Alzheimer's disease poses a significant global health challenge owing to the progressive cognitive decline of patients and absence of curative treatments. The current therapeutic strategies, primarily based on cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists, offer limited symptomatic relief without halting disease progression, highlighting an urgent need for novel research directions that address the key mechanisms underlying Alzheimer's disease. Recent studies have provided insights into the critical role of glycolysis, a fundamental energy metabolism pathway in the brain, in the pathogenesis of Alzheimer's disease. Alterations in glycolytic processes within neurons and glial cells, including microglia, astrocytes, and oligodendrocytes, have been identified as significant contributors to the pathological landscape of Alzheimer's disease. Glycolytic changes impact neuronal health and function, thus offering promising targets for therapeutic intervention. The purpose of this review is to consolidate current knowledge on the modifications in glycolysis associated with Alzheimer's disease and explore the mechanisms by which these abnormalities contribute to disease onset and progression. Comprehensive focus on the pathways through which glycolytic dysfunction influences Alzheimer's disease pathology should provide insights into potential therapeutic targets and strategies that pave the way for groundbreaking treatments, emphasizing the importance of understanding metabolic processes in the quest for clarification and management of Alzheimer's disease.

Vascular cognitive impairment (VCI) is a syndrome characterized by cognitive decline resulting from insufficient perfusion to the entire brain or specific brain regions. The lack of a clear understanding of the mechanisms linking cerebrovascular disease to cognitive impairment has impeded the development of targeted treatments for VCI. Increasing evidence indicates that exercise may offer significant benefits for patients with VCI. This study explores how neuroinflammatory mechanisms mediate the effects of exercise on VCI, focusing on the broader biological processes involved. Exercise plays a crucial role in mitigating vascular risk factors, reducing oxidative stress, and promoting neurogenesis. Furthermore, exercise influences neuroinflammatory mediators and central immune cells via various signaling pathways. Different types and intensities of exercise, including resistance and endurance training, have been shown to differentially modulate neuroinflammation during the progression of VCI. This paper summarizes the current mechanisms of action and proposes exercise interventions targeting neuroinflammatory pathways, along with biomarker studies, to enhance our understanding of VCI pathogenesis and inform clinical practice. A more in-depth understanding of the inflammatory mechanisms underlying VCI may facilitate the development of targeted therapeutic interventions.

Primary healthcare institutions find identifying individuals with dementia particularly challenging. This study aimed to develop machine learning models for identifying predictive features of older adults with normal cognition to develop dementia.

We developed four machine learning models: logistic regression, decision tree, random forest, and gradient-boosted trees, predicting dementia of 1,162 older adults with normal cognition at baseline from the Hubei Memory and Aging Cohort Study. All relevant variables collected were included in the models. The Shanghai Aging Study was selected as a replication cohort (n = 1,370) to validate the performance of models including the key features after a wrapper feature selection technique. Both cohorts adopted comparable diagnostic criteria for dementia to most previous cohort studies.

The random forest model exhibited slightly better predictive power using a series of auditory verbal learning test, education, and follow-up time, as measured by overall accuracy (93%) and an area under the curve (AUC) (mean [standard error]: 088 [0.07]). When assessed in the external validation cohort, its performance was deemed acceptable with an AUC of 0.81 (0.15). Conversely, the logistic regression model showed better results in the external validation set, attaining an AUC of 0.88 (0.20).

Our machine learning framework offers a viable strategy for predicting dementia using only memory tests in primary healthcare settings. This model can track cognitive changes and provide valuable insights for early intervention.

Fibrinogen has been reported as a potential risk factor for vascular dementia (VaD). However, the association between fibrinogen and cognition in patients with ischemic cerebrovascular disease (ICVD) has not been studied adequately. We aimed to examine the association of fibrinogen with cognitive impairment among patients with ICVD and to test whether white matter hyperintensities (WMH) and brain atrophy play a role under the association.

In this case-control study, ICVD patients were recruited from the Neurology Department. Cognitive function was assessed using the Montreal Cognitive Assessment. WMH and brain atrophy were quantified by brain magnetic resonance imaging (MRI). The associations of fibrinogen with cognition and MRI markers were investigated by conditional logistic regression models and generalized additive models.

The risk of cognitive impairment increased with each unit increase in fibrinogen (AOR = 1.92, 95 % CI = 1.06 - 3.48). Individuals with fibrinogen levels > 4 g/L presented a substantially higher risk of cognitive impairment than those with fibrinogen levels of 2-4 g/L (AOR = 5.72, 95 % CI = 1.22- 26.82). Fibrinogen was negatively correlated with global cognitive function (rs = -0.235) and visuospatial/executive function (rs = -0.251). A negative correlation between fibrinogen and normal-appearing white matter (NAWM) volume was observed (rs = -0.282).

Fibrinogen is associated with cognitive impairment among patients with ICVD, and significantly negatively impacts global cognitive function and visuospatial/executive function. Furthermore, the negative correlation between fibrinogen and NAWM volume supports further exploration of potential mechanistic paths.

Apolipoprotein E ε4 (APOE ε4) bring the higher risk of Alzheimer' Disease (AD). It is essential to evaluate whether the diagnostic performances and critical values of cerebrospinal fluid (CSF) biomarkers are influenced by APOE ε4, which has guiding significance for the clinical practical application.

The differences in CSF biomarkers and their performances between APOE ε4 carriers and non-carriers in distinguishing AD, mild cognitive impairment (MCI) and preclinical AD from normal controls (NCs) were analyzed. The receiver operating characteristic (ROC) curves were generated to compare the area under the curve (AUC) between APOE ε4 carriers and non-carriers, as well as the critical values corresponding Youden Index.

In a cross sectional convenience sample of 1610 participants, lower Aβ42 and Aβ42/Aβ40 and higher p-Tau 181/Aβ42 in CSF were observed among APOE ε4 carriers than non-carriers in NC, MCI, and AD groups (P< 0.05). The performance of CSF p-tau/Aβ42 in distinguishing MCI from NC among APOE ε4 carriers was superior to non-carriers [AUC: 0.714 (95%CI: 0.673- 0.752) vs 0.600 (95%CI: 0.564- 0.634), P< 0.001], although it was similar in distinguishing AD from NC between APOE ε4 carriers and non-carriers [AUC: 0.874 (95%CI: 0.835-0.906) vs 0.876 (95%CI: 0.843- 0.904)]. In the longitudinal cohort of 254 participants, the association of CSF Aβ42, Aβ42/Aβ40 and p-Tau181/Aβ42 with cognitive decline were stronger in APOE ε4 carriers compared to non-carriers (P< 0.05). Meanwhile, the critical values were different depending on APOE genotype.

The CSF level of p-Tau181/Aβ42 was significantly different between APOE ε4 carriers and non-carriers at different stages of AD. The results indicate that the performances of CSF biomarkers are influenced by APOE ε4, which should be considered in the practical application.

The neurotrophic factor Neuritin is known to enhance cognitive capacity and to mitigate synaptic impairments in the APP/PS1 Alzheimer's disease (AD) mouse model, suggesting therapeutic potential for clinical treatment. However, the core molecular mechanisms remain elusive. Ferroptosis, a form of programmed cell death linked to iron dysregulation and oxidative stress, contributes to neurodegeneration in AD in part by accelerating amyloid-β deposition and neurofibrillary tangle formation. Here we examined if Neuritin can mitigate cognitive decline and neural degeneration in AD model mice by suppressing ferroptosis. Age-dependent cognitive decline was associated with Neuritin downregulation and increased ferroptosis in the hippocampus. Intracerebroventricular injection of exogenous Neuritin mitigated spatial and fear learning deficits as well as neural oxidative stress, apoptosis, and ferroptosis in the hippocampus without causing deleterious side effects. Neuritin injection also upregulated the activity of NAD+ kinase (NADK), the enzyme responsible for converting NAD to anti-ferroptotic NADPH, in the hippocampus of AD mice as well as in cultured hippocampal neurons. Reduced Neuritin expression in the hippocampus AD mice was associated with reduced phosphorylation (activation) of Akt (p-Akt), and Neuritin administration enhanced p-Akt expression in both HT22 cells and AD model mice. Conversely, blocking the PI3K/Akt pathway in HT22 cells reversed the Neuritin-induced increase in NADK activity and reduction in ferroptosis, indicating that Neuritin protects neurons from AD-induced damage by enhancing NADK activity through the PI3K/Akt pathway. Collectively, our results support Neuritin upregulation as a potential therapeutic strategy for early-phase AD.

Depression and cognitive impairments are prevalent among older adults, with evidence suggesting potential links to obesity and lipid metabolism disturbances. This study investigates the relationships between the triglyceride-glucose (TyG) index, body mass index (BMI), depression, and cognitive dysfunction in older adults, leveraging data from the NHANES survey and employing machine learning techniques.

We analysed 1352 participants aged 60-79 from the 2011-2014 NHANES dataset, who underwent cognitive function testing, depression assessments, and TyG index measurements. Multivariate linear regression and subgroup analyses were conducted to examine associations between the TyG index and depression/cognitive impairment. Machine learning models evaluated the importance of predictive factors for depression, while Mendelian randomization (MR) was employed to explore the causal relationship between BMI and depression/cognitive function.

The TyG index was negatively associated with cognitive function scores and positively associated with depression scores in adjusted models (p < 0.001). In fully adjusted subgroup analyses, among obese individuals (BMI ≥ 28), a 100-unit increase in the TyG index was linked to a 3.79-point decrease in depression scores. Machine learning models (Xgboost, AUC = 0.960) identified BMI, TyG-BMI, gender, and comorbidities (e.g., asthma, stroke, emphysema) as key determinants of depression. MR analyses revealed a negative association between BMI and depression risk [OR: 0.9934; 95 % CI (0.9901-0.9968), p = 0.0001] and cognitive dysfunction risk [OR: 0.8514; 95 % CI (0.7929-0.9143), p < 0.05]. No evidence of heterogeneity or pleiotropy was detected.

Depression and cognitive impairments were self-reported, potentially introducing bias. The observed associations may be influenced by unmeasured confounders, necessitating further research into the underlying mechanisms.

Our findings reveal associations between the TyG index and psychocognitive health in older adults. While these results highlight lipid metabolism as a potential factor in depression and cognitive dysfunction, further studies are needed to validate these findings and explore underlying mechanisms.

Alzheimer's disease (AD) is a neurodegenerative disorder that primarily affects older adults. Selenium, an essential micronutrient for humans, plays a crucial role in the body's normal physiological and metabolic processes. A long-term deficiency in selenium intake can lead to various diseases and even contribute to the ageing process. This study aims to explore the ameliorative effect of selenium on cognitive impairment in 3 × Tg-AD mice and to determine if its effects are related to the BDNF/TrkB pathway.

We employed the APP/PS1/tau 3 × Tg-AD mouse model for dietary selenium intervention. Behavioural experiments were conducted to assess learning and memory. Additionally, we measured selenium and GSH-Px levels in whole blood and brain tissue. Neuronal apoptosis in the hippocampus was observed using transmission electron microscopy. The expressions of Aβ, P-tau, BDNF, TrkB, and CREB were measured via RT-qPCR, while the expressions of Aβ, P-tau, BDNF, TrkB, p-CREB, and CREB were quantified using Western blot analysis.

Our findings indicate that selenium supplementation can improve spatial learning and memory deficiencies in 3 × Tg-AD mice. Selenium supplementation increased selenium and GSH-Px levels in the brain tissue of 3 × Tg-AD mice and significantly enhanced neuronal conditions. Furthermore, the expression levels of proteins related to the BDNF/TrkB pathway significantly increased following selenium supplementation.

Our study demonstrates that selenium can ameliorate memory impairment in 3 × Tg-AD mice by activating the BDNF/TrkB pathway.

Alzheimer's disease (AD) is a neurodegenerative disorder primarily characterized by cognitive impairment, for which effective treatments remain lacking. Albumin (ALB) is an essential carrier protein found in various body fluids, playing crucial roles in anti-inflammatory processes, antioxidation, and signal transduction. Recent research indicates that ALB may play a significant role in the development and progression of AD, though its specific function is not yet fully understood. In this study, we observed a link between serum ALB levels and cognitive performance in the elderly. Administration of ALB intranasally was shown to enhance learning and memory in MAPT/P301S transgenic mice, markedly decreasing hyperphosphorylation of Tau protein and reducing neuronal apoptosis. In a neuronal cell model overexpressing Tau, ALB administration in vitro attenuated Tau-induced toxicity and reduced the production of phosphorylated Tau. Additionally, co-incubation of Tau with ALB significantly reduced the formation of neurofibrillary tangles. These results suggest that ALB improves AD-related cognitive function by preventing the pathological aggregation of Tau and reducing its abnormal phosphorylation. Furthermore, ALB's neuroprotective effect helps prevent neuronal apoptosis in the cortex and hippocampus, providing potential targets for AD prevention and treatment.

Both air pollution and low socioeconomic status (SES) are associated with worse cognitive function. The extent to which low SES may compound the adverse effect of air pollution on cognitive function remains unclear.

7,087 older adults aged 65 and above were included from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) and followed up in 4 waves during 2008-2018. Cognitive function was measured repeatedly at each wave using the modified Chinese Mini-Mental State Examination (MMSE). Concentrations of particulate matter (PM1, PM2.5, and PM10) were evaluated using satellite-based spatiotemporal models. SES was measured based on five components and categorized into three levels (low, middle, and high). Generalized estimating equation models were used to estimate the association of PM and SES with cognitive function. Stratified analyses and effect modification by SES levels were further conducted.

Each 10 µg/m3 increase in PM1, PM2.5, and PM10 was associated with a 0.43 (95 % CI: -0.58, -0.27), 0.29 (95% CI: -0.37, -0.20), and 0.17 (95 % CI: -0.22, -0.13) unit decrease in MMSE scores, respectively. Lower SES was associated with worse cognitive function. Significant effect modifications were observed by SES, with the corresponding association of PM exposure being more pronounced among participants with a lower SES (p-interaction = 0.006, 0.001, and 0.006 for PM1, PM2.5, and PM10, respectively).

SES is an important effect modifier, and lower SES may compound the detrimental effect of PM on cognitive health. This finding may have implications for identifying vulnerable populations and targeted interventions against air pollution.

There has been growing attention to the impact of copper exposure on cognitive function; however, current research on the specific information regarding urinary copper and cognitive function is limited, particularly detailed analyses in the Chinese adult population. This study aimed to explore the association between copper exposure and cognitive function in a cross-sectional design. A total of 2617 participants in a county, Guangxi Zhuang Autonomous Region (Guangxi), China, were included. The mini-mental state examination (MMSE) was used to assess cognitive function, and inductively coupled plasma mass spectrometry was used to measure urinary metal levels. Spearman's rank correlation was used to analyze the correlation between urinary copper levels and various cognitive function assessment indices. After adjusting for potential confounders, binary logistic regression was used to explore the association between urinary copper levels and the risk of cognitive impairment (CI) as revealed by MMSE, and restricted cubic spline regression was further used to explore the dose-response relationship. The results showed a negative correlation between urinary copper levels and orientation, attention and calculation, memory, language ability, and MMSE total scores (P < 0.05). Compared with the low copper exposure group, the high exposure group showed a 58.5% increased risk of CI (OR = 1.585, 95%CI: 1.125 to 2.235, P = 0.008). A significant linear dose-response relationship was observed between urinary copper levels and the risk of CI (P overall = 0.045, P nonlinearity = 0.081). Our findings suggest that higher copper exposure may be associated with CI in the population of a county, Guangxi, China.

Wnt signaling is believed to play an important role in the nervous system. However, few studies have examined the association between gene variants of the Wnt signaling pathway and mild cognitive impairment (MCI). Additionally, the potential modulation of this association by blood lipoproteins remains poorly understood. We aimed to investigate these associations in the present analysis. The cross-sectional study comprised 459 participants from 17 villages in Jimo District, Qingdao, Shandong Province. A total of 46 single nucleotide polymorphisms (SNPs) in nine Wnt signaling pathway genes were included. Cognitive function was measured using Montreal Cognitive Assessment (MOCA). Polygenic risk scores (PRS) were used to summarize the effect of each gene. Ordered logistic regression and Poisson regression with robust variance were applied to examine the associations of SNPs with MCI and the dimension score of MOCA. Interaction analysis was conducted to verify the interaction with lipoproteins. A random forest classifier was used to develop a predictive model for MCI. The SNP PRKCA-rs2286674 was associated with MCI across three models. The risk of MCI increased by 31% and 2% for each unit increase of PRS of PRKCA and WNT7B respectively. Based on the multiplicative interaction model, the effects of certain PRSs on the risk of MCI were modified by blood lipoproteins. Integrating total PRS into the prediction model significantly improved the ability to predict MCI. Genetic variations in Wnt signaling pathway were associated with MCI in older adults. Interaction effects between gene variants and blood lipoproteins on MCI were observed.

Evidence has shown that both smoking and periodontitis were linked to cognitive impairment. This study examines whether periodontitis mediates the effects of smoking status on cognitive function in older adults.

Using data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014, the study included 1728 older participants who have data on smoking, serum cotinine, periodontal examination, and cognitive function. Mediation analysis was performed to test whether extent of periodontitis mediated associations between smoking status and cognitive function, adjusted for sociodemographic and basic health factors.

Compared to never-smokers, daily smokers exhibited significantly worse global cognitive function, with periodontitis mediating this effect (effect= -0.16; 95% CI= -0.29, -0.05). Similarly, periodontitis mediated the association between serum cotinine levels and cognitive function in the total sample (effect= -0.02; 95% CI= -0.03, -0.00).

Periodontitis significantly mediates the impact of smoking on cognitive function. The findings highlight the potential roles of maintaining oral health and smoking cessation in mitigating cognitive decline.

This study aims to evaluate the effects of a creative expressive art-based storytelling accompanied by caregivers (CrEAS-AC) program on reducing behavioral and psychological symptoms of dementia (BPSD) in older adults with dementia and caregiver burden compared to a general social contact (SC) control group. In this two-arm randomized controlled trial, dyads comprising participants with dementia and their caregivers were randomly assigned to the CrEAS-AC (n = 39) and SC groups (n = 39). Interventions were applied twice per week for 12 weeks. The primary outcomes were BPSD (NPI and AES-I) and caregiver distress, while secondary outcomes included communication ability (SFACS-S and SFACS-C), caregiver burden (CBI), and other health-related outcomes (activities of daily living and QOL-AD). All variables were measured at baseline, 12-week follow-up, and 24-week follow-up. Linear mixed model analyses indicated that participants in the CrEAS-AC group showed significantly lower scores on NPI, AES-I, caregiver distress, and CBI post-intervention at the 12-week follow-up, compared with the SC group. They also showed higher scores on QOL-AD, SFACS-S, and SFACS-C. Baseline characteristics did not modify the effects of the interventions, which were maintained until at least 24-week follow-up. The CrEAS-AC program, as an art-based intervention, is therefore potentially effective in reducing behavioral and psychological symptoms of dementia and improving communication ability and quality of life in older adults with dementia, as well as reducing caregivers' distress and burden.Trial registration: The study was registered in the Chinese Clinical Trials Registry (ID: ChiCTR2200064838) on 19/10/2022.

As China's population continues to age, addressing cognitive decline related to aging has become increasingly important. Simultaneously, rapid economic development has led to rising concerns about lipid metabolism disorders, particularly those involving blood lipids. Identifying modifiable risk factors early is critical to enhancing cognitive function in older adults. Thus, this study focuses on the relationship between triglycerides (TG), high-density lipoprotein (HDL), and cognitive performance to investigate potential mechanisms. A cross-sectional study was conducted using data from the 2015 China Health and Retirement Longitudinal Study (CHARLS) survey. Cognitive function was assessed across three domains: global cognition, episodic memory, and mental status. Fasting blood samples were analyzed for triglycerides and high-density lipoprotein (HDL) levels. The relationship between triglycerides, HDL, and cognitive function was examined using restricted cubic spline (RCS) analysis, multivariate linear regression, and mediation analysis. The analysis identifies a non-linear, inverse U-shaped relationship between triglycerides and both global cognition and episodic memory, with significant inflection points at a triglyceride (TG) level of 202.65 for global cognition and 115.04 for episodic memory. No non-linear relationship was observed between High-Density Lipoprotein (HDL) and cognitive outcomes, including global cognition, episodic memory, or mental status (p > 0.05). Linear mixed models indicate that HDL has a positive association with episodic memory, as shown by HDLQ1 (B = 0.0033, 95% CI: 0, 0.569), HDLQ2 (B = 0.039, 95% CI: 0.051, 0.594), and HDLQ3 (B = 0.033, 95% CI: 0.004, 0.556) compared to HDLQ4. A combined analysis of TG and HDL on episodic memory further demonstrated that the ''High-TG-low-HDL'' group (B = 0.036, 95% CI: 0.043, 0.578) had a significantly positive effect compared to the "High-HDL-low-TG" group. Mediation analysis revealed that Body Mass Index (BMI) indirectly mediated the HDL-episodic memory relationship, with a mediation effect size of 22.2%. In conclusion, this study explored the interplay between triglyceride levels, high-density lipoprotein cholesterol (HDL-C) levels, and cognitive function among middle-aged and elderly individuals in China. The findings reveal a U-shaped inverse relationship between triglyceride concentrations and cognitive ability, underscoring the need to maintain optimal triglyceride levels for cognitive health. Additionally, lower HDL levels (HDLQ1-Q3) were found to positively affect cognitive function, particularly in overall cognition and episodic memory, compared to higher HDL levels (HDLQ4). Importantly, body mass index (BMI) mediated the influence of HDL on episodic memory, with an effect size of 22.2%.

Social isolation (SI), loneliness, and cognitive function (CF) are increasingly acknowledged as significant public health concerns globally. In this study, we aimed to investigate the bidirectional relationships and mediating effects between SI, loneliness, and CF among older adults in China.

We analysed data from six waves of the Chinese Longitudinal Healthy Longevity Survey conducted between 2002-18. The sample included individuals aged ≥65 years. We used the general cross-lagged panel model to account for confounding factors and reveal mediating effects.

The findings indicated that SI and loneliness can independently lower CF. Moreover, loneliness may lower CF through SI, and SI may also lower CF through loneliness. Finally, we revealed that decreased CF can increase SI and loneliness.

SI and loneliness are significantly intertwined with CF among older adults in China. Interventions aiming at reducing SI, loneliness, and CF should consider the interplay of these factors to enhance the health and well-being of older adults.

BackgroundMore than 60 independent single-nucleotide polymorphisms (SNPs) have been associated with Alzheimer's disease risk by genome-wide association studies in European.ObjectiveWe aimed to confirm these SNPs in Chinese Han populations and investigate the utility of these genetic markers.MethodsAltogether 1595 late-onset Alzheimer's disease (LOAD) patients and 2474 controls from Chinese population were recruited. We replicated the association of 68 SNPs with LOAD and established polygenetic risk score (PRS) prediction model using significant SNPs. Meta-analysis for MS4A6A rs610932 and PICALM rs3851179 were performed.ResultsAccording to our findings, 14 out of 68 SNPs are validated significantly associated with LOAD (adjusted p < 0.05) after adjusting age and sex in the Chinese population. Besides, after stratification by APOE ε4 status, almost all SNPs retain markedly relationship with LOAD in APOE ε4 noncarriers. However, few loci retain correlation in APOE ε4 carriers. Furthermore, the area under the receiver operating characteristic curve prediction model for distinguishing LOAD patients from normal subjects were 0.614 for PRS and 0.689 for PRS and APOE. In addition, meta-analysis including this study of East Asian populations confirmed that rs610932 and rs3851179 were dramatically related to the LOAD (OR = 0.85, 95% CI = 0.74-0.97; OR = 0.87, 95% CI = 0.83-0.91).ConclusionsDespite genetic heterogeneity, there are still common loci among different races. PRS based on AD risk-associated SNPs may supplement APOE for better assessing individual risk for AD in Chinese. Besides, interactions between genes and gene environment affect the impact of risk allele on diverse populations.

This study investigated the association between handgrip strength (HGS) asymmetry and weakness with cognitive function and depressive symptoms among 920 community-dwelling adults aged above 60 years in suburban Shanghai. Participants were selected using a multistage cluster-stratified sampling approach. Assessments included HGS measured with a dynamometer, the Montreal Cognitive Assessment (MoCA) for cognition, and the Geriatric Depression Scale (GDS) for depressive symptoms. Restricted cubic splines revealed a positive association between dominant HGS and MoCA scores, indicating better cognitive performance, and a negative association with GDS scores, suggesting fewer depressive symptoms. The association between the HGS ratio and MoCA scores and the HGS ratio and GDS scores varied by sex. Women with HGS weakness alone (odds ratio (OR) = 2.00, 95% confidence interval (CI) = 1.17-3.37), asymmetry alone (OR = 1.93, 95% CI = 1.14-3.29), or weakness and asymmetry together (OR = 2.57, 95% CI = 1.48-4.46) had a significantly increased risk of cognitive impairment. However, no such associations observed in men. These findings suggest that HGS weakness and asymmetrical HGS may be associated with a higher risk of cognitive decline and depressive symptoms, particularly in women. This study emphasizes the need for sex-specific assessments and prevention strategies to address cognitive and mental health issues among older adults.

The brain naturally synthesizes hydrogen sulfide (H2S) via enzymes such as cystathionine-β-synthase (CBS), 3-mercaptopyruvate sulfurtransferase (3-MST), cysteine aminotransferase (CAT), and cystathionine-γ-lyase (CSE). From a physiological point of view, H2S serves as a neuromodulator with antioxidant and neuroprotective properties. Recent research suggests that H2S is crucial in regulating learning and memory, as its downregulation is commonly observed in cognitive impairment diseases. Preclinical studies suggest that external supplementation, through donors like sodium hydrosulfide (NaHS), can improve cognitive impairment in various cognitive disorder models. Moreover, numerous molecular mechanisms have been proposed to explain the effects of these H2S donors. This review aims to detail the roles of H2S in various models of cognitive impairment and in human subjects, highlighting its potential mechanisms and providing experimental support for its use as a novel therapeutic approach in treating cognitive disorders. Overall, H2S plays a significant role in the treatment of cognitive impairment diseases, but further large-scale studies are still required to support the results of current research.

Background: Mild Cognitive Impairment (MCI) is a critical transitional phase between normal aging and dementia, and early detection is essential to mitigate cognitive decline. Traditional cognitive assessment tools, such as the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA), exhibit limitations in feasibility, which potentially and partially affects results for early-stage MCI detection. This study developed and tested a supportive cognitive assessment system for MCI auxiliary identification, leveraging eye-tracking features and convolutional neural network (CNN) analysis. Methods: The system employed eye-tracking technology in conjunction with machine learning to build a multimodal auxiliary identification model. Four eye movement tasks and two cognitive tests were administered to 128 participants (40 MCI patients, 57 elderly controls, 31 young adults as reference). We extracted 31 eye movement and 8 behavioral features to assess their contributions to classification accuracy using CNN analysis. Eye movement features only, behavioral features only, and combined features models were developed and tested respectively, to find out the most effective approach for MCI auxiliary identification. Results: Overall, the combined features model achieved a higher discrimination accuracy than models with single feature sets alone. Specifically, the model's ability to differentiate MCI from healthy individuals, including young adults, reached an average accuracy of 74.62%. For distinguishing MCI from elderly controls, the model's accuracy averaged 66.50%. Conclusions: Results show that a multimodal model significantly outperforms single-feature models in identifying MCI, highlighting the potential of eye-tracking for early detection. These findings suggest that integrating multimodal data can enhance the effectiveness of MCI auxiliary identification, providing a novel potential pathway for community-based early detection efforts.

Alzheimer's disease, the most prevalent cause of dementia, is a worldwide health problem. Proteomics is the systematic study of proteins and peptides to provide comprehensive descriptions. Aiming to obtain a more accurate and convenient clinical diagnosis, researchers are working on blood biomarkers.

This review synthesizes findings from previous studies investigating blood biomarkers for Alzheimer's disease using proteomic approaches.

We summarized the application of blood proteomics as diagnostic biomarkers and associations with clinical indicators such as neuropsychological performances, Aβ deposition and brain atrophy in Alzheimer's disease, and mild cognitive impairment.

In summary, blood proteomics is suggested to be promising in biomarkers of Alzheimer's disease.

BackgroundNeuropsychological assessments are essential tools for the screening and diagnosis of patients with cognitive impairments. Cultural background differences significantly affect cognitive test performance. For China, which is rapidly aging, a culturally adaptive picture naming test is urgently needed.ObjectiveThis study aims to develop a Chinese naming test (CNT) adapted to the cultural background of Chinese people and to explore its correlation with Alzheimer's disease (AD) biomarkers.MethodsA total of 1459 participants were recruited, including 744 with normal cognition (NC), 492 with mild cognitive impairment (MCI), and 223 with dementia. All participants underwent a comprehensive neuropsychological assessment. The diagnostic capability of CNT was determined using Receiver Operating Characteristic curves. Part of participants underwent amyloid-β (Aβ) PET scans, tau-PET scans, and MRI scans. The relationships between CNT scores and Aβ and tau deposition, as well as brain structural changes, were analyzed.ResultsThe diagnostic capability of CNT for MCI showed a sensitivity of 68.7%, specificity of 75.6%, and AUC of 0.81; for dementia, the sensitivity was 72.7%, specificity was 89.5%, and AUC was 0.89. The correlation coefficient between CNT scores and brain Aβ burden was -0.11 (p = 0.024). CNT scores correlated with tau burden in different Braak stages (p < 0.05). The correlation coefficient between CNT scores and hippocampus atrophy was -0.15 (p = 0.003).ConclusionsThe CNT has good diagnostic performance in detecting MCI and dementia in Chinese population. There is a correlation between CNT scores and AD imaging markers, indicating that the CNT might has potential value in predicting cognitive changes and disease progression.

Previous studies have shown that the referral situation after cognitive screening is not optimistic. However, little is known about the situation in China. The current study assessed the cognitive function of older adults with an Eight-item Ascertain Dementia (AD8) score of ≥ 2 in a community health center and investigated their willingness to accept referrals.

In our cross-sectional study, a total of 970 participants completed a cognitive screen using AD8. Those with a score of ≥ 2 were further assessed using the Mini-Mental State Examination. Sociodemographic information was collected. The participants were asked to respond to a questionnaire about their acceptance and uptake of referral after screening and their knowledge of cognitive impairment. The data were analyzed using descriptive statistics, the chi-square test, the Mann-Whitney U rank sum test, and binary logistic regression.

We screened 140 older adults with cognitive impairment from 970 participants. Among the 140 subjects, 37 (26.43%) indicated a willingness to be referred, and 103 (73.57%) declined to be referred. We investigated the reasons for declining referrals, and 69 (66.99%) indicated that they thought referrals were unnecessary. The knowledge of referrals, attitude toward referrals, and knowledge of cognitive impairment showed significant differences concerning participants' willingness to be referred(all p < 0.01). The participants with high knowledge of cognitive impairment were willing to accept referrals (p = 0.009; OR = 1.305; 95% CI: 1.070-1.591).

Chinese older adults with cognitive impairment exhibit a low willingness to be referred. Health education in older adults is needed to raise awareness of cognitive impairment, dementia prevention, treatment, and care.

Type 2 diabetes mellitus (T2DM) is a significant risk factor for cognitive impairment. Zinc deficiency contributes to T2DM development, while copper may exacerbate diabetes through prooxidant mechanisms. Higher zinc levels may protect against copper toxicity. This study investigates the association of plasma zinc and copper levels with mild cognitive impairment (MCI) in T2DM patients.

T2DM patients admitted to Tongji Hospital from 2012 to 2018 were classified into MCI (n = 136) and control (n = 136) groups, matched by age (± 3 years) and gender. Conditional logistic regression was used to assess the associations between plasma zinc, copper levels and MCI. A generalized additive model (GAM) evaluated the dose-response relationship between plasma zinc, copper levels and Mini-Mental State Examination (MMSE) scores.

The median of plasma metal levels in MCI and control groups were 831.31 μg/L and 936.29 μg/L for zinc, 932.07 μg/L and 860.47 μg/L for copper, and 0.91 and 1.11 for the zinc-to-copper (Zn/Cu) ratio. Compared to participants in the lowest tertile, the multivariable-adjusted odds ratios with 95% confidence intervals (CI) for MCI in the highest tertile were 0.33 (0.13, 0.79) for zinc, 3.56 (1.42, 8.94) for copper, and 0.37 (0.15, 0.93) for the Zn/Cu ratio. Plasma Aβ40 levels were significantly lower (p = 0.009) and plasma Aβ42/40 levels were significantly higher (p = 0.008) in MCI group compared with those in control group. Zinc concentration was positively associated with Aβ42. For per SD (327.71 μg/L) increase in plasma zinc levels, the percent change (95% CI) of Aβ42 were 2.90 (0.85, 4.99).

Higher plasma zinc levels and higher Zn/Cu ratio were associated with lower odds of MCI in T2DM patients, while higher copper levels increased the risk of MCI. This study provides insights on plasma zinc, copper, and Zn/Cu ratio and Aβ of MCI, further studies are needed to clarify the underlying mechanisms for novel therapies that could prevent or cure multiple T2DM-related cognitive impairments.

The purpose of this study is to present the findings of a cross-sectional survey on health state utility (HSU) values, a crucial metric for economic evaluations, and to analyze the primary factors influencing the HSU values of individuals with normal cognition (NC) or mild cognitive impairment (MCI).

A community-based survey was conducted in Haikou City, China, employing cluster random sampling to select participants. The presence of NC and MCI was determined through the administration of the Chinese version of the Mini-Mental State Examination (MMSE). The assessment of HSU was conducted using the Chinese version of the Short Form Six Dimensions version 2 (SF-6Dv2), in conjunction with a questionnaire that collected data on socio-demographic characteristics, health-related behaviors, and health conditions. The HSU values were calculated using the SF-6Dv2 value set, which was developed for the Chinese population. A multiple linear regression model was constructed to identify the factors influencing HSU values.

The survey indicated that 536 older individuals were identified with NC (mean age 70.7, SD 7.1, 51.4% females), 245 were identified with MCI (mean age 73.0, SD 7.8, 67.4% females). The mean HSU values in NC group and MCI group were 0.792 (SD: 0.174) and 0.720 (SD: 0.199), respectively. The optimal multiple regression model for the MCI group demonstrated a linear relationship between age, depression symptomatology, and MMSE score with HSU, with coefficients of -0.009 (p < 0.001) for age and -0.132 (p < 0.001) for depression symptomatology. And for NC group, the optimal multiple linear regression model included five variables: age, sex, monthly personal income, depression symptomatology, and number of comorbidities.

This study presented findings on HSU and its influencing factors in both the NC and MCI groups. The older adult individuals with MCI demonstrated lower HSU compared to their cognitively normal counterparts. The results of the factor analysis indicated that intervention programs designed to enhance the health-related quality of life for older adult individuals with MCI should include strategies to address depression.

This study aimed to determine balance, fall risk, and kinesiophobia in individuals with Alzheimer's Dementia (AD).

The study was completed with 18 AD and 18 healthy AD-free control group with early or moderate-stage AD diagnosed by a neurologist. Socio-demographic characteristics of the individuals were assessed using an evaluation form, and their balance was evaluated using the Tinetti Balance and Gait Assessment Test, Timed Up and Go Test, and Single Leg Standing Test. The Falls Risk Self-Assessment Scale (FRSAS) was used to assess the risk of falls. Kinesiophobia was assessed using the Tampa Scale for Kinesiophobia (TKS). Additionally, participants underwent the Mini-Mental State Examination (MMSE).

The mean age of individuals with AD was lower than that of healthy individuals, with means of 69 ± 3.66 years and 65.4 ± 4.10 years, respectively (p = 0.012). The Tinetti balance (p = 0.005), Tinetti gait (p < 0.001), Tinetti total (p < 0.001), and the Mini-Mental State Examination (MMSE) (p < 0,001) scores were lower in AD individuals relative to controls. The FRSAS (p < 0.001) scores were higher in AD individuals relative to controls. The TKS scores were found to be similar between individuals with AD and the control group (p = 0.860).

It was found that individuals with Alzheimer's disease (AD) have poorer balance and a higher risk of falls compared to healthy individuals. In light of these results, balance assessments should be included when developing rehabilitation protocols for individuals with AD. Treatment protocols designed for this patient group must incorporate balance-specific exercise and training programs. Additionally, individual and environmental preventive measures should be implemented to reduce the risk of falls in individuals with AD.

Clinical Trial Number: NCT05201768.

As the population in China rapidly ages, the prevalence of mild cognitive impairment (MCI) is increasing considerably. However, the causes of MCI vary. The continued lack of understanding of the various subtypes of MCI impedes the implementation of effective measures to reduce the risk of advancing to more severe cognitive diseases.

To estimate the prevalence and incidence rates of two MCI subtypes-amnestic MCI (aMCI) and vascular cognitive impairment without dementia (VCIND)-and to determine modifiable factors for them among older individuals in a multiregional Chinese cohort.

This 1-year longitudinal study surveyed a random sample of participants aged≥60 years from a large, community-dwelling cohort in China. Baseline lifestyle data were self-reported, while vascular and comorbid conditions were obtained from medical records and physical examinations. In total, 3514 and 2051 individuals completed the baseline and 1-year follow-up assessments, respectively. Logistic and linear regression analyses were used to identify the modifiable factors for MCI subtypes and predictors of cognitive decline, respectively.

Among our participants, aMCI and VCIND demonstrated prevalence of 14.83% and 2.71%, respectively, and annual incidence (per 1000 person-years) of 69.6 and 10.6, respectively. The risk factor for aMCI was age, whereas its protective factors were high education level, tea consumption and physical activity. Moreover, VCIND risk factors were age, hypertension and depression. The presence of endocrine disease, cerebral trauma or hypertension was associated with a faster decline in cognition over 1 year.

MCI is a serious health problem in China that will only worsen as the population ages if no widespread interventions are implemented. Preventive strategies that promote brain activity and support healthy lifestyle choices are required. We identified modifiable factors for MCI in older individuals. The easy-to-adopt solutions such as tea consumption and physical activity can aid in preventing MCI.

NCT03672448.

Various digital therapeutics (DTx), which utilize computerized cognitive training (CCT) to improve cognitive functioning, have been tested and released. However, the efficacy of these DTx approaches may be diverse. This study aims to meta-synthesize the associations between mobile applications and cognitive functioning outcomes in older adults with mild cognitive impairment (MCI) or dementia from randomized controlled trials (RCTs). We searched PubMed, EMBASE, Scopus, and Cochrane Library from the inception through the end of June 2024. We selected RCTs using mobile application interventions in older adults with MCI or dementia. Interventions and comparisons included: CCT, intensive CCT (CCT2x), computerized cognitive engagement, progressive resistance training (PRT), CCT plus medication, CCT plus PRT, and medications only. Outcomes of interest included cognitive functioning and other measures of functioning (e.g., activities of daily living [ADLs]). Network meta-analysis was conducted to estimate pooled standardized mean differences (SMDs) with corresponding 95 % confidence intervals (CIs). Of 1,189 studies extracted, 10 RCTs were included in our analysis. CCT2x demonstrated statistically significant improvements in global cognitive function (SMD, 1.21 [95 % CI, 0.69-1.73]), episodic memory (SMD, 0.87 [0.47-1.27]), and working memory (SMD, 0.93 [0.44-1.42]) when compared with controls. For ADLs, CCT significantly reduced functional impairment (SMD, -0.80 [-1.40 to -0.21]). In depressive symptoms, CCT2x was the most effective in reducing symptoms (SMD, -0.77 [-1.08 to -0.45]). Overall, the DTx may be effective in improving cognitive and other functioning outcomes in older adults with MCI or dementia.

The relationship between Alzheimer's disease (AD) and neuroimmunity has gradually begun to be unveiled. Emerging evidence indicates that cyclic GMP-AMP synthase (cGAS) acts as a cytosolic DNA sensor, recognizing cytosolic damage-associated molecular patterns (DAMPs), and inducing the innate immune response by activating stimulator of interferon genes (STING). Dysregulation of this pathway culminates in AD-related neuroinflammation and neurodegeneration. A substantial body of evidence indicates that mitochondria are involved in the critical pathogenic mechanisms of AD, whose damage leads to the release of mitochondrial DNA (mtDNA) into the extramitochondrial space. This leaked mtDNA serves as a DAMP, activating various pattern recognition receptors and immune defense networks in the brain, including the cGAS-STING pathway, ultimately leading to an imbalance in immune homeostasis. Therefore, modulation of the mtDNA-cGAS-STING pathway to restore neuroimmune homeostasis may offer promising prospects for improving AD treatment outcomes. In this review, we focus on the mechanisms of mtDNA release during stress and the activation of the cGAS-STING pathway. Additionally, we delve into the research progress on this pathway in AD, and further discuss the primary directions and potential hurdles in developing targeted therapeutic drugs, to gain a deeper understanding of the pathogenesis of AD and provide new approaches for its therapy.

Almost all physiological processes are modulated by microRNAs, therefore, dysregulation of these small regulatory RNAs is observed in a variety of diseases, including cognitive impairments.

In this study, 40 male Wistar rats were randomly divided into five groups of control, scopolamine, donepezil, memantine, and combined administration of donepezil + memantine. Rats in scopolamine, donepezil, memantine, and combined administration of donepezil + memantine groups received scopolamine (1 mg/kg-intraperitoneal) for 7 days. After the last administration of scopolamine, was started injecting donepezil (3 mg/kg-i.p.), memantine (10 mg/kg-i.p.), and combined administration of Donepezil + Memantine (0.5 mg/kg and 5 mg/kg-i.p., respectively), up to 21 days. Twenty-four hours after the last injection, elevated plus-maze, social interaction, open field tests, and gene expression analysis of miR-124, miR-125b, and miR-132 in the hippocampus were carried out.

The results of the behavioral tests indicate that donepezil and memantine significantly prevented Scopolamine-induced anxiety, sociability, and social memory decline. The gene expression of selected microRNAs did not significantly differ between the groups.

This study revealed that donepezil and memantine effectively prevent synaptic plasticity disruption and cognitive decline induced by scopolamine. Findings indicated that this treatment is unrelated to the expression of the selected microRNAs. The positive effects of memantine and donepezil depend on age, dosages, cognitive task demands, and possibly the length and timing of the treatment.

Acupuncture is a promising therapy for amnestic mild cognitive impairment (aMCI). Growing evidence suggest that alterations in the microbiota-gut-brain (MGB) axis contribute to the development and progression of aMCI. However, little is known about whether and how acupuncture change the MGB axis of aMCI individuals.

This was a randomized, controlled, clinical trial. Forty patients with aMCI were randomly allocated to either the acupuncture group or the waitlist group. The primary outcome was the change in the Alzheimer's Disease Assessment Scale-Cognitive Scale (ADAS-Cog) score. In addition, multi-omics was performed to detect changes in brain function, gut microbiota, and serum metabolites. Generalized estimating equations were used to estimate the outcomes, and correlational analyses were performed to explore the relationships between the clinical and multi-omics data.

Compared to a mean baseline to week 12 change of -3.94 in the acupuncture group, the mean change in the waitlist group was 1.72 (net difference, -5.66 [95 % CI, -6.98 to -4.35]). Compared to the waitlist group, acupuncture's MGB axis modulatory effect exhibited altered the regional homogeneity values of Frontal_Med_Orb_L, Cingulum_Mid_L, and Frontal_Sup_Medial_L, relative abundance of gut Ruminococcus_sp_AF43_11 and s_Eubacterium_coprostanoligenes, and levels of serum (11E,15Z)-9,10,13-trihydroxyoctadeca-11,15-dienoic acid, dipropylene glycol dimethyl ether, N6-Me-dA, and DPK, which correlated with changes in ADAS-Cog scores.

Our data imply that acupuncture ameliorates overall cognitive function, along with changes in brain activity, gut microbiota, and serum metabolites, providing preliminary evidence of the mechanisms acting through the MGB axis underlying the effects of acupuncture on aMCI.

This study assessed the effectiveness of three digital screening tools in detecting cognitive impairment (CI) in a large cohort of community-dwelling elderly individuals and investigated the relationship between key digital features and plasma p-tau217 levels.

This community-based cohort study included 1,083 participants aged 65 years or older, with 337 diagnosed with CI and 746 classified as normal controls (NC). We utilized two screening approaches: traditional methods (AD8, MMSE scale, and APOE genotyping) and digital tools (drawing, gait, and eye tracking). LightGBM-based machine learning models were developed for each digital screening tool and their combination, and their performance was evaluated. The correlation between key digital features and plasma p-tau217 levels was analyzed as well.

A total of 21 drawing, 71 gait, and 35 eye-tracking parameters showed significant differences between the two groups (all p < 0.05). The area under the curve (AUC) values for the drawing, gait, and eye-tracking models in distinguishing CI from NC were 0.860, 0.848, and 0.895, respectively. The combination of eye-tracking and drawing achieved the highest classification effectiveness, with an AUC of 0.958, and accuracy, sensitivity, and specificity all exceeded 85%. The fusion model achieved an AUC of 0.928 in distinguishing mild cognitive impairment (MCI) from NC. Additionally, several digital features (including two drawing, ten gait, and one eye-tracking parameters) were significantly correlated with plasma p-tau217 levels (all |r| > 0.3, p < 0.001).

Digital screening tools offer objective, accurate, and efficient alternatives for detecting CI in community settings, with the fusion of drawing and eye-tracking providing the best performance (AUC = 0.958).

To identify factors associated with dementia among older people in Malaysia.

This study used data from a nationwide cross-sectional survey in Malaysia. Participants involved were older people aged 60 years and above. Data collected were on dementia risk factors as well as dementia screening. Dementia screening was done using the Identification and Intervention for Dementia in Elderly Africans cognitive screening tool. Univariate analysis and multiple logistic regression were carried out to determine the factors associated with dementia.

There were 3774 participants involved in this study. Multiple logistic regression showed factors associated with dementia among older people were those aged 70 years and above, Indian ethnic group, being single, primary or no formal education, as well as those with hypertension. Interestingly, our findings also showed that older people with hypercholesterolemia have lower odds of having dementia.

Multiple factors were associated with dementia in Malaysia, highlighting the need to implement multiple interventions strategies, by taking a lifetime approach emphasizing education, physical as well as social aspects.

Individuals with mild cognitive impairment (MCI) exhibit poorer performance in cognition and dual-task paradigm, while the related cortical thickness and surface area alterations remains unclear.

Thirty participants with MCI and thirty healthy controls (HC) were recruited. Magnetic resonance imaging, cognitive assessments and dual-task Timed Up and Go test (DT-TUG) were performed to assess cerebral cortical thickness and surface area, cognitive functions, and dual-task cost (DTC) of the execution time in TUG. Spearman correlations were conducted to assess the relationships between the cognitive, TUG performance with the cortical morphological measures.

MCI participants performed worse in the Montreal cognitive assessment (MoCA), WAIS Digit Span, TMT and the modified Posner peripheral cuing task. Their execution time on the DT-TUG was also prolonged. WAIS Digit Span Backwards was correlated with DT-TUG in HC group. A significant between-group difference was observed in the surface area of the left SPC. The cortical thickness of this brain region was positively correlated with the total scores and attention subdomain of MoCA in HC group. The cortical thickness and the surface area were correlated with the time of DT-TUG in HC group only.

Individuals with MCI demonstrated declines in both cognitive function and dual-task walking performance. This study provides further evidence of surface-based structural differences in the left SPC in individuals with and without MCI, and supports the role of the left SPC in cognition and dual-task walking.

Qiangji Decoction (QJD), a Chinese medicine, is widely used in Traditional Chinese Medicine to treat amnesia and Alzheimer's disease (AD), showing significant anti-AD effects. However, the precise mechanisms behind these effects are not well understood and require more research.

This study aims to elucidate the mechanisms by which QJD ameliorates neuronal damage, synaptic dysfunction, and mitochondrial impairment in AD through the regulation of ROCK2/Drp1-mediated mitochondrial dynamics.

UPLC-Q-TOF-MS/MS was used to identify active components in QJD extract. The study used SAMP8 mice for AD modeling and SAMR1 mice as controls. Cognitive function in SAMP8 mice was assessed with the Morris Water Maze after following treatment with QJD and the mitochondrial fission inhibitor Mdivi-1. Nissl and FJB staining evaluated QJD's effect on hippocampal injury. Synaptic integrity was examined with Golgi-Cox staining, transmission electron microscopy, and immunofluorescence. Mitochondrial function in hippocampal neurons was assessed using electron microscopy, JC-1 staining, and reagent kits. Western blot analyzed expression of proteins related to mitochondrial fission (ROCK2, Drp1, Fis1, Mff) and fusion (Mfn1, Mfn2, OPA1).

The analysis of QJD extract via UPLC-Q-TOF-MS/MS led to the identification of 46 active compounds. In SAMP8 mice, administration of QJD resulted in decreased escape latency, increased platform crossings, and extended duration in the target quadrant. Additionally, QJD exhibited neuroprotective effects on the hippocampus of SAMP8 mice, effectively preventing neuronal loss and damage. QJD also facilitated the extension and thickening of dendritic spines, enhanced the ultrastructure of hippocampal synapses, and upregulated synaptic function-related proteins, including PSD95 and SYN1. Furthermore, QJD ameliorated mitochondrial damage, improved mitochondrial membrane potential and ATP content, and reduced ROS expression in hippocampal neurons of SAMP8 mice. These effects were mediated through the downregulation of ROCK2, phosphorylated Drp1 (Ser616), Fis1, and Mff, as well as the upregulation of Mfn1, Mfn2, and OPA1.

QJD may reduce neuronal damage, synaptic dysfunction, and mitochondrial impairment in SAMP8 mice by regulating mitochondrial dynamics through the ROCK2/Drp1 pathway.

The atherogenic index of plasma (AIP) has been proposed as a novel biomarker predictor for dyslipidemia and has been linked to various diseases. In this study, we explored the relationship between AIP levels and cognitive impairment in a middle-aged and older population.

This study utilized data from the China Health and Retirement Longitudinal Study (CHARLS) for 7,918 individuals aged 45 and older. The AIP was calculated as the logarithmic ratio of triglycerides to high-density lipoprotein cholesterol. To assess the relationship between the AIP and cognitive impairment, logistic regression models were employed, while restricted cubic spline analysis was conducted to explore potential non-linear associations between AIP levels and cognitive impairment.

The study participants had a mean age of 58.4 ± 8.8 years, and 49.1% were female. From 2011 to 2018, 2,911 participants (36.8%) developed cognitive impairment. After adjusting for potential confounders, the AIP was found to be significantly associated with cognitive impairment. In particular, participants in the higher AIP quartiles (Q2: odds ratio [OR]: 1.45, 95% confidence interval [CI]: 1.24-1.69, P < 0.001, Q3: OR: 1.63, 95% CI: 1.40-1.91, P < 0.001, and Q4: OR: 1.68, 95% CI: 1.43-1.98, P < 0.001) showed an increased risk of cognitive impairment compared to those in the lowest quartile (Q1). Additionally, a non-linear relationship was observed between AIP levels and cognitive impairment risk (P for nonlinear < 0.001).

The study finds that elevated AIP levels are linked to an increased risk of cognitive impairment in middle-aged and older adults, suggesting that managing dyslipidemia could help reduce this risk.

The aging population in China is confronted with considerable challenges, with 14.71% of elderly individuals affected by mild cognitive impairment (MCI). The practice of Tai Chi has been demonstrated to enhance cognitive function, while sensory stimulation has been shown to facilitate neural activity. Nevertheless, the combined impact of Tai Chi and sensory stimulation on cognitive, sensory functions, and brain activation in older adults with MCI remains uncertain. This study aims to ascertain whether the integration of Tai Chi with sensory stimulation can facilitate more efficacious interventions for these outcomes.

The TaiChi-MSS (Tai Chi and Multisensory Stimulation for Cognitive Function) study is a multi-center, randomized controlled trial (RCT) conducted in Suzhou and Shanghai, enrolling 88 participants aged 60 years or older with MCI. Participants will be randomly assigned to one of four groups: Tai Chi, multisensory stimulation, Tai Chi combined with multisensory stimulation or control. The intervention will last 6 months, with follow-up assessments at 3, 6, and 9 months. Primary outcomes include cognitive and sensory assessments, assessed using the Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), domain-specific cognitive tests, Pure Tone Audiometry (PTA), and Sniffin' Sticks Odor Identification Test. Secondary outcomes involve brain activation, measured through functional Magnetic Resonance Imaging (fMRI) scans. fMRI will be used to assess brain structure and connectivity changes, focusing on neuroplasticity. Data will be analyzed using mixed-effects models. The False Discovery Rate (FDR) will be the correction method for multiple comparisons to control for the expected proportion of false positives.

This study was approved by the ethics committee of Shanghai University of Sport (No. 102772023RT200). The results of this study will be disseminated in peer-reviewed journals and presented at academic conferences.

Cognitive training has been confirmed to significantly improve the overall cognitive function in patients. For patients with coronary heart disease, in addition to controlling common risk factors, there is a lack of effective evidence for the treatment of cognitive function in patients with coronary heart disease and its effectiveness. This randomized controlled study was designed to evaluate the effectiveness of computer-based cognitive training for improving cognitive function in such patients.

COG-T CHD is a multicenter, double-blind, parallel-designed, randomized controlled trial. The patients will be divided 1:1 into two groups by a central randomized system, a cognitive digital therapy group or a positive control group. Patients assigned to the cognitive digital therapy group will undergo computer-based cognitive training for 30 min at least five times a week for 12 weeks. At the end of the 12 weeks, the subjects were randomly divided into two groups. One group continued the 12 weeks of cognitive digital therapy training and the other group stopped the training. Patients assigned to the positive control group will undergo computer-based cognitive training with little or no difficulty changes for 30 min at least five times a week for 12 weeks. The study will last approximately 2 years, with enrollment completed in approximately 18 months, with the last enrolled patient followed for at least 24 weeks. The primary outcome is the proportion of improvement in overall cognitive function at 12 weeks, using the Basic Cognitive Ability Test (BCAT). Secondary outcomes are the proportion of improvement in the overall cognitive function from baseline at 24 weeks, the change in overall cognitive function scores at 12 and 24 weeks, and the proportion of improvement in each cognitive domain, General Self-Efficacy Scale score, EuroQol five-dimension three-level questionnaire score, and Generalized Anxiety Disorder-7 score at 12 and 24 weeks from baseline. The investigational outcome is the change in head MRI structure and function from baseline at weeks 12/24.

COG-T CHD is the first clinical trial to evaluate the efficacy of computer-based cognitive training in patients with coronary heart disease, filling an important gap in the treatment evidence for cognitive digital therapy.

ClinicalTrials.gov, NCT05735041. Registered on Jan. 18, 2023.