Domain-specific Cognitive Function Research Articles

The effects of balance training on cognitive function in persons with multiple sclerosis: A systematic review and meta-analysis.

There is growing literature examining the effects of balance training on cognitive function in individuals with multiple sclerosis (MS), yet the findings remain inconsistent. This study aimed to investigate methodological characteristics of balance training studies and examine the effects of this modality on cognitive function. This study performed literature search using MEDLINE, EMBASE, PsycINFO, SPORTSDiscus, and CINAHL databases from inception to April 2024. Randomized and non-randomized controlled trials of balance training studies that assessed cognitive function were included. The Tool for the Assessment of Study Quality and Reporting in Exercise was used to evaluate methodological quality of included studies. We calculated effect sizes as standardized mean differences (SMD) using Hedge's g and employed multi-level random-effects model for meta-analysis. Fourteen articles with 1,020 participants were included in this review, and a subset of seven studies with 26 effect sizes were further used for meta-analysis. Balance training indicated medium effects on global cognition (SMD [95 % CI] = 0.39 [0.13, 0.64]), processing speed (SMD [95 % CI] = 0.36 [0.00, 0.73]), and visuospatial memory (SMD [95 % CI] = 0.53 [0.12, 0.93]) and large effect on verbal memory (SMD [95 % CI] = 0.66 [0.25, 1.06]). We found that intervention characteristics and exercise doses significantly moderated the effects on cognition. Balance training may effectively improve overall and specific domains of cognitive function in persons with MS. Exercise doses of at least 120 min per week and a total duration of 720 min or more were significant moderators for greater cognitive improvement.

Physical activity, cathepsin B, and cognitive health.

Regular physical activity (PA) is beneficial for cognitive health, and cathepsin B (CTSB) - a protease released by skeletal muscle during PA - acts as a potential molecular mediator of this association. PA-induced metabolic and mechanical stress appears to increase plasma/serum CTSB levels. CTSB facilitates neurogenesis and synaptic plasticity in brain regions (e.g., hippocampus and prefrontal cortex) that support performance in specific cognitive domains including memory, learning, and executive function. However, the evidence regarding the role of PA-induced changes in CTSB as a mediator of PA-induced cognitive health in humans is mixed. To guide future research, this article identifies key factors that may explain the observed heterogeneity in the findings from human studies and proposes a PA-CTSB-cognition model.

Physical activity and the outcome of cognitive trajectory: a machine learning approach

BackgroundPhysical activity (PA) may have an impact on cognitive function. Machine learning (ML) techniques are increasingly used in dementia research, e.g., for diagnosis and risk stratification. Less is known about the value of ML for predicting cognitive decline in people with dementia (PwD). The aim of this study was to use an ML approach to identify variables associated with a multimodal PA intervention that may impact cognitive changes in PwD, i.e., by distinguishing between cognitive decliners and non-decliners.MethodsThis is a secondary, exploratory analysis using data from a Randomized Controlled Trial that included a 16-week multimodal PA intervention for the intervention group (IG) and treatment as usual for the control group (CG) in nursing homes. Predictors included in the ML models were related to the intervention (e.g., adherence), physical performance (e.g., mobility, balance), and pertinent health-related variables (e.g., health status, dementia form and severity). Primary outcomes were global and domain-specific cognitive performance (i.e., attention/ executive function, language, visuospatial skills, memory) assessed by standardized tests. A Support Vector Machine model was used to perform the classification of each primary outcome into the two classes of decline and non-decline. GridSearchCV with fivefold cross-validation was used for model training, and area under the ROC curve (AUC) and accuracy were calculated to assess model performance.ResultsThe study sample consisted of 319 PwD (IG, N = 161; CG, N = 158). The proportion of PwD experiencing cognitive decline, in the different domains measured, ranged from 27–48% in CG, and from 23–49% in IG, with no statistically significant differences and no time*group effects. ML models showed accuracy and AUC values ranging from 40.6–75.6. The strongest predictors of cognitive decline or non-decline were performance of activities of daily living in IG and CG, and adherence and mobility in IG.ConclusionsML models showed moderate performance, suggesting that the selected variables only had limited value for classification, with adherence and performance of activities of daily living appearing to be predictors of cognitive decline. While the study provides preliminary evidence of the potential use of ML approaches, larger studies are needed to confirm our observations and to include other variables in the prediction of cognitive decline, such as emotional health or biomarker abnormalities.

Pre-treatment subjective sleep quality as a predictive biomarker of tDCS effects in preclinical Alzheimer's disease patients: Secondary analysis of a randomised clinical trial.

Despite transcranial direct current stimulation (tDCS) has demonstrated encouraging potential for modulating the circadian rhythm, little is known about how well and sustainably tDCS might improve the subjective sleep quality in older adults. This study sought to determine how tDCS affected sleep quality and cognition, as well as how well pre-treatment sleep quality predicted tDCS effects on domain-specific cognitive functions in patients with mild neurocognitive disorder due to Alzheimer's disease (NCD-AD). This clinical trial aimed to compare the effectiveness of tDCS and cognitive training in mild NCD-AD patients (n = 201). Over the course of four weeks, patients were randomized to receive either tDCS plus working memory training, or sham tDCS plus working memory training, or tDCS plus controlled cognitive training. The Pittsburgh Sleep Quality Index (PSQI) was used to measured subjective sleep quality. The Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog) was used to evaluate domain-specific cognitive functions. Recurrent tDCS treatments enhanced subjective sleep quality and cognition considerably. The poor sleepers (i.e., PSQI > 5) who received tDCS treatment had more cognitive benefits (p = 0.031, Cohen's d = 0.605) and sleep improvements (p < 0.001, Cohen's d = 1.209) in comparison to cognitive training. Pre-treatment subjective sleep quality was linked to tDCS-induced improvement in memory function. During the course of two months, repeated tDCS could considerably enhance subjective sleep quality. For the cognitive benefits of the treatments, the status of pre-treatment subjective sleep quality is crucial. More thorough research is necessary to explore an efficient approach to managing comorbidities for preclinical AD patients.

The Role of Fatty Acid Amide Hydrolase, a Key Regulatory Endocannabinoid Enzyme, in Domain-Specific Cognitive Performance in Psychosis.

Cognitive impairments are particularly disabling for patients with a psychotic disorder and often persist despite optimization of antipsychotic treatment. Thus, motivating an extension of the research focus on the endocannabinoid system. The aim of this study was to evaluate group differences in brain fatty acid amid hydrolase (FAAH), an endocannabinoid enzyme between first-episode psychosis (FEP), individuals with clinical high risk (CHR) for psychosis and healthy controls (HCs). Furthermore, to test the hypothesis that FAAH is linked with cognition using positron emission tomography (PET). We analyzed 80 PET scans with the highly selective FAAH radioligand [11C]CURB, including 30 patients with FEP (6 female), 15 CHR (5 female), and 35 HC (19 female). The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Berg Card Sorting Test (BCST) were applied to test cognitive performance. There was no difference in FAAH activity between groups (F2, 75 = 0.75, P = .48; Cohen's f = 0.141; small effect). Overall, there was a difference in the association between groups regarding FAAH activity and the domain visuospatial construction (F2, 72 = 4.67, P = .01; Cohen's f = .36; medium effect). Furthermore, across the sample, lower FAAH activity was associated with a higher percentage of perseverative responses (F1, 66 = 5.06, P = .03; Cohen's f = 0.28, medium effect). We report evidence for associations between endocannabinoid alterations in FEP and CHR with specific domains of cognition (visuospatial construction and perseverative response), not overall cognition.

Hypothalamic volume is associated with age, sex and cognitive function across lifespan: a comparative analysis of two large population-based cohort studies.

Emerging findings indicate that the hypothalamus, the body's principal homeostatic centre, plays a crucial role in modulating cognition, but comprehensive population-based studies are lacking. We used cross-sectional data from the Rhineland Study (N=5812, 55.2±13.6 years, 58% women) and the UK Biobank Imaging Study (UKB) (N=45,076, 64.2±7.7 years, 53% women), two large-scale population-based cohort studies. Volumes of hypothalamic structures were obtained from 3T structural magnetic resonance images through an automatic parcellation procedure (FastSurfer-HypVINN). The standardised cognitive domain scores were derived from extensive neuropsychological test batteries. We employed multivariable linear regression to assess associations of hypothalamic volumes with age, sex and cognitive performance. In older individuals, volumes of total, anterior and posterior hypothalamus, and mammillary bodies were smaller, while those of medial hypothalamus and tuberal region were larger. Larger medial hypothalamus volume was related to higher cortisol levels in older individuals, providing functional validation. Volumes of all hypothalamic structures were larger in men compared to women. In both sexes, larger volumes of total, anterior and posterior hypothalamus, and mammillary bodies were associated with better domain-specific cognitive performance, whereas larger volumes of medial hypothalamus and tuberal region were associated with worse domain-specific cognitive performance. We found strong age and sex effects on hypothalamic structures, as well as robust associations between these structures and domain-specific cognitive functions. Overall, these findings thus implicate specific hypothalamic subregions as potential therapeutic targets against age-associated cognitive decline. Institutional funds, Federal Ministry of Education and Research of Germany, Alzheimer's Association.

Life Course Patterns of Work History and Cognitive Trajectories Among Community-Dwelling Older Adults.

Prior research indicated that diverse work experiences in early and middle life stages are associated with cognitive function in later life. However, whether life course patterns of work history are associated with later life cognitive function in China remains unknown. Data were derived from the China Health and Retirement Longitudinal Study, and 5,800 participants aged 60 years or older were included. We used sequence analysis to identify the work history patterns between ages 18 and 60. Growth curve modeling was performed to evaluate how the work-history patterns are associated with global and domain-specific (i.e., mental intactness and episodic memory) cognitive function. We identified 8 work patterns, distinguished by duration, transitions, timing, and sequence of work history. Compared with individuals exposed to lifelong agricultural work, those engaged in lifelong nonagricultural employed work had better cognitive function in later life and experienced slower rates of cognitive decline in both global cognitive function and the mental intactness domain. In addition, individuals who shifted from agricultural to nonagricultural employed work early (around age 30) had better global cognitive function in later life, whereas the association was not significant for such a transition later (around age 50). Our study highlights the importance of the duration, sequence, and timing of transitions in work history for cognitive health among older Chinese. Future interventions and policies aimed at improving cognitive function should fully consider the cumulative and dynamic nature of work from a life course perspective.

Post-stroke fatigue severity is associated with executive dysfunction in chronic stroke

ABSTRACT Following stroke, fatigue is highly prevalent and managing fatigue is consistently rated a key unmet need by stroke survivors and professionals. Domain-specific cognitive impairments have been associated with greater fatigue severity in earlier stages of stroke recovery, but it is unclear whether these associations hold in chronic (>2 years) stroke. The present cross-sectional observational study evaluates the relationship between domain-specific cognitive functioning and the severity of self-reported fatigue among chronic stroke survivors. Participants (N = 105; mean age = 72.92, 41.90% female; mean years post-stroke = 4.57) were assessed in domains of attention (Hearts Cancellation test), language (Boston Naming Test), episodic memory (Logical Memory Test), working memory (Digit Span Backwards task), and executive functioning (set-shifting: Trail Making Test, Part B), as part of the OX-CHRONIC study, a longitudinal stroke cohort. Fatigue was assessed using the Fatigue Severity Scale. In a multiple linear regression analysis inclusive of above cognitive domains, only poorer executive functioning was associated with increased fatigue severity. This provides insight into the cognitive impairment profile of post-stroke fatigue long-term after stroke, with executive functioning deficits as the key hallmark.

Functional connectivity in resting-state networks relates to short-term global cognitive functioning in cardiac arrest survivors.

Long-term cognitive impairment is common in cardiac arrest survivors. Screening to identify patients at risk is recommended. Functional magnetic resonance brain imaging (fMRI) holds potential to contribute to prediction of cognitive outcomes. In this study, we investigated the possible value of early changes in resting-state networks for predicting short and long-term cognitive functioning of cardiac arrest survivors. We performed a prospective multicenter cohort study in cardiac arrest survivors in three Dutch hospitals. Resting-state fMRI scans were acquired within a month after cardiac arrest. We primarily focused on functional connectivity within the default-mode network (DMN) and salience network (SN), and additionally explored functional connectivity in seven other networks. Cognitive outcome was measured using the Montreal Cognitive Assessment (MoCA) during hospital admission and at 3 and 12 months, and by neuropsychological examination (NPE) at 12 months. We tested mixed effects models to evaluate the value of connectivity within the networks for predicting global cognitive outcomes at the three time points, and long-term cognitive outcomes in the memory, attention, and executive functioning domains. We included 80 patients (age 60 ± 11 years, 72 (90%) male). MoCA scores increased significantly between hospital admission and 3 months (ΔMoCAhospital-3M = 2.89, p < 0.01), but not between 3 and 12 months (ΔMoCA3M-12M = 0.38, p = 0.52). Connectivity within the DMN, SN, and dorsal attention network (DAN) was positively related to global cognitive functioning during hospital admission (βDMN = 0.85, p = 0.03; βSN = 1.48, p < 0.01; βDAN = 0.96, p = 0.01), but not at 3 and 12 months. Network connectivity was also unrelated to long-term memory, attention, or executive functioning. Resting-state functional connectivity in the DMN, SN, and DAN measured in the first month after cardiac arrest is related to short-term global, but not long-term global or domain-specific cognitive performance of survivors. These results do not support the value of functional connectivity within these RSNs for prediction of long-term cognitive performance after cardiac arrest.

Effect of particulate matter on cognitive function among middle-aged and older adults in China: An instrumental variable approach

Emerging studies have suggested the association of ambient air pollution with worse cognitive function; however, causal evidence remains scarce. We aimed to estimate the effect of particulate matter (PM) exposure on overall and domain-specific cognitive function. A total of 14,205 participants aged 45 years and above were drawn from the 2015 wave of the China Health and Retirement Longitudinal Study (CHARLS). Cognitive function was assessed using a standardized questionnaire consisting of two domains: episodic memory and mental status. Participants’ exposure to city-level PM (PM1, PM2.5, and PM10) was evaluated using satellite-based spatiotemporal models. To avoid potential endogenous biases, an instrumental variable method with two-stage least squares estimation was employed to examine the effect of air pollution on overall and domain-specific cognitive function. Stratified analysis was further performed based on sociodemographic characteristics. We found PM exposure exertedsignificant adverse effects on overall and domain-specific cognitive function, with mental status being more adversely affected as compared to episodic memory. The effect of PM exposure was more pronounced with smaller particle sizes, with PM1 exhibiting the largest effect size. Moreover, participants with lower education attainment were more adversely affected by PM exposure. Our findings add additional evidence of the potential causal role of PM exposure in worsening overall and domain-specific cognitive function. Efforts to further reduce PM are needed to protect the cognitive health of the aging Chinese population.

Investigating Transcutaneous Vagus Nerve Stimulation in Amnestic Mild Cognitive Impairment

Abstract Background New treatments are urgently needed for individuals with Mild Cognitive Impairment (MCI) - in particular for those with amnestic MCI, of whom a high proportion have underlying Alzheimer's Disease (AD). Transcutaneous Vagus Nerve Stimulation (tVNS) is a non-invasive neuro-modulatory treatment which has not been extensively examined in older adults with amnestic MCI. Methods A single site, single-blind, randomised three-arm crossover pilot trial of acute (60 minutes) tVNS (baseline, sham or active stimulation) was conducted a Regional Specialist Memory Service. Forty participants (age 71.7 ±6.9; 22/40 male) with diagnosed amnestic MCI were recruited. Given the links between AD and neuro-cardiovascular instability, potential adverse effects of active tVNS were assessed using beat-to-beat peripheral (Blood Pressure (BP) and Heart Rate [HR]) and central (via Near Infra-red Spectroscopy) haemodynamic responses to Active Stand (AS). Cognition was assessed between 21.3 ±4.9 and 60.5 ±4.4 minutes using a domain-specific cognitive performance battery with results analysed using mixed-effects linear regression. Results In older adults with amnestic MCI, tVNS was safe, tolerable and acceptable with 98% of participants stating they would use the device again. There was no significant effect on BP, or HR responses to AS and cerebral oxygenation remained stable during AS. After tVNS stimulation, performance on tests of spatial navigation were significantly improved compared to both baseline (ß= -8.76; [-14.91, -2.56]; p=0.01) and sham (ß= -4.15; [-7.32, -0.99]; p=0.01) conditions. Conclusion tVNS is a safe and tolerable treatment modality in older adults with amnestic MCI. Future studies should explore sustained effects and feasibility of domiciliary use.

Skin Carotenoids Are Related to Cognitive Abilities among Toddlers

BackgroundCarotenoids are antioxidant pigments that deposit in human tissues (e.g., skin, macula, and brain) upon dietary consumption. The health implications of skin carotenoids, which reflect overall dietary carotenoid consumption, have not been adequately studied in younger populations. ObjectivesThis work aimed to examine links between skin carotenoids and cognitive, language, and motor skills among toddlers. A secondary aim explored relationships between skin carotenoids and neurophysiologic outcomes of sensory memory [i.e., mismatch negativity (MMN)] and the functional integrity of the visual pathway [i.e., visual evoked potentials (VEPs)]. MethodsToddlers aged 12–18 mo (n = 45) were included in a cross-sectional study. Skin carotenoids were measured with reflection spectroscopy via the Veggie Meter®. Cognitive, language, and motor skills were measured using the Bayley Scale of Infant and Toddler Development IV Screening Test (BSID-IV). MMN and VEPs were collected with an auditory oddball task and a pattern reversal task, respectively, using electroencephalography. Analyses adjusted for age, household income, highest level of parental education, and total carotenoid intake (mg/1000 kcal). ResultsRegression modeling revealed that skin carotenoids significantly related to cognition (β = 0.24; P = 0.04) and not to any other BSID-IV subsets. Neither MMN nor VEP outcomes significantly related to skin carotenoids. ConclusionsGreater skin carotenoids were selectively related to cognition, indicating that carotenoids may play a role in cognition in toddlers. Additional research is needed to understand links between skin carotenoids and specific domains of cognitive function and brain health in early life.

Effects of a nurse-led staged integral art-based cognitive intervention for older adults on the Alzheimer's disease spectrum: A randomized controlled trial

BackgroundCombined art activities can improve the neural network function within various brain regions involved in emotions, cognition, and behavior, thereby preventing or reversing cognitive decline. However, few studies have systematically examined its effects. Furthermore, the impact of nurse-led art-based cognitive intervention on cognitive and psychological health is unclear. ObjectiveTo evaluate the effects of a nurse-led staged integral art-based cognitive intervention in older adults on the Alzheimer's disease spectrum. DesignThis was a randomized wait-list controlled trial with allocation concealment and blinding of outcome assessors and data analysts. All data were collected between April 2021 and January 2023 and analyzed from January to March 2023. SettingOne memory clinic and four medical partnership communities. ParticipantsA total of 144 participants with subjective or objective memory decline (aged ≥60 years). MethodsParticipants were randomized into an intervention group (n = 72) and a wait-list control group (n = 72), in a 1:1 ratio. The intervention group underwent a 16-week, 24-session nurse-led staged integral art-based cognitive intervention program, which was based on neurocognitive function training patterns. The control group underwent the program after the follow-up assessment. General and specific domains of cognitive function and other health-related outcomes were measured at baseline (T0), immediately after the intervention (T1), and at the 6-month follow-up (T2). ResultsOf the 144 participants (mean [SD] age, 71.6 [5.8] years; 50 [34.7 %] males and 94 [65.3 %] females), 130 and 115 completed the questionnaires at T1 and T2, respectively. The average attendance rate in the intervention group was 86.0 %. At T1, the intervention group showed greater improvement than the control group did in general cognitive functions (MoCA, between-group mean difference, 1.4 [95 % CIs, 0.4 to 2.5], p = 0.009). Additionally, the intervention group demonstrated statistically significant improvement compared to the control group in language, memory, quality of life, sleep quality and physical activity level at T1. Statistically significant group differences remained in sleep quality (PSQI, between-group mean difference, −1.3 [95 % CIs, −2.5 to −0.1], p = 0.035) at the 6-month follow-up. ConclusionsIn this randomized controlled trial of a nurse-led staged integral art-based cognitive intervention program, older adults on the Alzheimer's disease spectrum who participated in the program experienced improved cognition and psychological health. RegistrationThis study was registered with ChiCTR.org (ChiCTR2100044959) on April 3, 2021. Tweetable abstractA nurse-led staged integral art-based intervention for older adults on the Alzheimer's disease spectrum experienced improved cognition and psychological health.

Dietary patterns, inflammatory biomarkers and cognition in older adults: An analysis of three population-based cohorts

BackgroundTargeting effective strategies to prevent cognitive decline is key in the aging population. Some diets have been linked to a slower cognitive decline, potentially through reducing inflammation. We aimed at determining the effect of inflammatory dietary patterns (IDPs) on cognitive function in three population-based cohorts. MethodsIn this longitudinal study, we analyzed data from the Canadian Longitudinal Study of Aging, CoLaus|PsyCoLaus and Rotterdam Study. Our analytical sample included participants over 55 years old with baseline data on cognition, dietary intake, and inflammatory markers. IDPs were derived for each cohort using reduced rank regression to reflect maximal variation in three inflammatory markers. We calculated scores of consumption of the IDPs, higher scores indicating more IDP consumption. We used inverse probability of treatment and censoring weights in the marginal structural models to estimate associations of higher versus lower quarters of consumption of an IDP on general cognition (Mini-Mental State Evaluation) and four cognitive domains (memory, verbal fluency, verbal learning and processing speed and executive function) during at least 3 years of follow-up. ResultsWe included 10,366 participants (mean age 68) followed-up for a mean of 5 years. Diet explained between 1 and 2% of the variation of the inflammatory markers. There were no mean differences in general cognition when comparing the highest to the lowest quarter of consumption of IDPs among the three cohorts. Mean differences for the four cognitive domains were of small magnitude across cohorts and not clinically relevant. ConclusionDiet explained low variation in inflammatory markers. Consuming IDPs was not associated with mean differences in general or domain-specific cognitive function.

Relationship between domain-specific physical activity and cognitive function in older adults - findings from NHANES 2011-2014.

To determine the relationship between domain-specific physical activity (PA) (e.g., occupational PA [OPA], transport-related PA [TPA], and recreational PA [RPA]) and cognitive function in older adults. The data was obtained from the 2011-2014 cycle of the NHANES. We utilized weighted multivariate linear regression models among the included 2,924 people aged 60 years or older for our purposes. RPA and total PA according to WHO guidelines were associated with verbal fluency (RPA β: 1.400, 95% CI: 0.776, 2.024, p = 0.002; total PA β: 1.115, 95% CI: 0.571, 1.659, p = 0.001), processing speed and executive function (RPA β: 2.912, 95% CI. 1.291, 4.534, p = 0.005; total PA β: 2.974, 95% CI: 1.683, 4.265, p < 0.001) were positively correlated, and total PA was correlated with delayed memory performance (β: 0.254, 95% CI: 0.058, 0.449, p = 0.019). No significant association was observed between OPA, TPA, and various aspects of cognitive function among individuals over 60 years. There was no noteworthy correlation discovered between OPA and TPA in relation to cognitive function. However, RPA and total PA exhibited significant associations with verbal fluency, processing speed, and executive function. Additionally, maintaining PA levels ranging from 600 to 1,200 MET-min/week would yield the most favorable outcomes for cognitive function.

The relationship between personality and cognition in older adults with and without early-onset depression.

It is well established that personality traits impact cognition, as certain personality factors are associated with performance in specific cognitive domains. However, the findings on the relationships between the Big Five traits and cognition are mixed. Additionally, few studies have explored these relationships in older adults with a history of depression. The present study aimed to (a) evaluate the impact of the Big Five personality traits in older adults with and without a lifetime history of depression; and (b) test the hypotheses that higher trait neuroticism would correlate negatively with cognitive performance, while openness to experience would correlate positively with cognition. The sample consisted of 138 participants between the ages of 55 and 78 (M = 65.56, SD = 6.36). Sixty-two participants met criteria for current or remitted Major Depressive Disorder, while 76 had no history of depression or other mental health disorders. Participants underwent comprehensive neuropsychological testing. Personality was assessed using the NEO Personality Inventory-Revised (NEO-PI-R), while depression status was determined using the Structured Clinical Interview for DSM-5 (SCID-5). Following a series of Pearson correlations of cognitive variables and the five personality factors, linear regression models were estimated for each significant correlation. Demographic variables (i.e., age, education and sex) were entered in block 1, depression status (never vs. ever) was entered in block 2, and the personality factor score, or sub-facet was entered in block 3. Neuroticism was not associated with cognitive performance on any outcome measure. The facets Openness to Feelings and Openness to Values were positively related to phonemic fluency. Further Openness to Values was positively related to cognitive flexibility. Our results suggest that older people who are (a) more capable of identifying and understanding their feelings and the feelings of others, and (b) who are more willing to re-examine social, political, and religious values perform stronger on tasks measuring verbal fluency and cognitive flexibility, which are aspects of executive functioning. Interventions that aim to enhance open mindedness in older adults may have a parallel impact on improving executive functioning, though this would need to be examined prospectively.

Spontaneous cortical activity is altered in persons with HIV and related to domain-specific cognitive function.

Whilst the average lifespan of persons with HIV now approximates that of the general population, these individuals are at a much higher risk of developing cognitive impairment with ∼35-70% experiencing at least subtle cognitive deficits. Previous works suggest that HIV impacts both low-level primary sensory regions and higher-level association cortices. Notably, multiple neuroHIV studies have reported elevated levels of spontaneous cortical activity during the pre-stimulus baseline period of task-based experiments, but only a few have examined such activity during resting-state conditions. In the current study, we examined such spontaneous cortical activity using magnetoencephalography in 79 persons with HIV and 83 demographically matched seronegative controls and related this neural activity to performance on neuropsychological assessments of cognitive function. Consistent with previous works, persons with HIV exhibited stronger spontaneous gamma activity, particularly in inferior parietal, prefrontal and superior temporal cortices. In addition, serostatus moderated the relationship between spontaneous beta activity and attention, motor and processing speed scores, with controls but not persons with HIV showing stronger beta activity with better performance. The current results suggest that HIV predominantly impacts spontaneous activity in association cortices, consistent with alterations in higher-order brain function, and may be attributable to deficient GABAergic signalling, given its known role in the generation of gamma and beta oscillations. Overall, these effects align with previous studies showing aberrant spontaneous activity in persons with HIV and provide a critical new linkage to domain-specific cognitive dysfunction.

Association between possible sarcopenia and domain-specific cognitive impairment in middle-aged and older adults: Insights from the Gan-Dau Healthy Longevity Plan

BackgroundGiven the established association between sarcopenia and cognitive impairment was mainly in the older and oldest-old population or people with relatively limited education, this study extends the investigation to community-dwelling middle-to-old age adults in urban communities, emphasizing the need for preventive intervention for muscle health and healthy longevity. MethodsData of 712 participants from the Gan-Dau Healthy Longevity Plan were retrieved for analysis, and all participants were stratified by age (50–64, 65–74 and 75+ years old). Possible sarcopenia was defined by 2019 consensus report of the Asian Working Group for Sarcopenia (AWGS). This study used four neuropsychological tests for analysis, i.e., Mini-Mental Status Examination (MMSE), California Verbal Learning Test II (CVLT-SF), Digital Symbol Substitution Test (DSST) and Verbal fluency (VF) for global and domain-specific cognitive function. Multivariate generalized linear models (GLMs) were employed to investigate the associations between possible sarcopenia and cognitive function in each age-specific groups. ResultsThe prevalence of possible sarcopenia increased with age, with 31.8 %, 37.7 %, and 55.6 % in participants aged 5064, 65–74 and, 75+ years, respectively. On the other hand, cognitive performance declined with age. In particular, among participants aged 75+ years with possible sarcopenia, their cognitive performance were poorer than robust counterparts, including MMSE (26.6 [3.4] vs. 27.4 [2.6]), CVTL-SF (total score: 21.5 [5.4] vs. 23.8 [5.5]; 30-second delayed recall: 6.0 [1.7] vs. 6.5 [1.6]), DSST (32.8 [14.3] vs. 41.3 [18.7]), and VF (12.8 [5.1] vs. 14.8 [4.9]). Multivariate generalized linear model indicated that possible sarcopenia was associated with lower MMSE (β: −0.70, p = 0.014) and lower DSST (β: −7.00, p = 0.010) in those aged 50–64 years. Moreover, possible sarcopenia was associated with lower CVLT-SF (total score β:-1.90, p = 0.028), lower DSST (β: −6.45, p < 0.001), and lower VF (β: −1.64, p=0.026) in 75+ years group. ConclusionsAn association exists between possible sarcopenia and cognitive impairment, encompassing global cognition, delayed memory, verbal fluency, and executive function, among community-dwelling adults of mid-to-old age. Future research is warranted to explore the temporal alterations in this association and the potential effects of interventions aimed at fostering healthy longevity.

Brain Cell-based Genetic Subtyping and Drug Repositioning for Alzheimer Disease.

Alzheimer's Disease (AD) is characterized by its complex and heterogeneous etiology and gradual progression, leading to high drug failure rates in late-stage clinical trials. In order to better stratify individuals at risk for AD and discern potential therapeutic targets we employed a novel procedure utilizing cell-based co-regulated gene networks and polygenic risk scores (cbPRSs). After defining genetic subtypes using extremes of cbPRS distributions, we evaluated correlations of the genetic subtypes with previously defined AD subtypes defined on the basis of domain-specific cognitive functioning and neuroimaging biomarkers. Employing a PageRank algorithm, we identified priority gene targets for the genetic subtypes. Pathway analysis of priority genes demonstrated associations with neurodegeneration and suggested candidate drugs currently utilized in diabetes, hypertension, and epilepsy for repositioning in AD. Experimental validation utilizing human induced pluripotent stem cell (hiPSC)-derived astrocytes demonstrated the modifying effects of estradiol, levetiracetam, and pioglitazone on expression of APOE and complement C4 genes, suggesting potential repositioning for AD.

Effect of apolipoprotein E ε4 and its modification by sociodemographic characteristics on cognitive measures in South Asians from LASI-DAD.

We investigated the effects of apolipoprotein E (APOE) ε4 and its interactions with sociodemographic characteristics on cognitive measures in South Asians from the Diagnostic Assessment of Dementia for the Longitudinal Aging Study of India (LASI-DAD). Linear regression was used to assess the association between APOE ε4 and global- and domain-specific cognitive function in 2563 participants (mean age 69.6±7.3 years; 53% female). Effect modification by age, sex, and education were explored using interaction terms and subgroup analyses. APOE ε4 was inversely associated with most cognitive measures (p<0.05). This association was stronger with advancing age for the Hindi Mental State Examination (HMSE) score (βε4×age=-0.44, p=0.03), orientation (βε4×age=-0.07, p=0.01), and language/fluency (βε4×age=-0.07, p=0.01), as well as in females for memory (βε4×male=0.17, p=0.02) and language/fluency (βε4×male=0.12, p=0.03). APOEε4 is associated with lower cognitive function in South Asians from India, with a more pronounced impact observed in females and older individuals. APOEε4 carriers had lower global and domain-specific cognitive performance. Females and older individuals may be more susceptible to ε4 effects. For most cognitive measures, there was no interaction between ε4 and education.