OBJECTIVE To investigate whether a healthy lifestyle is associated with lower risk of dementia regardless of genetic risk. DESIGN, SETTING, AND PARTICIPANTS A retrospective cohort study that included adults of European ancestry aged at least 60 years without cognitive impairment or dementia at baseline. Participants joined the UK Biobank study from 2006 to 2010 and were followed up until 2016 or 2017. EXPOSURES A polygenic risk score for dementia with low (lowest quintile), intermediate (quintiles 2 to 4), and high (highest quintile) risk categories and a weighted healthy lifestyle score, including no current smoking, regular physical activity, healthy diet, and moderate alcohol consumption, categorized into favorable, intermediate, and unfavorable lifestyles. MAIN OUTCOMES AND MEASURES Incident all-cause dementia, ascertained through hospital inpatient and death records. RESULTS A total of 196 383 individuals (mean [SD] age, 64.1 [2.9] years; 52.7% were women) were followed up for 1 545 433 person-years (median [interquartile range] follow-up, 8.0 [7.4-8.6] years). Overall, 68.1% of participants followed a favorable lifestyle, 23.6% followed an intermediate lifestyle, and 8.2% followed an unfavorable lifestyle. Twenty percent had high polygenic risk scores, 60% had intermediate risk scores, and 20% had low risk scores. Of the participants with high genetic risk, 1.23% (95% CI, 1.13%-1.35%) developed dementia compared with 0.63% (95% CI, 0.56%-0.71%) of the participants with low genetic risk (adjusted hazard ratio, 1.91 [95% CI, 1.64-2.23]). Of the participants with a high genetic risk and unfavorable lifestyle, 1.78% (95% CI, 1.38%-2.28%) developed dementia compared with 0.56% (95% CI, 0.48%-0.66%) of participants with low genetic risk and favorable lifestyle (hazard ratio, 2.83 [95% CI, 2.09-3.83]). There was no significant interaction between genetic risk and lifestyle factors (P = .99). Among participants with high genetic risk, 1.13% (95% CI, 1.01%-1.26%) of those with a favorable lifestyle developed dementia compared with 1.78% (95% CI, 1.38%-2.28%) with an unfavorable lifestyle (hazard ratio, 0.68 [95% CI, 0.51-0.90]). CONCLUSIONS AND RELEVANCE Among older adults without cognitive impairment or dementia, both an unfavorable lifestyle and high genetic risk were significantly associated with higher dementia risk. A favorable lifestyle was associated with a lower dementia risk among participants with high genetic risk.

INTRODUCTION: Stroke is an established risk factor for all-cause dementia, though meta-analyses are needed to quantify this risk. METHODS: We searched Medline, PsycINFO and Embase for studies assessing prevalent or incident stroke versus a no-stroke comparison group and the risk of all-cause dementia. Random effects meta-analysis was used to pool adjusted estimates across studies and meta-regression was used to investigate potential effect modifiers. RESULTS: We identified 36 studies of prevalent stroke (1.9 million participants) and 12 studies of incident stroke (1.3 million participants). For prevalent stroke, the pooled hazard ratio for all-cause dementia was 1.69 (95% CI: 1.49–1.92; p<0.00001; I2 = 87%). For incident stroke, the pooled risk ratio was 2.18 (95% CI: 1.90–2.50; p<0.00001; I2 = 88%). Study characteristics did not modify these associations, with the exception of sex which explained 50.2% of between-study heterogeneity for prevalent stroke. DISCUSSION: Stroke is a strong, independent, and potentially modifiable risk factor for all-cause dementia.

Research on relationships between personality and cognitive abilities has so far resulted in inconsistent findings regarding the strength of the associations. Moreover, relationships have rarely been compared longitudinally and bidirectionally between midlife versus late-life cohorts by considering different personality traits as well as multiple cognitive domains over a long-term follow-up period. We hypothesize that the interplay between the "Big Five" personality traits (Neuroticism, Extraversion, Openness to Experience, Agreeableness and Conscientiousness) and cognitive abilities (information processing speed, crystallized intelligence, fluid intelligence) may change from midlife to old age due to age-associated changes in cognitive and personality plasticity. We used data from the German Interdisciplinary Longitudinal Study of Adult Development (ILSE study; n = 1,002). Participants were either born in 1950/52 (midlife sample, n = 502) or in 1930/32 (late-life sample, n = 500) and followed up for up to 12 years. Based on bivariate latent change score regression models (adjusted for gender, education, self-rated and physician-rated health), we observed that, apart from very few exceptions, the intervariable cross-lagged associations between personality traits and cognitive abilities were generally similar between cohorts. Moreover, in case of neuroticism, extraversion, and openness, the effects of cognitive abilities on change in personality were stronger than the reversed effects. Our findings thus suggest that the so far predominant perspective of personality in middle adulthood and late-life as a predictor, rather than as an outcome, of cognitive abilities needs more differentiation and reconsideration. (PsycINFO Database Record