BACKGROUND: Depression has been found to be associated with cognitive decline, but whether longer depressive durations lead to more severe cognitive declines has not been investigated. We aimed to estimate the association between depressive duration and cognitive decline in middle-aged and older Americans based on a large-scale representative population study.
METHODS: We included 27,886 participants from the Health and Retirement Study (HRS) in 2010-2018. Four datasets with 2-, 4-, 6-, and 8-year consecutive interviews were further derived which involving persistent depressed and persistent depression-free individuals. Multiple linear regressions were constructed to estimate the effects of each depressive duration on the decline in global cognition, memory and mental status. Meta-regressions were performed to test the linear trends and to explore the heterogeneity between sex, age and baseline cognitive function along with subgroup analyses.
RESULTS: Depressive durations of 2, 4, 6, and 8 years were associated with reductions in global cognitive scores of 0.62 points (95 % CI: 0.51-0.73), 0.77 points (95 % CI: 0.60-0.94), 0.83 points (95 % CI: 0.55-1.10), and 1.09 points (95 % CI: 0.63-1.55), respectively, indicating a linear trend (P = 0.016). More pronounced associations were observed in middle-aged adults and females. Similar patterns were found in the associations between depressive duration and two subdomains, i.e., memory and mental health.
CONCLUSIONS: This study is essentially a cross-sectional study and therefore cannot provide causal associations.
CONCLUSIONS: Longer depressive durations were linearly related to more severe cognitive declines. Timely intervention for depression targeted middle-aged adults can more effectively alleviate cognition-related burdens.

OBJECTIVE: Our current study aimed to investigate the determinants of dementia among the oldest old using longitudinal data from a representative sample covering both community-dwelling and institutionalized individuals.
METHODS: Longitudinal representative data were taken from the \"Survey on quality of life and subjective well-being of the very old in North Rhine-Westphalia (NRW80+)\" that surveyed community-dwelling and institutionalized individuals aged 80 years and above (n = 1,296 observations in the analytic sample), living in North Rhine-Westphalia (most populous state of Germany). The established DemTect was used to measure cognitive impairment (i.e., probable dementia). A logistic random effects model was used to examine the determinants of probable dementia.
RESULTS: The mean age was 86.3 years (SD: 4.2 years). Multiple logistic regressions revealed that a higher likelihood of probable dementia was positively associated with lower education (e.g., low education compared to medium education: OR: 3.31 [95% CI: 1.10-9.98]), a smaller network size (OR: 0.87 [95% CI: 0.79-0.96]), lower health literacy (OR: 0.29 [95% CI: 0.14-0.60]), and higher functional impairment (OR: 13.45 [3.86-46.92]), whereas it was not significantly associated with sex, age, marital status, loneliness, and depressive symptoms in the total sample. Regressions stratified by sex were also reported.
CONCLUSIONS: Our study identified factors associated with dementia among the oldest old. This study extends current knowledge by using data from the oldest old; and by presenting findings based on longitudinal, representative data (also including individuals residing in institutionalized settings).
CONCLUSIONS: Efforts to increase, among other things, formal education, network size, and health literacy may be fruitful in postponing dementia, particularly among older women. Developing health literacy programs, for example, may be beneficial to reduce the burden associated with dementia.

BACKGROUND: Older Latino adults with HIV are at increased risk for mild cognitive impairment and earlier onset of aging-related cognitive decline. Improvements in cognitive functioning and cognitive outcomes are possible among people with HIV who adopt health promotion behaviors. However, health promotion interventions for older Latino adults with HIV have not been extensively used or widely recognized as viable treatment options. Happy Older Latinos are Active (HOLA) is a multicomponent, health promotion intervention that is uniquely tailored for older Latino adults with HIV.
OBJECTIVE: This study aims to (1) determine the feasibility and acceptability of an adapted version of HOLA aimed at improving cognitive functioning among older Latino adults with HIV; (2) explore whether HOLA will produce changes in cognitive functioning; (3) explore whether HOLA will produce changes in activity, psychosocial functioning, or biomarkers of cognition; and (4) explore whether changes in activity, psychosocial functioning or cognitive biomarkers correlate with changes in cognition, while accounting for genetic risk for dementia.
METHODS: A single-arm pilot trial with 30 Latino (aged 50 years and older) men and women with HIV was conducted to assess feasibility, acceptability, and preliminary effects on cognition. Participants were assessed at 2 time points (baseline and postintervention) on measures of neurocognitive and psychosocial functioning. In addition, blood samples were collected to determine biomarkers of cognition at baseline and postintervention. Successful recruitment was defined as meeting 100% of the targeted sample (N=30), with 20% (n=6) or less of eligible participants refusing to participate. Adequate retention was defined as 85% (n=25) or more of participants completing the postintervention assessment and acceptability was defined as 80% (n=38) or more of sessions attended by participants.
RESULTS: Participant recruitment began on February 22, 2022, and was completed on August 15, 2022. The last study visit took place on February 20, 2023. Data analysis is currently ongoing.
CONCLUSIONS: Encouraging findings from this exploratory study may provide a blueprint for scaling up the HOLA intervention to a larger cohort of older Latino adults with HIV who may be currently experiencing or are at risk for HIV-related cognitive challenges.
BACKGROUND: ClinicalTrials.gov NCT04791709; https://clinicaltrials.gov/study/NCT04791709.
UNASSIGNED: DERR1-10.2196/55507.

BACKGROUND: Whether circulating levels of sphingolipids are prospectively associated with cognitive decline and dementia risk is uncertain.
METHODS: We measured 14 sphingolipid species in plasma samples from 4488 participants (mean age 76.2 years; 40% male; and 25% apolipoprotein E (APOE) ε4 allele carriers). Cognitive decline was assessed annually across 6 years using modified Mini-Mental State Examination (3MSE) and Digital Symbol Substitution Test (DSST). Additionally, a subset of 3050 participants were followed for clinically adjudicated dementia.
RESULTS: Higher plasma levels of sphingomyelin-d18:1/16:0 (SM-16) were associated with a faster cognitive decline measured with 3MSE, in contrast, higher levels of sphingomyelin-d18:1/22:0 (SM-22) were associated with slower decline in cognition measured with DSST. In Cox regression, higher levels of SM-16 (hazard ration [HR] = 1.24 [95% confidence interval [CI]: 1.08-1.44]) and ceramide-d18:1/16:0 (Cer-16) (HR = 1.26 [95% CI: 1.10-1.45]) were associated with higher risk of incident dementia.
CONCLUSIONS: Several sphingolipid species appear to be involved in cognitive decline and dementia risk.
UNASSIGNED: Plasma levels of sphingolipids were associated with cognitive decline and dementia risk.Ceramides and sphingomyelins with palmitic acid were associated with faster annual cognitive decline and increased risk of dementia.The direction of association depended on the covalently bound saturated fatty acid chain length in analysis of cognitive decline.

UNASSIGNED: Age-related cognitive decline is accelerated by vascular risk factors for cerebral small vessel disease. However, the association of vascular risk factors with cerebral small vessel disease contributing to the sex differences in cognitive decline remains unclear.
UNASSIGNED: The purpose of this study was to evaluate sex differences in cognitive decline and the association between vascular risk factors and cognitive decline by sex.
UNASSIGNED: We used data from the UK Biobank (>55 years of age; n = 19,067) to assess cognitive tests (executive function, processing speed, and memory) while adjusting for baseline measurements to examine how vascular risk factors affect cognition. A univariate regression analysis was used to assess sex differences at the first time point (2014). A repeated measure analysis with a mixed effect model was used to determine cognitive decline (between 2014 and 2019). Any significant interaction between vascular risk factors and sex was investigated.
UNASSIGNED: Females had lower scores in all 3 domains at the first cognitive tests (2014). We found a significant sex-by-time interaction over a 5-year period in matrix pattern completion (P = 0.03). After adjusting for vascular risk factors, this interaction was reduced (P = 0.08). High low-density lipoprotein, low education, and high blood pressure had a greater effect on the rate of cognitive decline in the executive function for females compared to males for the sex∗vascular risk factor interaction (P < 0.05).
UNASSIGNED: The rate of cognitive decline did not differ significantly between males and females. However, the impact of several vascular risk factors on cognitive decline was greater in females than in males.

BACKGROUND: Dietary patterns are associated with dementia risk, but the underlying molecular mechanisms are largely unknown.
METHODS: We used RNA sequencing data from post mortem prefrontal cortex tissue and annual cognitive evaluations from 1204 participants in the Religious Orders Study and Memory and Aging Project. We identified a transcriptomic profile correlated with the MIND diet (Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay) among 482 individuals who completed ante mortem food frequency questionnaires; and examined its associations with cognitive health in the remaining 722 participants.
RESULTS: We identified a transcriptomic profile, consisting of 50 genes, correlated with the MIND diet score (p = 0.001). Each standard deviation increase in the transcriptomic profile score was associated with a slower annual rate of decline in global cognition (β = 0.011, p = 0.003) and lower odds of dementia (odds ratio = 0.76, p = 0.0002). Expressions of several genes (including TCIM and IGSF5) appeared to mediate the association between MIND diet and dementia.
CONCLUSIONS: A brain transcriptomic profile for healthy diets revealed novel genes potentially associated with cognitive health.
CONCLUSIONS: Why healthy dietary patterns are associated with lower dementia risk are unknown. We integrated dietary, brain transcriptomic, and cognitive data in older adults. Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) diet intake is correlated with a specific brain transcriptomic profile. This brain transcriptomic profile score is associated with better cognitive health. More data are needed to elucidate the causality and functionality of identified genes.

UNASSIGNED: Parkinson\'s disease (PD) involves the progressive loss of dopaminergic neurons and the accumulation of α-synuclein. Elevated cholesterol levels may exacerbate α-synuclein aggregation, potentially contributing to PD. This study investigates the link between lipid profiles and PD severity, as well as cognitive functions in patients, aiming to inform pathogenesis and management strategies.
UNASSIGNED: Data from 250 PD patients and 100 healthy controls were analyzed. Serum cholesterol levels were compared with disease severity using Unified Parkinson\'s Disease Rating Scale (UPDRS) and modified Hoehn & Yahr Rating Scale (mH&Y). Mini-Mental State Examination (MMSE) assessed cognitive functions.
UNASSIGNED: Of the participants, 45.4% were female, 54.6% male, with a mean age of 69.09 ± 11.13 years. Mean UPDRS score was 52.34 ± 26.32, mH&Y was 2.28 ± 0.91. Patients had significantly higher HDL levels (47.92 ± 11.63) than controls (45.40 ± 13.89) (p = 0.024). HDL levels were significantly higher in patients with cognitive impairment than in patients with cognitive normal (p = 0.004). On the contrary, triglyceride levels were significantly lower in those with cognitive impairment compared to those with cognitively normal (p = 0.005). Multivariate logistic regression showed being male associated with 3.796 times higher risk of illness, and HDL is associated with 1.030 times increased illness risk.
UNASSIGNED: High HDL levels and male gender particularly increase the risk of Parkinson\'s disease. Additionally, HDL and triglyceride levels affect the cognition of PD patients. Further studies on the impact of cholesterol metabolism on the pathogenesis of PD could contribute to identifying effective treatment targets.

BACKGROUND: Falls in older adults significantly impact overall health and healthcare costs. Intrinsic capacity (IC) reflects functional reserve and is an indicator of healthy aging.
OBJECTIVE: To explore the association between IC and recent falls (≤ 90 days) in community-dwelling octogenarians from the Aging and Longevity in the Sirente geographic area (IlSIRENTE) study.
METHODS: The Minimum Data Set for Home Care (MDS-HC) and supplementary questionnaires and tests were used to assess the five IC domains: locomotion, cognition, vitality, psychology, and sensory. Scores in each domain were rescaled using the percent of maximum possible score method and averaged to obtain an overall IC score (range 0-100).
RESULTS: The study included 319 participants (mean age 85.5 ± 4.8 years, 67.1% women). Mean IC score was 80.5 ± 14.2. The optimal IC score cut-off for predicting the two-year risk of incident loss of at least one activity of daily living (ADL) was determined and validated in a subset of 240 individuals without ADL disability at baseline (mean age 84.7 ± 4.4 years, 67.1% women). Participants were then stratified into low (< 77.6) and high (≥ 77.6) IC categories. Those with high IC (63.9%) were younger, more often males, and had lower prevalence of recent falls, disability, multimorbidity, and polypharmacy. Logistic regression models including IC as a continuous variable revealed a significant association between higher IC and lower odds of falls. This association was significant in the unadjusted (odds ratio [OR] 0.96, 95% confidence interval [CI] 0.94-0.98, p < 0.001), age- and sex-adjusted (OR 0.96, 95% CI 0.94-0.98, p < 0.001), and fully adjusted models (OR 0.96, 95% CI 0.93-0.99, p = 0.003). When considering IC as a categorical variable, unadjusted logistic regression showed a strong association between high IC and lower odds of falls (OR 0.31, 95% CI 0.16-0.60, p < 0.001). This association remained significant in both the age- and sex-adjusted (OR 0.30, 95% CI 0.15-0.59, p < 0.001) and fully adjusted models (OR 0.33, 95% CI 0.16-0.82, p = 0.007). The locomotion domain was independently associated with falls in the unadjusted (OR 0.98, 95% CI 0.97-0.99, p < 0.001), age- and sex-adjusted (OR 0.97, 95% CI 0.96-0.99, p < 0.001), and fully adjusted model (OR 0.98, 95% CI 0.96-0.99, p < 0.001).
CONCLUSIONS: This is the first study using an MDS-HC-derived instrument to assess IC. Individuals with higher IC were less likely to report recent falls, with locomotion being an independently associated domain.
CONCLUSIONS: Lower IC is linked to increased odds of falls. Interventions to maintain and improve IC, especially the locomotion domain, may reduce fall risk in community-dwelling octogenarians.

UNASSIGNED: Synaptic dysfunction is closely associated with cognitive function in Alzheimer\'s disease (AD), and is present already in an early stage of the disease.
UNASSIGNED: Using serial cerebrospinal fluid (CSF) sampling, we aimed to investigate slopes of CSF synaptic proteins, and their relation with cognition along the AD continuum.
UNASSIGNED: We included subjects with subjective cognitive decline (SCD) or mild cognitive impairment (MCI) (n = 50 amyloid-β+ [A +], n = 50 A-) and 50 patients with AD dementia from the Amsterdam dementia cohort, with CSF at two time points (median[IQR] 2.1[1.4-2.7] years). We analyzed 17 synaptic proteins and neurofilament light (NfL). Using linear mixed models we assessed trajectories of protein levels, and associations with cognitive decline (repeated Mini-Mental State Examination). We used Cox regression models to assess predictive value of protein levels for progression to AD dementia.
UNASSIGNED: At baseline most proteins showed increased levels in AD dementia compared to the other groups. In contrast NPTX2 levels were lower in AD dementia. Higher baseline levels of SNAP25, β-syn, and 14-3-3 proteins were associated with faster cognitive decline (St.B[SE] -0.27[0.12] to -0.61[0.12]). Longitudinal analyses showed that SYT1 and NPTX levels decreased over time in AD dementia (st.B[SE] -0.10[0.04] to -0.15[0.05]) and SCD/MCI-A+ (St.B[SE] -0.07[0.03] to -0.12[0.03]), but not in SCD/MCI-A- (pinteraction < 0.05). Increase over time in NfL levels was associated with faster cognitive decline in AD dementia (St.B[SE] -1.75[0.58]), but not in the other groups (pinteraction < 0.05).
UNASSIGNED: CSF synaptic proteins showed different slopes over time, suggesting complex synaptic dynamics. High levels of especially SNAP-25 may have value for prediction of cognitive decline in early AD stages, while increase in NfL over time correlates better with cognitive decline in later stages.

UNASSIGNED: There is renewed interest in whether sex differences in dementia risk exist, and what influence social and biological factors have.
UNASSIGNED: To review evidence from the Cognitive Function and Ageing Studies (CFAS), a multi-center population-representative cohort study in the UK; focusing on dementia and cognition, incorporating findings on participants\' health and social circumstances.
UNASSIGNED: After identifying all CFAS publications, the results of all sex-stratified primary analyses of CFAS data were narratively reviewed.
UNASSIGNED: Of 337 publications, 94 report results by sex (including null findings), which are summarized by theme: dementia epidemiology, cognition, mental health, health expectancy, social context and biological resource (including neuropathology).
UNASSIGNED: Where differences are found they most commonly favor men; however, greater mortality in men may confound associations with age-related outcomes. This \'survival bias\' may explain findings of greater risk of dementia and faster cognitive decline in women. Age-specific dementia incidence was similar between sexes, although reduced incidence across study generations was more pronounced in men. Mood disorders were more prevalent in women, but adjusting for disability and deprivation attenuated the association. Prominent findings from other cohorts that women have more Alzheimer\'s disease pathology and greater risk of dementia from the Apolipoprotein E ɛ4 allele were not observed, warranting further investigation. The \'male-female health-survival paradox\' is demonstrated whereby women live longer but with more comorbidity and disability. Examining why health expectancies changed differently over two decades for each sex (interacting with deprivation) may inform population interventions to improve cognitive, mental and physical health in later life.