BackgroundVariation in the clinical manifestation of dementia has been associated with differences in cognitive reserve, although less is known about the cumulative effects of exposure to cognitive reserve factors over the life course. We examined the association of cognitive reserve-related factors over the lifespan with the risk of dementia in a community-based cohort of older adults.Methods and findingsInformation on early-life education, socioeconomic status, work complexity at age 20, midlife occupation attainment, and late-life leisure activities was collected in a cohort of dementia-free community dwellers aged 75+ y residing in the Kungsholmen district of Stockholm, Sweden, in 1987–1989. The cohort was followed up to 9 y (until 1996) to detect incident dementia cases. To exclude preclinical phases of disease, participants who developed dementia at the first follow-up examination 3 y after the baseline were excluded (n = 602 after exclusions). Structural equation modelling was used to generate latent factors of cognitive reserve from three periods over the life course: early (before 20 y), adulthood (around 30–55 y), and late life (75 y and older). The correlation between early- and adult-life latent factors was strong (γ = 0.9), whereas early–late (γ = 0.27) and adult–late (γ = 0.16) latent factor correlations were weak. One hundred forty-eight participants developed dementia during follow-up, and 454 remained dementia-free. The relative risk (RR) of dementia was estimated using Cox models with life-course cognitive reserve-enhancing factors modelled separately and simultaneously to assess direct and indirect effects. The analysis was repeated among carriers and noncarriers of the apolipoprotein E (APOE) ε4 allele. A reduced risk of dementia was associated with early- (RR 0.57; 95% CI 0.36–0.90), adult- (RR 0.60; 95% CI 0.42–0.87), and late-life (RR 0.52; 95% CI 0.37–0.73) reserve-enhancing latent factors in separate multivariable Cox models. In a mutually adjusted model, which may have been imprecisely estimated because of strong correlation between early- and adult-life factors, the late-life factor preserved its association (RR 0.65; 95% CI 0.45–0.94), whereas the effect of midlife (RR 0.73; 95% CI 0.50–1.06) and early-life factors (RR 0.76; 95% CI 0.47–1.23) on the risk of dementia was attenuated. The risk declined progressively with cumulative exposure to reserve-enhancing latent factors, and having high scores on cognitive reserve-enhancing composite factors in all three periods over the life course was associated with the lowest risk of dementia (RR 0.40; 95% CI 0.20–0.81). Similar associations were detected among APOE ε4 allele carriers and noncarriers. Limitations include measurement error and nonresponse, with both biases likely favouring the null. Strong correlation between early- and adult-life latent factors may have led to a loss in precision when estimating mutually adjusted effects of all periods.ConclusionsIn this study, cumulative exposure to reserve-enhancing factors over the lifespan w...

Higher childhood school performance is protective of dementia risk, particularly when preserved through complex work environments in adulthood, although it will remain protective even in the absence of later-life educational or occupational stimulation.

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Highlights COVID-19 disproportionately affects individuals who are not only biologically, but also socially vulnerable. Research focusing on the interplay between the biological and social determinants of COVID-19 burden is currently lacking. Interdisciplinary collaboration and biological, clinical and social data integration will be crucial to guide actions aimed at reducing older adults’ vulnerability to COVID-19.

IntroductionWe aimed to describe the distribution of excess mortality (EM) during the first weeks of the COVID-19 outbreak in the Stockholm Region, Sweden, according to age, sex and sociodemographic context.MethodsWeekly all-cause mortality data were obtained from Statistics Sweden for the period 1 January 2015 to 17 May 2020. EM during the first 20 weeks of 2020 was estimated by comparing observed mortality rates with expected mortality rates during the five previous years (N=2 379 792). EM variation by socioeconomic status (tertiles of income, education, Swedish-born, gainful employment) and age distribution (share of 70+-year-old persons) was explored based on Demographic Statistics Area (DeSO) data.ResultsEM was first detected during the week of 23–29 March 2020. During the peak week of the epidemic (6–12 April 2020), an EM of 150% was observed (152% in 80+-year-old women; 183% in 80+-year-old men). During the same week, the highest EM was observed for DeSOs with lowest income (171%), lowest education (162%), lowest share of Swedish-born (178%) and lowest share of gainfully employed residents (174%). EM was further increased in areas with higher versus lower proportion of younger people (magnitude of increase: 1.2–1.7 times depending on socioeconomic measure).ConclusionLiving in areas characterised by lower socioeconomic status and younger populations was linked to excess mortality during the COVID-19 pandemic in the Stockholm Region. These conditions might have facilitated viral spread. Our findings highlight the well-documented vulnerability linked to increasing age and sociodemographic context for COVID-19–related death.

Low early-life school performance is associated with an elevated risk of dementia, independent of subsequent educational and occupational attainment.

Objective We investigated whether cognitive reserve modifies the risk of dementia attributable to apolipoprotein ε4 ( APOE‐ ε4), a well‐known genetic risk factor for dementia. Methods We followed 2,556 cognitively intact participants aged ≥60 years from the ongoing prospective community‐based Swedish National Study on Aging and Care in Kungsholmen (SNAC‐K). Dementia was ascertained through clinical and neuropsychological assessments and diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria. Structural equation modeling was used to generate a cognitive reserve indicator from 4 previously validated contributors: early life education, midlife substantive work complexity, late life leisure activities, and late life social networks. Cox proportional hazard models estimated dementia risk in relation to cognitive reserve indicator. The interaction between the cognitive reserve indicator and APOE‐ ε4 was assessed on multiplicative and additive scales. Results After an average of 6.3 years (range = 2.1–10.7) of follow‐up, 232 dementia cases were ascertained. Relative to individuals in the lowest tertile of cognitive reserve indicator, those with moderate and high reserve were at a reduced risk of dementia. There was no multiplicative interaction between APOE‐ ε4 status and cognitive reserve indicator ( p = 0.113). Additive interaction was statistically significant. Relative to APOE‐ ε4 carriers with low cognitive reserve, ε4 carriers with high reserve had a reduced risk of dementia (hazard ratio [HR] = 0.28, 95% confidence interval [CI] = 0.13–0.59). The magnitude of risk reduction was similar in ε4 noncarriers with a high cognitive reserve indicator (HR = 0.24, 95% CI = 0.15–0.40). Interpretation Lifelong engagement in reserve‐enhancing activities attenuates the risk of dementia attributable to APOE ‐ε4. Promoting cognitive reserve might be especially effective in subpopulations with high genetic risk of dementia. ANN NEUROL 2019

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