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

Abstract

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...

Genetic risk of dementia mitigated by cognitive reserve: A cohort study

“…This suggests that cognitive reserve is a formative, rather than a reflective latent indicator. 9 Building on the findings from that study, which suggested that cumulative engagement in reserve-enhancing activities might be more relevant than the specific stages at which these contributors were acquired, we devised a cognitive reserve indicator that considered simultaneous contributions of several inputs. Even though several neuroimaging and clinicopathological studies have largely supported the presence of a neural basis for efficiency and compensation, 24,25 there is still much need for methodological development of the cognitive reserve concept.…”

“…27 A recent study from our group has attempted to test the relevant importance of stages (early, mid-, and late life) at which cognitive reserve exerted the largest protection against dementia risk. 9 Building on the findings from that study, which suggested that cumulative engagement in reserve-enhancing activities might be more relevant than the specific stages at which these contributors were acquired, we devised a cognitive reserve indicator that considered simultaneous contributions of several inputs. Among these, we also included social network and accumulated substantive complexity across 5 midlife occupations that were not considered in the previous study.…”

“…7,8 In a previous study, we attempted to uncover the relative importance of life stages (early, mid-, and late life) at which exposure to reserve-enhancing factors was most associated with the risk of dementia. 9 Due to the strong correlation between the early and the midlife reserve indicators, we were unable to assess the relative importance of each life period. However, we found that having a high reserve score in all 3 life stages was associated with the largest reduction in dementia risk.…”

“…However, we found that having a high reserve score in all 3 life stages was associated with the largest reduction in dementia risk. 9 This suggested that continued engagement in activities with reserve-enhancing properties might be especially important.…”

Influences of the Global Deterioration Scale according to Routine Blood Chemistry Results

“…Various risk or protective factors for dementia syndrome or cognitive impairment have been suggested by numerous epidemiological studies [25]. However, we still do not know much about the mechanisms through which various lifetime experiences such as physical and mental activity, social relationships, stress experiences, personality, diet and nutrition, and sleep, and many aging-related physiological or pathological changes in the human body, such as vascular status, hormonal changes, glucose or lipid metabolism, and body mass index (BMI).…”