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Evidence suggests that depression may be a risk factor for dementia in older adults, but the link between depressive symptoms and brain health earlier in life is less understood. Our aim was to investigate the association between long-term depressive symptoms in young to mid-adulthood and a measure of brain age derived from structural MRI.From the Coronary Artery Risk Development in Young Adults study, we identified 649 participants (age 23-36 at baseline) with brain MRI and cognitive testing. Long-term depressive symptoms were measured with the Center for Epidemiological Studies Depression scale (CESD) six times across 25 years and analyzed as time-weighted averages (TWA). Brain age was derived using previously validated high dimensional neuroimaging pattern analysis, quantifying individual differences in age-related atrophy. Elevated depressive symptoms were defined as CES-D ≥16. Linear regression was used to test the association between TWA depressive symptoms, brain aging, and cognition.Each standard deviation (5-points) increment in TWA depression symptoms over 25 years was associated with one-year greater brain age (β: 1.14, 95 % confidence interval [CI]: 0.57 to 1.71). Participants with elevated TWA depressive symptoms had on average a 3-year greater brain age (β: 2.75, 95 % CI: 0.43 to 5.08). Moreover, elevated depressive symptoms were associated with higher odds of poor cognitive function in midlife (OR: 3.30, 95 % CI: 1.37 to 7.97).Brain age was assessed at one time, limiting our ability to evaluate the temporality of depressive symptoms and brain aging.Elevated depressive symptoms in early adulthood may have implications for brain health as early as in midlife.

In this article, the authors discuss primarily what is known about the epidemiology of all-cause dementia. Dementia is caused by a complex interplay of genetics, comorbidities, and lifestyle factors, and drug development has been challenging. However, evidence from large, prospective, observational studies has identified a variety of factors that may prevent or delay the onset of dementia. Several of these factors are modifiable and lend themselves to well to treatments currently available. The authors discuss the state of current evidence on dementia risk factors, the most promising avenues, and future directions for dementia prevention and management.

Background: Poor social health is likely associated with cognitive decline and risk of dementia; however, studies show inconsistent results. Additionally, few studies separate social health components or control for mental health. Objective: To investigate whether loneliness and social support are independently associated with cognitive decline and risk of dementia, and whether depressive symptoms confound the association. Methods: We included 4,514 participants from the population-based Rotterdam Study (RS; aged 71±7SD years) followed up to 14 years (median 10.8, interquartile range 7.4–11.6), and 2,112 participants from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K; aged 72±10SD years) followed up to 10 years (mean 5.9±1.6SD). At baseline, participants were free of major depression and scored on the Mini-Mental State Examination (MMSE) ≥26 for RS and ≥25 for SNAC-K. We investigated loneliness, perceived social support, and structural social support (specifically marital status and number of children). In both cohorts, dementia was diagnosed and cognitive function was repeatedly assessed with MMSE and a global cognitive factor (g-factor). Results: Loneliness was prospectively associated with a decline in the MMSE in both cohorts. Consistently, persons who were lonely had an increased risk of developing dementia (RS: HR 1.34, 95%CI 1.08–1.67; SNAC-K: HR 2.16, 95%CI 1.12–4.17). Adjustment for depressive symptoms and exclusion of the first 5 years of follow-up did not alter results. Neither perceived or structural social support was associated with cognitive decline or dementia risk. Conclusion: Loneliness, not social support, predicted cognitive decline and incident dementia independently of depressive symptoms.

High blood pressure (BP) is a risk factor for late-life brain health; however, the association of elevated BP with brain health in mid-life is unclear.We identified 661 participants from the Coronary Artery Risk Development in Young Adults Study (age 18-30 at baseline) with 30 years of follow-up and brain magnetic resonance imaging at year 30. Cumulative exposure of BP was estimated by time-weighted averages (TWA). Ideal cardiovascular health was defined as systolic BP 120 mm Hg, diastolic BP 80 mm Hg. Brain age was calculated using previously validated high dimensional machine learning pattern analyses.Every 5 mmHg increment in TWA systolic BP was associated with approximately 1-year greater brain age (95% confidence interval [CI]: 0.50-1.36) Participants with TWA systolic or diastolic BP over the recommended guidelines for ideal cardiovascular health, had on average 3-year greater brain age (95% CI: 1.00-4.67; 95% CI: 1.45-5.13, respectively).Elevated BP from early to mid adulthood, even below clinical cut-offs, is associated with advanced brain aging in mid-life.

INTRODUCTION: Stroke, especially ischemic stroke's (IS) link with Alzheimer's disease (AD) remains unclear. METHODS: This prospective cohort study included 2459 AD- and cerebrovascular disease-free older adults at baseline (mean age 71.9 ± 10.3 years, Stockholm, Sweden). Using Cox regressions, shared risk factors (SRFs) and shared protective factors (SPFs) between AD and IS were recognized when their hazard ratios in both AD and IS models were significant and in the same direction. RESULTS: During the follow-up period of up to 15 years, 132 AD and 260 IS mutually exclusive cases were identified. SRFs were low education, sedentary lifestyle, and heart diseases. High levels of psychological well-being, actively engaging in leisure activities, and a rich social network were SPFs. Having ≥1 SPF reduced 47% of AD and 28% of IS risk among people with a low risk profile (

Introduction The effect of comorbid cardiometabolic diseases (CMDs), including diabetes, heart diseases, and stroke, on dementia remains unclear. Methods A cohort of 2648 dementia-free adults aged ≥60 years was followed up for 12 years. An active lifestyle was defined in accordance with the engagement in leisure activities and/or a social network. Cox models were used in data analysis. Results The multiadjusted hazard ratio (HR, 95% confidence interval) of dementia was 1.41 (1.07–1.86) for one, 2.38 (1.58–3.59) for two, and 4.76 (2.04–11.13) for three CMDs. In joint exposure analysis, the HR of dementia was 3.36 (2.14–5.30) for participants with CMDs plus an inactive lifestyle and 1.32 (0.95–1.84) for those with CMDs plus an active lifestyle (reference: no CMDs plus active lifestyle). An active lifestyle delayed dementia onset by 3.50 years in people with CMDs. Discussion CMDs, especially when comorbid, are associated with increased dementia risk; however, leisure activities and social integration mitigate this risk.

Emerging evidence suggests that olfactory function is closely linked to memory function. The aims of this study were to assess whether olfactory and episodic memory functions follow similar age-related decline trajectories, to identify different patterns of decline, as well as predictors of the patterns. 1023 participants from the Memory and Aging Project were followed for up to 8 years with annual episodic memory and odor identification assessments. Trajectories were modelled using growth mixture models. Multivariate logistic regression was used to identify pattern predictors. Three patterns of joint trajectories were identified; Class 1- stable average performance in both functions (n=690, 67.4%); Class 2- stable average episodic memory and declining odor identification (n=231, 22.6%); and Class 3- decline in both functions (n= 102, 10.0%). Class predictors included age, sex, APOE ε4 status, cognitive activity level and BMI. Participants in Class 3 were most likely to develop dementia. Episodic memory and olfactory function show similar trajectories in aging. Such classification can contribute to a better understanding of the factors related to cognitive decline and dementia.

The impact of cardiovascular risk burden on cognitive trajectories and brain structure changes remains unclear.This study aimed to examine whether cardiovascular risk burden assessed by the Framingham General Cardiovascular Risk Score (FGCRS) is associated with cognitive decline and structural brain differences.Within the Rush Memory and Aging Project, 1,588 dementia-free participants (mean age: 79.5 years) were followed for up to 21 years. FGCRS was assessed at baseline and categorized into tertiles (lowest, middle, and highest). Episodic memory, semantic memory, working memory, visuospatial ability, and perceptual speed were assessed annually with a battery of 19 tests, from which composite scores were derived. A subsample (n = 378) of participants underwent magnetic resonance imaging. Structural total and regional brain volumes were estimated. Data were analyzed using linear mixed-effects models and linear regression models.In all participants, FGCRS ranged from 4 to 28 (mean score: 15.6 ± 3.7). Compared with the lowest tertile of FGCRS, the highest tertile was associated with faster decline in global cognition (β = -0.019; 95% confidence interval [CI]: -0.035 to -0.003), episodic memory (β = -0.023; 95% CI: -0.041 to -0.004), working memory (β = -0.021; 95% CI: -0.035 to -0.007), and perceptual speed (β = -0.027; 95% CI: -0.042 to -0.011) over the follow-up. In magnetic resonance imaging data analyses, higher FGCRS was related to smaller volumes of the hippocampus (β = -0.021; 95% CI: -0.042 to -0.000), gray matter (β = -1.569; 95% CI: -2.757 to -0.382), and total brain (β = -1.588; 95% CI: -2.832 to -0.344), and greater volume of white matter hyperintensities (β = 0.035; 95% CI: 0.001 to 0.069).Higher cardiovascular risk burden may predict decline in episodic memory, working memory, and perceptual speed and is associated with neurodegeneration and vascular lesions in the brain.

We investigated the effect of poor masticatory ability on cognitive trajectories and dementia risk in older adults. 544 cognitively intact adults aged ≥50 were followed for up to 22 years. Cognitive domains (verbal, spatial/fluid, memory, and perceptual speed) were assessed at baseline and follow-ups. Dementia was ascertained according to standard criteria. Masticatory ability was assessed using the Eichner Index and categorized according to the number of posterior occlusal zones: A (all four), B (3-1), and C (none). At baseline, 147 (27.0%) participants were in Eichner category A, 169 (31.1%) in B and 228 (41.9%) in C. After the age of 65, participants in Eichner category B and C showed an accelerated decline in spatial/fluid abilities (β: -0.16, 95% CI: -0.30 to -0.03) and (β: -0.15, 95% CI: -0.28 to -0.02), respectively. Over the follow-up, 52 incident dementia cases were identified. Eichner categories B or C were not associated with an increased risk of dementia, compared to category A (Hazard Ratio [HR]: 0.83, 95% CI: 0.39 to 1.76 and HR: 0.63, 95% CI: 0.30 to 1.29, respectively). Poor masticatory ability is associated with an accelerated cognitive decline in fluid/spatial abilities, however it was not related to a higher risk of dementia.

Importance Evidence on the association of lifespan cognitive reserve (CR) with dementia is limited, and the strength of this association in the presence of brain pathologies is unknown. Objective To examine the association of lifespan CR with dementia risk, taking brain pathologies into account. Design, Setting, and Participants This study used data from 2022 participants in the Rush Memory and Aging Project, an ongoing community-based cohort study with annual follow-up from 1997 to 2018 (mean follow-up, 6 years; maximum follow-up, 20 years). After excluding 420 individuals who had prevalent dementia, missing data on CR, or dropped out, 1602 dementia-free adults were identified at baseline and evaluated to detect incident dementia. During follow-up, 611 died and underwent autopsies. Data were analyzed from May to September 2018. Exposures Information on CR factors (education; early-life, midlife, and late-life cognitive activities; and social activities in late life) was obtained at baseline. Based on these factors, lifespan CR scores were captured using a latent variable from a structural equation model and was divided into tertiles (lowest, middle, and highest). Main Outcomes and Measures Dementia was diagnosed following international criteria. Neuropathologic evaluations for Alzheimer disease and other brain pathologies were performed in autopsied participants. The association of lifespan CR with dementia or brain pathologies was estimated using Cox regression models or logistic regression. Results Of the 1602 included participants, 1216 (75.9%) were women, and the mean (SD) age was 79.6 (7.5) years. During follow-up, 386 participants developed dementia (24.1%), including 357 participants with Alzheimer disease–related dementia (22.3%). The multiadjusted hazards ratios (HRs) of dementia were 0.77 (95% CI, 0.59-0.99) for participants in the middle CR score tertile and 0.61 (95% CI, 0.47-0.81) for those in the highest CR score tertile compared with those in the lowest CR score tertile. In autopsied participants, CR was not associated with most brain pathologies, and the association of CR with dementia remained significant after additional adjustment for brain pathologies (HR, 0.60; 95% CI, 0.42-0.86). The highest CR score tertile was associated with a reduction in dementia risk, even among participants with high Alzheimer disease pathology (HR, 0.57; 95% CI, 0.37-0.87) and any gross infarcts (HR, 0.34; 95% CI, 0.18-0.62). Conclusions and Relevance High lifespan CR is associated with a reduction in dementia risk, even in the presence of high brain pathologies. Our findings highlight the importance of lifespan CR accumulation in dementia prevention.

Objective This study aimed to examine the relationship between sleep duration and all-cause mortality, and to assess the role of cognitive impairment, physical disability, and chronic conditions on this association among very old adults. Design A prospective cohort study. Setting and Participants Within the Chinese Longitudinal Healthy Longevity Surveys, 17,637 oldest-old aged 80-105 years were followed up to 10 years (2005- 2014). Measures Data on sleep duration at baseline were based on self-report and were categorized as short ( 9 hours). Information on cognitive function using the Mini-Mental State Examination (MMSE), physical disability using Activities of Daily Living (ADL), and chronic conditions including diabetes, heart disease, stroke, asthma, and cancer were collected at baseline based on a structured questionnaire. Information about vital status was ascertained and confirmed by a close family member or village doctor of the participant during the follow-up. Data were analyzed using Cox proportional hazards models, with adjustment for potential confounders. Results During the follow-up of 10 years, 11,067 (62.7%) participants died. The multivariate-adjusted hazard ratios (HRs) with 95% confidence interval (CI) for mortality were 1.03 (0.98-1.09) for short sleep and 1.13 (1.08-1.18) for long sleep compared with moderate sleep duration. In stratified analysis by cognitive impairment, physical disability, and chronic conditions, the risk of morality was present only among people with MMSE scores ≤24 but did not differ much when stratified by physical disability and chronic conditions. There was a statistically significant interaction between long sleep and cognitive impairment on mortality (P for interaction = .002). Conclusions and Implications Long sleep duration is associated with higher risk of mortality in very old adults independently of health conditions. Cognitive impairment may enhance this association. These findings suggest that health practitioners and families should be aware of the potential adverse prognosis associated with long sleep.

Tooth loss has been related to cognitive impairment; however, its relation to structural brain differences in humans is unknown. Dementia-free participants (n = 2715) of age ≥60 years were followed up for up to 9 years. A subsample (n = 394) underwent magnetic resonance imaging at baseline. Information on tooth loss was collected at baseline, and cognitive function was assessed using the Mini-Mental State Examination at baseline and at follow-ups. Data were analyzed using linear mixed effects models and linear regression models. At baseline, 404 (14.9%) participants had partial tooth loss, and 206 (7.6%) had complete tooth loss. Tooth loss was significantly associated with a steeper cognitive decline (β: -0.18, 95% confidence interval [CI]: -0.24 to -0.11) and remained significant after adjusting for or stratifying by potential confounders. In cross-sectional analyses, persons with complete or partial tooth loss had significantly lower total brain volume (β: -28.89, 95% CI: -49.33 to -8.45) and gray matter volume (β: -22.60, 95% CI: -38.26 to -6.94). Thus, tooth loss may be a risk factor for accelerated cognitive aging.

Introduction The association of lifespan cognitive reserve (CR) with mild cognitive impairment (MCI) remains controversial. We aimed to examine the association of lifespan CR indicator with the risk of MCI and its progression to dementia, taking brain pathologies into account. Methods In a community-based cohort study (mean age, 79 years) with annual follow-up (median, 5.16 years; maximum, 20 years), a cognitively intact group (n = 1182) and an MCI group (n = 420) were identified at baseline. During the follow-up, 611 participants died and underwent autopsies. CR indicator encompassing education, early life to late-life cognitive and social activities were obtained and tertiled. Results The multi-adjusted hazard ratio (HR) of MCI was 0.72 (95% confidence interval [CI] 0.58 to 0.90) in the cognitively intact group, and the HR of dementia was 0.66 (95% CI 0.45 to 0.97) in the MCI group for participants with the highest CR indicator (reference: the lowest CR indicator). Among MCI participants with brain pathologies, dementia incidence was about 50% lower in people with the highest CR indicator than the lowest CR indicator. Discussion High lifespan CR indicator reduces risk of MCI, and delays its progression to dementia.