetically engineered models and environmental interventions), and experimentally dissociated to control for potential confounding factors. Here, we provide a narrative synthesis of preclinical studies investigating the association between hyperglycaemia - as a proxy of insulin-related metabolic dysfunctions - and impairments in working and spatial memory, and attention. Ultimately, this review will advance our knowledge on the role of glucose metabolism in the comorbidity between somatic and mental illnesses.
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Affiliation(s)
- Angela Maria Ottomana
- Centre for Behavioural Sciences and Mental Health, Istituto Superiore di Sanità, 00161 Rome, Italy; Neuroscience Unit, Department of Medicine, University of Parma, 43100 Parma, Italy
| | - Martina Presta
- Centre for Behavioural Sciences and Mental Health, Istituto Superiore di Sanità, 00161 Rome, Italy; Department of Physiology and Pharmacology, Sapienza University of Rome, 00185 Rome, Italy
| | - Aet O'Leary
- Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt, Germany; Chair of Neuropsychopharmacology, Institute of Chemistry, University of Tartu, Tartu, Estonia
| | - Mairéad Sullivan
- Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Ireland
| | - Edoardo Pisa
- Centre for Behavioural Sciences and Mental Health, Istituto Superiore di Sanità, 00161 Rome, Italy
| | - Giovanni Laviola
- Centre for Behavioural Sciences and Mental Health, Istituto Superiore di Sanità, 00161 Rome, Italy
| | - Jeffrey C Glennon
- Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Ireland
| | - Francesca Zoratto
- Centre for Behavioural Sciences and Mental Health, Istituto Superiore di Sanità, 00161 Rome, Italy
| | - David A Slattery
- Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt, Germany
| | - Simone Macrì
- Centre for Behavioural Sciences and Mental Health, Istituto Superiore di Sanità, 00161 Rome, Italy.
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8
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Brown AD, Liese AD, Shapiro ALB, Frongillo EA, Wilkening G, Fridriksson J, Merchant AT, Henkin L, Jensen ET, Reboussin BA, Shah AS, Marcovina S, Dolan LM, Dabelea D, Pihoker C, Mendoza JA. Household Food Insecurity and Cognition in Youth and Young Adults with Youth-Onset Diabetes. Pediatr Diabetes 2023; 2023:6382663. [PMID: 38765732 PMCID: PMC11100256 DOI: 10.1155/2023/6382663] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/22/2024] Open
Abstract
Objective We evaluated the association of household food insecurity (FI) with cognition in youth and young adults with type 1 diabetes (T1D) or type 2 diabetes (T2D). Design In this cross-sectional study, age-adjusted scores for composite Fluid Cognition, and sub-domain scores for Receptive Language and Inhibitory Control and Attention, were modeled stratified by diabetes-type using linear regression, with FI in the past year as the predictor, controlling for covariates. Tests for processing speed, inhibitory control/attention, working memory, episodic memory, and cognitive flexibility were administered to measure composite Fluid Cognition score. The NIHT-CB Picture Vocabulary Test was used to assess Crystallized Cognition score and rapid identification of congruent versus noncongruent items were used to assess Inhibitory Control and Attention score. Setting The SEARCH for Diabetes in Youth study, representative of 5 U.S. states. Participants Included 1574 youth and young adults with T1D or T2D, mean age of 21 years, mean diabetes duration of 11 years, 51% non-Hispanic white, and 47% had higher HbA1c levels (>9% HbA1c). Results Approximately 18% of the 1,240 participants with T1D and 31% of the 334 with T2D experienced FI. The food-insecure group with T1D had a lower composite Fluid Cognition score (β= -2.5, 95% confidence interval (CI)= -4.8, -0.1) and a lower Crystallized Cognition score (β= -3.4, CI= -5.6, -1.3) than food-secure peers. Findings were attenuated to non-significance after adjustment for demographics. Among T2D participants, no associations were observed. In participants with T1D effect modification by glycemic levels were found in the association between FI and composite Fluid Cognition score but adjustment for socioeconomic characteristics attenuated the interaction (p=0.0531). Conclusions Food-insecure youth and young adults with T1D or T2D did not have different cognition compared to those who were food-secure after adjustment for confounders. Longitudinal research is needed to further understand relations amongst these factors.
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Affiliation(s)
- Andrea D. Brown
- Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, 915 Greene Street, Columbia, SC, USA 29208
| | - Angela D. Liese
- Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, 915 Greene Street, Columbia, SC, USA 29208
| | - Allison L. B. Shapiro
- Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, 13123 E 16th Ave, Aurora, CO, USA 80045
| | - Edward A. Frongillo
- Department of Health Promotion, Education, and Behavior, University of South Carolina, 915 Greene Street Columbia, SC, USA 29208
| | - Greta Wilkening
- Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, 13123 E 16th Ave, Aurora, CO, USA 80045
| | - Julius Fridriksson
- Department of Communication Sciences & Disorders, University of South Carolina, 1705 College Street Columbia, SC, USA 29208
| | - Anwar T. Merchant
- Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, 915 Greene Street, Columbia, SC, USA 29208
| | - Leora Henkin
- Department of Biostatistics and Data Science, Wake Forest School of Medicine, 475 Vine Street, Winston-Salem, NC, USA 27101
| | - Elizabeth T. Jensen
- Department of Epidemiology and Prevention, Wake Forest School of Medicine, 475 Vine Street, Winston-Salem, NC USA 27101
| | - Beth A. Reboussin
- Department of Biostatistics and Data Science, Wake Forest School of Medicine, 475 Vine Street, Winston-Salem, NC, USA 27101
| | - Amy S. Shah
- Department of Pediatrics, Division of Endocrinology, Cincinnati Children’s Hospital Medical Center and The University of Cincinnati, 3333 Burnet Avenue, MLC 4002 Cincinnati, OH, USA 45229
| | - Santica Marcovina
- Medpace Reference Laboratories, 5365 Medpace Way, Cincinnati, OH, USA 45227
| | - Lawrence M. Dolan
- Department of Pediatrics, Division of Endocrinology, Cincinnati Children’s Hospital Medical Center and The University of Cincinnati, 3333 Burnet Avenue, MLC 4002 Cincinnati, OH, USA 45229
| | - Dana Dabelea
- Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, 13123 E 16th Ave, Aurora, CO, USA 80045
- Department of Epidemiology, Colorado School of Public Health, Anschutz Medical Campus, 13001 E. 17th Place, Mail Stop B119, Aurora, CO, USA 80045
| | - Catherine Pihoker
- Department of Pediatrics, University of Washington, Box 356320, Seattle WA, USA 98115-8160
| | - Jason A. Mendoza
- Department of Pediatrics, University of Washington, Box 356320, Seattle WA, USA 98115-8160
- Seattle Children’s Research Institute, PO Box 5371, Seattle, WA, USA 98145-5005
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Diviccaro S, Cioffi L, Piazza R, Caruso D, Melcangi RC, Giatti S. Neuroactive Steroid-Gut Microbiota Interaction in T2DM Diabetic Encephalopathy. Biomolecules 2023; 13:1325. [PMID: 37759725 PMCID: PMC10527303 DOI: 10.3390/biom13091325] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Revised: 08/11/2023] [Accepted: 08/21/2023] [Indexed: 09/29/2023] Open
Abstract
The pathological consequences of type 2 diabetes mellitus (T2DM) also involve the central nervous system; indeed, T2DM patients suffer from learning and memory disabilities with a higher risk of developing dementia. Although several factors have been proposed as possible contributors, how neuroactive steroids and the gut microbiome impact brain pathophysiology in T2DM remain unexplored. On this basis, in male Zucker diabetic fatty (ZDF) rats, we studied whether T2DM alters memory abilities using the novel object recognition test, neuroactive steroid levels by liquid chromatography-tandem mass spectrometry, hippocampal parameters using molecular assessments, and gut microbiome composition using 16S next-generation sequencing. Results obtained reveal that T2DM worsens memory abilities and that these are correlated with increased levels of corticosterone in plasma and with a decrease in allopregnanolone in the hippocampus, where neuroinflammation, oxidative stress, and mitochondrial dysfunction were reported. Interestingly, our analysis highlighted a small group of taxa strictly related to both memory impairment and neuroactive steroid levels. Overall, the data underline an interesting role for allopregnanolone and microbiota that may represent candidates for the development of therapeutic strategies.
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Affiliation(s)
- Silvia Diviccaro
- Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, 20133 Milan, Italy; (S.D.); (L.C.); (D.C.); (R.C.M.)
| | - Lucia Cioffi
- Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, 20133 Milan, Italy; (S.D.); (L.C.); (D.C.); (R.C.M.)
| | - Rocco Piazza
- Dipartimento di Medicina e Chirurgia, Università di Milano—Bicocca, 20126 Milan, Italy;
| | - Donatella Caruso
- Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, 20133 Milan, Italy; (S.D.); (L.C.); (D.C.); (R.C.M.)
| | - Roberto Cosimo Melcangi
- Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, 20133 Milan, Italy; (S.D.); (L.C.); (D.C.); (R.C.M.)
| | - Silvia Giatti
- Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, 20133 Milan, Italy; (S.D.); (L.C.); (D.C.); (R.C.M.)
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10
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Sullivan M, Fernandez-Aranda F, Camacho-Barcia L, Harkin A, Macrì S, Mora-Maltas B, Jiménez-Murcia S, O'Leary A, Ottomana AM, Presta M, Slattery D, Scholtz S, Glennon JC. Insulin and Disorders of Behavioural Flexibility. Neurosci Biobehav Rev 2023; 150:105169. [PMID: 37059405 DOI: 10.1016/j.neubiorev.2023.105169] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 04/03/2023] [Accepted: 04/10/2023] [Indexed: 04/16/2023]
Abstract
Behavioural inflexibility is a symptom of neuropsychiatric and neurodegenerative disorders such as Obsessive-Compulsive Disorder, Autism Spectrum Disorder and Alzheimer's Disease, encompassing the maintenance of a behaviour even when no longer appropriate. Recent evidence suggests that insulin signalling has roles apart from its regulation of peripheral metabolism and mediates behaviourally-relevant central nervous system (CNS) functions including behavioural flexibility. Indeed, insulin resistance is reported to generate anxious, perseverative phenotypes in animal models, with the Type 2 diabetes medication metformin proving to be beneficial for disorders including Alzheimer's Disease. Structural and functional neuroimaging studies of Type 2 diabetes patients have highlighted aberrant connectivity in regions governing salience detection, attention, inhibition and memory. As currently available therapeutic strategies feature high rates of resistance, there is an urgent need to better understand the complex aetiology of behaviour and develop improved therapeutics. In this review, we explore the circuitry underlying behavioural flexibility, changes in Type 2 diabetes, the role of insulin in CNS outcomes and mechanisms of insulin involvement across disorders of behavioural inflexibility.
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Affiliation(s)
- Mairéad Sullivan
- Conway Institute of Biomedical and Biomolecular Research, School of Medicine, University College Dublin, Dublin, Ireland.
| | - Fernando Fernandez-Aranda
- Department of Psychiatry, University Hospital of Bellvitge, Barcelona, Spain; Psychoneurobiology of Eating and Addictive Behaviors Group, Neurosciences Program, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain; CIBER Fisiopatología Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Barcelona, Spain; Department of Clinical Sciences, School of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain
| | - Lucía Camacho-Barcia
- Department of Psychiatry, University Hospital of Bellvitge, Barcelona, Spain; Psychoneurobiology of Eating and Addictive Behaviors Group, Neurosciences Program, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain; CIBER Fisiopatología Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Barcelona, Spain
| | - Andrew Harkin
- School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Ireland
| | - Simone Macrì
- Centre for Behavioural Sciences and Mental Health, Istituto Superiore di Sanità, 00161 Rome, Italy
| | - Bernat Mora-Maltas
- Department of Psychiatry, University Hospital of Bellvitge, Barcelona, Spain; Psychoneurobiology of Eating and Addictive Behaviors Group, Neurosciences Program, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain
| | - Susana Jiménez-Murcia
- Department of Psychiatry, University Hospital of Bellvitge, Barcelona, Spain; Psychoneurobiology of Eating and Addictive Behaviors Group, Neurosciences Program, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain; CIBER Fisiopatología Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Barcelona, Spain; Department of Clinical Sciences, School of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain
| | - Aet O'Leary
- University Hospital Frankfurt, Frankfurt, Germany
| | - Angela Maria Ottomana
- Centre for Behavioural Sciences and Mental Health, Istituto Superiore di Sanità, 00161 Rome, Italy; Neuroscience Unit, Department of Medicine, University of Parma, 43100 Parma, Italy
| | - Martina Presta
- Centre for Behavioural Sciences and Mental Health, Istituto Superiore di Sanità, 00161 Rome, Italy; Department of Physiology and Pharmacology, Sapienza University of Rome, 00185 Rome, Italy
| | | | | | - Jeffrey C Glennon
- Conway Institute of Biomedical and Biomolecular Research, School of Medicine, University College Dublin, Dublin, Ireland
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11
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Zhang W, Chen S, Zhuang X. Research Progress on Lipocalin-2 in Diabetic Encephalopathy. Neuroscience 2023; 515:74-82. [PMID: 36805002 DOI: 10.1016/j.neuroscience.2023.02.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2022] [Revised: 02/07/2023] [Accepted: 02/12/2023] [Indexed: 02/18/2023]
Abstract
Diabetic encephalopathy is a central nervous complication of diabetes mellitus which is characterized by cognitive impairment and structural and neurochemical abnormalities, which is easily neglected. Lipocalin-2 (LCN2) is a 25 kDa transporter in the lipocalin family that can transport small molecules, including fatty acids, iron, steroids, and lipopolysaccharides in the circulation. Recently, LCN2 has been found to be a significant regulator of insulin resistance and glucose homeostasis. Numerous studies have shown that LCN2 is connected to central nervous system abnormalities, including neuroinflammation and neurodegeneration, while the latest researches have found that LCN2 is closely related to the development of diabetic encephalopathy. Nevertheless, its precise role in the pathogenesis of diabetic encephalopathy remains to be determined. In this paper, we review recent evidence on the role of LCN2 in diabetic encephalopathy from multiple perspectives in order to decipher the impact of LCN2 in both the aetiology and treatment of diabetic encephalopathy.
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Affiliation(s)
- Wenjie Zhang
- Cheeloo College of Medicine, Shangdong University, Jinan 250000, China
| | - Shihong Chen
- Department of Endocrinology, The Second Hospital of Shandong University, Jinan 250000, China.
| | - Xianghua Zhuang
- Department of Endocrinology, The Second Hospital of Shandong University, Jinan 250000, China.
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12
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Kálcza Jánosi K, Lukács A. Independent and interactive effect of type 2 diabetes and hypertension on memory functions in middle aged adults. BMC Endocr Disord 2023; 23:59. [PMID: 36894922 PMCID: PMC9999571 DOI: 10.1186/s12902-023-01308-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Accepted: 02/21/2023] [Indexed: 03/11/2023] Open
Abstract
BACKGROUND The study distinguishes the effect of type 2 diabetes and hypertension on cognitive functions when the two diseases are alone or when they occur together, compared to healthy individuals. METHODS A total of 143 middle-aged adults were screened using the Wechsler Memory Scale - Revised psychometric test (verbal memory, visual memory, attention/concentration and delayed memory). Participants were divided into four groups based on their diseases: patients with type 2 diabetes (36), patients with hypertension (30), patients having both diseases (33), and healthy controls (44). RESULTS This study found no differences among investigated groups in verbal and visual memory, however, hypertension and both-disease group performed unfavorably compared to patients with diabetes and to healthy individuals in attention/concentration and delayed memory. CONCLUSIONS The findings of this study suggest that there is a relationship between hypertension and cognitive dysfunction, whereas type 2 diabetes without consequences was not proved to have an association with cognitive decline in middle-aged people.
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Affiliation(s)
- Kinga Kálcza Jánosi
- Faculty of Psychology and Educational Sciences, Babes-Bolyai University, 7, Sindicatelor Street, 400604 Cluj-Napoca-Napoca, Romania
| | - Andrea Lukács
- Faculty of Health Sciences, University of Miskolc, 3515 Miskolc-Egyetemváros, Hungary
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13
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Zhang G, Liu T, Wei W, Zhang R, Wang H, Wang M. Evaluation of altered brain activity in type 2 diabetes using various indices of brain function: A resting-state functional magnetic resonance imaging study. Front Hum Neurosci 2023; 16:1032264. [PMID: 36699964 PMCID: PMC9870028 DOI: 10.3389/fnhum.2022.1032264] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Accepted: 12/05/2022] [Indexed: 01/11/2023] Open
Abstract
Background Type 2 diabetes mellitus (T2DM) has been identified as a risk factor that increases the rate of cognitive decline. Previous studies showed that patients with T2DM had brain function alterations based on a single index of resting-state functional magnetic resonance imaging (rs-fMRI). The present study aimed to explore spontaneous brain activity in patients with T2DM by comparing various rs-fMRI indices, and to determine the relationship between these changes and cognitive dysfunction. Methods A total of 52 patients with T2DM and age- and sex-matched control participants were included in this study. The amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), and voxel-mirrored homotopic connectivity (VMHC) values were calculated to represent the status of spontaneous neural activity. The Montreal Cognitive Assessment (MoCA) was used for the rapid evaluation of cognition in all subjects. Pearson correlation and mediation analyses were conducted to investigate the relationship between rs-fMRI indices and clinical parameters such as fasting glucose, disease duration, and MoCA. Results Patients with T2DM had alterations of concordant spontaneous brain activity in brain areas including the bilateral cerebellum posterior lobe, the left inferior temporal gyrus (ITG.L), the parahippocampal gyrus, and the left supplementary motor area (SMA.L). The indices were significantly correlated to each other in most of the detected brain areas. Positive correlations were observed between fasting glucose and neural activity in the surrounding areas of the left insula and the inferior frontal gyrus. MoCA scores were negatively correlated with the ReHo values extracted from the left anterior occipital lobe and the superior cerebellar cortex and were positively correlated with VMHC values extracted from the left caudate and the precentral gyrus (PreCG). No significant mediation effect of abnormal brain activity was found in the relationship between clinical parameters and MoCA scores. Conclusion The current study demonstrated the functional concordance of abnormal brain activities in patients with T2DM by comparing ALFF, ReHo, and VMHC measurements. Widespread abnormalities mainly involved in motor and sensory processing functions may provide insight into examining T2DM-related neurological pathophysiology.
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Affiliation(s)
- Ge Zhang
- Department of Radiology, Henan Provincial People's Hospital, Zhengzhou, China,Department of Radiology, Bethune International Peace Hospital, Shijiazhuang, China
| | - Taiyuan Liu
- Department of Radiology, Henan Provincial People's Hospital, Zhengzhou, China
| | - Wei Wei
- Department of Radiology, Henan Provincial People's Hospital, Zhengzhou, China
| | - Rui Zhang
- Department of Radiology, Henan Provincial People's Hospital, Zhengzhou, China
| | - Huilin Wang
- Department of Radiology, Bethune International Peace Hospital, Shijiazhuang, China,*Correspondence: Huilin Wang ✉
| | - Meiyun Wang
- Department of Radiology, Henan Provincial People's Hospital, Zhengzhou, China,Laboratory of Brian Science and Brain-Like Intelligence Technology, Institute for Integrated Medical Science and Engineering, Henan Academy of Sciences, Zhengzhou, China,Meiyun Wang ✉
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14
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Snyder LL, Foland-Ross LC, Cato A, Reiss AL, Shah C, Hossain J, Elmufti H, Nelly Mauras. Impact of dysglycemia and obesity on the brain in adolescents with and without type 2 diabetes: A pilot study. Pediatr Diabetes 2022; 23:1674-1686. [PMID: 36131363 DOI: 10.1111/pedi.13420] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Revised: 08/04/2022] [Accepted: 09/17/2022] [Indexed: 12/29/2022] Open
Abstract
OBJECTIVE Both diabetes and obesity can affect the brain, yet their impact is not well characterized in children with type 2 (T2) diabetes and obesity. This pilot study aims to explore differences in brain function and cognition in adolescents with T2 diabetes and obesity and nondiabetic controls with obesity and lean controls. RESEARCH DESIGN AND METHODS Participants were 12-17 years old (5 T2 diabetes with obesity [mean HgbA1C 10.9%], 6 nondiabetic controls with obesity and 10 lean controls). Functional MRI (FMRI) during hyperglycemic/euglycemic clamps was performed in the T2 diabetes group. RESULTS When children with obesity, with and without diabetes, were grouped (mean BMI 98.8%), cognitive scores were lower than lean controls (BMI 58.4%) on verbal, full scale, and performance IQ, visual-spatial and executive function tests. Lower scores correlated with adiposity and insulin resistance but not HgbA1C. No significant brain activation differences during task based and resting state FMRI were noted between children with obesity (with or without diabetes) and lean controls, but a notable effect size for the visual-spatial working memory task and resting state was observed. CONCLUSIONS In conclusion, our pilot study suggests that obesity, insulin resistance, and dysglycemia may contribute to relatively poorer cognitive function in adolescents with T2 diabetes and obesity. Further studies with larger sample size are needed to assess if cognitive decline in children with obesity, with and without T2 diabetes, can be prevented or reversed.
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Affiliation(s)
- Lydia L Snyder
- Nemours Children's Health, Pediatric Endocrinology, Jacksonville, Florida, USA
| | - Lara C Foland-Ross
- Center for Interdisciplinary Brain Sciences Research, Stanford University, Stanford, California, USA
| | - Allison Cato
- Nemours Children's Health, Pediatric Neuropsychology, Jacksonville, Florida, USA
| | - Allan L Reiss
- Center for Interdisciplinary Brain Sciences Research, Stanford University, Stanford, California, USA
| | - Chetan Shah
- Nemours Children's Health, Pediatric Neuroradiology, Jacksonville, Florida, USA
| | - Jobayer Hossain
- Nemours Children's Health, Nemours Biomedical Research, Biostatistics Core, Wilmington, Delaware, USA
| | - Hussein Elmufti
- Nemours Children's Health, Pediatric Endocrinology, Jacksonville, Florida, USA
| | - Nelly Mauras
- Nemours Children's Health, Pediatric Endocrinology, Jacksonville, Florida, USA
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15
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Pasqualetti G, Thayanandan T, Edison P. Influence of genetic and cardiometabolic risk factors in Alzheimer's disease. Ageing Res Rev 2022; 81:101723. [PMID: 36038112 DOI: 10.1016/j.arr.2022.101723] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2022] [Revised: 08/18/2022] [Accepted: 08/21/2022] [Indexed: 01/31/2023]
Abstract
Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder. Cardiometabolic and genetic risk factors play an important role in the trajectory of AD. Cardiometabolic risk factors including diabetes, mid-life obesity, mid-life hypertension and elevated cholesterol have been linked with cognitive decline in AD subjects. These potential risk factors associated with cerebral metabolic changes which fuel AD pathogenesis have been suggested to be the reason for the disappointing clinical trial results. In appreciation of the risks involved, using search engines such as PubMed, Scopus, MEDLINE and Google Scholar, a relevant literature search on cardiometabolic and genetic risk factors in AD was conducted. We discuss the role of genetic as well as established cardiovascular risk factors in the neuropathology of AD. Moreover, we show new evidence of genetic interaction between several genes potentially involved in different pathways related to both neurodegenerative process and cardiovascular damage.
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Affiliation(s)
| | - Tony Thayanandan
- Department of Brain Sciences, Faculty of Medicine, Imperial College London, UK
| | - Paul Edison
- Department of Brain Sciences, Faculty of Medicine, Imperial College London, UK; School of Medicine, Cardiff University, UK.
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16
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Guo Y, Luo N, Kang X. Potential mechanism of the Shunaoxin pill for preventing cognitive impairment in type 2 diabetes mellitus. Front Neurol 2022; 13:977953. [PMID: 36341127 PMCID: PMC9633951 DOI: 10.3389/fneur.2022.977953] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2022] [Accepted: 09/26/2022] [Indexed: 11/13/2022] Open
Abstract
Objective This study aims to analyze the efficacy and mechanism of action of the Shunaoxin pill in preventing cognitive impairment in diabetic patients using network pharmacology. Methods The main active compounds of the Shunaoxin pills and their action targets were identified via the TCMSP and Batman-TCM databases. The GEO database was used to identify the genes in type 2 diabetic individuals associated with cognitive impairment. Subsequently, a common target protein-protein interaction (PPI) network was constructed using the STRING database, and targets associated with diabetes and cognitive impairment were screened by performing a topological analysis of the PPI network. The AutoDock Vina software was used for molecular docking to evaluate the reliability of the bioinformatic analysis predictions and validate the interactions between the active ingredients of the Shunaoxin pill and proteins associated with diabetes and cognitive impairment. Results Based on the TCMSP and Batman-Tcm platform, 48 active ingredients of the Shunaoxin pill were identified, corresponding to 222 potential action targets. Further analysis revealed that 18 active components of the Shunaoxin pill might contribute to cognitive impairment in type 2 diabetic patients. Molecular docking simulations demonstrated that the active ingredients of the Shunaoxin pill (hexadecanoic acid, stigmasterol, beta-sitosterol, and angelicin) targeted four core proteins: OPRK1, GABRA5, GABRP, and SCN3B. Conclusion Active ingredients of the Shunaoxin pill may alleviate cognitive impairment in diabetic patients by targeting the proteins OPRK1, GABRA5, GABRP, and SCN3B.
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Affiliation(s)
- Yuejie Guo
- Department of Geriatrics, The First People's Hospital of Chenzhou, Chenzhou, China
- *Correspondence: Yuejie Guo
| | - Ning Luo
- Department of Endocrinology, The First People's Hospital of Chenzhou, Chenzhou, China
| | - Xueran Kang
- Shanghai Jiao Tong University College of Basic Sciences, Shanghai, China
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Verhagen C, Janssen J, Minderhoud CA, van den Berg E, Wanner C, Passera A, Johansen OE, Biessels GJ. Chronic kidney disease and cognitive decline in patients with type 2 diabetes at elevated cardiovascular risk. J Diabetes Complications 2022; 36:108303. [PMID: 36116359 DOI: 10.1016/j.jdiacomp.2022.108303] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Revised: 08/24/2022] [Accepted: 08/27/2022] [Indexed: 11/18/2022]
Abstract
AIMS We addressed the question whether chronic kidney disease (CKD) may contribute to cognitive decline in type 2 diabetes. METHODS Participants with type 2 diabetes with elevated cardiovascular risk or CKD from cognition substudies of two large trials were studied prospectively (CARMELINA: n = 2666, mean ± SD age 68.1 ± 8.7 years, CAROLINA: n = 4296; 64.7 ± 9.4 years). Estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) at baseline were related to cognitive performance (Mini-Mental State Examination (MMSE) and attention and executive functioning score (A&E)) in linear regression analyses, adjusted for demographics, cardiovascular risk factors and treatment, at baseline and follow-up. RESULTS CKD at baseline was more common in CARMELINA than CAROLINA (eGFR<60 in 72.6 % and 19.6 %, macroalbuminuria in 35.0 % and 4.1 %, respectively). Baseline eGFR was related to A&E in CARMELINA (b = 0.02 per 10 ml/min/1.73m2, 95%CI [0.01,0.03]). Baseline UACR was related to A&E in CAROLINA (b = -0.01 per doubling of UACR mg/g, 95%CI [-0.02,-0.002]). Baseline UACR predicted decline in A&E in CAROLINA (median 6.1 years follow-up; b = -0.01, 95%CI [-0.03,-0.0001] per doubling of UACR mg/g). CONCLUSIONS eGFR and UACR were associated with A&E in two cohorts with type 2 diabetes, enriched for CKD and cardiovascular disease. The small effect size estimates indicate limited impact of kidney dysfunction on cognition in this setting. GOV IDENTIFIERS NCT01897532 NCT01243424.
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Affiliation(s)
- Chloë Verhagen
- Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, the Netherlands.
| | - Jolien Janssen
- Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, the Netherlands.
| | - Crista A Minderhoud
- Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, the Netherlands.
| | - Esther van den Berg
- Department of Neurology and Alzheimer Center Erasmus MC, Erasmus MC University Medical Center, Rotterdam, the Netherlands.
| | - Christoph Wanner
- Department of Medicine, Division of Nephrology, Würzburg University Clinic, Würzburg, Germany.
| | - Anna Passera
- Clinical Development & Analytics, Novartis Pharma, Basel, Switzerland.
| | - Odd Erik Johansen
- Cardiometabolic Clinical Development, Nestlé Health Science, Vevey, Switzerland.
| | - Geert Jan Biessels
- Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, the Netherlands.
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Marissal-Arvy N, Moisan MP. Diabetes and associated cognitive disorders: Role of the Hypothalamic-Pituitary Adrenal axis. Metabol Open 2022; 15:100202. [PMID: 35958117 PMCID: PMC9357829 DOI: 10.1016/j.metop.2022.100202] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Revised: 07/18/2022] [Accepted: 07/20/2022] [Indexed: 11/12/2022] Open
Abstract
Both diabetes types, types 1 and 2, are associated with cognitive impairments. Each period of life is concerned, and this is an increasing public health problem. Animal models have been developed to investigate the biological actors involved in such impairments. Many levels of the brain function (structure, volume, neurogenesis, neurotransmission, behavior) are involved. In this review, we detailed the part potentially played by the Hypothalamic-Pituitary Adrenal axis in these dysfunctions. Notably, regulating glucocorticoid levels, their receptors and their bioavailability appear to be relevant for future research studies, and treatment development.
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Affiliation(s)
- Nathalie Marissal-Arvy
- INRAE, Laboratoire de Nutrition et Neurobiologie Intégrée, UMR 1286, UFR de Pharmacie, 146 Rue Léo Saignat, 33076, Bordeaux Cedex, France
| | - Marie-Pierre Moisan
- University of Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286, 33000, Bordeaux, France
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Could salt intake directly affect the cerebral microvasculature in hypertension? J Stroke Cerebrovasc Dis 2022; 31:106632. [PMID: 35870266 DOI: 10.1016/j.jstrokecerebrovasdis.2022.106632] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Revised: 06/26/2022] [Accepted: 06/30/2022] [Indexed: 11/23/2022] Open
Abstract
OBJECTIVES Excess dietary salt and chronic kidney disease (CKD) are acknowledged stroke risk factors. The development of small vessel disease, similarly affecting the cerebral and renal microvasculatures, may be an important mechanistic link underlying this interaction. Therefore, we aimed to evaluate if the dietary salt intake and markers of CKD (estimated glomerular filtration rate, albuminuria) relate to transcranial Doppler (TCD) markers of cerebral small vessel disease (CSVD) in hypertensive patients. MATERIALS AND METHODS Fifty-six hypertensive patients (57% with diabetes) underwent TCD monitoring in the middle (MCA) and posterior (PCA) cerebral arteries for evaluating neurovascular coupling (NVC), dynamic cerebral autoregulation (dCA), and vasoreactivity to carbon dioxide (VRCO2). We investigated the relation between renal parameters and TCD studies using Pearson's correlation coefficient and linear regression analyses. RESULTS There were no associations between dCA, VRCO2, NVC, and renal function tests. However, there was a negative association between the daily salt intake and the natural frequency during visual stimulation (r2=0.101, ß=-0.340, p=0.035), indicative of increased rigidity of the cerebral resistance vessels that react to cognitive activation. CONCLUSIONS In this cross-sectional study, we found an association between excess dietary salt consumption and CSVD in hypertensive patients. Future research is needed to evaluate whether the natural frequency could be an early, non-invasive, surrogate marker for microvascular dysfunction in hypertension.
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Xie K, Perna L, Schöttker B, Kliegel M, Brenner H, Mons U. Type 2 diabetes mellitus and cognitive decline in older adults in Germany - results from a population-based cohort. BMC Geriatr 2022; 22:455. [PMID: 35619073 PMCID: PMC9137064 DOI: 10.1186/s12877-022-03151-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Accepted: 05/09/2022] [Indexed: 11/11/2022] Open
Abstract
Background A large body of evidence supports a link between type 2 diabetes mellitus (T2DM) and cognitive function, including dementia. However, longitudinal studies on the association between T2DM and decline of cognitive function are scarce and reported mixed results, and we hence set out to investigate the cross-sectional and longitudinal association between T2DM and global as well as domain-specific cognitive performance. Methods We used multivariable regression models to assess associations of T2DM with cognitive performance and cognitive decline in a subsample of a population-based prospective cohort study (ESTHER). This subsample (n = 732) was aged 70 years and older and had participated in telephone-based cognitive function assessment (COGTEL) measuring global and domain-specific cognitive performance during the 5- and 8-year follow-up. Results Total COGTEL scores of patients with prevalent T2DM were 27.4 ± 8.3 and 29.4 ± 8.7 at the 5- and 8-year measurements, respectively, and were roughly two points lower than those of T2DM-free participants after adjustment for age and sex. In cross-sectional models, after adjustment for several potential confounders, performance in verbal short-term and long-term memory tasks was statistically significantly lower in participants with T2DM, but the association was attenuated after further adjustment for vascular risk factors. The difference in total COGTEL scores reflecting global cognitive function by T2DM status after full adjustment for confounders and vascular risk factors was equivalent to a decrement in global cognitive function associated with a four-year age difference. In longitudinal models, a statistically significantly stronger cognitive decline in patients with T2DM was observed for working memory. Conclusions In this sample of older individuals, T2DM was associated with worse performance and stronger decline in a cognitive function test. Memory-related domains were found to be particularly sensitive to T2DM. Further large-scale prospective studies are needed to clarify potential T2DM-related predictors of cognitive decline and possible consequences on the abilities to perform patient self-management tasks in diabetes care. Supplementary Information The online version contains supplementary material available at 10.1186/s12877-022-03151-y.
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Affiliation(s)
- Kun Xie
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.,Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany
| | - Laura Perna
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.,Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany
| | - Ben Schöttker
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.,Network Aging Research (NAR), Heidelberg University, Heidelberg, Germany
| | - Matthias Kliegel
- Department of Psychology, University of Geneva, Geneva, Switzerland
| | - Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.,Network Aging Research (NAR), Heidelberg University, Heidelberg, Germany
| | - Ute Mons
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. .,Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.
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21
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Zhou H, Hu J, Xie P, Dong Y, Chen W, Wu H, Jiang Y, Lei H, Luo G, Liu J. Lacunes and type 2 diabetes mellitus have a joint effect on cognitive impairment: a retrospective study. PeerJ 2022; 10:e13069. [PMID: 35261824 PMCID: PMC8898547 DOI: 10.7717/peerj.13069] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Accepted: 02/15/2022] [Indexed: 01/12/2023] Open
Abstract
Objective To evaluate the joint effects of cerebral small vessel disease (CSVD)-related imaging biomarkers in patients of type 2 diabetes mellitus (T2DM) with cognitive impairment. Methods This study is a retrospective cohort study. A total of 227 participants (115 patients with T2DM and 112 healthy control subjects) were enrolled in this study. Cognitive function assessments were evaluated using the Mini-Mental State Examination and the Montreal Cognitive Assessment. The burden of CSVD markers, including the lacunes, white matter hyperintensities (WMH), cerebral microbleeds (CMBs), and enlarged perivascular spaces (PVS), was identified by magnetic resonance imaging and evaluated using small vessel disease (SVD) scores (0-4). The subjects were divided into two groups based on the results of the cognitive function assessments. The synergy index was used to estimate the biological interactions between T2DM and lacunes. Results There was a significant correlation between T2DM and cognitive impairment (p < 0.001, χ2 test). In patients with diabetes, cognitive impairment was significantly associated with both the presence of lacunes (p < 0.01, χ2 test) and increased total SVD burden scores (p < 0.01, χ2 test). Regarding CMBs, only the existence of lobar CMBs was correlated with cognitive impairment (p < 0.05, χ2 test). The joint effect tended to be larger than the independent effects of T2DM and lacunes on cognitive impairment (adjusted odds ratio [OR]: 7.084, 95% CI [2.836-17.698]; synergy index: 10.018, 95% CI [0.344-291.414]). Conclusions T2DM and the presence of lacunes are significantly correlated with cognitive impairment. There was a joint effect of T2DM and lacunes on cognitive impairment.
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Verhagen C, Janssen J, Biessels GJ, Johansen OE, Exalto LG. Females with type 2 diabetes are at higher risk for accelerated cognitive decline than males: CAROLINA-COGNITION study. Nutr Metab Cardiovasc Dis 2022; 32:355-364. [PMID: 34895804 DOI: 10.1016/j.numecd.2021.10.013] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 10/02/2021] [Accepted: 10/18/2021] [Indexed: 01/21/2023]
Abstract
BACKGROUND AND AIM Cognitive dysfunction is increasingly recognized as an important comorbidity of type 2 diabetes (T2D). We aimed to establish if the risk of accelerated cognitive decline (ACD) is higher in females with T2D than males. METHODS AND RESULTS 3163 participants (38% female) with T2D from the cognition substudy of CAROLINA® (NCT01243424) were included (mean age 64.4 ± 9.2 years; T2D duration 7.6 ± 6.1 years). The cognitive outcome was occurrence of ACD at end of follow-up, defined as a regression based index score ≤16th percentile on either the Mini-Mental State Examination (MMSE) or a composite measure of attention and executive functioning (Trail Making and Verbal Fluency Test). Potential confounders, were taken into account at an individual patient level. Logistic regression analysis was used to investigate ACD risk by sex. We assessed potential mediators for sex differences in ACD using Causal Mediation Analysis (CMA). After a median follow-up duration of 6.1 ± 0.7 years, 361 (30.0%) females compared to 494 (25.2%) males exhibited ACD (OR 1.27 [95%CI 1.08-1.49], p = .003). Depressive symptoms, which were more common in females (24.3% vs 12.5%), mediated between sex and ACD (mediation effect 20.3%, p = 0.03). There were no other significant mediators. CONCLUSION Females with T2D had a higher risk of ACD compared to males. This was partly explained by depressive symptoms. After evaluation of vascular and diabetes-related risk factors, complications and treatment, a major share of the higher risk of ACD in females remained unexplained. Our results highlight the need for further research on causes of sex-specific ACD in T2D.
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Affiliation(s)
- Chloë Verhagen
- Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, the Netherlands.
| | - Jolien Janssen
- Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, the Netherlands.
| | - Geert Jan Biessels
- Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, the Netherlands.
| | - Odd Erik Johansen
- Cardiometabolic Clinical Development, Nestlé Health Science, Vevey, Switzerland.
| | - Lieza G Exalto
- Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, the Netherlands.
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Lei H, Hu R, Luo G, Yang T, Shen H, Deng H, Chen C, Zhao H, Liu J. Altered Structural and Functional MRI Connectivity in Type 2 Diabetes Mellitus Related Cognitive Impairment: A Review. Front Hum Neurosci 2022; 15:755017. [PMID: 35069149 PMCID: PMC8770326 DOI: 10.3389/fnhum.2021.755017] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Accepted: 12/13/2021] [Indexed: 12/16/2022] Open
Abstract
Type 2 diabetes mellitus (T2DM) is associated with cognitive impairment in many domains. There are several pieces of evidence that changes in neuronal neuropathies and metabolism have been observed in T2DM. Structural and functional MRI shows that abnormal connections and synchronization occur in T2DM brain circuits and related networks. Neuroplasticity and energy metabolism appear to be principal effector systems, which may be related to amyloid beta (Aβ) deposition, although there is no unified explanation that includes the complex etiology of T2DM with cognitive impairment. Herein, we assume that cognitive impairment in diabetes may lead to abnormalities in neuroplasticity and energy metabolism in the brain, and those reflected to MRI structural connectivity and functional connectivity, respectively.
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Borhaninejad V, Saber M. Comparison of cognitive status of diabetic and non-diabetic elderly in the last ten years in primary health care in Iran. ACTA FACULTATIS MEDICAE NAISSENSIS 2022. [DOI: 10.5937/afmnai39-34820] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022] Open
Abstract
Introduction. Cognitive disorders and chronic diseases such as diabetes are common problems of aging. The aim of this study was to determine and compare the cognitive status of diabetic and non-diabetic elderly in the past ten years in primary health care in Iran. Method: This cross-sectional study was performed on people aged 60 years and older in Kerman, Iran in 2020. In total, this study was performed on 200 patients (100 diabetic and 100 non-diabetic) meeting inclusion criteria. The Short Mental Status Questionnaire (MMSE) and The Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE) were used to assess cognitive function. The validity and reliability of the questionnaires were confirmed in this study. Data were analyzed using Chi-square, T-test, and ANOVA analysis in SPSS 21 software. Results. The results showed that there was a statistically significant difference between diabetic and non-diabetic groups in the current cognitive status and cognitive status in the last ten years. The mean scores of cognitive function from the short mental status questionnaire in the diabetic group were lower than in the non-diabetic group (p = 0.001). The mean scores of the cognitive deficit screening questionnaire in diabetic elderly were higher than in non-diabetic elderly (p < 0.001). Conclusion. Based on the results of this study, health care providers and family physicians should focus on controlling diabetes and identifying any cognitive impairment in the early stages of comprehensive care of diabetic patients.
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Klein C, Müssig K, Adamek HE. Sport reduziert den diabetesassoziierten Verlust kognitiver Fähigkeiten bei Typ-2-Diabetes-Patienten. DIABETOL STOFFWECHS 2021. [DOI: 10.1055/a-1527-9733] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
ZusammenfassungKognitive Defizite entwickeln sich bei T2D-Patienten häufig auf dem Boden metabolischer Störungen. Neben den eher mild ausfallenden, aber klinisch relevanten diabetesassoziierten kognitiven Dysfunktionen geht T2 D ebenfalls mit einem erhöhten Risiko für Demenz verschiedener Ursachen einher. Die zugrunde liegenden Mechanismen, die zu einer diabetesassoziierten kognitiven Dysfunktion führen, sind nicht vollständig geklärt. Trainingsinterventionen bieten die Möglichkeit, mögliche metabolische Risikofaktoren zu verringern und gleichzeitig dadurch die diabetesassoziierten kognitiven Verschlechterungen zu reduzieren. Unklar ist allerdings noch, welche Trainingsart und -intensität den größten gesundheitlichen Nutzen bringt, da bisherige Studienergebnisse wegen unterschiedlicher Kohorten, Interventionsmethoden und Interventionsdauern schwer zu vergleichen sind.
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Affiliation(s)
- Caroline Klein
- Medizinische Klinik 2 (Gastroenterologie, Hepatologie, Diabetologie), Klinikum Leverkusen, Leverkusen
| | - Karsten Müssig
- Klinik für Innere Medizin und Gastroenterologie, Niels-Stensen-Kliniken, Franziskus-Hospital Harderberg, Georgsmarienhütte
| | - Henning E. Adamek
- Medizinische Klinik 2 (Gastroenterologie, Hepatologie, Diabetologie), Klinikum Leverkusen, Leverkusen
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26
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Lutski M, Zucker I, Bardugo A, Bendor CD, Derazne E, Tzur D, Novick D, Raz I, Pinhas-Hamiel O, Mosenzon O, Afek A, Gerstein HC, Twig G, Cukierman-Yaffe T. Adolescent cognitive function and incident early-onset type 2 diabetes. EClinicalMedicine 2021; 41:101138. [PMID: 34622185 PMCID: PMC8479622 DOI: 10.1016/j.eclinm.2021.101138] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Revised: 08/29/2021] [Accepted: 09/06/2021] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Cognitive function among apparently healthy adolescents has been associated with cardiovascular morbidity and mortality. We examined the relationship between global and subdomain cognitive scores in adolescence and early-onset type 2 diabetes (T2D) in men and women. METHODS A nationwide, population-based study of 971,677 Israeli born adolescents (56% men; mean age 17.4 years) who were medically examined and their cognitive performance was assessed before compulsory military service during 1992-2010. Data included global and subdomain cognitive Z-scores (problem-solving, verbal abstraction and categorization, verbal comprehension, and mathematical abilities). Data were linked to the Israeli National Diabetes Registry. The relations between global and subdomain scores and incident T2D was determined using Cox proportional hazard models and logistic regression models. Analyses were conducted separately for men and women. FINDINGS During 16,095,122 person-years, 3,570 individuals developed T2D. After adjustment, those in the low compared to the high quintile of global cognitive Z-score had the highest risk for T2D; HR 2.46, (95% CI 2.10-2.88) for men and 2.33 (95% CI 1.88-2.89) for women. A one-unit lower global cognitive Z-score was associated with 1.41 (95% CI 1.34-1.48) and 1.46 (95% CI 1.36-1.56) increased risks for men and women, respectively. The relationship was noted for the cognitive subdomains scores as well as for the global cognitive score, with no heterogeneity across cognitive subdomains. INTERPRETATION This large nationally representative cohort suggests relationship between global, as well as subdomain cognitive scores in late adolescence, and incident early onset T2D in both sexes, which was independent of socioeconomic status.
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Affiliation(s)
- Miri Lutski
- The Israel Center for Disease Control, Ministry of Health, Ramat Gan, Israel
- Department of Epidemiology and Preventive Medicine, Sackler Faculty of Medicine, School of Public Health, Tel Aviv University, Tel-Aviv, Israel
| | - Inbar Zucker
- The Israel Center for Disease Control, Ministry of Health, Ramat Gan, Israel
- Department of Epidemiology and Preventive Medicine, Sackler Faculty of Medicine, School of Public Health, Tel Aviv University, Tel-Aviv, Israel
| | - Aya Bardugo
- Department of Military Medicine, Hebrew University, Jerusalem and the Israel Defense Forces Medical Corps, Ramat Gan, Israel
| | - Cole D. Bendor
- Department of Military Medicine, Hebrew University, Jerusalem and the Israel Defense Forces Medical Corps, Ramat Gan, Israel
| | - Estela Derazne
- Department of Epidemiology and Preventive Medicine, Sackler Faculty of Medicine, School of Public Health, Tel Aviv University, Tel-Aviv, Israel
| | - Dorit Tzur
- Department of Military Medicine, Hebrew University, Jerusalem and the Israel Defense Forces Medical Corps, Ramat Gan, Israel
| | - Deborah Novick
- The Israel Center for Disease Control, Ministry of Health, Ramat Gan, Israel
| | - Itamar Raz
- Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
- Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Center, Jerusalem, Israel
| | - Orit Pinhas-Hamiel
- Department of Epidemiology and Preventive Medicine, Sackler Faculty of Medicine, School of Public Health, Tel Aviv University, Tel-Aviv, Israel
- Pediatric Endocrine and Diabetes Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Israel
| | - Ofri Mosenzon
- Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
- Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Center, Jerusalem, Israel
| | - Arnon Afek
- Central Management, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
| | - Hertzel C. Gerstein
- Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Canada
| | - Gilad Twig
- Department of Epidemiology and Preventive Medicine, Sackler Faculty of Medicine, School of Public Health, Tel Aviv University, Tel-Aviv, Israel
- Department of Military Medicine, Hebrew University, Jerusalem and the Israel Defense Forces Medical Corps, Ramat Gan, Israel
- Institute of Endocrinology, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
- Corresponding author at: Department of Military Medicine, Hebrew University, Jerusalem and the Israel Defense Forces Medical Corps, and Institute of Endocrinology, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.
| | - Tali Cukierman-Yaffe
- Department of Epidemiology and Preventive Medicine, Sackler Faculty of Medicine, School of Public Health, Tel Aviv University, Tel-Aviv, Israel
- Institute of Endocrinology, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
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Gómez-Martínez C, Babio N, Júlvez J, Becerra-Tomás N, Martínez-González MÁ, Corella D, Castañer O, Romaguera D, Vioque J, Alonso-Gómez ÁM, Wärnberg J, Martínez JA, Serra-Majem L, Estruch R, Tinahones FJ, Lapetra J, Pintó X, Tur JA, López-Miranda J, Bueno-Cavanillas A, Gaforio JJ, Matía-Martín P, Daimiel L, Martín-Sánchez V, Vidal J, Vázquez C, Ros E, Dalsgaard S, Sayón-Orea C, Sorlí JV, de la Torre R, Abete I, Tojal-Sierra L, Barón-López FJ, Fernández-Brufal N, Konieczna J, García-Ríos A, Sacanella E, Bernal-López MR, Santos-Lozano JM, Razquin C, Alvarez-Sala A, Goday A, Zulet MA, Vaquero-Luna J, Diez-Espino J, Cuenca-Royo A, Fernández-Aranda F, Bulló M, Salas-Salvadó J. Glycemic Dysregulations Are Associated With Worsening Cognitive Function in Older Participants at High Risk of Cardiovascular Disease: Two-Year Follow-up in the PREDIMED-Plus Study. Front Endocrinol (Lausanne) 2021; 12:754347. [PMID: 34777250 PMCID: PMC8586462 DOI: 10.3389/fendo.2021.754347] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Accepted: 09/22/2021] [Indexed: 11/28/2022] Open
Abstract
Introduction Type 2 diabetes has been linked to greater cognitive decline, but other glycemic parameters such as prediabetes, diabetes control and treatment, and HOMA-IR and HbA1c diabetes-related biomarkers have shown inconsistent results. Furthermore, there is limited research assessing these relationships in short-term studies. Thus, we aimed to examine 2-year associations between baseline diabetes/glycemic status and changes in cognitive function in older participants at high risk of cardiovascular disease. Methods We conducted a 2-year prospective cohort study (n=6,874) within the framework of the PREDIMED-Plus study. The participants (with overweight/obesity and metabolic syndrome; mean age 64.9 years; 48.5% women) completed a battery of 8 cognitive tests, and a global cognitive function Z-score (GCF) was estimated. At baseline, participants were categorized by diabetes status (no-diabetes, prediabetes, and <5 or ≥5-year diabetes duration), and also by diabetes control. Furthermore, insulin resistance (HOMA-IR) and glycated hemoglobin (HbA1c) levels were measured, and antidiabetic medications were recorded. Linear and logistic regression models, adjusted by potential confounders, were fitted to assess associations between glycemic status and changes in cognitive function. Results Prediabetes status was unrelated to cognitive decline. However, compared to participants without diabetes, those with ≥5-year diabetes duration had greater reductions in GCF (β=-0.11 (95%CI -0.16;-0.06)], as well as in processing speed and executive function measurements. Inverse associations were observed between baseline HOMA-IR and changes in GCF [β=-0.0094 (95%CI -0.0164;-0.0023)], but also between HbA1c levels and changes in GCF [β=-0.0085 (95%CI -0.0115, -0.0055)], the Mini-Mental State Examination, and other executive function tests. Poor diabetes control was inversely associated with phonologic fluency. The use of insulin treatment was inversely related to cognitive function as measured by the GCF [β=-0.31 (95%CI -0.44, -0.18)], and other cognitive tests. Conclusions Insulin resistance, diabetes status, longer diabetes duration, poor glycemic control, and insulin treatment were associated with worsening cognitive function changes in the short term in a population at high cardiovascular risk. Clinical Trial Registration http://www.isrctn.com/ISRCTN89898870, identifier ISRCTN: 89898870.
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Affiliation(s)
- Carlos Gómez-Martínez
- Universitat Rovira i Virgili, Departament de Bioquímica i Biotecnologia, Unitat de Nutrició Humana, Reus, Spain
- Institut d’Investigació Sanitària Pere Virgili (IISPV), Hospital Universitari San Joan de Reus, Reus, Spain
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Nancy Babio
- Universitat Rovira i Virgili, Departament de Bioquímica i Biotecnologia, Unitat de Nutrició Humana, Reus, Spain
- Institut d’Investigació Sanitària Pere Virgili (IISPV), Hospital Universitari San Joan de Reus, Reus, Spain
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Nutrition Unit, University Hospital of Sant Joan de Reus, Reus, Spain
| | - Jordi Júlvez
- Institut d’Investigació Sanitària Pere Virgili (IISPV), Hospital Universitari San Joan de Reus, Reus, Spain
| | - Nerea Becerra-Tomás
- Universitat Rovira i Virgili, Departament de Bioquímica i Biotecnologia, Unitat de Nutrició Humana, Reus, Spain
- Institut d’Investigació Sanitària Pere Virgili (IISPV), Hospital Universitari San Joan de Reus, Reus, Spain
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Miguel Á. Martínez-González
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Department of Preventive Medicine and Public Health, Instituto de Investigación Sanitaria de Navarra (IdISNA), University of Navarra, Pamplona, Spain
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, United States
| | - Dolores Corella
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Department of Preventive Medicine, University of Valencia, Valencia, Spain
| | - Olga Castañer
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Cardiovascular Risk and Nutrition Research Group (CARIN), Hospital del Mar Research Institute (IMIM), Barcelona, Spain
| | - Dora Romaguera
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Health Research Institute of the Balearic Islands (IdISBa), University Hospital Son Espases, Palma, Spain
| | - Jesús Vioque
- CIBER de Epidemiología y Salud Pública (CIBERESP), ISCIII, Madrid, Spain
- Nutritional Epidemiology Unit, Miguel Hernandez University, Alicante, Spain
- Instituto de Investigación Sanitaria y Biomédica de Alicante-Universidad Miguel Hernández (ISABIAL-UMH), Alicante, Spain
| | - Ángel M. Alonso-Gómez
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Bioaraba Health Research Institute, Osakidetza Basque Health Service, Araba University Hospital, University of the Basque Country Universidad del País Vasco / Euskal Herriko Unibertsitatea (UPV/EHU), Vitoria-Gasteiz, Spain
| | - Julia Wärnberg
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- EpiPHAAN Research Group, School of Health Sciences, Instituto de Investigación Biomédica de Málaga (IBIMA), University of Malaga, Malaga, Spain
| | - José A. Martínez
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Department of Nutrition, Food Science and Physiology, Instituto de Investigación Sanitaria de Navarra (IdISNA), University of Navarra, Pamplona, Spain
- Cardiometabolic Nutrition Group, Precision Nutrition and Cardiometabolic Health Program, IMDEA Food, Campus de Excelencia Internacional Universidad Autónoma de Madrid + Consejo Superior de Investigaciones Científicas (CEI UAM + CSIC), Madrid, Spain
| | - Luís Serra-Majem
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Research Institute of Biomedical and Health Sciences (IUIBS), Preventive Medicine Service, Centro Hospitalario Universitario Insular Materno Infantil (CHUIMI), Canarian Health Service, University of Las Palmas de Gran Canaria, Las Palmas, Spain
| | - Ramón Estruch
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Department of Internal Medicine, Institut d’Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Hospital Clinic, University of Barcelona, Barcelona, Spain
| | - Francisco J. Tinahones
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Department of Endocrinology, Instituto de Investigación Biomédica de Málaga (IBIMA), Virgen de la Victoria Hospital, University of Malaga, Malaga, Spain
| | - José Lapetra
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Research Unit, Department of Family Medicine, Distrito Sanitario Atención Primaria Sevilla, Sevilla, Spain
| | - Xavier Pintó
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Lipids and Vascular Risk Unit, Internal Medicine, Hospital Universitario de Bellvitge-IBIDELL, Hospitalet de Llobregat, Barcelona, Spain
- Universitat de Barcelona, Barcelona, Spain
| | - Josep A. Tur
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Research Group on Community Nutrition & Oxidative Stress, University of Balearic Islands-Instituto Universitario de Investigación en Ciencias de la Salud (IUNICS) & Health Research Institute of the Balearic Islands (IdISBa), Palma de Mallorca, Spain
| | - José López-Miranda
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Department of Internal Medicine, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain
| | - Aurora Bueno-Cavanillas
- CIBER de Epidemiología y Salud Pública (CIBERESP), ISCIII, Madrid, Spain
- Department of Preventive Medicine, University of Granada, Granada, Spain
- Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain
| | - José J. Gaforio
- CIBER de Epidemiología y Salud Pública (CIBERESP), ISCIII, Madrid, Spain
- Departamento de Ciencias de la Salud, Instituto Universitario de Investigación en Olivar y Aceites de Oliva, Universidad de Jaén, Jaén, Spain
| | - Pilar Matía-Martín
- Department of Endocrinology and Nutrition, Instituto de Investigación Sanitaria Hospital Clínico San Carlos (IdISSC), Madrid, Spain
| | - Lidia Daimiel
- Nutritional Control of the Epigenome Group, Precision Nutrition and Obesity Program, IMDEA Food, CEI UAM + CSIC, Madrid, Spain
| | - Vicente Martín-Sánchez
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Institute of Biomedicine (IBIOMED), University of León, León, Spain
| | - Josep Vidal
- CIBER Diabetes y Enfermedades Metabólicas (CIBERDEM), ISCIII, Madrid, Spain
- Departament of Endocrinology, Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Barcelona, Spain
| | - Clotilde Vázquez
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Department of Endocrinology, Fundación Jiménez-Díaz, Madrid, Spain
| | - Emilio Ros
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Lipid Clinic, Department of Endocrinology and Nutrition, IDIBAPS, Hospital Clínic, Barcelona, Spain
| | - Søren Dalsgaard
- Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark
- National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark
| | - Carmen Sayón-Orea
- Department of Preventive Medicine and Public Health, Instituto de Investigación Sanitaria de Navarra (IdISNA), University of Navarra, Pamplona, Spain
| | - José V. Sorlí
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Department of Preventive Medicine, University of Valencia, Valencia, Spain
| | - Rafael de la Torre
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Integrated Pharmacology and Systems Neurosciences Research Group, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain
- Departamento de Ciencias Experimentales y de la Salud (CEXS), Universitat Pompeu Fabra, Barcelona, Spain
| | - Itziar Abete
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Department of Nutrition, Food Science and Physiology, Instituto de Investigación Sanitaria de Navarra (IdISNA), University of Navarra, Pamplona, Spain
| | - Lucas Tojal-Sierra
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Bioaraba Health Research Institute, Osakidetza Basque Health Service, Araba University Hospital, University of the Basque Country Universidad del País Vasco / Euskal Herriko Unibertsitatea (UPV/EHU), Vitoria-Gasteiz, Spain
| | - Francisco J. Barón-López
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- EpiPHAAN Research Group, School of Health Sciences, Instituto de Investigación Biomédica de Málaga (IBIMA), University of Malaga, Malaga, Spain
| | | | - Jadwiga Konieczna
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Health Research Institute of the Balearic Islands (IdISBa), University Hospital Son Espases, Palma, Spain
| | - Antonio García-Ríos
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Department of Internal Medicine, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain
| | - Emilio Sacanella
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Department of Internal Medicine, Institut d’Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Hospital Clinic, University of Barcelona, Barcelona, Spain
| | - M. Rosa Bernal-López
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Department of Internal Medicine, Regional University Hospital of Malaga, Instituto de Investigación Biomédica de Málaga (IBIMA), University of Malaga, Malaga, Spain
| | - José M. Santos-Lozano
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Research Unit, Department of Family Medicine, Distrito Sanitario Atención Primaria Sevilla, Sevilla, Spain
| | - Cristina Razquin
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Department of Preventive Medicine and Public Health, Instituto de Investigación Sanitaria de Navarra (IdISNA), University of Navarra, Pamplona, Spain
| | - Andrea Alvarez-Sala
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Department of Preventive Medicine, University of Valencia, Valencia, Spain
| | - Albert Goday
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Cardiovascular Risk and Nutrition Research Group (CARIN), Hospital del Mar Research Institute (IMIM), Barcelona, Spain
| | - M. Angeles Zulet
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Department of Nutrition, Food Science and Physiology, Instituto de Investigación Sanitaria de Navarra (IdISNA), University of Navarra, Pamplona, Spain
| | - Jessica Vaquero-Luna
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Bioaraba Health Research Institute, Osakidetza Basque Health Service, Araba University Hospital, University of the Basque Country Universidad del País Vasco / Euskal Herriko Unibertsitatea (UPV/EHU), Vitoria-Gasteiz, Spain
| | - Javier Diez-Espino
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Department of Preventive Medicine and Public Health, Instituto de Investigación Sanitaria de Navarra (IdISNA), University of Navarra, Pamplona, Spain
- Gerencia de Atención Primaria Servicio Navarro de Salud-Osasunbidea, Navarra, Spain
| | - Aida Cuenca-Royo
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Cardiovascular Risk and Nutrition Research Group (CARIN), Hospital del Mar Research Institute (IMIM), Barcelona, Spain
| | - Fernando Fernández-Aranda
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Department of Psychiatry, University Hospital of Bellvitge-Instituto de Investigación Biomédica de Bellvitge (IDIBELL), Barcelona, Spain
- Department of Clinical Sciences, School of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain
| | - Mònica Bulló
- Universitat Rovira i Virgili, Departament de Bioquímica i Biotecnologia, Unitat de Nutrició Humana, Reus, Spain
- Institut d’Investigació Sanitària Pere Virgili (IISPV), Hospital Universitari San Joan de Reus, Reus, Spain
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Jordi Salas-Salvadó
- Universitat Rovira i Virgili, Departament de Bioquímica i Biotecnologia, Unitat de Nutrició Humana, Reus, Spain
- Institut d’Investigació Sanitària Pere Virgili (IISPV), Hospital Universitari San Joan de Reus, Reus, Spain
- Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Nutrition Unit, University Hospital of Sant Joan de Reus, Reus, Spain
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Yu KKK, Cheing GLY, Cheung C, Kranz GS, Cheung AKK. Gray Matter Abnormalities in Type 1 and Type 2 Diabetes: A Dual Disorder ALE Quantification. Front Neurosci 2021; 15:638861. [PMID: 34163319 PMCID: PMC8215122 DOI: 10.3389/fnins.2021.638861] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Accepted: 05/07/2021] [Indexed: 12/06/2022] Open
Abstract
Aims/hypothesis: Diabetes mellitus (DM) is associated with comorbid brain disorders. Neuroimaging studies in DM revealed neuronal degeneration in several cortical and subcortical brain regions. Previous studies indicate more pronounced brain alterations in type 2 diabetes mellitus (T2DM) than in type 1 diabetes mellitus (T1DM). However, a comparison of both types of DM in a single analysis has not been done so far. The aim of this meta-analysis was to conduct an unbiased objective investigation of neuroanatomical differences in DM by combining voxel-based morphometry (VBM) studies of T1DM and T2DM using dual disorder anatomical likelihood estimation (ALE) quantification. Methods: PubMed, Web of Science and Medline were systematically searched for publications until June 15, 2020. VBM studies comparing gray matter volume (GMV) differences between DM patients and controls at the whole-brain level were included. Study coordinates were entered into the ALE meta-analysis to investigate the extent to which T1DM, T2DM, or both conditions contribute to gray matter volume differences compared to controls. Results: Twenty studies (comprising of 1,175 patients matched with 1,013 controls) were included, with seven studies on GMV alterations in T1DM and 13 studies on GMV alterations in T2DM. ALE analysis revealed seven clusters of significantly lower GMV in T1DM and T2DM patients relative to controls across studies. Both DM subtypes showed GMV reductions in the left caudate, right superior temporal lobe, and left cuneus. Conversely, GMV reductions associated exclusively with T2DM (>99% contribution) were found in the left cingulate, right posterior lobe, right caudate and left occipital lobe. Meta-regression revealed no significant influence of study size, disease duration, and HbA1c values. Conclusions/interpretation: Our findings suggest a more pronounced gray matter atrophy in T2DM compared to T1DM. The increased risk of microvascular or macrovascular complications, as well as the disease-specific pathology of T2DM may contribute to observed GMV reductions. Systematic Review Registration: [PROSPERO], identifier [CRD42020142525].
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Affiliation(s)
- Kevin K K Yu
- Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Kowloon, Hong Kong.,University Research Facility in Behavioral and Systems Neuroscience (UBSN), The Hong Kong Polytechnic University, Kowloon, Hong Kong
| | - Gladys L Y Cheing
- Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Kowloon, Hong Kong.,University Research Facility in Behavioral and Systems Neuroscience (UBSN), The Hong Kong Polytechnic University, Kowloon, Hong Kong
| | - Charlton Cheung
- Department of Psychiatry, The University of Hong Kong, Pokfulam, Hong Kong
| | - Georg S Kranz
- Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Kowloon, Hong Kong.,The State Key Laboratory for Brain and Cognitive Sciences, The University of Hong Kong, Pokfulam, Hong Kong.,Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
| | - Alex Kwok-Kuen Cheung
- Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Kowloon, Hong Kong
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Fithrie A, Fitri FI, Putra MR. Association of Vitamin D Level and Nerve Conduction Study Parameters with Cognitive Function in Diabetic Neuropathy Patients. Open Access Maced J Med Sci 2021. [DOI: 10.3889/oamjms.2021.5938] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
BACKGROUND: Type 2 diabetes mellitus (T2DM) and its major long-term complication, diabetic polyneuropathy (DPN), continue to be a major global health problem and are important contributors of significant disability worldwide. Vitamin D plays a significant role in their pathogenesis as well as in the development of dementia in non-diabetic patients. Nevertheless, the role of Vitamin D in the development of cognitive impairment in DPN patients has not yet been extensively studied.
AIM: We aimed to investigate the association between Vitamin D level and cognitive function in DPN patients and to evaluate several potential contributor factors to cognition, including demographic factors, glycemic control, and nerve conduction study (NCS) parameters.
METHODS: Thirty-one DPN patients were included in this cross-sectional study. Patients were recruited from the outpatient endocrinology and neurology clinic of Haji Adam Malik General Hospital Medan Indonesia. We used the diabetic neuropathy examination (DNE) scale, diabetic neuropathy symptom (DNS) scale, and NCS to determine the presence and severity of the neuropathy. We measured the levels of Vitamin D, random blood sugar, and glycated hemoglobin (HbA1c). Cognitive function was assessed using the Indonesian version of Montreal Cognitive Assessment (MoCA-INA), trail making test A and B (TMT A and TMT B), and verbal fluency test.
RESULTS: Most of the patients were female (80.6%), with a mean age of 55.71 ± 8.34 years. The proportion of patients with abnormal cognitive function was higher than cognitively unimpaired patients. The mean of MoCA-INA score and level of Vitamin D was lower than normal, 23.32 ± 3.00 and 24.91 ± 13.59 ng/ml, respectively. Using the Pearson correlation test, we did not find any significant association of Vitamin D level, NCS parameters, and other clinical characteristics with global cognitive function. Age and level of education were significantly associated with MoCA-INA score. Blood sugar level was significantly higher in patients with normal TMT-A and TMT-B tests compared to patients with abnormal results.
CONCLUSION: Vitamin D and NCS parameters are not associated with cognitive function. Of the demographic and clinical characteristics, a significant association exists between age, level of education, and blood sugar level and cognition. This might suggest the complexity underlying cognitive impairment in T2DM patients.
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Cukierman-Yaffe T, McClure LA, Risoli T, Bosch J, Sharma M, Gerstein HC, Benavente O. The Relationship Between Glucose Control and Cognitive Function in People With Diabetes After a Lacunar Stroke. J Clin Endocrinol Metab 2021; 106:e1521-e1528. [PMID: 33481011 PMCID: PMC7993572 DOI: 10.1210/clinem/dgab022] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Indexed: 11/19/2022]
Abstract
CONTEXT Lacunar strokes and diabetes are risk factors for cognitive dysfunction. Elucidating modifiable risk factors for cognitive dysfunction has great public health implications. One factor may be glycemic status, as measured by glycated hemoglobin (A1c). OBJECTIVE The aim of this study was to assess the relationship between A1c and cognitive function in lacunar stroke patients with diabetes. METHODS The effect of baseline and follow-up A1c on the baseline and the change in Cognitive Assessment Screening Instrument (CASI) score over time among participants with a median of 2 cognitive assessments (range, 1-5) was examined in 942 individuals with diabetes and a lacunar stroke who participated in the Secondary Prevention of Small Subcortical Strokes (SPS3) trial (ClinicalTrials.gov No. NCT00059306). RESULTS Every 1% higher baseline A1c was associated with a 0.06 lower standardized CASI z score (95% CI, -0.101 to -0.018). Higher baseline A1c values were associated with lower CASI z scores over time (P for interaction = .037). A 1% increase in A1c over time corresponded with a CASI score decrease of 0.021 (95% CI, -0.0043 to -0.038) during follow-up. All these remained statistically significant after adjustment for age, sex, education, race, depression, hypertension, hyperlipidemia, body mass index, cardiovascular disease, obstructive sleep apnea, diabetic retinopathy, nephropathy insulin use, and white-matter abnormalities. CONCLUSION This analysis of lacunar stroke patients with diabetes demonstrates a relationship between A1c and change in cognitive scores over time. Intervention studies are needed to delineate whether better glucose control could slow the rate of cognitive decline in this high-risk population.
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Affiliation(s)
- Tali Cukierman-Yaffe
- Endocrinology Institute, Gertner Institute Sheba Medical Center, Tel-Aviv, Israel
- Epidemiology Department, Sackler School of Medicine, Herczeg Institute on Aging, Tel-Aviv University, Tel-Aviv, Israel
- Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada
- Correspondence: Tali Cukierman-Yaffe, MD, MSC, Endocrinology Institute, Gertner Institute Sheba Medical Center, 6 Tritsh St, Tel-Aviv, 6986006 Israel.
| | - Leslie A McClure
- Department of Epidemiology & Biostatistics Dornsife School of Public Health, Drexel University, Philadelphia, USA
| | - Thomas Risoli
- Duke CTSI Biostatistics, Epidemiology and Research Design (BERD) Methods Core Duke University School of Medicine, Durham, North Carolina, USA
| | - Jackie Bosch
- Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada
- School of Rehabilitation Sciences, McMaster University, Hamilton, Ontario, Canada
| | - Mike Sharma
- Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada
| | - Hertzel C Gerstein
- Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada
| | - Oscar Benavente
- Department of Medicine, Division of Neurology, University of British Columbia, Vancouver, British Columbia, Canada
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Maiuolo J, Gliozzi M, Musolino V, Carresi C, Scarano F, Nucera S, Scicchitano M, Bosco F, Ruga S, Zito MC, Macri R, Bulotta R, Muscoli C, Mollace V. From Metabolic Syndrome to Neurological Diseases: Role of Autophagy. Front Cell Dev Biol 2021; 9:651021. [PMID: 33816502 PMCID: PMC8017166 DOI: 10.3389/fcell.2021.651021] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Accepted: 02/26/2021] [Indexed: 12/17/2022] Open
Abstract
Metabolic syndrome is not a single pathology, but a constellation of cardiovascular disease risk factors including: central and abdominal obesity, systemic hypertension, insulin resistance (or type 2 diabetes mellitus), and atherogenic dyslipidemia. The global incidence of Metabolic syndrome is estimated to be about one quarter of the world population; for this reason, it would be desirable to better understand the underlying mechanisms involved in order to develop treatments that can reduce or eliminate the damage caused. The effects of Metabolic syndrome are multiple and wide ranging; some of which have an impact on the central nervous system and cause neurological and neurodegenerative diseases. Autophagy is a catabolic intracellular process, essential for the recycling of cytoplasmic materials and for the degradation of damaged cellular organelle. Therefore, autophagy is primarily a cytoprotective mechanism; even if excessive cellular degradation can be detrimental. To date, it is known that systemic autophagic insufficiency is able to cause metabolic balance deterioration and facilitate the onset of metabolic syndrome. This review aims to highlight the current state of knowledge regarding the connection between metabolic syndrome and the onset of several neurological diseases related to it. Furthermore, since autophagy has been found to be of particular importance in metabolic disorders, the probable involvement of this degradative process is assumed to be responsible for the attenuation of neurological disorders resulting from metabolic syndrome.
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Affiliation(s)
- Jessica Maiuolo
- IRC-FSH Department of Health Sciences, University “Magna Graecia” of Catanzaro, Catanzaro, Italy
| | - Micaela Gliozzi
- IRC-FSH Department of Health Sciences, University “Magna Graecia” of Catanzaro, Catanzaro, Italy
| | - Vincenzo Musolino
- IRC-FSH Department of Health Sciences, University “Magna Graecia” of Catanzaro, Catanzaro, Italy
| | - Cristina Carresi
- IRC-FSH Department of Health Sciences, University “Magna Graecia” of Catanzaro, Catanzaro, Italy
| | - Federica Scarano
- IRC-FSH Department of Health Sciences, University “Magna Graecia” of Catanzaro, Catanzaro, Italy
| | - Saverio Nucera
- IRC-FSH Department of Health Sciences, University “Magna Graecia” of Catanzaro, Catanzaro, Italy
| | - Miriam Scicchitano
- IRC-FSH Department of Health Sciences, University “Magna Graecia” of Catanzaro, Catanzaro, Italy
| | - Francesca Bosco
- IRC-FSH Department of Health Sciences, University “Magna Graecia” of Catanzaro, Catanzaro, Italy
| | - Stefano Ruga
- IRC-FSH Department of Health Sciences, University “Magna Graecia” of Catanzaro, Catanzaro, Italy
| | - Maria Caterina Zito
- IRC-FSH Department of Health Sciences, University “Magna Graecia” of Catanzaro, Catanzaro, Italy
| | - Roberta Macri
- IRC-FSH Department of Health Sciences, University “Magna Graecia” of Catanzaro, Catanzaro, Italy
| | - Rosamaria Bulotta
- IRC-FSH Department of Health Sciences, University “Magna Graecia” of Catanzaro, Catanzaro, Italy
| | - Carolina Muscoli
- IRC-FSH Department of Health Sciences, University “Magna Graecia” of Catanzaro, Catanzaro, Italy
- IRCCS San Raffaele, Rome, Italy
| | - Vincenzo Mollace
- IRC-FSH Department of Health Sciences, University “Magna Graecia” of Catanzaro, Catanzaro, Italy
- IRCCS San Raffaele, Rome, Italy
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Elesawy BH, Raafat BM, Muqbali AA, Abbas AM, Sakr HF. The Impact of Intermittent Fasting on Brain-Derived Neurotrophic Factor, Neurotrophin 3, and Rat Behavior in a Rat Model of Type 2 Diabetes Mellitus. Brain Sci 2021; 11:brainsci11020242. [PMID: 33671898 PMCID: PMC7918995 DOI: 10.3390/brainsci11020242] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Revised: 01/25/2021] [Accepted: 02/10/2021] [Indexed: 01/17/2023] Open
Abstract
Type 2 diabetes mellitus (T2DM) is known to be associated with an increased risk of dementia, specifically Alzheimer’s disease and vascular dementia. Intermittent fasting (IF) has been proposed to produce neuroprotective effects through the activation of several signaling pathways. In this study, we investigated the effect of IF on rat behavior in type 2 diabetic rats. Forty male Wistar Kyoto rats were divided into four groups (n = 10 for each): the ad libitum (Ad) group, the intermittent fasting group (IF), the streptozotocin-induced diabetic 2 group (T2DM) fed a high-fat diet for 4 weeks followed by a single intraperitoneal (i.p.) injection of streptozotocin (STZ) 25 mg kg−1, and the diabetic group with intermittent fasting (T2DM+IF). We evaluated the impact of 3 months of IF (16 h of food deprivation daily) on the levels of brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT3), serotonin, dopamine, and glutamate in the hippocampus, and rat behavior was assessed by the forced swim test and elevated plus maze. IF for 12 weeks significantly increased (p < 0.05) the levels of NT3 and BDNF in both control and T2DM rats. Additionally, it increased serotonin, dopamine, and glutamic acid in diabetic rats. Moreover, IF modulated glucose homeostasis parameters, with a significant decrease (p < 0.05) in insulin resistance and downregulation of serum corticosterone level. Interestingly, T2DM rats showed a significant increase in anxiety and depression behaviors, which were ameliorated by IF. These findings suggest that IF could produce a potentially protective effect by increasing the levels of BDNF and NT3 in both control and T2DM rats. IF could be considered as an additional therapy for depression, anxiety, and neurodegenerative diseases.
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Affiliation(s)
- Basem H. Elesawy
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia;
| | - Bassem M. Raafat
- Radiological Sciences Department, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia;
| | - Aya Al Muqbali
- Department of Physiology, College of Medicine and Health Sciences, Sultan Qaboos University, P.O. Box 35, Al Koudh, Muscat PC 123, Oman;
| | - Amr M. Abbas
- Department of Physiology, College of Medicine, King Khalid University, Abha 61421, Saudi Arabia;
- Medical Physiology Department, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
| | - Hussein F. Sakr
- Department of Physiology, College of Medicine and Health Sciences, Sultan Qaboos University, P.O. Box 35, Al Koudh, Muscat PC 123, Oman;
- Medical Physiology Department, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
- Correspondence:
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Sabbatinelli J, Ramini D, Giuliani A, Recchioni R, Spazzafumo L, Olivieri F. Connecting vascular aging and frailty in Alzheimer's disease. Mech Ageing Dev 2021; 195:111444. [PMID: 33539904 DOI: 10.1016/j.mad.2021.111444] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Revised: 01/05/2021] [Accepted: 01/26/2021] [Indexed: 12/15/2022]
Abstract
Aging plays an important role in the etiology of the most common age-related diseases (ARDs), including Alzheimer's disease (AD). The increasing number of AD patients and the lack of disease-modifying drugs warranted intensive research to tackle the pathophysiological mechanisms underpinning AD development. Vascular aging/dysfunction is a common feature of almost all ARDs, including cardiovascular (CV) diseases, diabetes and AD. To this regard, interventions aimed at modifying CV outcomes are under extensive investigation for their pleiotropic role in ameliorating and slowing down cognitive impairment in middle-life and elderly individuals. Evidence from observational and clinical studies confirm the notion that the earlier the interventions are conducted, the most favorable are the effects on cognitive function. Therefore, epidemiological research should focus on the early detection of deviations from a healthy cognitive aging trajectory, through the stratification of adult individuals according to the rate of aging. Here, we review the interplay between vascular and cognitive dysfunctions associated with aging, to disentangle the complex mechanisms underpinning the development and progression of neurodegenerative disorders, with a specific focus on AD.
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Affiliation(s)
- Jacopo Sabbatinelli
- Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, Italy
| | - Deborah Ramini
- Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, Italy
| | - Angelica Giuliani
- Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, Italy.
| | - Rina Recchioni
- Center of Clinical Pathology and Innovative Therapy, IRCCS INRCA, Ancona, Italy
| | - Liana Spazzafumo
- Epidemiologic Observatory, Regional Health Agency, Regione Marche, Ancona, Italy
| | - Fabiola Olivieri
- Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, Italy; Center of Clinical Pathology and Innovative Therapy, IRCCS INRCA, Ancona, Italy
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Domergue H, Regueme SC, Zafra OL, Manaz-Rodriguez L, Sinclair A, Bourdel-Marchasson I. Gait Speed and Evolution of Verbal Fluencies in Frail or Prefrail Older People with Type 2 Diabetes. A Pilot Study. J Nutr Health Aging 2021; 25:802-807. [PMID: 34179937 DOI: 10.1007/s12603-021-1636-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
OBJECTIVES Type 2 diabetes (T2D) is a risk factor of frailty and cognitive impairment. Impaired gait in older people is associated with incident vascular dementia. We aimed to assess whether in frail or prefrail older subjects with T2D, lower gait speed can be associated with faster cognitive decline. DESIGN Case-control study nested in a large randomized control trial (RCT, MID-frail); post hoc analysis. SETTING AND PARTICIPANTS Older frail and prefrail subjects (>70y) with T2D and with no history of cognitive problems were enrolled in a single recruiting center. Participants were divided into two groups depending on their walking speed - above (fast walkers) or below (slow walkers) using a cut off of 1 m/sec. MEASURE Cognitive function was assessed at baseline and during follow-up with the MMSE, category and letter fluencies at 15 sec (initiation) and 15-60 sec (late). RESULTS 48 subjects were included, 22 were fast walkers, 26 were slow walkers. The mean follow-up was 60.9 (SD 17.5) weeks. The baseline 0-15 sec letter fluency was higher in fast walkers (p=0.008). There was no difference at baseline with MMSE scores and category fluency. The MID-Frail intervention did not change the evolution of any cognitive changes. Comparisons were adjusted for age, sex and baseline performance, and showed a steeper decline of category fluency score in slow walkers (fast walkers +0.04 (-1.49 to1.56) compared with -0.89 (-2.15 to 0.38), p=0.049) with a moderate effect size. CONCLUSION In frail or prefrail older adults with diabetes, we observed a decline in category fluency in those with low gait speed.
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Affiliation(s)
- H Domergue
- Professor Isabelle Bourdel-Marchasson, Centre Henri Choussat, Hôpital Xavier Arnozan, 33604 Pessac cedex, France, tel: 33 (0)5 57 65 65 71, fax 33 (0)5 57 65 62 26,
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Altered regional homogeneity and functional brain networks in Type 2 diabetes with and without mild cognitive impairment. Sci Rep 2020; 10:21254. [PMID: 33277510 PMCID: PMC7718881 DOI: 10.1038/s41598-020-76495-3] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2020] [Accepted: 10/26/2020] [Indexed: 11/16/2022] Open
Abstract
Patients with Type-2 Diabetes Mellitus (T2DM) have a considerably higher risk of developing mild cognitive impairment (MCI) and dementia. The initial symptoms are very insidious at onset. We investigated the alterations in spontaneous brain activity and network connectivity through regional homogeneity (ReHo) and graph theoretical network analyses, respectively, of resting-state functional Magnetic Resonance Imaging (rs-fMRI) in T2DM patients with and without MCI, so as to facilitate early diagnose. Twenty-five T2DM patients with MCI (DM-MCI), 25 T2DM patients with normal cognition (DM-NC), 27 healthy controls were enrolled. Whole-brain ReHo values were calculated and topological properties of functional networks were analyzed. The DM-MCI group exhibited decreased ReHo in the left inferior/middle occipital gyrus and right inferior temporal gyrus, and increased ReHo in frontal gyrus compared to the DM-NCs. Significant correlations were found between ReHo values and clinical measurements. The DM-MCI group illustrated greater clustering coefficient/local efficiency and altered nodal characteristics (efficiency, degree and betweenness), which increased in certain occipital, temporal and parietal regions but decreased in the right inferior temporal gyrus, compared to the DM-NCs. The altered ReHo and impaired network organization may underlie the impaired cognitive functions in T2DM and suggesting a compensation mechanism. These rs-fMRI measures have the potential as biomarkers of disease progression in diabetic encephalopathy.
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Osama A, Khalil TH, Negm M, AbdEl-Razek R, AbouElhamd H. Association between microstructural white matter abnormalities and cognitive functioning in patients with type 2 diabetes mellitus: a diffusion tensor imaging study. THE EGYPTIAN JOURNAL OF NEUROLOGY, PSYCHIATRY AND NEUROSURGERY 2020. [DOI: 10.1186/s41983-020-00232-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Diffusion tensor imaging (DTI) technique is important for exploring more sensitive imaging-based biomarkers in prevention and early treatment of cognitive dysfunction induced by type 2 diabetes mellitus (DM).
Objectives
To predict early cognitive dysfunction and detection of microstructural white matter changes in patients with type 2 DM by diffusion tensor imaging.
Patients and methods
A case-control study included thirty patients aged ≥ 18 years old of both sexes with type 2 DM and 30 controls. All subjects underwent to Montreal Cognitive Assessment (MoCA) “Arabic version”: to detect mild cognitive impairment (MCI) and diffusion tensor imaging study (DTI).
Results
Mild cognitive impairment is related to type 2 DM (56.7% of diabetic group), reduced fractional anisotropy (FA) values, and elevated mean diffusivity (MD) values were related to cognitive impairment evaluated through Montreal Cognitive Assessment (MoCA) in patients with type 2 DM.
Conclusion
The integrity of the white matter measured using DTI vary in MCI diabetics compared with non-MCI diabetics. Such changes have major implications on the cognitive function.
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Mejía-Rodríguez O, Zavala-Calderón E, Magaña-García N, González-Campos R, López-Loeza E, Rangel-Argueta AR, López-Vázquez MÁ, Olvera-Cortés ME. Diabetic patients are deficient in intentional visuospatial learning and show different learning-related patterns of theta and gamma EEG activity. J Clin Exp Neuropsychol 2020; 43:15-32. [PMID: 33641640 DOI: 10.1080/13803395.2020.1853065] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Introduction: We hypothesized that diabetic patients without mild cognitive impairment would present deficiencies in visuospatial incidental/intentional memory processing and alterations in the underlying EEG alpha, theta and gamma patterns.Methods: Non-diabetic, diabetic-controlled, and diabetic-uncontrolled patients underwent a visuospatial incidental-intentional memory test under simultaneous recording of temporal, parietal, and frontal EEG. The test required patients to solve a maze, with eight objects irrelevant to the task, embedded in it, after an interference instruction, participants were asked to recall the positions of the objects (incidental test). Finally, the participants were explicitly told to study the object positions, and then were asked to recall the objects again (intentional test). Power from baseline, incidental learning, incidental memory, and intentional learning conditions was obtained in alpha, theta, and low-gamma bands. Comparisons were made across groups and conditions for each band, with age, sex, and years from the diagnosis as covariates (ANCOVA with blocking).Results: Diabetic patients showed spared incidental but deficient intentional visuospatial learning. Uncontrolled patients showed a more profound intentional learning deficit as they scored similar numbers of correct positions under incidental and intentional conditions; whereas, non-diabetic and diabetic-controlled patients increased their number after the intentional study. Non-diabetic participants showed increased power during intentional learning compared with the baseline condition in frontal theta, frontoparietal gamma (Fp2 and P4) and frontal alpha (F4) bands; whereas in diabetic patients the power increased in the theta band, in T5 (uncontrolled) and T5 and F7 (controlled).Conclusions: Diabetic patients without mild cognitive impairment show deficient intentional visuospatial learning which was worse in uncontrolled patients. Theta and gamma power increased in healthy participants during intentional learning principally in frontal areas. These EEG power changes were absent in diabetic patients. The reduced accuracy of diabetic patients in intentional visuospatial learning was associated with different EEG learning-related patterns.
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Affiliation(s)
- Oliva Mejía-Rodríguez
- Instituto Mexicano del Seguro Social, Hospital General de Zona N° 83 Morelia, Michoacán, México.,Instituto Mexicano del Seguro Social, Centro de Investigación Biomédica de Michoacán, Michoacán, México
| | | | - Nancy Magaña-García
- Facultad de Ciencias Físico-Matemáticas, Universidad Michoacana de San Nicolás de Hidalgo, Michoacán, México
| | | | - Elisa López-Loeza
- Laboratorio de Biofisica, Instituto de Investigaciones en Física y Matemáticas, Universidad Michoacana de San Nicolás de Hidalgo, Michoacán, México
| | - Ana Rosa Rangel-Argueta
- Laboratorio de Biofisica, Instituto de Investigaciones en Física y Matemáticas, Universidad Michoacana de San Nicolás de Hidalgo, Michoacán, México
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Levine A, Sacktor N, Becker JT. Studying the neuropsychological sequelae of SARS-CoV-2: lessons learned from 35 years of neuroHIV research. J Neurovirol 2020; 26:809-823. [PMID: 32880873 PMCID: PMC7471564 DOI: 10.1007/s13365-020-00897-2] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Revised: 08/11/2020] [Accepted: 08/18/2020] [Indexed: 01/14/2023]
Abstract
The virology of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and the human immune response to the virus are under vigorous investigation. There are now several reports describing neurological symptoms in individuals who develop coronavirus disease 2019 (COVID-19), the syndrome associated with SARS-CoV-2 infection. The prevalence, incidence, and clinical course of these symptoms will become clearer in the coming months and years through epidemiological studies. However, the long-term neurological and cognitive consequence of SARS-CoV-2 infection will remain conjectural for some time and will likely require the creation of cohort studies that include uninfected individuals. Considering the early evidence for neurological involvement in COVID-19 it may prove helpful to compare SARS-CoV-2 with another endemic and neurovirulent virus, human immunodeficiency virus-1 (HIV-1), when designing such cohort studies and when making predictions about neuropsychological outcomes. In this paper, similarities and differences between SARS-CoV-2 and HIV-1 are reviewed, including routes of neuroinvasion, putative mechanisms of neurovirulence, and factors involved in possible long-term neuropsychological sequelae. Application of the knowledge gained from over three decades of neuroHIV research is discussed, with a focus on alerting researchers and clinicians to the challenges in determining the cause of neurocognitive deficits among long-term survivors.
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Affiliation(s)
- Andrew Levine
- Department of Neurology David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
| | - Ned Sacktor
- Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA
| | - James T Becker
- Departments of Psychiatry, Neurology, and Psychology, University of Pittsburgh, Pittsburgh, PA, 15260, USA
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Yulug B, Saatci O, Işıklar A, Hanoglu L, Kilic U, Ozansoy M, Cankaya S, Cankaya B, Kilic E. The Association between HbA1c Levels, Olfactory Memory and Cognition in Normal, Pre-Diabetic and Diabetic Persons. Endocr Metab Immune Disord Drug Targets 2020; 20:198-212. [PMID: 31203811 DOI: 10.2174/1871530319666190614121738] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2019] [Revised: 03/26/2019] [Accepted: 05/10/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIM Recent data have shown that olfactory dysfunction is strongly related to Alzheimer's Disease (AD) that is often preceded by olfactory deficits suggesting that olfactory dysfunction might represent an early indicator of future cognitive in prediabetes. METHODS We have applied to a group of normal (n=15), prediabetic (n=16) and type 2 diabetic outpatients (n=15) olfactory testing, 1.5-T MRI scanner and detailed cognitive evaluation including the standard Mini-Mental State Examination (MMSE) form, Short Blessed Test (SBT), Letter Fluency Test (LFT) and the category fluency test with animal, Fruit and Vegetable Naming (CFT). RESULTS We have shown that Odour Threshold (OT), Discrimination (OD), and Identification (OI) scores and most cognitive test results were significantly different in the prediabetes and diabetes group compared to those in the control group. OD and OT were significantly different between the prediabetes and diabetes group, although the cognitive test results were only significantly different in the prediabetes and diabetes group compared to those in the control group. In evaluating the association between OI, OT, OD scores and specific cognitive tests, we have found, that impaired olfactory identification was the only parameter that correlated significantly with the SBT both in the pre-diabetes and diabetes group. Although spot glucose values were only correlated with OT, HbA1c levels were correlated with OT, OD, and OI, as well as results of the letter fluency test suggesting that HbA1c levels rather than the spot glucose values play a critical role in specific cognitive dysfunction. CONCLUSION To the best of our knowledge, this is the first prospective study to demonstrate a strong association between olfactory dysfunction and specific memory impairment in a population with prediabetes and diabetes suggesting that impaired olfactory identification might play an important role as a specific predictor of memory decline.
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Affiliation(s)
- Burak Yulug
- Department of Neurology, Alanya AlaaddinKeykubat University, Antalya/Alanya, Turkey.,Istanbul Medipol University, Restorative and Regenerative Medicine Center, Istanbul, Turkey
| | - Ozlem Saatci
- Department of Otorhinolaryngology, Istanbul Sancaktepe, Education and Research Hospital, Istanbul, Turkey
| | - Aysun Işıklar
- Department of Internal Medicine, Istanbul Sancaktepe, Education and Research Hospital, Istanbul, Turkey
| | - Lutfu Hanoglu
- Department of Neurology, Istanbul Medipol University, Istanbul, Turkey
| | - Ulkan Kilic
- Department of Medical Biology, University of Health Sciences, Faculty of Medicine, Istanbul, Turkey
| | - Mehmet Ozansoy
- Istanbul Medipol University, Restorative and Regenerative Medicine Center, Istanbul, Turkey
| | - Seyda Cankaya
- Department of Neurology, Alanya AlaaddinKeykubat University, Antalya/Alanya, Turkey
| | - Baris Cankaya
- Department of Anesthesiology and Reanimation, Marmara University Pendik Education and Research Hospital, Istanbul, Turkey
| | - Ertugrul Kilic
- Istanbul Medipol University, Restorative and Regenerative Medicine Center, Istanbul, Turkey.,Department of Physiology, Istanbul Medipol University, International School of Medicine, Istanbul, Turkey
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Verhagen C, Janssen J, Exalto LG, van den Berg E, Johansen OE, Biessels GJ. Diabetes-specific dementia risk score (DSDRS) predicts cognitive performance in patients with type 2 diabetes at high cardio-renal risk. J Diabetes Complications 2020; 34:107674. [PMID: 32723590 DOI: 10.1016/j.jdiacomp.2020.107674] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Revised: 06/19/2020] [Accepted: 07/08/2020] [Indexed: 12/23/2022]
Abstract
AIM To investigate the relationship between the diabetes-specific dementia risk score (DSDRS) and concurrent and future cognitive impairment (CI) in type 2 diabetes (T2D). METHODS DSDRS were calculated for participants with T2D aged ≥60 years from the CARMELINA-cognition substudy (ClinicalTrials.gov Identifier: NCT01897532). Cognitive assessment included Mini-Mental State Examination (MMSE) and a composite attention and executive functioning score (A&E). The relation between baseline DSDRS and probability of CI (MMSE < 24) and variation in cognitive performance was assessed at baseline (n = 2241) and after 2.5 years follow-up in patients without baseline CI (n = 1312). RESULTS Higher DSDRS was associated with a higher probability of CI at baseline (OR = 1.17 per point, 95% CI 1.12-1.22) and follow-up (OR = 1.24 per point, 95% CI 1.14-1.35). Moreover, in patients without baseline CI, higher DSDRS was also associated with lower baseline cognitive performance (MMSE: F(1, 1930) = 47.07, p < .0001, R2 = 0.02); A&E z-score: (F(1, 1871) = 33.44 p < .0001, R2 = 0.02) and faster cognitive decline at follow-up (MMSE: F(3, 1279) = 38.41, p < .0001; A&E z-score: F(3, 1206) = 148.48, p < .0001). CONCLUSIONS The DSDRS identifies patients with T2D at risk of concurrent as well as future CI. The DSDRS may thus be a supportive tool in screening strategies for cognitive dysfunction in patients with T2D.
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Affiliation(s)
- Chloë Verhagen
- Department of Neurology, UMCU Brain Centre, University Medical Center Utrecht, the Netherlands.
| | - Jolien Janssen
- Department of Neurology, UMCU Brain Centre, University Medical Center Utrecht, the Netherlands; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, the Netherlands.
| | - Lieza G Exalto
- Department of Neurology, UMCU Brain Centre, University Medical Center Utrecht, the Netherlands.
| | - Esther van den Berg
- Department of Neurology, UMCU Brain Centre, University Medical Center Utrecht, the Netherlands; Department of Neurology, Erasmus MC - University Medical Center, Rotterdam, the Netherlands.
| | - Odd Erik Johansen
- Clinical Development, Therapeutic Area Cardio Metabolism, Boehringer Ingelheim, Asker, Norway.
| | - Geert Jan Biessels
- Department of Neurology, UMCU Brain Centre, University Medical Center Utrecht, the Netherlands.
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Bello-Chavolla OY, Aguilar-Salinas CA, Avila-Funes JA. The type 2 diabetes-specific dementia risk score (DSDRS) is associated with frailty, cognitive and functional status amongst Mexican community-dwelling older adults. BMC Geriatr 2020; 20:363. [PMID: 32962659 PMCID: PMC7510254 DOI: 10.1186/s12877-020-01776-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Accepted: 09/16/2020] [Indexed: 11/21/2022] Open
Abstract
Background The type 2 diabetes (T2D) specific dementia-risk score (DSDRS) was developed to evaluate dementia risk in older adults with T2D. T2D-related factors have been shown increase the risk of age-related conditions, which might also increase dementia risk. Here, we investigate the associations of DSDRS with frailty, disability, quality of life (QoL) and cognition in community-dwelling older adults with T2D. Methods We included 257 community-dwelling older adults with T2D to evaluate the association between DSDRS and Mini-mental state examination (MMSE), Isaac’s set-test (IST), clock drawing test (CDT), quality of life (SF-36), risk of malnutrition (Mini-Nutritional Assessment or MNA), as well as frailty, Katz’ and Lawton-Brody scores. We also assessed the phenotype and correlates of high-estimated dementia risk by assessing individuals with DSDRS >75th age-specific percentiles. Results Mean age of participants was 78.0 ± 6.2 years. DSDRS showed a significant correlation with MMSE test, IST, CDT, SF-36, MNA, Lawton-Brody and Katz scores, and an increasing number of frailty components. DSDRS was higher among frail, pre-frail, and subjects with limited ADL and IADL (p < 0.001). Participants with DSDRS >75th age-specific percentiles had lower education, MMSE, IST, SF-36, MNA, Katz, Lawton-Brody, and higher frailty scores. High-estimated 10-year dementia risk was associated with ADL and IADL disability, frailty and risk of malnutrition. When assessing individual components of DSDRS, T2D-related microvascular complications were associated to all outcome measures. Conclusion The DSDRS is associated with frailty, disability, malnutrition and lower cognitive performance. These findings support that T2D-related factors have significant burden on functional status, QoL, disability and dementia risk.
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Affiliation(s)
- Omar Yaxmehen Bello-Chavolla
- Dirección de Investigación, Instituto Nacional de Geriatría, Mexico City, Mexico. .,Unidad de Investigación de Enfermedades Metabólicas, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15. CP 14080, Tlalpan, Mexico City, Mexico. .,Department of Physiology, Facultad de Medicina, Universidad Nacional Autónoma de Mexico, Mexico City, Mexico.
| | - Carlos Alberto Aguilar-Salinas
- Unidad de Investigación de Enfermedades Metabólicas, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15. CP 14080, Tlalpan, Mexico City, Mexico.,Departamento de Endocrinología y Metabolismo, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.,Instituto Tecnologico y de Estudios Superiores de Monterrey Tec Salud, Nuevo León, Mexico
| | - José Alberto Avila-Funes
- Geriatrics Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.,Centre de recherche INSERM, U1219, F-33076, Bordeaux, France
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Wang J, Huang R, Tian S, Lin H, Guo D, An K, Wang S. Elevated Plasma Level of D-dimer Predicts the High Risk of Early Cognitive Impairment in Type 2 Diabetic Patients as Carotid Artery Plaques become Vulnerable or Get Aggravated. Curr Alzheimer Res 2020; 16:396-404. [PMID: 30919777 DOI: 10.2174/1567205016666190321164741] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2018] [Revised: 02/27/2019] [Accepted: 03/15/2019] [Indexed: 12/26/2022]
Abstract
BACKGROUND AND OBJECTIVE D-dimer prompts fibrinolysis system, which is involved in Alzheimer's disease and the complications of type 2 diabetic patients, especially among those with carotid artery plaques. Hence, this study aims to investigate the role of D-dimer in early cognitive impairment among type 2 diabetic patients with carotid artery plaques. METHODS A total of 175 Chinese patients with type 2 diabetes were recruited and divided into two groups according to the Montreal Cognitive Assessment score. Demographic data were collected, plasma D-dimer was tested through VIDAS D-dimer New, neuropsychological tests were examined, and carotid artery plaques were detected by ultrasound and further stratified by vulnerability and level. RESULTS A total of 67 types 2 diabetic patients with Mild Cognitive Impairment (MCI) displayed significantly increased plasma D-dimer levels compared with their health-cognition controls (p = 0.011). Plasma D-dimer concentration was negatively related with Digit Span Test scores in diabetic patients with vulnerable plaques (r=-0.471, p=0.023) and Stroop Color Word Test C (number) in diabetic patients with stable plaques (r=-0.482, p<0.001). Multivariable regression analysis further showed that D-dimer concentration was an independent factor of diabetic MCI with carotid artery plaque (p=0.005), and D-dimer concentration especially contributed to the high risk of MCI with vulnerable plaques (p=0.028) or high levels of carotid plaque (p=0.023). CONCLUSION Elevated D-dimer level predicts the high risk of early cognitive impairment in type 2 diabetic patients with carotid artery plaques, especially vulnerable plaques or high levels of carotid plaques.
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Affiliation(s)
- Jiaqi Wang
- Department of Endocrinology, Affiliated Zhongda Hospital of Southeast University, No.87 DingJiaQiao Road, Nanjing 210009, China.,Medical School of Southeast University, Nanjing 210009, China
| | - Rong Huang
- Department of Endocrinology, Affiliated Zhongda Hospital of Southeast University, No.87 DingJiaQiao Road, Nanjing 210009, China.,Medical School of Southeast University, Nanjing 210009, China
| | - Sai Tian
- Department of Endocrinology, Affiliated Zhongda Hospital of Southeast University, No.87 DingJiaQiao Road, Nanjing 210009, China.,Medical School of Southeast University, Nanjing 210009, China
| | - Hongyan Lin
- Department of Endocrinology, Affiliated Zhongda Hospital of Southeast University, No.87 DingJiaQiao Road, Nanjing 210009, China.,Medical School of Southeast University, Nanjing 210009, China
| | - Dan Guo
- Department of Endocrinology, Affiliated Zhongda Hospital of Southeast University, No.87 DingJiaQiao Road, Nanjing 210009, China.,Medical School of Southeast University, Nanjing 210009, China
| | - Ke An
- Department of Endocrinology, Affiliated Zhongda Hospital of Southeast University, No.87 DingJiaQiao Road, Nanjing 210009, China.,Medical School of Southeast University, Nanjing 210009, China
| | - Shaohua Wang
- Department of Endocrinology, Affiliated Zhongda Hospital of Southeast University, No.87 DingJiaQiao Road, Nanjing 210009, China
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Kaseda ET, Levine AJ. Post-traumatic stress disorder: A differential diagnostic consideration for COVID-19 survivors. Clin Neuropsychol 2020; 34:1498-1514. [PMID: 32847484 DOI: 10.1080/13854046.2020.1811894] [Citation(s) in RCA: 97] [Impact Index Per Article: 19.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Objective: SARS-CoV-2 infection and its oft-associated illness COVID-19 may lead to neuropsychological deficits, either through direct mechanisms (i.e., neurovirulance) or indirect mechanisms, most notably complications caused by the virus (e.g., stroke) or medical procedures (e.g., intubation). The history of past human coronavirus outbreaks resulting in similar health emergencies suggests there will be a substantial prevalence of post-traumatic stress disorder (PTSD) among COVID-19 survivors. To prepare neuropsychologists for the difficult task of differentiating PTSD-related from neuropathology-related deficits in the oncoming wave of COVID-19 survivors, we integrate research across a spectrum of related areas.Methods: Several areas of literature were reviewed: psychiatric, neurologic, and neuropathological outcomes of SARS and MERS patients; neurological outcomes in COVID-19 survivors; PTSD associated with procedures common to COVID-19 patients; and differentiating neuropsychological deficits due to PTSD from those due to acquired brain injuries in other patient groups.Conclusions: Heightened risk of PTSD occurred in MERS and SARS survivors. While data concerning COVID-19 is lacking, PTSD is known to occur in patient groups who undergo similar hospital courses, including ICU survivors, patients who are intubated and mechanically ventilated, and those that experience delirium. Research with patients who develop PTSD in the context of mild traumatic brain injury further suggests that PTSD may account for some or all of a patient's subjective cognitive complaints and neuropsychological test performance. Recommendations are provided for assessing PTSD in the context of COVID-19.
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Affiliation(s)
- Erin T Kaseda
- Department of Psychology, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA
| | - Andrew J Levine
- Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
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Guo M, Kang K, Wang A, Jia J, Zhang J, Wang Y, Wang D, Chen S, Zhao X. Association of diabetes status with cognitive impairment in two Chinese rural communities. J Neurol Sci 2020; 415:116894. [PMID: 32446011 DOI: 10.1016/j.jns.2020.116894] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2019] [Revised: 04/20/2020] [Accepted: 05/07/2020] [Indexed: 01/21/2023]
Abstract
BACKGROUND AND PURPOSE Diabetes may be one of the risk factors of cognitive impairment. In this study, we aimed to investigate the relationship between diabetes status and cognitive impairment among the middle-aged and elderly population (≥40 years) in Chinese rural communities. METHODS A sample of 3392 participants aged 40 years or older from the China National Stroke Prevention Project (CSPP) between 2015 and 2017 were enrolled in this study. Cognitive function was assessed by the Beijing edition of the Montreal cognitive assessment (MoCA) scale. Cognitive impairment was diagnosed as a MoCA score < 26. Diabetes status was divided into three groups------Normal: fasting plasma glucose (FPG) ≤ 5.5 mmol/L, Prediabetes: 5.6 ≤ FPG ≤ 6.9 mmol/L, Diabetes: FPG ≥ 7.0 mmol/L or with a history of diabetes. Multivariate logistic regression was used to analyze the association between diabetes status and cognitive impairment. RESULTS Out of the 3392 enrolled participants, 2023(59.6%) had cognitive impairment, 1586(46.8%) had abnormal fasting plasma glucose including 867(25.6%) prediabetes and 719(21.2%) diabetes. After adjusting for potential risk factors, we found prediabetes (OR: 1.22, 95%CI: 1.03-1.45) and diabetes (OR: 1.28, 95%CI: 1.06-1.55) are all associated with cognitive impairment, especially in the domains of language (prediabetes: OR: 1.14, 95%CI: 1.05-1.25; diabetes: OR:1.13, 95%CI: 1.03-1.24), visuospatial/executive functions (diabetes: OR: 1.50, 95%CI: 1.22-1.84) and attention (diabetes: OR: 1.15, 95%CI: 1.02-1.31). CONCLUSIONS In this large community-based study, we found diabetes status may be an independent risk factor for cognitive impairment, particularly in domains of language, visuospatial/executive functions, and attention.
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Affiliation(s)
- Mengyi Guo
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing, China; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Kaijiang Kang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing, China; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Anxin Wang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Jiaokun Jia
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing, China; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Jia Zhang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing, China; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Yu Wang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing, China; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Dandan Wang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing, China; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Shengyun Chen
- Department of Neurology, Beijing Sanbo Brain Hospital, Capital Medical University, Beijing, China.
| | - Xingquan Zhao
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing, China; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China.
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He YX, Shen QY, Tian JH, Wu Q, Xue Q, Zhang GP, Wei W, Liu YH. Zonisamide Ameliorates Cognitive Impairment by Inhibiting ER Stress in a Mouse Model of Type 2 Diabetes Mellitus. Front Aging Neurosci 2020; 12:192. [PMID: 32754028 PMCID: PMC7367218 DOI: 10.3389/fnagi.2020.00192] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Accepted: 06/02/2020] [Indexed: 01/08/2023] Open
Abstract
Type 2 diabetes mellitus (T2DM) increases the risk of Alzheimer’s disease (AD)-like dementia and pathology. Endoplasmic reticulum stress (ERS) plays a key role in the development of cognitive impairment in T2DM. Zonisamide (ZNS) was found to suppress ERS-induced neuronal cell damage in the experimental models of Parkinson’s disease (PD). However, the protective effect of Zonisamide in the treatment of diabetes-related dementia is not determined. Here, we studied whether ZNS can attenuate cognitive impairments in T2DM mice. C57BL/6J mice were fed with a high-fat diet (HFD) and received one intraperitoneal injection of streptozotocin (STZ) to develop T2DM. After the 9-week diet, the mice were orally gavaged with ZNS or vehicle for 16 consecutive weeks. We found that ZNS improved spatial learning and memory ability and slightly attenuated hyperglycemia. In addition, the expression levels of synaptic-related proteins, such as postsynaptic density 95 (PSD95) and synaptophysin, were increased along with the activation of the cyclic AMP response element-binding (CREB) protein and cAMP-dependent protein kinase (PKA) both in the hippocampus and cortex of T2DM mice. Meanwhile, ZNS attenuated Aβ deposition, Tau hyperphosphorylation at Ser-396/404, and also decreased the activity of Tau upstream kinases including extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). Moreover, ZNS also decreased the ERS hallmark protein levels. These data suggest that ZNS can efficiently prevent cognitive impairment and improve AD-like pathologies by attenuating ERS in T2DM mice.
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Affiliation(s)
- Yong-Xiang He
- Department of Pharmacology, Key Laboratory of Molecular Target & Clinical Pharmacology, School of Pharmaceutical Sciences & the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
| | - Qi-Ying Shen
- Department of Pharmacology, Key Laboratory of Molecular Target & Clinical Pharmacology, School of Pharmaceutical Sciences & the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
| | - Jia-Hui Tian
- Department of Pharmacology, Key Laboratory of Molecular Target & Clinical Pharmacology, School of Pharmaceutical Sciences & the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
| | - Qian Wu
- Department of Pharmacology, Key Laboratory of Molecular Target & Clinical Pharmacology, School of Pharmaceutical Sciences & the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
| | - Qin Xue
- Department of Pharmacology, Key Laboratory of Molecular Target & Clinical Pharmacology, School of Pharmaceutical Sciences & the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
| | - Gui-Ping Zhang
- Department of Pharmacology, Key Laboratory of Molecular Target & Clinical Pharmacology, School of Pharmaceutical Sciences & the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
| | - Wei Wei
- Department of Pathophysiology, School of Medicine, Institute of Brain Research, Key Laboratory of State Administration of Traditional Chinese Medicine of China, Jinan University, Guangzhou, China
| | - Ying-Hua Liu
- Department of Pharmacology, Key Laboratory of Molecular Target & Clinical Pharmacology, School of Pharmaceutical Sciences & the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
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Choi SE, Roy B, Freeby M, Mullur R, Woo MA, Kumar R. Prefrontal cortex brain damage and glycemic control in patients with type 2 diabetes. J Diabetes 2020; 12:465-473. [PMID: 31886635 PMCID: PMC7210044 DOI: 10.1111/1753-0407.13019] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2019] [Revised: 11/25/2019] [Accepted: 12/26/2019] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND This study examined brain tissue integrity in sites that controls cognition (prefrontal cortices; PFC) and its relationships to glycemic outcomes in adults with type 2 diabetes mellitus (T2DM). METHODS We examined 28 T2DM patients (median age 57.1 years; median body mass index [BMI] 30.6 kg/m2 ;11 males) and 47 healthy controls (median age 55.0 years; median BMI 25.8 kg/m2 ; 29 males) for cognition (Montreal Cognitive Assessment [MoCA]), glycemic control (hemoglobin A1c [HbA1c]), and PFC tissue status via brain magnetic resonance imaging (MRI). High-resolution T1-weighted images were collected using a 3.0-Tesla MRI scanner, and PFC tissue changes (tissue density) were examined with voxel-based morphometry procedures. RESULTS Reduced PFC density values were observed in T2DM patients compared to controls (left, 0.41 ± 0.02 mm3 /voxel vs 0.44 ± 0.02 mm3 /voxel, P < 0.001; right, 0.41 ± 0.03 mm3 /voxel vs 0.45 ± 0.02 mm3 /voxel, P < 0.001). PFC density values were positively correlated with cognition; left PFC region (r = 0.53, P = 0.005) and right PFC region (r = 0.56, P = 0.003), with age and sex as covariates. Significant negative correlations were found between PFC densities and HbA1c values; left PFC region (r = -0.39, P = 0.049) and right PFC region (r = -0.48, P = 0.01), with age and sex as covariates. CONCLUSIONS T2DM patients showed PFC brain tissue damage, which is associated with cognitive deficits and poor glycemic control. Further research is needed to identify causal relationships between HbA1c, cognition, and brain changes in T2DM and to evaluate the impact of interventions to prevent brain tissue injury or neuroregeneration in this high-risk patient population, to eventually preserve or enhance cognition and improve glucose outcomes.
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Affiliation(s)
- Sarah E Choi
- School of Nursing, University of California Los Angeles, Los Angeles, California
| | - Bhaswati Roy
- Department of Anesthesiology, David Geffen School of Medicine, Los Angeles, California
| | - Matthew Freeby
- Division of Endocrinology, Diabetes, & Metabolism, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California
| | - Rashmi Mullur
- Division of Endocrinology, Diabetes, & Metabolism, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California
| | - Mary A Woo
- School of Nursing, University of California Los Angeles, Los Angeles, California
| | - Rajesh Kumar
- Department of Anesthesiology, David Geffen School of Medicine, Los Angeles, California
- Radiological Sciences, University of California Los Angeles, Los Angeles, California
- Bioengineering, University of California Los Angeles, Los Angeles, California
- Brain Research Institute, University of California Los Angeles, Los Angeles, California
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González HM, Tarraf W, González KA, Fornage M, Zeng D, Gallo LC, Talavera GA, Daviglus ML, Lipton RB, Kaplan R, Ramos AR, Lamar M, Cai J, DeCarli C, Schneiderman N. Diabetes, Cognitive Decline, and Mild Cognitive Impairment Among Diverse Hispanics/Latinos: Study of Latinos-Investigation of Neurocognitive Aging Results (HCHS/SOL). Diabetes Care 2020; 43:1111-1117. [PMID: 32139382 PMCID: PMC7171942 DOI: 10.2337/dc19-1676] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2019] [Accepted: 01/27/2020] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Hispanics/Latinos are the largest ethnic/racial group in the U.S., have the highest prevalence of diabetes, and are at increased risk for neurodegenerative disorders. Currently, little is known about the relationship between diabetes and cognitive decline and disorders among diverse Hispanics/Latinos. The purpose of this study is to clarify these relationships in diverse middle-aged and older Hispanics/Latinos. RESEARCH DESIGN AND METHODS The Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA) is an ancillary study of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). HCHS/SOL is a multisite (Bronx, NY; Chicago, IL; Miami, FL; and San Diego, CA), probability-sampled (i.e., representative of targeted populations), and prospective cohort study. Between 2016 and 2018, SOL-INCA enrolled diverse Hispanics/Latinos aged ≥50 years (n = 6,377). Global cognitive decline and mild cognitive impairment (MCI) were the primary outcomes. RESULTS Prevalent diabetes at visit 1, but not incident diabetes at visit 2, was associated with significantly steeper global cognitive decline (βGC = -0.16 [95% CI -0.25; -0.07]; P < 0.001), domain-specific cognitive decline, and higher odds of MCI (odds ratio 1.74 [95% CI 1.34; 2.26]; P < 0.001) compared with no diabetes in age- and sex-adjusted models. CONCLUSIONS Diabetes was associated with cognitive decline and increased MCI prevalence among diverse Hispanics/Latinos, primarily among those with prevalent diabetes at visit 1. Our findings suggest that significant cognitive decline and MCI may be considered additional disease complications of diabetes among diverse middle-aged and older Hispanics/Latinos.
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Affiliation(s)
- Hector M González
- Department of Neurosciences and Shiley-Marcos Alzheimer's Disease Research Center, University of California, San Diego, San Diego, CA
| | - Wassim Tarraf
- Institute of Gerontology and Department of Healthcare Sciences, Wayne State University, Detroit, MI
| | - Kevin A González
- Department of Neurosciences and Shiley-Marcos Alzheimer's Disease Research Center, University of California, San Diego, San Diego, CA
| | | | - Donglin Zeng
- Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC
| | - Linda C Gallo
- Department of Psychology, San Diego State University, San Diego, CA
| | | | - Martha L Daviglus
- Institute for Minority Health Research, College of Medicine, University of Illinois at Chicago, Chicago, IL
| | | | - Robert Kaplan
- Albert Einstein College of Medicine, New York, NY.,Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA
| | | | - Melissa Lamar
- Institute for Minority Health Research, College of Medicine, University of Illinois at Chicago, Chicago, IL.,Department of Psychiatry and Behavioral Sciences and Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL
| | - Jianwen Cai
- Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC
| | - Charles DeCarli
- Department of Neurology and Alzheimer's Disease Center, University of California, Davis, Sacramento, CA
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de Brito Robalo BM, Vlegels N, Meier J, Leemans A, Biessels GJ, Reijmer YD. Effect of Fixed-Density Thresholding on Structural Brain Networks: A Demonstration in Cerebral Small Vessel Disease. Brain Connect 2020; 10:121-133. [PMID: 32103679 DOI: 10.1089/brain.2019.0686] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
A popular solution to control for edge density variability in structural brain network analysis is to threshold the networks to a fixed density across all subjects. However, it remains unclear how this type of thresholding affects the basic network architecture in terms of edge weights, hub location, and hub connectivity and, especially, how it affects the sensitivity to detect disease-related abnormalities. We investigated these two questions in a cohort of patients with cerebral small vessel disease and age-matched controls. Brain networks were reconstructed from diffusion magnetic resonance imaging data using deterministic fiber tractography. Networks were thresholded to a fixed density by removing edges with the lowest number of streamlines. We compared edge length (mm), fractional anisotropy (FA), proportion of hub connections, and hub location between the unthresholded and the thresholded networks of each subject. Moreover, we compared weighted graph measures of global and local connectivity obtained from the (un)thresholded networks between patients and controls. We performed these analyses over a range of densities (2-20%). Results indicate that fixed-density thresholding disproportionally removes edges composed of long streamlines, but is independent of FA. The edges removed were not preferentially connected to hub or nonhub nodes. Over half of the original hubs were reproducible when networks were thresholded to a density ≥10%. Furthermore, the between-group differences in graph measures observed in the unthresholded network remained present after thresholding, irrespective of the chosen density. We therefore conclude that moderate fixed-density thresholds can successfully be applied to control for the effects of density in structural brain network analysis.
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Affiliation(s)
- Bruno M de Brito Robalo
- Department of Neurology and Neurosurgery, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Naomi Vlegels
- Department of Neurology and Neurosurgery, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Jil Meier
- Department of Neurology and Neurosurgery, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Alexander Leemans
- PROVIDI Lab, Image Sciences Institute, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Geert Jan Biessels
- Department of Neurology and Neurosurgery, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Yael D Reijmer
- Department of Neurology and Neurosurgery, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands
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50
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Diabetes mellitus in the young and the old: Effects on cognitive functioning across the life span. Neurobiol Dis 2020; 134:104608. [DOI: 10.1016/j.nbd.2019.104608] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2019] [Revised: 08/06/2019] [Accepted: 09/04/2019] [Indexed: 01/12/2023] Open
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