Structural brain networks correlating with poststroke cognition.

Cognitive deficits are a common and debilitating consequence of stroke, yet our understanding of the structural neurobiological biomarkers predicting recovery of cognition after stroke remains limited. In this longitudinal observational study, we set out to investigate the effect of both focal lesions and structural connectivity on poststroke cognition. Sixty-two patients with stroke underwent advanced brain imaging and cognitive assessment, utilizing the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE), at 3-month and 12-month poststroke. We first evaluated the relationship between lesions and cognition at 3 months using voxel-based lesion-symptom mapping. Next, a novel correlational tractography approach, using multi-shell diffusion-weighted magnetic resonance imaging (MRI) data collected at both time points, was used to evaluate the relationship between the white matter connectome and cognition cross-sectionally at 3 months, and longitudinally (12 minus 3 months). Lesion-symptom mapping did not yield significant findings. In turn, correlational tractography analyses revealed positive associations between both MoCA and MMSE scores and bilateral cingulum and the corpus callosum, both cross-sectionally at the 3-month stage, and longitudinally. These results demonstrate that rather than focal neural structures, a consistent structural connectome underpins the performance of two frequently used cognitive screening tools, the MoCA and the MMSE, in people after stroke. This finding should encourage clinicians and researchers to not only suspect cognitive decline when lesions affect these tracts, but also to refine their investigation of novel approaches to differentially diagnosing pathology associated with cognitive decline, regardless of the aetiology.

Disentangling and quantifying the relative cognitive impact of concurrent mixed neurodegenerative pathologies.

Neurodegenerative pathologies such as Alzheimer disease neuropathologic change (ADNC), Lewy body disease (LBD), limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC), and cerebrovascular disease (CVD) frequently coexist, but little is known about the exact contribution of each pathology to cognitive decline and dementia in subjects with mixed pathologies. We explored the relative cognitive impact of concurrent common and rare neurodegenerative pathologies employing multivariate logistic regression analysis adjusted for age, gender, and level of education. We analyzed a cohort of 6,262 subjects from the National Alzheimer's Coordinating Center database, ranging from 0 to 6 comorbid neuropathologic findings per individual, where 95.7% of individuals had at least 1 neurodegenerative finding at autopsy and 75.5% had at least 2 neurodegenerative findings. We identified which neuropathologic entities correlate most frequently with one another and demonstrated that the total number of pathologies per individual was directly correlated with cognitive performance as assessed by Clinical Dementia Rating (CDR®) and Mini-Mental State Examination (MMSE). We show that ADNC, LBD, LATE-NC, CVD, hippocampal sclerosis, Pick disease, and FTLD-TDP significantly impact overall cognition as independent variables. More specifically, ADNC significantly affected all assessed cognitive domains, LBD affected attention, processing speed, and language, LATE-NC primarily affected tests related to logical memory and language, while CVD and other less common pathologies (including Pick disease, progressive supranuclear palsy, and corticobasal degeneration) had more variable neurocognitive effects. Additionally, ADNC, LBD, and higher numbers of comorbid neuropathologies were associated with the presence of at least one APOE ε4 allele, and ADNC and higher numbers of neuropathologies were inversely correlated with APOE ε2 alleles. Understanding the mechanisms by which individual and concomitant neuropathologies affect cognition and the degree to which each contributes is an imperative step in the development of biomarkers and disease-modifying therapeutics, particularly as these medical interventions become more targeted and personalized.

Cognitive impairment in children and adults with cerebrotendinous xanthomatosis: A French cohort study.

Cerebrotendinous xanthomatosis is a rare and treatable metabolic disorder related to the accumulation of cholestanol. This disorder is primarily associated with motor and cognitive impairments, although the latter has not been extensively characterized. The objectives of this work were to define the cognitive profile found in cerebrotendinous xanthomatosis patients, investigate the progression of cognitive impairment over time, and search for radio-clinical correlations. Through a multicentric chart review study, we collected cognitive and radiological data from nine children and eighteen adults with genetically proven cerebrotendinous xanthomatosis. We performed a volumetric and morphological analysis of the brain magnetic resonance imaging. In our cohort, 44% (4/9) of children and 78% (14/18) of adults exhibited cognitive impairment that can be severe. The study revealed a significant impairment in various cognitive domains, specifically executive, attentional, language, and visuo-spatial. Among adults, 16% (3/18) developed dementia after age 50. These three patients had delayed chenodeoxycholic acid treatment and important cerebral atrophy. Besides these three cases of late-onset cognitive decline, Mini-Mental State Evaluation was generally stable, suggesting cognitive impairment due to a neurodevelopmental disorder and persisting in adulthood. Cognitive impairment was less common in children, possibly related to early chenodeoxycholic acid treatment in our cohort. The severity of magnetic resonance imaging abnormalities did not predict cognitive impairment in patients. Overall, in cerebrotendinous xanthomatosis, cognitive impairment can be severe and mainly neurodevelopmental. Early chenodeoxycholic acid treatment might be associated with a reduced risk of cognitive decline.

The SNP rs6859 in NECTIN2 gene is associated with underlying heterogeneous trajectories of cognitive changes in older adults.

BACKGROUND: Functional decline associated with dementia, including in Alzheimer's disease (AD), is not uniform across individuals, and respective heterogeneity is not yet fully explained. Such heterogeneity may in part be related to genetic variability among individuals. In this study, we investigated whether the SNP rs6859 in nectin cell adhesion molecule 2 (NECTIN2) gene (a major risk factor for AD) influences trajectories of cognitive decline in older participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI). METHODS: We retrospectively analyzed records on 1310 participants from the ADNI database for the multivariate analysis. We used longitudinal measures of Mini-Mental State Examination (MMSE) scores in participants, who were cognitively normal, or having AD, or other cognitive deficits to investigate the trajectories of cognitive changes. Multiple linear regression, linear mixed models and latent class analyses were conducted to investigate the association of the SNP rs6859 with MMSE. RESULTS: The regression coefficient per one allele dose of the SNP rs6859 was independently associated with MMSE in both cross-sectional (-2.23, p < 0.01) and linear mixed models (-2.26, p < 0.01) analyses. The latent class model with three distinct subgroups (class 1: stable and gradual decline, class 2: intermediate and late decline, and class 3: lowest and irregular) performed best in the posterior classification, 42.67% (n = 559), 21.45% (n = 281), 35.88% (n = 470) were classified as class 1, class 2, and class 3. In the heterogeneous linear mixed model, the regression coefficient per one allele dose of rs6859 - A risk allele was significantly associated with MMSE class 1 and class 2 memberships and related decline; Class 1 (-2.28, 95% CI: -4.05, -0.50, p < 0.05), Class 2 (-5.56, 95% CI: -9.61, -1.51, p < 0.01) and Class 3 (-0.37, 95% CI: -1.62, 0.87, p = 0.55). CONCLUSIONS: This study found statistical evidence supporting the classification of three latent subclass groups representing complex MMSE trajectories in the ADNI cohort. The SNP rs6859 can be suggested as a candidate genetic predictor of variation in modeling MMSE trajectory, as well as for identifying latent classes with higher baseline MMSE. Functional studies may help further elucidate this relationship.

Efficacy of rTMS for poststroke epilepsy and its effects on patients' cognitive function and depressive status.

OBJECTIVE: This study aimed to investigate the efficacy of rTMS in the treatment of poststroke epilepsy and the effect of rTMS on patients' cognitive function and depressive status. METHODS: One hundred and twenty-one poststroke epilepsy patients with mild cognitive impairment and depressive status admitted to the Department of Neurology of the Second People's Hospital of Nanning from January 1, 2017, to April 31, 2023, were selected and divided into the rTMS treatment group (treated group) and the control group. MMSE scores and HAMD scores were recorded before and after treatment. The frequency of EEG spiky waves recorded before and after treatment within 24 h and the frequency of any clinical seizure form (the number of clinical seizures within 1 month after treatment) and changes in observed indices before and after treatment were calculated. The differences between the data of the two groups were analyzed, to further assess the efficacy of rTMS in the treatment of poststroke epilepsy and the rTMS' effects on cognition and depression. RESULTS: Compared with drug treatment alone, rTMS significantly decreased clinical seizures and epileptiform discharges after stroke, especially in patients with lesions in the frontal, temporal, and parietal lobes. Compared with drug treatment alone, rTMS treatment can effectively reduce cognitive impairment and mood disorders, such as depression, especially for patients with lesions in the frontal and temporal lobes. The results of this experiment suggest that rTMS treatment does not increase adverse effects. CONCLUSION: rTMS reduces clinical seizures while improving cognitive impairment and depression in patients with epilepsy. Therefore, we suggest that low-frequency rTMS can be used as an adjunctive treatment for patients with epilepsy and provide some ideas and references for the treatment of epilepsy with cognitive impairment and depression.

Adjunctive silymarin supplementation and its effects on disease severity, oxidative stress, and inflammation in patients with Alzheimer's disease.

BACKGROUND: Brain tissue in Alzheimer's patients is exposed to oxidative stress. Silymarin is an adjunct drug that has anti-inflammatory and antioxidant properties. OBJECTIVE: This study aimed to evaluate the effect of silymarin on biomarkers of oxidative stress, inflammation, and disease severity in Alzheimer's patients. METHODS: This randomized, single-blind clinical trial study was performed on 33 patients with Alzheimer's disease (AD) whose disease was confirmed by DSM-5 criteria and by brain imaging. Patients in the case group received three 250 mg silymarin capsules daily (each containing 150 mg silymarin), as an adjunctive medication in addition to the routine medication regimen. In the placebo group (control), patients received the same amount of placebo. All patients underwent Mini Mental State Exam (MMSE) and a panel of blood tests including malondialdehyde, neopterin, catalase, paraoxonase-1, total oxidative status, and total antioxidant capacity to reevaluate the changes pre/postintervention at the end of the trimester. RESULTS: The catalase and MDA serum levels after the adjunctive silymarin treatment decreased significantly (Catalasebefore silymarin = 9.29 ± 7.02 vs Catalaseafter silymarin = 5.32 ± 2.97, p = 0.007 and MDAbefore silymarin = 4.29 ± 1.90 vs MDAafter silymarin = 1.66 ± 0.84, p < 0.001) while MMSE increased notably (MMSEbefore silymarin = 10.39 ± 6.42 vs MMSEafter silymarin = 13.37 ± 6.81, p < 0.001). CONCLUSION: Silymarin can be effective as an adjunct drug and a powerful antioxidant in reducing oxidative stress and improving the course of AD.

Mediterranean diet related to 3-year incidence of cognitive decline: results from a cohort study in Chinese rural elders.

OBJECTIVE: This study aims to examine the effect of the Mediterranean diet (MeDi) on cognitive decline among the Chinese elderly with a 3-year follow-up. METHODS: This study is divided into two waves: wave-1 January 2019 to June 2019 (n = 2313); wave-2 January 2022 to March 2022 (n = 1648). MeDi scores were calculated from the Mediterranean Diet Adherence Screener (MEDAS), with the scoring of low compliance (0-6 points) and high compliance (7-14 points). The Mini-Mental State Examination (MMSE) was used to assess cognitive function. An MMSE score dropping ≥ 2 points from baseline was defined as cognitive decline. The relationships between MeDi score and cognitive decline were analyzed by linear regression models or Binary logistic regression. RESULTS: During the 3-year follow-up, 23.8% of patients exhibited cognitive decline. The study revealed a significant difference in MMSE score changes between low and high MeDi adherence groups (p < 0.001). MeDi score was negatively correlated with cognitive deterioration (ß = -0.020, p = 0.026). MeDi score was only negatively associated with cognitive decline in the female subgroup aged ≥65 years (ß = -0.034, p = 0.033). The food beans (OR = 0.65, 95%CI:0.51, 0.84), fish (OR = 0.72, 95%CI:0.54, 0.97), and cooked vegetables (OR = 0.68, 95%CI:0.53, 0.84) were protective factors for cognitive decline. CONCLUSIONS: This study suggests that greater adherence to the MeDi is linked to a reduced risk of cognitive decline in elderly people. However, this is found only in women who are 65 years old or older. It also found long-term adherence to beans, fish, and vegetables are more effective in improving cognitive function.

Screening for Cognitive Impairment in Bilinguals: What Is the Influence of the Language of Assessment?

BACKGROUND: Bilingualism's impact on cognitive assessment remains underexplored. This study analyzes the efficacy of the Mini-Mental State Examination (MMSE) as a screening tool for bilinguals, specifically examining the influence of language choice on balanced and unbalanced Lebanese bilinguals (Arabic-French) and its implications for diagnosing cognitive impairment. METHODS: Ninety-three bilingual healthy controls (mean age = 67.99 ± 9.3) and 29 Alzheimer's disease patients (mean age = 77.2 ± 5.9), including 26 with mild and 3 with moderate dementia, underwent MMSE assessments in both Arabic and French. The study aimed to assess language impact on cognitive screening outcomes in different bilingual subtypes. RESULTS: Sensitivity in screening for cognitive impairment using the MMSE varied based on language and bilingualism subtype. For unbalanced bilinguals, using the prominent language increased sensitivity. Conversely, in balanced bilinguals, employing the societal majority language enhanced sensitivity. This suggests that the conventional use of the non-prominent language in cognitive screening for foreigners/immigrants may result in a subtle loss of MMSE sensitivity. CONCLUSION: This study emphasizes the critical role of language choice in cognitive assessment for bilinguals. The MMSE's sensitivity is influenced by language selection, with clinical implications for screening procedures. Recommendations include using the prominent language for cognitive screening in dominant bilinguals and the societal majority language for balanced bilinguals. This nuanced approach aims to improve the accuracy and cultural sensitivity of cognitive screening in bilingual populations, addressing the gap in current assessment practices.

Combining Mini-Mental State Examination and Montreal Cognitive Assessment for assessing the clinical efficacy of cholinesterase inhibitors in mild Alzheimer's disease: a pilot study.

Current drugs for Alzheimer's Disease (AD), such as cholinesterase inhibitors (ChEIs), exert only symptomatic activity. Different psychometric tools are needed to assess cognitive and non-cognitive dimensions during pharmacological treatment. In this pilot study, we monitored 33 mild-AD patients treated with ChEIs. Specifically, we evaluated the effects of 6 months (Group 1 = 17 patients) and 9 months (Group 2 = 16 patients) of ChEIs administration on cognition with the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), and the Frontal Assessment Battery (FAB), while depressive symptoms were measured with the Hamilton Depression Rating Scale (HDRS). After 6 months (Group 1), a significant decrease in MoCA performance was detected. After 9 months (Group 2), a significant decrease in MMSE, MoCA, and FAB performance was observed. ChEIs did not modify depressive symptoms. Overall, our data suggest MoCA is a potentially useful tool for evaluating the effectiveness of ChEIs.

Effect of a multimodal training on the ability of medical students to administer the MMSE: a comparative study.

BACKGROUNDS: The Mini-Mental State Examination (MMSE) is the main screening and follow-up test for neurocognitive disorders. In France, it is often administered by medical students. Conditions allowing to administer the MMSE are strict but not well known by students, leading to mistakes in scoring. Our objectives were to assess the effect of a multimodal training on medical students' ability to administer the MMSE and to describe their previous training. METHODS: 75 medical students between the 4th and 6th year of study were included. Previous MMSE training was assessed by a standardized questionnaire. The teaching material used for our training was the article validating MMSE in French, a video explaining the steps on how to administer the MMSE test, and MMSE's scoring exercises. The ability to administer the MMSE was assessed by a Standardized practical exam (SPE). Students were self-selected and then assigned in two groups, one benefiting from all the training before SPE, and the other receiving only the article before SPE. RESULTS: 41 students were included in the training group and 34 in the control group. There was no difference between groups regarding previous training. 71% of the students had already administered a MMSE test and only 17% had received specific training. Students considered their previous training as insufficient in most cases. The overall score and scores of each subpart of the SPE were significantly higher in the training group than in the control group (overall score: median [IQR]: 71 [62-78] vs. 52 [41-57], p < 0.001). The rate of students able to complete the MMSE was higher in the training group compared to the control (85% vs. 44%, p < 0.001). Quality of the training and its usefulness were judged to be good or very good by all participants. CONCLUSIONS: A multimodal training improves the ability of medical students to administer the MMSE.

Cognitive Impairment in Nonagenarians: Potential Metabolic Mechanisms Revealed by the Synergy of In Silico Gene Expression Modeling and Pathway Enrichment Analysis.

Previous studies examining the molecular and genetic basis of cognitive impairment, particularly in cohorts of long-living adults, have mainly focused on associations at the genome or transcriptome level. Dozens of significant dementia-associated genes have been identified, including APOE, APOC1, and TOMM40. However, most of these studies did not consider the intergenic interactions and functional gene modules involved in cognitive function, nor did they assess the metabolic changes in individual brain regions. By combining functional analysis with a transcriptome-wide association study, we aimed to address this gap and examine metabolic pathways in different areas of the brain of older adults. The findings from our previous genome-wide association study in 1155 older adults, 179 of whom had cognitive impairment, were used as input for the PrediXcan gene prediction algorithm. Based on the predicted changes in gene expression levels, we conducted a transcriptome-wide association study and functional analysis using the KEGG and HALLMARK databases. For a subsample of long-living adults, we used logistic regression to examine the associations between blood biochemical markers and cognitive impairment. The functional analysis revealed a significant association between cognitive impairment and the expression of NADH oxidoreductase in the cerebral cortex. Significant associations were also detected between cognitive impairment and signaling pathways involved in peroxisome function, apoptosis, and the degradation of lysine and glycan in other brain regions. Our approach combined the strengths of a transcriptome-wide association study with the advantages of functional analysis. It demonstrated that apoptosis and oxidative stress play important roles in cognitive impairment.

Alzheimer's Amyloid Hypothesis and Antibody Therapy: Melting Glaciers?

The amyloid cascade hypothesis for Alzheimer's disease is still alive, although heavily challenged. Effective anti-amyloid immunotherapy would confirm the hypothesis' claim that the protein amyloid-beta is the cause of the disease. Two antibodies, aducanumab and lecanemab, have been approved by the U.S. Food and Drug Administration, while a third, donanemab, is under review. The main argument for the FDA approvals is a presumed therapy-induced removal of cerebral amyloid deposits. Lecanemab and donanemab are also thought to cause some statistical delay in the determination of cognitive decline. However, clinical efficacy that is less than with conventional treatment, selection of amyloid-positive trial patients with non-specific amyloid-PET imaging, and uncertain therapy-induced removal of cerebral amyloids in clinical trials cast doubt on this anti-Alzheimer's antibody therapy and hence on the amyloid hypothesis, calling for a more thorough investigation of the negative impact of this type of therapy on the brain.

Attention to the domains of Revised Hasegawa Dementia Scale and Mini-Mental State Examination in patients with Alzheimer's disease dementia.

BACKGROUND: In Japan, Alzheimer's disease dementia (AD) is the most common cognitive disease, and the most widely used dementia screening tests are the Revised Hasegawa Dementia Scale (HDS-R) and Mini-Mental State Examination (MMSE). This study sought to elucidate the relationships of the individual domains of these tests with age and duration of school education in a large group of patients with AD. METHODS: Participants were 505 new outpatients diagnosed with AD who completed the HDS-R and MMSE at the first visit. We investigated the relationships of total and individual domains of these tests with age and duration of school education using the least squares method. Next, we plotted regression lines of the individual domain scores against the total test scores. RESULTS: Younger age and longer duration of school education were significantly associated with higher total HDS-R and MMSE scores in AD. Domain-specific results indicated that younger age was significantly associated with a higher immediate memory score on both the HDS-R and MMSE and with a higher orientation (time), repetition score on the MMSE. Longer duration of school education was significantly associated with a higher working memory score on the HDS-R and with higher serial 7, repetition and writing scores on the MMSE. In addition, shorter duration of school education was significantly associated with higher naming score on the MMSE. The regression lines of orientation of time, remote memory, visual memory, and verbal frequency hit the bottom on the HDS-R (4/30, 8/30, 4/30, and 6/30, respectively) and of orientation of time, serial 7, remote memory, and writing also hit the bottom on the MMSE (8/30, 9/30, 11/30, and 8/30, respectively). CONCLUSIONS: We should pay attention to age, duration of school education, and the individual domains when using the HDS-R or MMSE to assess patients with AD.

Late Life Cognitive Function Trajectory Among the Chinese Oldest-Old Population-A Machine Learning Approach.

Informed by the biopsychosocial framework, our study uses the Chinese Longitudinal Healthy Longevity Survey (CLHLS) dataset to examine cognitive function trajectories among the oldest-old (80+). Employing K-means clustering, we identified two latent groups: High Stability (HS) and Low Stability (LS). The HS group maintained satisfactory cognitive function, while the LS group exhibited consistently low function. Lasso regression revealed predictive factors, including socioeconomic status, biological conditions, mental health, lifestyle, psychological, and behavioral factors. This data-driven approach sheds light on cognitive aging patterns and informs policies for healthy aging. Our study pioneers non-parametric machine learning methods in this context.

An exploratory study of delayed flash visual evoked potential P2 wave latency in subcortical arteriosclerotic encephalopathy.

BACKGROUND: Patients with cognitive dysfunction may present with significantly prolonged the P2 wave latency of flash visual evoked potential. However, no studies have been reported on whether the P2 wave latency of flash visual evoked potential is prolonged in patients with subcortical arteriosclerotic encephalopathy (SAE). OBJECTIVE: To examine the relationship between flash visual evoked potential P2 wave latency (FVEP-P2 wave latency) and cognitive impairment in patients with SAE. METHODS: Overall, we recruited 38 SAE patients as the observation cohort (OC) and 34 healthy volunteers as the control cohort (CC). We measured the FVEP-P2 wave latency for both groups. The SAE patients' cognitive abilities were evaluated via mini-mental state examination (MMSE) and the association between the latency of FVEP-P2 and MMSE score was explored by Pearsons´s correlation test. RESULTS: There is no significant difference between OC (21 males and 17 females; 68.6 ± 6.7 years of age and 9.6 ± 2.8 years of education) and CC (19 males and 15 females; 65.3 ± 5.9 years of age and 10.1 ± 2.6 years of education) in gender and age composition and education level. The FVEP-P2 wave latency of the CC group was (108.80 ± 16.70) ms and the OC FVEP-P2 wave latency was (152.31 ± 20.70) ms. The OC FVEP-P2 wave latency was significantly longer than the CC (P < 0.05). In terms of MMSE scores, the MMSE scores of CC was (28.41 ± 2.34), and that of OC was (9.08 ± 4.39). Compared to the CC, the OC MMSE score was significantly lower (P < 0.05). In addition, the FVEP-P2 wave latency was inversely related to the MMSE (r = -0.4465, P < 0.05) in SAE patients. CONCLUSION: The FVEP-P2 wave latency wave latency was significantly prolonged in SAE patients and strongly associated with the degree of cognitive dysfunction.

Positive association between weight-adjusted-waist index and dementia in the Chinese population with hypertension: a cross-sectional study.

PURPOSE: The links between obesity and dementia remain equivocal. Therefore, this study aimed to explore the association between weight-adjusted waist index (WWI), a new anthropometric indicator reflecting obesity, and dementia in the Chinese population with hypertension. METHODS: A total of 10,289 participants with hypertension were enrolled in this cross-sectional study, a subset of the China H-type hypertension registry study. WWI was calculated as waist circumference (WC) divided by the square root of bodyweight. Mini-mental state examination (MMSE) scale was performed to evaluate the cognitive function. According to educational background, different MMSE cut-off values were applied to define dementia: < 24 for participants with ≥ 7 years of education, < 20 for those with 1-6 years of education, and < 17 for illiterate participants. Multivariable linear regression and multivariable binary logistic regression analyses were conducted to assess the associations between WWI and MMSE and dementia, respectively. RESULTS: Overall, the mean age was 63.7 ± 9.7 years, and 49.0% were males. Multivariate linear regression analyses showed that WWI was negatively associated with MMSE (ß, -1.09; 95% confidence interval [CI]: -1.24, -0.94). Consistently, multivariable binary logistic regression analyses found a positive association between WWI and the risk of dementia (odds ratio [OR], 1.45; 95% CI: 1.35, 1.56). Compared with individuals in quartile 1 of WWI, the adjusted ß and OR values of WWI for MMSE and dementia were -2.28 (95% CI: -2.62, -1.94) and 2.12 (95% CI: 1.81, 2.48), respectively. Results of smoothing curve fitting confirmed the linear association between WWI and MMSE and dementia. Subgroup analysis showed a stronger association between WWI and dementia in participants with hypertension with midday napping. CONCLUSION: WWI was independently and positively associated with dementia among the population with hypertension, especially in those with midday napping. The data suggests that WWI may serve as a simple and effective tool for the assessment of the risk of dementia in clinical practice.

Dipeptidyl peptidase-4 inhibitors alleviate cognitive dysfunction in type 2 diabetes mellitus.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) are commonly at high risk for developing cognitive dysfunction. Antidiabetic agents might be repurposed for targeting cognitive dysfunction in addition to modulation on glucose homeostasis. This study aimed to evaluate the impact of dipeptidyl peptidase-4 inhibitors (DPP-4i) on cognitive function in T2DM. METHODS: PubMed, Embase, Cochrane Library and Web of Science were systematically searched from inception to September 30, 2023. Weighted mean differences were calculated using the Mantel-Haenszel (M-H) fixed or random effects model based on the degree of heterogeneity among studies. Heterogeneity was evaluated using a Chi-squared test and quantified with Higgins I2. Sensitivity analysis was performed with the leave-one-out method, and publication bias was evaluated according to Begg's and Egger's tests. RESULTS: Six clinical trials involving 5,178 participants were included in the pooled analysis. Administration of DPP-4i generally correlated with an increase of Mini-Mental State Examination (MMSE) scores (1.09, 95% CI: 0.22 to 1.96). DPP-4i alleviated cognitive impairment in the copying skill subdomain of MMSE (0.26, 95% CI: 0.12 to 0.40). Treatment with DPP-4i also resulted in an increase of Instrumental Activities of Daily Living (IADL) scores (0.82, 95% CI: 0.30 to 1.34). However, DPP-4i produced no significant effects on Barthel Activities of Daily Living (BADL) scores (0.37, 95% CI: -1.26 to 1.99) or other test scores. CONCLUSIONS: DPP-4i treatment favourably improved cognitive function in patients with T2DM. Further trials with larger samples should be performed to confirm these estimates and investigate the association of different DPP-4i with cognitive function among diabetic patients. TRIAL REGISTRATION IN PROSPERO: CRD42023430873.

Association between walking and square dancing-oriented leisure-time physical activity and cognitive function among middle-aged and elderly people in Southwest China.

BACKGROUND: Southwest China is facing a serious aging problem across the country, but the status of cognitive function in middle-aged and elderly people in this region is superior to the national average. This study intends to reveal the leisure-time physical activity (LTPA) pattern in this region and explore whether this pattern is beneficial for cognitive function. METHODS: The data came from the 2019-2021 baseline survey on cognitive function of a natural population cohort conducted by West China Hospital of Sichuan University. A structured questionnaire was used to investigate the LTPA status of the participants, and the Mini-Mental State Examination was used to evaluate their cognitive function. Then, we used multiple linear regression to analyze the association between LTPA and cognitive level, and further subgroup analysis was carried out according to sex, age and waist-to-hip ratio. RESULTS: A total of 2697 participants were enrolled, with an average age of 66.19 ± 6.68 years. The average cognitive function score was 27.23 ± 2.72, of which 8.60% indicated mild cognitive impairment. Their median LTPA level was 24.50 MET-hours per week, of which 70.37% reached the activity level recommended by WHO, with the main types being walking (1340 cases, 49.68%), square dancing (270 cases, 10.01%), or walking + square dancing (172 cases, 6.38%). Multiple linear regression showed that cognitive function increased with the amount of LTPA from 11.25 MET-hours/week to 36.40 MET-hours/week (ß 0.09 for 11.25 ~ 24.50 MET-hours/week, ß 0.38 for 24.50 ~ 36.40 MET-hours/week) but stabilized at more (ß 0.39 for ≥36.40 MET-hours/week). The positive association persisted even for those who only walked (ß 0.37 for 24.50 ~ 36.40 MET-hours/week, P = 0.008). CONCLUSIONS: Middle-aged and elderly people in Southwest China hold a relatively high level of LTPA status, and walking and square dancing-oriented LTPA are positively correlated with cognitive function.

The impact of social support, physical and psychological performance on sleep outcomes in Iranian older adults: a case-control study.

BACKGROUND: Sleep quality is one of the most important factors to improve the quality of life in older adults and physical and mental health plays an essential role in better sleep quality. This study aimed to determine the impact of social support, and physical and psychological performance on sleep outcomes in Iranian older adults. METHODS: In this case-control study, 400 elder people, who were exposed to sleep problems, and 400 people without sleep problems were randomly selected during 2016-2017 in Amirkola, Iran. Subjects in the case and control groups were matched in terms of gender and age. The demographic characteristics, Duke Social Support Questionnaire (DSSI), Physical Activity Scale for the Elderly (PASE), Activity of Daily Living (ADL), Instrumental Activity of Daily Living (IADL), Mini-Mental State Examination (MMSE), and Pittsburgh Sleep Quality Questionnaire (PSQI) questionnaires were used to collect data. T-test, Chi-square, Pearson Correlation coefficient, and multiple Logistic regression were used for data analysis. RESULTS: The mean score of DSSI and its domains including social interaction (DSSI.Int) and social satisfaction (DSSI.Sat) were 28.15 ± 3.55, 9.31 ± 1.23, and 18.84 ± 2.88 in the case group and 28.87 ± 3.20, 9.48 ± 1.10, and 19.83 ± 2.44 in the control group, respectively. In this study, the mean scores of MMSE, PASE, ADL, and IADL were 25.36 ± 3.95, 101.71 ± 56.99, 13/97 ± 0.37, 20.59 ± 2/79; respectively. There was a significant inverse correlation between poor sleep quality with DSSI score (rho = -0.165, P < 0.0001), DSSI.Int (rho = -0.113, P < 0.001), DSSI.Sat (rho = -0.160, P < 0.0001), PASE (rho=-0.160, P < 0.0001), and IADL (rho = -0.112, P < 0.001) score. Therefore, more social support and physical activity improved the quality of sleep. There was a significant negative relationship between DSSI, and its domains with sleep quality in terms of gender. DSSI (rho = 0.25, P < 0.0001), DSSI.Int (P < 0.0001, rho=-0.18), and DSSI.Sat (P < 0.0001, rho=-0.22) was significant in men but not in women. The results of the adjusted logistic regression revealed a significant association between sleep quality problems and DSSI (p < 0.045, OR = 1.40), the use of hypnotic drugs (p < 0.0001, OR = 7.56), and occupation (p <0.03, OR= 12.66). CONCLUSIONS: The results of the present study suggest that low social support and all its domains, PASE, IADL, and using hypnotic drugs may play a role in the development of sleep problems. It can be used as an effective, safe, and low-cost strategy for promoting sleep quality in older adults.

Protein Plasma Levels of the IGF Signalling System Are Altered in Major Depressive Disorder.

The Insulin-like growth factor 2 (IGF-2) has been recently proven to alleviate depressive-like behaviors in both rats and mice models. However, its potential role as a peripheral biomarker has not been evaluated in depression. To do this, we measured plasma IGF-2 and other members of the IGF family such as Binding Proteins (IGFBP-1, IGFBP-3, IGFBP-5 and IGFBP-7) in a depressed group of patients (n = 51) and in a healthy control group (n = 48). In some of these patients (n = 15), we measured these proteins after a period (19 ± 6 days) of treatment with antidepressants. The Hamilton Depressive Rating Scale (HDRS) and the Self-Assessment Anhedonia Scale (SAAS) were used to measure depression severity and anhedonia, respectively. The general cognition state was assessed by the Mini-Mental State Examination (MMSE) test and memory with the Free and Cued Selective Reminding Test (FCSRT). The levels of both IGF-2 and IGFBP-7 were found to be significantly increased in the depressed group; however, only IGF-2 remained significantly elevated after correction by age and sex. On the other hand, the levels of IGF-2, IGFBP-3 and IGFBP-5 were significantly decreased after treatment, whereas only IGFBP-7 was significantly increased. Therefore, peripheral changes in the IGF family and their response to antidepressants might represent alterations at the brain level in depression.