BACKGROUND AND OBJECTIVES: Prior studies on cognitive reserve (CR) and cognitive trajectories are limited and have had conflicting results. Furthermore, most studies have used a single measure of CR that may not reflect a comprehensive exposure. The objective of this study is to determine the impact of individual and composite CR measures on cognitive decline over a 6-year period. RESEARCH DESIGN AND METHODS: We studied 55,340 participants from 16 European countries, aged 50 and older, who participated in the Survey of Health, Aging, and Retirement in Europe. We used cognitive measures (including immediate memory, delayed memory, verbal fluency, and numeracy) and 3 CR factors (education, occupation, and cognitive activities) collected in 4 waves from 2011 to 2017. Structural equation modeling was used to construct the composite CR score, analyzed as tertile. Linear mixed-effect models were used to examine the study aims. RESULTS: At baseline, the highest composite CR tertile was associated with a higher cognition score than the middle and lowest CR tertiles (β: -0.28, 95% confidence interval [CI]: -0.29 to -0.26; β: -0.71, 95% CI: -0.72 to -0.70, respectively), as well as for all individual cognitive domains. At longitudinal results, compared with the lowest CR, the highest but not the middle CR tertile demonstrated a slower 6-year decline in global cognition (β: -0.02, 95 % CI: -0.03 to -0.01), as well as in all cognitive domains (p < .05). DISCUSSION AND IMPLICATIONS: A composite CR could be a protective factor for cognitive performance and cognitive decline, and it is more sensitive and inclusive than an individual CR indicator alone.

Depressive symptoms may either be a risk factor or prodromal to dementia. Investigating this association in midlife may help clarify the role of depression in cognitive aging. We aimed to identify trajectories in depressive symptoms in early to mid-life and related cognitive and brain outcomes in midlife. This study includes 3944 Black and White participants (ages 26-45 years at baseline) from the Coronary Artery Risk Development in Young Adults (CARDIA) study with 20 years of follow-up. Depressive symptoms were assessed using the Center for Epidemiological Studies Depression scale at five time points over 20 years. Growth mixture modeling (GMM) was used to identify depressive symptom trajectories. Participants completed a neuropsychological battery 20 years after baseline, including the Digit Symbol Substitution Test (DSST), Rey-Auditory Verbal Learning Test (RAVLT), Stroop Test, Montreal Cognitive Assessment (MoCA), and category and letter fluency tests. A sub-sample of participants (n = 662) underwent brain magnetic resonance imaging (MRI) to characterize gray matter volumes and white matter hyperintensities (WMHs). We identified four classes of depressive symptom trajectories: a declining class (n = 286, 7.3%) with initially high symptoms and subsequent decline, a class with consistently high symptoms (steady high; n = 264, 6.7%), a class with late increases in symptoms (increasing; n = 277, 7%), and a class with consistently low symptoms (steady low; n = 3117, 79.0%). The steady high and the increasing classes had poorer performance on all cognitive tests, while the declining class had poorer performance on the DSST, verbal fluency, and MoCA. Compared to the steady low symptom class, the steady high class had lower volumes in the entorhinal cortex (β: -180.80, 95% CI: -336.69 to -24.91) and the amygdala (β: -40.97, 95% CI: -74.09 to -7.85), the increasing class had more WMHs (β: 0.55, 95% CI: 0.22 to 0.89), and the declining class was not significantly different in any brain measures. Trajectories in depressive symptoms in young to mid-adulthood show distinct cognitive and brain phenotypes in midlife. Steady high depressive symptoms may represent a group that is at risk for dementia, whereas increasing symptoms in midlife may be associated with white matter damage.

BACKGROUND: Evidence suggests that sensory impairment is linked to dementia; however, the role of social network and leisure activity in this relationship is unclear. OBJECTIVE: Examine the association of hearing and visual impairment with dementia, and whether a rich social network and leisure activity moderates this association. METHODS: Dementia-free older adults from the Swedish National Study on Aging and Care in Kungsholmen (n = 2,579) were followed up for up for a median of 10 years (interquartile range = 6). Visual impairment was assessed with a reading acuity test, and hearing impairment was ascertained via self-report and medical records. Dementia was diagnosed following international criteria. Data on social network and leisure activity was collected via self-report. Hazard ratios (HRs) of dementia risk were derived from Cox regression models. RESULTS: Dual impairment, but not single impairment in hearing and vision was associated with a higher risk of dementia (HR: 1.62, 95% CI: 1.16 to 2.27). Compared to participants with no sensory impairment and a moderate-to-rich social network, those with dual impairment and low social network or leisure activity had higher dementia risk (HR: 2.08, 95% CI: 1.43 to 3.22; HR: 2.08, 95% CI: 1.43 to 3.22, respectively), whereas participants with dual impairment with a moderate-to-rich social network or leisure activity did not have significantly higher dementia risk (HR; 1.42, 95% CI: 0.87 to 2.33; HR; 1.42, 95% CI: 0.87 to 2.33, respectively). CONCLUSION: A richer social network and participation in stimulating activities may mitigate the higher dementia risk in older adults with dual impairment in vision and hearing.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). LIMITATIONS: Brain age was assessed at one time, limiting our ability to evaluate the temporality of depressive symptoms and brain aging. CONCLUSIONS: Elevated depressive symptoms in early adulthood may have implications for brain health as early as in midlife.

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.

Background

Cardiovascular disease risk factors play a critical role in brain aging. The metabolic syndrome (MetS), a constellation of cardiovascular risk factors, has been associated with poorer cognition in old age; however, it is unclear if it is connected to brain health earlier in life.

Methods

We investigated the association of MetS (n = 534, 18.5%) vs. no MetS (n = 2,346, 81.5%) with cognition in midlife within the prospective study, Coronary Artery Risk Development in Young Adults (CARDIA). At midlife (mean age 50), MetS was defined using National Cholesterol Education Program guidelines. At the 5-year follow-up, a cognitive battery was administered including tests of processing speed (Digit Symbol Substitution Test, DSST), executive function (the Stroop Test), verbal memory (Rey Auditory Verbal Learning Test, RAVLT), verbal fluency (category and letter fluency), and global cognitive function (Montreal Cognitive Assessment, MoCA). A sub-sample (n = 453) underwent brain MRI.

Results

Participants with MetS had worse performance on tests of verbal fluency, processing speed, executive function, and verbal memory (p < 0.05), but not on global cognition. MetS was also associated with lower frontal, parietal, temporal, and total white matter integrity (p < 0.05), as assessed with fractional anisotropy.

Conclusions

MetS is associated with lower cognition and microstructural brain alterations already at midlife, suggesting that MetS should be targeted earlier in life in order to prevent adverse brain and cognitive outcomes.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: Elevated BP from early to mid adulthood, even below clinical cut-offs, is associated with advanced brain aging in mid-life.

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.