Association of lifelong exposure to cognitive reserve-enhancing factors with dementia risk: A community-based cohort study

Abstract

Background

Variation 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 findings

Information 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.

Conclusions

In this study, cumulative exposure to reserve-enhancing factors over the lifespan was associated with reduced risk of dementia in late life, even among individuals with genetic predisposition.

Abstract

In a community-based cohort study, Serhiy Dekhtyar and colleagues examine the association between engagement in various cognitive reserve-enhancing factors at early, mid, and late life and risk of dementia concurrence after 75.

Author summary

Why was this study done?

• It has emerged from previous literature that lifestyle factors such as physical exercise, intellectual stimulation, or leisure activities are associated with a reduced risk of dementia occurrence in late life. One possibility is that these activities provide protection in the form of reserve, facilitating the maintenance of cognitive function in the face of cumulative brain damage.

• It is, however, still largely unknown how the risk of dementia is shaped by various reserve-stimulating lifestyle factors simultaneously taking place throughout the entire life course.

• Our study was designed to examine the association between the risk of dementia occurrence after age 75 and engagement in a variety of reserve-enhancing activities over the entire life course.

What did the researchers do and find?

• We estimated the risk of dementia occurrence in a cohort of individuals aged 75 y and older conditional on their engagement in ten activities that were expected to promote reserve in three stages over the life course.

• We found that, on its own, engagement in early-, adulthood-, and late-life reserve-enhancing activities was associated with a reduced risk of dementia. However, when all three factors were simultaneously evaluated for their association with dementia, the effects of early-life and adulthood factors were attenuated. This could be due to the strong correlation between early-life and adulthood factors, whereas the late-life factor was only moderately related to either early-life or adulthood markers of reserve.

• An important finding was that increased frequency of engagement in stimulating activities over the life course was associated with a progressively reduced risk of dementia, suggesting a dose-response effect between life-course reserve and dementia risk. This effect appeared to operate irrespective of genetic predisposition to dementia.

What do these findings mean?

• These findings strongly suggest that development of dementia is a lifelong process that begins decades before the onset of the disease.

• At the same time, it is never too late to initiate interventions aimed at risk modifying, since late-life engagement in stimulating activities was associated with a lower risk of dementia.

• However, because reserve-enhancing activities are correlated over the life course, and because the lowest risk is enjoyed by individuals with increased frequency of stimulating engagements, the most effective strategies are likely to be those emphasizing risk reduction throughout the entire life course.