The objective of this study is to develop a predictive model combining multiple indicators to quantify the risk of mild cognitive impairment (MCI) in T2DM patients.

This study included Chinese T2DM patients who were hospitalized at Zhongda Hospital between November 2021 and May 2023. Clinical data, including demographics, medical history, biochemical tests, and cognitive status, were collected. Cognitive assessment was performed using neuropsychological tests, and MCI was diagnosed based on the Montreal Cognitive Assessment (MoCA) scores. The dataset was randomly divided into a training set and a validation set in a 7:3 ratio. Logistic regression analysis was conducted to identify factors influencing MCI in the training set. A nomogram-based scoring model was then developed by integrating these findings with high-risk clinical variables, and its performance was validated in the validation set.

In this study, T2DM patients were divided into a training set and a validation set in a 7:3 ratio. There were no significant differences in MCI incidence, demographics, or clinical characteristics between the two groups, confirming the appropriateness of model construction. In the training set, Galectin-3 and CVAI were significantly negatively correlated with cognitive function (MoCA and MMSE scores), and this negative correlation remained after adjusting for confounding variables. Logistic regression analysis revealed that age, CVAI, and Galectin-3 significantly increased the risk of MCI, while years of education had a protective effect. The constructed nomogram model, which integrated age, sex, education level, hypertension, CVAI, and Galectin-3 levels, exhibited high predictive performance (C-index of 0.816), with AUCs of 0.816 in the training set and 0.858 in the validation set, outperforming single indicators. PR curve analysis further validated the superiority of the nomogram model.

The straightforward, highly accurate, and interactive nomogram model developed in this study facilitate the early risk prediction of MCI in individuals with T2DM by incorporating Galectin-3, CVAI, and other common clinical risk factors.

Diabetes is a chronic disease that affects many people, with both its incidence and prevalence rising globally. Diabetes can lead to various complications, among which cognitive impairment in diabetic patients significantly impacts their daily life and blood glucose management, complicating treatment and worsening prognosis. Therefore, the early diagnosis and treatment of cognitive impairment are essential to ensure the health of diabetic patients. However, there is currently no widely accepted and effective method for the early diagnosis of diabetes-related cognitive impairment. This review aims to summarize potential screening and diagnostic methods, as well as biomarkers, for cognitive impairment in diabetes, including retinal structure and function examination, brain imaging, and peripheral blood biomarkers, providing valuable information and support for clinical decision making and future research.

Episodic memory decline is a common complication of type 2 diabetes (T2D). To comprehensively explore the neural mechanisms underlying it, we aimed to explore the sequence that episodic memory-related behavioral and brain-imaging biomarkers appear abnormal in the progression of T2D.

We enrolled 62 healthy controls and 110 patients with T2D. The California Verbal Learning Test, Montreal cognitive assessment, and Stroop color word test was used to assess the episodic memory, general cognitive function, and executive function. Principal component analysis was applied to extract behavioral biomarkers. Imaging biomarkers included structural and functional MRI features of the entorhinal cortex-hippocampus and hippocampus-anterior cingulate cortex pathways. We used a novel discriminative event-based model to determine the sequence that memory-related biomarkers appear abnormal and estimate the stage of memory decline.

T2D patients exhibited poorer memory, general cognitive function, and executive function compared to healthy controls after controlling age, sex, and education level. In the progression of T2D, functional interaction between brain regions showed abnormalities first, followed by memory tests, the cerebral spontaneous neural activity, and finally the gray matter volume. Besides, abnormalities appeared earlier in the entorhinal cortex than in the anterior cingulate cortex. Later stage of memory decline was distributed in older patients with T2D and was associated with higher systolic blood pressure, postprandial blood glucose, and low-density lipoprotein.

In T2D, behavioral and brain imaging biomarkers of episodic memory appear abnormal in a specific sequence, and the stage of memory decline was closely associated with old age and vascular risk factors.

NCT02420470, ClinicalTrials.gov ( https://www.

gov/ ).

Early detection of cognitive dysfunction in patients with type 2 diabetes mellitus (T2DM) is important for preventive measures due to the lack of effective treatments. The purpose of this study is to investigate the relationship between enlarged perivascular space in the hippocampus (H-EPVS) and cognitive performance in patients with T2DM, and to determine whether it can serve as an imaging marker for cognitive dysfunction. 66 T2DM patients with cognitive impairment (T2DM-CI) and 71 T2DM patients with normal cognitive function (T2DM-NC) underwent cranial MRI scans and comprehensive neuropsychological assessments. H-EPVS counts were visually calculated on T2WI imaging according to a previous scale. The differences in the counts of H-EPVS, demographic data, laboratory test results, and cognitive assessment scores between the two groups were compared. The partial correlation analysis was used to explore the relationship between H-EPVS and glymphatic system function (indicated by the DTI-ALPS index), as well as markers of CSVD. Multiple linear regression models were conducted to explore the association between H-EPVS and cognitive functions. Compared with the T2DM-NC group, T2DM-CI exhibited significantly higher counts of H-EPVS in both the total (sum of the left and right side) and left side (P < 0.001). The T2DM-CI group had lower DTI-ALPS index and RAVLT total score. The total H-EPVS counts were significantly correlated with the DTI-ALPS index (r = - 0.240, P = 0.005), BG-EPVS (r = 0.325, P < 0.001), and CSO-EPVS (r = 0.183, P = 0.033). Multiple linear regression showed the total H-EPVS counts exhibited a negative correlation with MMSE (β = - 0.324, 95% CI: - 0.091, - 0.320), immediate memory (β = - 0.380, 95% CI: - 0.673, - 1.766) and delayed recall (β = - 0.252, 95% CI: - 0.052, - 0.463). H-EPVS may serve as a potential neuroimaging biomarker for cognitive impairment in patients with T2DM, warranting further investigation and validation in future studies.

We aimed to determine whether a history of gestational diabetes mellitus (GDM) is associated with cognitive function in midlife.

We conducted a secondary data analysis of the prospective Nurses' Health Study II. From 1989 to 2001, and then in 2009, participants reported their history of GDM. A subset participated in a cognition sub-study in 2014-2019 (wave 1) or 2018-2022 (wave 2). We included 15,906 parous participants (≥1 birth at ≥18 years) who completed a cognitive assessment and were free of CVD, cancer and diabetes before their first birth. The primary exposure was a history of GDM. Additionally, we studied exposure to GDM and subsequent type 2 diabetes mellitus (neither GDM nor type 2 diabetes, GDM only, type 2 diabetes only or GDM followed by type 2 diabetes) and conducted mediation analysis by type 2 diabetes. The outcomes were composite z scores measuring psychomotor speed/attention, learning/working memory and global cognition obtained with the Cogstate brief battery. Mean differences (β and 95% CI) in cognitive function by GDM were estimated using linear regression.

The 15,906 participants were a mean of 62.0 years (SD 4.9) at cognitive assessment, and 4.7% (n=749) had a history of GDM. In models adjusted for age at cognitive assessment, race and ethnicity, education, wave of enrolment in the cognition sub-study, socioeconomic status and pre-pregnancy characteristics, women with a history of GDM had lower performance in psychomotor speed/attention (β -0.08; 95% CI -0.14, -0.01) and global cognition (β -0.06; 95% CI -0.11, -0.01) than those without a history of GDM. The lower cognitive performance in women with GDM was only partially explained by the development of type 2 diabetes.

Women with a history of GDM had poorer cognition than those without GDM. If replicated, our findings support future research on early risk modification strategies for women with a history of GDM as a potential avenue to decrease their risk of cognitive impairment.

Type 2 diabetes mellitus (T2DM) is linked to abnormal brain structure and cognitive dysfunction. However, there is a lack of studies conducted to assess the impact of diabetes on cortical gyrification and cognition. The aim of this cross-sectional study was to assess the potential negative effects of glucose metabolism levels on cognition and cortical gyrification in T2DM.

The current study comprised 83 patients with T2DM and 60 individuals with normal glucose metabolism (NGM). The calculation of the local gyrification index (LGI) was performed utilizing the FreeSurfer software. Subsequently, between-group differences were examined through the utilization of analysis of covariance. Multivariable linear regression and mediation models were employed to investigate the relationships among LGI, glucose metabolism and cognition.

Our study found that the mean LGI of the entire brain in individuals with T2DM was lower than that of NGM, and these significant hypogyria were mainly located in the bilateral temporal lobes, including the left superior temporal cortex, left transverse temporal cortex, and bilateral temporal pole, with the greatest effect size in the left temporal pole (p = 5.7×10-7, Cohen's f2 = 0.169). In addition, the relationship between fasting blood glucose and working memory was mediated by the LGI in the right temporal pole.

Our experiment suggests that the decreased LGI in the right temporal pole explains poorer working memory performance in patients with T2DM.

Cognitive disorders represent one of the most common chronic complications of diabetes. Our previous study has demonstrated that long non-coding RNA (lncRNA) Vof-16 is upregulated in the hippocampal tissue of streptozotocin (STZ)-induced diabetic rats. Despite this finding, the specific roles and underlying mechanisms of lncRNA Vof-16 in diabetes-related cognitive dysfunction remain largely unexplored. To elucidate the mechanism involved, lncRNA Vof-16 was overexpressed in rat hippocampal cell line H19-7 through lentivirus transfection. We integrated metabolomics and transcriptomics approaches to identify potential targets and metabolic pathways influenced by lncRNA Vof-16. Key proteins and pathways were subsequently validated using western blotting and immunofluorescence staining. Transcriptomics indicated that lncRNA Vof-16 overexpression may modulate autophagic activity in H19-7 cells. Metabolomic profiling revealed that the primary differential metabolic pathways included trehalose degradation, tryptophan metabolism, vitamin B6 metabolism, glycolysis, pterine biosynthesis, and the pentose phosphate pathway. Ingenuity Pathway Analysis (IPA) of gene-metabolite networks demonstrated that the high lncRNA Vof-16 expression group exhibited a significantly higher association with autophagy compared to the low lncRNA Vof-16 expression group. Western blot results confirmed that lncRNA Vof-16 overexpression led to decreased protein expression levels of ATG3 and ATG12. Specifically, lncRNA Vof-16 reduces autophagy in hippocampal neurons by targeting the elevated levels of phospho-p70S6K, a downstream effector of mTORC1, potentially contributing to the pathogenesis of diabetic cognitive impairment. The construction of gene-metabolite networks may offer promising new strategies for addressing the growing issue of diabetic cognitive impairment.

Multiple systematic reviews have found that type 2 diabetes is associated with cognitive decrements. However, these reviews are heterogeneous in terms of methodology, quality and results, making it difficult for researchers and clinicians to build an informed overall picture. We therefore conducted a review of systematic reviews on the association between type 2 diabetes and cognitive decrements in relation to healthy controls.

Following a pre-registered research protocol, we searched four major databases. Nine systematic reviews met our inclusion criteria: seven were meta-analyses and two were narrative syntheses. We assessed the risk of bias in each review and reported all effect sizes and confidence intervals obtained.

Type 2 diabetes was associated with cognitive decrements in all reviews, with small or negligible effect sizes obtained in the largest meta-analyses. The most studied cognitive domains were attention, executive functions, memory, processing speed and working memory. All reviews had methodological issues and were rated as having a high or an unclear risk of bias.

Type 2 diabetes appears to be associated with lower cognitive performance in several cognitive domains and in different age groups. However, high-quality meta-analyses on the subject are still needed. Future reviews must follow the PRISMA guidelines and take into account the risk of bias of the original studies through sensitivity analyses and the heterogeneity of the studies by conducting subgroup analyses for example according to age group and disease duration. The meta-analyses that aim to study the entire type 2 diabetes population without excluding severe comorbidities, should assess concept formation and reasoning, construction and motor performance, perception, and verbal functions and language skills in addition to the cognitive domains that have been most frequently analysed in the reviews conducted so far.

Idiopathic normal pressure hydrocephalus (iNPH) is a prevalent neurological disorder, but its diagnosis remains challenging. Dual-task (DT) walking performance is a reliable indicator of iNPH but less is known about the role of cognitive reserve (CR) in predicting DT walking performance.

The objective of this study was to evaluate the contribution of CR on DT walking in healthy controls (HC) and in iNPH patients (iNPH-P).

68 iNPH-P (77.2 +/- 6.7 years old) and 28 HC (74.5 +/- 5.7 years old) were evaluated on their single-task walking (Vsimple) and on 4 DT walking (walking and counting or counting backwards, naming animals, naming words beginning with the letter P) (Vcount, VcountB, Vanimals and Vletter respectively). The contribution of CR on the different DT walking speeds was compared between HC and iNPH-P. In iNPH-P, the contribution of CR on the walking speeds was compared with regard to other cognitive, functional, and socio-demographic variables.

Simple linear regression demonstrated a moderate influence of CR on single and DT walking speed in iNPH-P (β > 0.3, p < .001) but not in HC where the relation was not significant. In iNPH-P, results showed that CR played a major role in explaining each of the single and DT walking speeds with NPH-scale.

As CR could be improved through the life cycle, these results support the idea of developing and supporting physical activity programs that will enrich social, physical, and cognitive resources to protect against age-related functional decline, especially in iNPH-P patients where the age-related deficits are greater.

We investigated associations of glycemic measures, and insulin resistance and secretion measures with hippocampal and subfield volumes. In this cross-sectional study, 7400 community-dwelling participants underwent brain MRI and health checkups between 2016 and 2018. Hemoglobin A1c (HbA1c), glycated albumin (GA), homeostasis model assessment for insulin resistance (HOMA-IR), and HOMA of percent β-cell function (HOMA-β) were evaluated. The associations of each measure with a smaller volume of the hippocampus and twelve hippocampal subfields were investigated. As a result, higher HbA1c or GA and lower HOMA-β levels were significantly associated with smaller volumes in multiple hippocampal subfields. Furthermore, even when we analyzed non-diabetic individuals, substantial associations remained between higher GA or lower HOMA-β levels and smaller volumes of the whole hippocampus or the fimbria. Our findings indicate that postprandial glucose fluctuations, postprandial hyperglycemia, and low insulin secretion have a specific effect on the development of smaller hippocampal volume, suggesting that primary prevention of diabetes and/or sufficient glucose control are important for the prevention of dementia.

The incidence of diabetes-associated cognitive dysfunction (DACD) is increasing; however, few clinical intervention measures are available for the prevention and treatment of this disease. Research has shown that proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, particularly SBC-115076, have a protective effect against various neurodegenerative diseases. However, their role in DACD remains unknown. In this study, we aimed to explore the impact of PCSK9 inhibitors on DACD.

Male Sprague-Dawley (SD) rats were used to establish an animal model of type 2 diabetes mellitus (T2DM). The rats were randomly divided into three groups: the Control group (Control, healthy rats, n = 8), the Model group (Model, rats with T2DM, n = 8), and the PCSK9 inhibitor-treated group (Treat, T2DM rats treated with PCSK9 inhibitors, n = 8). To assess the spatial learning and memory of the rats in each group, the Morris water maze (MWM) test was conducted. Hematoxylin-eosin staining and Nissl staining procedures were performed to assess the structural characteristics and functional status of the neurons of rats from each group. Transmission electron microscopy was used to examine the morphology and structure of the hippocampal neurons. Determine serum PCSK9 and lipid metabolism indicators in each group of rats. Use qRT-PCR to detect the expression levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) in the hippocampal tissues of each group of rats. Western blot was used to detect the expression of PCSK9 and low-density lipoprotein receptor (LDLR) in the hippocampal tissues of rats. In addition, a 4D label-free quantitative proteomics approach was used to analyse protein expression in rat hippocampal tissues. The expression of selected proteins in hippocampal tissues was verified by parallel reaction monitoring (PRM) and immunohistochemistry (IHC).

The results showed that the PCSK9 inhibitor alleviated cognitive dysfunction in T2DM rats. PCSK9 inhibitors can reduce PCSK9, total cholesterol (TC), and low-density lipoprotein (LDL) levels in the serum of T2DM rats. Meanwhile, it was found that PCSK9 inhibitors can reduce the expression of PCSK9, IL-1β, IL-6, and TNF-α in the hippocampal tissues of T2DM rats, while increasing the expression of LDLR. Thirteen potential target proteins for the action of PCSK9 inhibitors on DACD rats were identified. PRM and IHC revealed that PCSK9 inhibitors effectively counteracted the downregulation of transthyretin in DACD rats.

This study uncovered the target proteins and specific mechanisms of PCSK9 inhibitors in DACD, providing an experimental basis for the clinical application of PCSK9 inhibitors for the potential treatment of DACD.

We aimed to analyze the trajectories of cognitive decline as a function of the presence of type 2 diabetes and glycemic control in analyzes stratified by sex in an 8-year follow-up period.

A total of 1 752 men and 2 232 women aged ≥50 years who participated in the English Longitudinal Study of Ageing (ELSA), conducted from 2004 to 2012, were analyzed. The outcomes of interest were performance on the cognitive domains of memory, executive function, and temporal orientation as well as the global cognition score. Cognitive performance was standardized in z-scores in strata based on schooling and age. The participants were classified as without diabetes, with controlled glycemia, and with uncontrolled glycemia, according to medical diagnosis, glucose-lowering medications use and HbA1c levels. Generalized linear mixed models controlled by sociodemographic, behavioral, and health-related characteristics were used for the trajectory analyses.

No differences in z-scores were found for global cognition or cognitive domains based on diabetes classification in men and women at baseline. More than 8 years of follow up, women with uncontrolled glycemia had a greater decline in z-scores for global cognition (-0.037 SD/year [95% CI: -0.073; -0.001]) and executive function (-0.049 SD/year [95% CI: -0.092; -0.007]) compared with those without diabetes. No significant difference in trajectories of global cognition or any cognitive domain was found in men as a function of diabetes classification.

Women with uncontrolled glycemia are at greater risk of a decline in global cognition and executive function than those without diabetes.

Cognitive flexibility is a mental ability that aids in smoothly alternating between them tasks in the brain. Diabetes Mellitus (DM) is a, common disorder that has been associated with impairments in cognitive functions. This research is a retrospective case-control study aimed at establishing a clear relationship between cognitive flexibility and diabetes among Jordanians, considering demographic, anthropometric, and therapeutic variables.

The Wisconsin Card Sorting Test (WCST)-64 item and the Trail Making Test (TMT) assessed cognitive flexibility in 268 people with diabetes and healthy control. Demographic, therapeutic data were collected. We also measured waist-to-hip ratio (WHR) and body mass index (BMI). As the variables were non-normally distributed, non-parametric statistical tests were used to examine differences (Kruskal-Wallis) and correlation (Spearman) between variables.

The patient group did worse on the WCST In contrast to the control group, patients exhibited more significant delays for both Part A and Part B of the TMT (p<0.05). Males had higher WCST conceptual level responses than females. In addition, participants with professional jobs showed less delay in TMT Part A (p<0.05). Age was positively correlated with WCST's total errors and TMT's Parts A and B (p<0.05). BMI was negatively correlated with the WCST's conceptual level of responses and positively correlated with TMT's Part B (p<0.05). In addition, urea and albumin levels were positively correlated with TMT's Part A (p<0.05). Furthermore, creatinine was positively correlated with WCST's total errors and TMT's Part A (p<0.05).

Some measures of cognitive flexibility are associated with DM status in the studied sample of Jordanians and other variables (educational levels, occupation, lifestyle, average duration of illness, and age).

The objective of this study was to evaluate the gender differences in the correlation between physical activity (PA) and cognitive subdomains in elderly individuals with type 2 diabetes (T2D) and mild cognitive impairment (MCI).

Cross-sectional study.

The research was carried out in communities located in Fuzhou, Fujian Province and Beijing Municipality.

Community-dwelling elders with T2D and MCI aged 60 years or older were eligible for this study.

The weekly PA score was assessed using the International Physical Activity Questionnaire (IPAQ). The cognitive subdomains were evaluated through a battery of cognitive assessments, including the Rey Auditory Verbal Learning Test (RAVLT), Trail Making Test Part B, Digit Symbol Substitution Test (DSST) and the Stroop Color-Word Test (SCWT). Multiple linear regression models were employed to examine the association between PA and cognitive subdomains in both male and female individuals.

In older men, higher total IPAQ score was positively correlated with higher RAVLT (P=0.011) and SCWT (P=0.049). There was a significant interaction between the total PA score and gender in relation to RAVLT (P=0.008) and SCWT (P=0.027). Moreover, there was a positive correlation between moderate-vigorous PA level and RAVLT in older men (P=0.007). Additionally, a positive correlation was found between moderate-vigorous PA level and DSST in older women (P=0.038).

In older individuals with T2D and MCI, the association between PA and cognitive subdomains differs between men and women. This discrepancy may impact the customisation of exercise recommendations.

The prevalence of cardiovascular risk factors (CVRFs) in the older adults population and their specific impact on their cognitive profiles still requires further research. For this purpose, a cross-sectional study was carried out to describe the presence of CVRFs and their association with cognitive performance in a sample of older adults (65-85 years old) with Mild Cognitive Impairment (MCI). Participants (n = 185) were divided into three groups concerning their cardiovascular risk level determined by the presence of different CVRFs, including Type 2 Diabetes (T2D), dyslipidemia, hypertension, and obesity. The primary outcome measures were the participant's scores in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Sociodemographic, clinical, and psychosocial data were collected. Non-parametrical statistical analyses and effect sizes were calculated. Findings revealed that a greater presence of CVRFs was not associated with a worse overall cognitive performance. High-risk patients were more likely to have significantly worse performance in the attentional domain compared to medium-risk (p = 0.029, r = 0.42) and compared to low-risk (p = 0.041, r = 0.35), specifically in the digits repetition subtest (p = 0.042). T2D alone was the CVRF associated with cognitive differences (p = 0.037, r = 0.32), possibly mediated by the duration of the condition. Consequently, a higher presence of CVRFs did not lead to a worse overall cognitive performance. However, high-risk individuals were more likely to experience cognitive impairment, particularly in the attentional domain. T2D played a significant role in these cognitive profile differences, possibly influenced by its duration.

There is a high prevalence of vitamin D deficiency and impaired cognitive function in people with type 2 diabetes mellitus (T2DM).

To critically and systematically review the literature on the association between vitamin D status and cognitive performance in people with type 2 diabetes.

This review was conducted according to PRISMA recommendations. MEDLINE, SCOPUS, the Cochrane Library, and Web of Science databases were searched using the terms "Diabetes Mellitus, Type 2", "Cognitive Function", and "Vitamin D".

Eight observational and 1 randomized study were included, containing data of 14 648 adult and elderly individuals (19-74 y). All extracted data were compiled, compared, and critically analyzed.

There is no strong evidence that lower serum concentrations of vitamin D and vitamin D-binding protein are associated with worsening cognitive function in individuals with T2DM. Vitamin D supplementation (12 wk) improved the scores of some executive functioning tests, although there was no difference between low doses (5000 IU/wk) and high doses (50 000 IU/wk).

There is no high-quality evidence demonstrating an association between vitamin D status and cognitive function, or clinical benefits on cognition from vitamin D supplementation in individuals with T2DM. Future studies are needed. Systematic Review Registration: PROSPERO registration no. CRD42021261520.

Type 2 diabetes (T2D) often impairs memory functions, suggesting specific vulnerability of the hippocampus. In vivo neuroimaging studies relating encoding and retrieval of memory information with endogenous neuroprotection are lacking. The neuroprotector glucagon-like peptide (GLP-1) has a high receptor density in anterior/ventral hippocampus, as shown by animal models. Using an innovative event-related fMRI design in 34 participants we investigated patterns of hippocampal activity in T2D (n = 17) without mild cognitive impairment (MCI) versus healthy controls (n = 17) during an episodic memory task. We directly measured neurovascular coupling by estimating the hemodynamic response function using event-related analysis related to encoding and retrieval of episodic information in the hippocampus. We applied a mixed-effects general linear model analysis and a two-factor ANOVA to test for group differences. Significant between-group differences were found for memory encoding, showing evidence for functional reorganization: T2D patients showed an augmented activation in the posterior hippocampus while anterior activation was reduced. The latter was negatively correlated with both GLP-1 pre- and post-breakfast levels, in the absence of grey matter changes. These results suggest that patients with T2D without MCI have pre-symptomatic functional reorganization in brain regions underlying episodic memory, as a function of the concentration of the neuroprotective neuropeptide GLP-1.

Neurovascular coupling (NVC) is an important mechanism to ensure adequate blood supply to active neurons in the brain. NVC damage can lead to chronic impairment of neuronal function. Diabetes is characterized by high blood sugar and is considered an important risk factor for cognitive impairment. In this review, we provide fMRI evidence of NVC damage in diabetic patients with cognitive decline. Combined with the exploration of the major mechanisms and signaling pathways of NVC, we discuss the effects of chronic hyperglycemia on the cellular structure of NVC signaling, including key receptors, ion channels, and intercellular connections. Studying these diabetes-related changes in cell structure will help us understand the underlying causes behind diabetes-induced NVC damage and early cognitive decline, ultimately helping to identify the most effective drug targets for treatment.

To characterize the comparative contributions of different glycaemic indicators to cognitive dysfunction, and further investigate the associations between the most significant indicator and cognitive function, along with related cerebral alterations.

We performed a cross-sectional study in 449 subjects with type 2 diabetes who completed continuous glucose monitoring and cognitive assessments. Of these, 139 underwent functional magnetic resonance imaging to evaluate cerebral structure and olfactory neural circuit alterations. Relative weight and Sobol's sensitivity analyses were employed to characterize the comparative contributions of different glycaemic indicators to cognitive dysfunction.

Complexity of glucose time series index (CGI) was found to have a more pronounced association with mild cognitive impairment (MCI) compared to glycated haemoglobin, time in range, and standard deviation. The proportion and multivariable-adjusted odds ratios (ORs) for MCI increased with descending CGI tertile (Tertile 1: reference group [≥4.0]; Tertile 2 [3.6-4.0] OR 1.23, 95% confidence interval [CI] 0.68-2.24; Tertile 3 [<3.6] OR 2.27, 95% CI 1.29-4.00). Decreased CGI was associated with cognitive decline in executive function and attention. Furthermore, individuals with decreased CGI displayed reduced olfactory activation in the left orbitofrontal cortex (OFC) and disrupted functional connectivity between the left OFC and right posterior cingulate gyrus. Mediation analysis demonstrated that the left OFC activation partially mediated the associations between CGI and executive function.

Decreased glucose complexity closely relates to cognitive dysfunction and olfactory brain activation abnormalities in diabetes.

The hippocampus is a critical brain substrate for learning and memory; events that harm the hippocampus can seriously impair mental and behavioral functioning. Hippocampal pathophysiologies have been identified as potential causes and effects of a remarkably diverse array of medical diseases, psychological disorders, and environmental sources of damage. It may be that the hippocampus is more vulnerable than other brain areas to insults that are related to these conditions. One purpose of this review is to assess the vulnerability of the hippocampus to the most prevalent types of insults in multiple biomedical domains (i.e., neuroactive pathogens, neurotoxins, neurological conditions, trauma, aging, neurodegenerative disease, acquired brain injury, mental health conditions, endocrine disorders, developmental disabilities, nutrition) and to evaluate whether these insults affect the hippocampus first and more prominently compared to other brain loci. A second purpose is to consider the role of hippocampal blood-brain barrier (BBB) breakdown in either causing or worsening the harmful effects of each insult. Recent research suggests that the hippocampal BBB is more fragile compared to other brain areas and may also be more prone to the disruption of the transport mechanisms that act to maintain the internal milieu. Moreover, a compromised BBB could be a factor that is common to many different types of insults. Our analysis indicates that the hippocampus is more vulnerable to insults compared to other parts of the brain, and that developing interventions that protect the hippocampal BBB may help to prevent or ameliorate the harmful effects of many insults on memory and cognition.

The objective of this umbrella review and meta-analysis was to evaluate the effect of diabetes on risk of dementia, as well as the mitigating effect of antidiabetic treatments.

We conducted a systematic umbrella review on diabetes and its treatment, and a meta-analysis focusing on treatment. We searched MEDLINE/PubMed, Embase, PsycINFO, CINAHL and the Cochrane Library for systematic reviews and meta-analyses assessing the risk of cognitive decline/dementia in individuals with diabetes until 2 July 2023. We conducted random-effects meta-analyses to obtain risk ratios and 95% confidence intervals estimating the association of metformin, thiazolidinediones, pioglitazone, dipeptidyl peptidase-4 inhibitors, α-glucosidase inhibitors, meglitinides, insulin, sulphonylureas, glucagon-like peptide-1 receptor agonists (GLP1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) with risk of dementia from cohort/case-control studies. The subgroups analysed included country and world region. Risk of bias was assessed with the AMSTAR tool and Newcastle-Ottawa Scale.

We included 100 reviews and 27 cohort/case-control studies (N = 3 046 661). Metformin, thiazolidinediones, pioglitazone, GLP1RAs and SGLT2is were associated with significant reduction in risk of dementia. When studies examining metformin were divided by country, the only significant effect was for the United States. Moreover, the effect of metformin was significant in Western but not Eastern populations. No significant effect was observed for dipeptidyl peptidase-4 inhibitors, α-glucosidase inhibitors, or insulin, while meglitinides and sulphonylureas were associated with increased risk.

Metformin, thiazolidinediones, pioglitazone, GLP1RAs and SGLT2is were associated with reduced risk of dementia. More longitudinal studies aimed at determining their relative benefit in different populations should be conducted.

To determine whether longitudinal progression of small vessel disease in chronic stroke survivors is associated with longitudinal worsening of chronic aphasia severity.

A longitudinal retrospective study. Severity of white matter hyperintensities (WMHs) as a marker for small vessel disease was assessed on fluid-attenuated inversion recovery (FLAIR) scans using the Fazekas scale, with ratings for deep WMHs (DWMHs) and periventricular WMHs (PVHs).

University research laboratories.

This study includes data from 49 chronic stroke survivors with aphasia (N=49; 15 women, 34 men, age range=32-81 years, >6 months post-stroke, stroke type: [46 ischemic, 3 hemorrhagic], community dwelling). All participants completed the Western Aphasia Battery-Revised (WAB) and had FLAIR scans at 2 timepoints (average years between timepoints: 1.87 years, SD=3.21 years).

Not applicable.

Change in white matter hyperintensity severity (calculated using the Fazekas scale) and change in aphasia severity (difference in Western Aphasia Battery scores) were calculated between timepoints. Separate stepwise regression models were used to identify predictors of WMH severity change, with lesion volume, age, time between timepoints, body mass index (BMI), and presence of diabetes as independent variables. Additional stepwise regression models investigated predictors of change in aphasia severity, with PVH change, DWMH change, lesion volume, time between timepoints, and age as independent predictors.

22.5% of participants (11/49) had increased WMH severity. Increased BMI was associated with increases in PVH severity (P=.007), whereas the presence of diabetes was associated with increased DWMH severity (P=.002). Twenty-five percent of participants had increased aphasia severity which was significantly associated with increased severity of PVH (P<.001, 16.8% variance explained).

Increased small vessel disease burden is associated with contributing to chronic changes in aphasia severity. These findings support the idea that good cardiovascular risk factor control may play an important role in the prevention of long-term worsening of aphasic symptoms.

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.

Diabetes is recognized as a significant risk factor for cognitive impairment. However, this association has not been thoroughly examined using large-scale population-based datasets in the Canadian context. The objective of this study was to investigate the potential association between cognitive function and diabetes in a large population-based sample of middle-aged and older Canadians.

We utilized baseline data from the Canadian Longitudinal Study on Aging (N=30,097) to test our hypotheses, using five indicators of cognitive function (animal fluency, Stroop interference, reaction time, immediate and delayed memory recall). We conducted multivariate multivariable linear regression and subsequently performed tests for moderation analysis with lifestyle factors and health status.

The analysis revealed that type 2 diabetes (T2DM) was associated with lower performance on most cognitive tasks, including those assessing executive function (b=0.60, 95% CI 0.31 to 0.90), reaction time (b=16.94, 95% CI 9.18 to 24.70), immediate memory recall (b=-0.10, 95% CI -0.18 to -0.02), and delayed memory recall (b=-0.12, 95% CI -0.21 to -0.02). However, no significant association was observed between other types of diabetes and cognitive performance. Moderation effects were largely null for T2DM, with the exception of alcohol intake for reaction time, and physical activity for animal fluency.

The study showed that individuals with T2DM exhibit poor performance on tasks that assess executive function, reaction time, and memory. Therefore, optimizing cognitive health among individuals with T2DM should be a priority in primary care. Additionally, further studies should examine this association using longitudinal data.

We investigated whether prediabetes, type 2 diabetes, and continuous measures of hyperglycemia are associated with tissue volume differences in specific subfields of the hippocampus.

We used cross-sectional data from 4,724 participants (58.7 ± 8.5 years, 51.5% women) of The Maastricht Study, a population-based prospective cohort. Glucose metabolism status was assessed with an oral glucose tolerance test, and defined as type 2 diabetes (n = 869), prediabetes (n = 671), or normal glucose metabolism (n = 3184). We extracted 12 hippocampal subfield volumes per hemisphere with FreeSurfer v6.0 using T1w and FLAIR 3T MRI images. We used multiple linear regression and linear trend analysis, and adjusted for total intracranial volume, demographic, lifestyle, and cardiovascular risk factors.

Type 2 diabetes was significantly associated with smaller volumes in the hippocampal subfield fimbria (standardized beta coefficient ± standard error (β ± SE) = -0.195 ± 0.04, p-value < 0.001), the hippocampus proper, i.e. Cornu Ammonis (CA) 1, CA2/3, CA4, dentate gyrus, subiculum and presubiculum (β ± SE < -0.105 ± 0.04, p-value < 0.006); as well as the hippocampal tail (β ± SE = -0.162 ± 0.04, p-value < 0.001). Prediabetes showed no significant associations. However, linear trend analysis indicated a dose-response relation from normal glucose metabolism, to prediabetes, to type 2 diabetes. Multiple continuous measures of hyperglycemia were associated with smaller volumes of the subfields fimbria (β ± SE < -0.010 ± 0.011, p-value < 0.001), dentate gyrus (β ± SE < -0.013 ± 0.010, p-value < 0.002), CA3 (β ± SE < -0.014 ± 0.011, p-value < 0.001), and tail (β ± SE < -0.006 ± 0.012, p-value < 0.003).

Type 2 diabetes and measures of hyperglycemia are associated with hippocampal subfield atrophy, independently of lifestyle and cardiovascular risk factors. We found evidence for a dose-response relationship from normal glucose metabolism, to prediabetes, to type 2 diabetes. Prediabetes stages could give a window of opportunity for the early prevention of brain disease.

In post-stroke aphasia, language improvements following speech therapy are variable and can only be partially explained by the lesion. Brain tissue integrity beyond the lesion (brain health) may influence language recovery and can be impacted by cardiovascular risk factors, notably diabetes. We examined the impact of diabetes on structural network integrity and language recovery. Seventy-eight participants with chronic post-stroke aphasia underwent six weeks of semantic and phonological language therapy. To quantify structural network integrity, we evaluated the ratio of long-to-short-range white matter fibers within each participant's whole brain connectome, as long-range fibers are more susceptible to vascular injury and have been linked to high level cognitive processing. We found that diabetes moderated the relationship between structural network integrity and naming improvement at 1 month post treatment. For participants without diabetes (n = 59), there was a positive relationship between structural network integrity and naming improvement (t = 2.19, p = 0.032). Among individuals with diabetes (n = 19), there were fewer treatment gains and virtually no association between structural network integrity and naming improvement. Our results indicate that structural network integrity is associated with treatment gains in aphasia for those without diabetes. These results highlight the importance of post-stroke structural white matter architectural integrity in aphasia recovery.

Mild cognitive impairment (MCI) is considered a preclinical stage of Alzheimer's disease (AD). People with MCI have a higher risk of developing dementia than healthy people. As one of the risk factors for MCI, stroke has been actively treated and intervened. Therefore, selecting the high-risk population of stroke as the research object and discovering the risk factors of MCI as early as possible can prevent the occurrence of MCI more effectively.

The Boruta algorithm was used to screen variables, and eight machine learning models were established and evaluated. The best performing models were used to assess variable importance and build an online risk calculator. Shapley additive explanation is used to explain the model.

A total of 199 patients were included in the study, 99 of whom were male. Transient ischemic attack (TIA), homocysteine, education, hematocrit (HCT), diabetes, hemoglobin, red blood cells (RBC), hypertension, prothrombin time (PT) were selected by Boruta algorithm. Logistic regression (AUC = 0.8595) was the best model for predicting MCI in high-risk groups of stroke, followed by elastic network (ENET) (AUC = 0.8312), multilayer perceptron (MLP) (AUC = 0.7908), extreme gradient boosting (XGBoost) (AUC = 0.7691), and support vector machine (SVM) (AUC = 0.7527), random forest (RF) (AUC = 0.7451), K-nearest neighbors (KNN) (AUC = 0.7380), decision tree (DT) (AUC = 0.6972). The importance of variables suggests that TIA, diabetes, education, and hypertension are the top four variables of importance.

Transient ischemic attack (TIA), diabetes, education, and hypertension are the most important risk factors for MCI in high-risk groups of stroke, and early intervention should be performed to reduce the occurrence of MCI.

With rapid aging of the population worldwide, the number of people with dementia is dramatically increasing. Some studies have emphasized that metabolic syndrome, which includes obesity and diabetes, leads to increased risks of dementia and cognitive decline. Factors such as insulin resistance, hyperglycemia, high blood pressure, dyslipidemia, and central obesity in metabolic syndrome are associated with synaptic failure, neuroinflammation, and imbalanced neurotransmitter levels, leading to the progression of dementia. Due to the positive correlation between diabetes and dementia, some studies have called it "type 3 diabetes". Recently, the number of patients with cognitive decline due to metabolic imbalances has considerably increased. In addition, recent studies have reported that neuropsychiatric issues such as anxiety, depressive behavior, and impaired attention are common factors in patients with metabolic disease and those with dementia. In the central nervous system (CNS), the amygdala is a central region that regulates emotional memory, mood disorders, anxiety, attention, and cognitive function. The connectivity of the amygdala with other brain regions, such as the hippocampus, and the activity of the amygdala contribute to diverse neuropathological and neuropsychiatric issues. Thus, this review summarizes the significant consequences of the critical roles of amygdala connectivity in both metabolic syndromes and dementia. Further studies on amygdala function in metabolic imbalance-related dementia are needed to treat neuropsychiatric problems in patients with this type of dementia.

Type 2 diabetes has been associated with cognitive decrements already in middle-age. However, the sample sizes of the studies have been small and the neuropsychological tests used have been heterogeneous. In addition, only a few studies have matched the groups in terms of age, education and gender. In this cross-sectional matched pairs study, we investigated the cognitive performance of Finnish middle-aged type 2 diabetes patients compared to healthy individuals.

A neuropsychological test battery consisting of 16 tests and 21 outcome measures was applied to 28 patients and 28 age-, education- and gender-matched healthy individuals. Various exclusion criteria were applied to minimize the risk of cognitive dysfunction due to factors other than diabetes.

We did not find between-group differences in any of the neuropsychological tests measuring attention, concept formation and reasoning, construction and motor performance, executive functions, memory, processing speed or working memory. In addition, there were no group differences in the frequency or severity of subjective cognitive symptoms, or in anxiety, depression, burnout, fatigue or alcohol use disorder symptoms. The effect sizes in this study were mostly negligible or small, with the mean effect size being -0.12.

In a carefully matched sample of middle-aged type 2 diabetes patients and healthy individuals, we found no significant effects and no meaningful evidence of cognitive differences between the groups.

Increasing data suggest a crucial role of circadian rhythm in regulating metabolic and neurological diseases, and Bmal1 is regarded as a key regulator of circadian transcription. The aim of this study is to investigate the role of Bmal1 in the disruption of circadian rhythm and neuropsychiatric injuries in type 2 diabetes mellitus (T2DM). A T2DM model was induced by the combination of high-fat-diet (HFD) and streptozotocin (STZ) in vivo or HT-22 cells challenged with palmitic-acid (PA) in vitro. The glucolipid metabolism indicators, behavioral performance, and expression of synaptic plasticity proteins and circadian rhythm-related proteins were detected. These changes were also observed after interference of Bmal1 expression via overexpressed plasmid or small interfering RNAs in vitro. The results showed that HFD/STZ could induce T2DM-like glycolipid metabolic turmoil and abnormal neuropsychiatric behaviors in mice, as indicated by the increased concentrations of fasting blood-glucose (FBG), HbA1c and lipids, the impaired glucose tolerance, and the decreased preference index of novel object or novel arm in the novel object recognition test (NOR) and Y-maze test (Y-maze). Consistently, the protein expression of synaptic plasticity proteins and circadian rhythm-related proteins and the positive fluorescence intensity of MT1B and Bmal1 were decreased in the hippocampus of HFD/STZ-induced mice or PA-challenged HT-22 cells. Furthermore, overexpression of Bmal1 could improve the PA-induced lipid metabolic dysfunction and increase the decreased expressions of synaptic plasticity proteins and circadian rhythm-related proteins, and vice versa. These results suggested a crucial role of Bmal1 in T2DM-related glycolipid metabolic disorder and neuropsychiatric injury, which mechanism might be involved in the regulation of synaptic plasticity and circadian rhythms.

Cardiovascular and cerebrovascular diseases are prevalent in individuals with type 2 diabetes (T2D). Among people with T2D aged over 70 years, up to 45% might have cognitive dysfunction. Cardiorespiratory fitness (V˙O₂max) correlates with cognitive performances in healthy younger and older adults, and individuals with cardiovascular diseases (CVD). The relationship between cognitive performances, V˙O₂max, cardiac output and cerebral oxygenation/perfusion responses during exercise has not been studied in patients with T2D. Studying cardiac hemodynamics and cerebrovascular responses during a maximal cardiopulmonary exercise test (CPET) and during the recovery phase, as well as studying their relationship with cognitive performances could be useful to detect patients at greater risk of future cognitive impairment. Purposes: (1) to compare cerebral oxygenation/perfusion during a CPET and during its post-exercise period (recovery); (2) to compare cognitive performances in patients with T2D to those in healthy controls; and (3) to examine if V˙O₂max, maximal cardiac output and cerebral oxygenation/perfusion are associated with cognitive function in individuals with T2D and healthy controls. Nineteen patients with T2D (61.9 ± 7 years old) and 22 healthy controls (HC) (61.8 ± 10 years old) were evaluated on the following: a CPET test with impedance cardiography and cerebral oxygenation/perfusion using a near-infrared spectroscopy. Prior to the CPET, the cognitive performance assessment was performed, targeting: short-term and working memory, processing speed, executive functions, and long-term verbal memory. Patients with T2D had lower V˙O₂max values compared to HC (34.5 ± 5.6 vs. 46.4 ± 7.6 mL/kg fat free mass/min; p < 0.001). Compared to HC, patients with T2D showed lower maximal cardiac index (6.27 ± 2.09 vs. 8.70 ± 1.09 L/min/m², p < 0.05) and higher values of systemic vascular resistance index (826.21 ± 308.21 vs. 583.35 ± 90.36 Dyn·s/cm⁵·m²) and systolic blood pressure at maximal exercise (204.94 ± 26.21 vs. 183.61 ± 19.09 mmHg, p = 0.005). Cerebral HHb during the 1st and 2nd min of recovery was significantly higher in HC compared to T2D (p < 0.05). Executive functions performance (Z score) was significantly lower in patients with T2D compared to HC (-0.18 ± 0.7 vs. -0.40 ± 0.60, p = 0.016). Processing speed, working and verbal memory performances were similar in both groups. Brain tHb during exercise and recovery (-0.50, -0.68, p < 0.05), and O₂Hb during recovery (-0.68, p < 0.05) only negatively correlated with executive functions performance in patients with T2D (lower tHb values associated with longer response times, indicating a lower performance). In addition to reduced V˙O₂max, cardiac index and elevated vascular resistance, patients with T2D showed reduced cerebral hemoglobin (O₂Hb and HHb) during early recovery (0-2 min) after the CPET, and lower performances in executive functions compared to healthy controls. Cerebrovascular responses to the CPET and during the recovery phase could be a biological marker of cognitive impairment in T2D.

Type 2 diabetes is a systemic, multifactorial disease that is a leading cause of morbidity and mortality globally. Despite a rise in the number of available medications and treatments available for management, exercise remains a first-line prevention and intervention strategy due to established safety, efficacy, and tolerability in the general population. Herein we review the predisposing risk factors for, prevention, pathophysiology, and treatment of type 2 diabetes. We emphasize key cellular and molecular adaptive processes that provide insight into our evolving understanding of how, when, and what types of exercise may improve glycemic control. © 2023 American Physiological Society. Compr Physiol 13:1-27, 2023.

To systematically evaluate the prevalence of cognitive impairment in elderly patients with diabetes in China.

Computerized searches of the Chinese Biomedical, WanFang, Vip, Chinese National Knowledge Infrastructure, PubMed, Embase, and the Cochrane Library databases were used to collect research literature on cognitive impairment in older Chinese patients with diabetes from the time of database creation to May 5, 2021. A meta-analysis was performed using the Stata v14.0 software after two investigators independently screened the literature, extracted the information, and evaluated the bias risk of the included studies.

A total of 17 studies containing the records of 4380 elderly patients with diabetes were included. The meta-analysis results showed that the incidence of cognitive impairment in elderly patients with diabetes was 48% (95% confidence interval [0.40-0.55]). The results of the subgroup analysis showed that the incidence of cognitive impairment was higher in the elderly population with diabetes who were female, older, with a lower education level, no spouse, living alone, and with a monthly income of less than 2000 yuan.

Current evidence showed that the incidence of cognitive impairment in elderly patients with diabetes in China was 48%, with a higher incidence in the elderly population who were female, older, with a lower education level, a low income, no spouse, and living alone.

This study aims to explore the changes in the structure, perfusion, and function of the bilateral hippocampus in type 2 diabetes mellitus (T2DM) applying multimodal MRI methods, hoping to provide reliable neuroimaging evidence for the diagnosis of hippocampus-related brain injury in T2DM.

We recruited 30 T2DM patients and 45 healthy controls (HCs), on which we performed 3D T1-weighted images, resting-state functional MRI (rs-fMRI), arterial spin labeling (ASL) sequences, and a series of cognitive tests. Then, we compared the differences of two groups in the cerebral blood flow (CBF) value, amplitude of low-frequency fluctuation (ALFF) value, fractional ALFF (fALFF) value, coherence-based regional homogeneity (Cohe-ReHo) value, and degree centrality (DC) values of the bilateral hippocampus.

In the T2DM group, the bilateral hippocampal volumes and the CBF value of the right hippocampus were lower than those in the HCs, while the ALFF value, fALFF value, and Cohe-ReHo value of the bilateral hippocampus were higher than those in the HCs. Correlation analysis showed that fasting blood glucose (FBG) was negatively correlated with the residuals of left hippocampal volume (r = -0.407, P = 0.025) and right hippocampal volume (r = -0.420, P = 0.021). The residual of the auditory-verbal learning test (AVLT) (immediate) score was positively correlated with the residual of right hippocampal volume (r = 0.369, P = 0.045).

This study indicated that the volume and perfusion of the hippocampus are decreased in T2DM patients that related to chronic hyperglycemia. Local spontaneous neural activity and coordination are increased in the hippocampus of T2DM patients, possibly as an adaptive compensation for cognitive decline.

Cognitive impairment in type 2 diabetes mellitus (T2DM) is associated with functional and structural abnormalities of brain networks, especially the damage to hub nodes in networks. This study explored the abnormal hub nodes of brain functional networks in patients with T2DM under different cognitive states. Sixty-five patients with T2DM and 34 healthy controls (HCs) underwent neuropsychological assessment. Then, degree centrality (DC) analysis and seed-based functional connectivity (FC) analysis were performed to identify the abnormal hub nodes and the FC patterns of these hubs in T2DM patients with mild cognitive impairment (MCI) (DMCI group, N = 31) and without MCI (DMCN group, N = 34). Correlation analyzes examined the relationship between abnormal DC and FC and clinical/cognitive variables. Compared with HCs, both T2DM groups showed decreased DC values in the visual cortex, and the T2DM patients with MCI (DMCI) showed more extensive alterations in the right parahippocampal gyrus (PHG), bilateral posterior cingulate cortex (PCC), and left superior frontal gyrus (SFG) regions than T2DM patients with normal cognitive function. Seed-based FC analysis of PHG and PCC nodes showed that functional disconnection mainly occurred in visual and memory connectivity in patients with DMCI. Multiple abnormal DC values correlated with neuropsychological tests in patients with T2DM. In conclusion, this study found that the DMCI group displayed more extensive alterations in hub nodes and FC in vision and memory-related brain regions, suggesting that visual-related regions dysfunctions and disconnection may be involved in the neuropathology of visuospatial function impairment in patients with DMCI.

Examine the association between glycemic control and cognition. Included subjects ≥60 years who participated in the 2013 to 2014 National Health and Nutrition Examination Survey and completed one of the followings: Consortium to Establish a Registry for Alzheimer's Disease Word List (CERAD-WL), Animal Fluency (AF), Digit Symbol Substitution Test (DSST), and CERAD-Delayed Recall (CERAD-DR). Stratified participants into: No type 2 diabetes (T2D; N = 557), Controlled T2D (N = 41), Uncontrolled T2D (N = 120), and Untreated T2D (N = 86). Multiple regression was used to examine the association between variables. After adjusting for demographics and cardiovascular risk factors, Uncontrolled T2D was associated with lower DSST (β = -3.164, p = .04), and Untreated T2D was associated with a trend for having lower CERAD-DR (β = -.496, p = .06) scores. T2D, independent of glycemic control, is associated with cognitive impairment and this relationship is influenced by modifiable and non-modifiable risk factors.