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About the Authors:
Hui-Xin Wang
* E-mail: [email protected]
Affiliations College of Public Health, Zhengzhou University, Zhengzhou, China, Aging Research Center, Department of Neurobiology, Caring Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden, Stress Research Institute, Stockholm University, Stockholm, Sweden
Stuart W. S. MacDonald
Affiliations Department of Psychology, University of Victoria, Victoria, British Columbia, Canada, Institute on Aging and Lifelong Health, University of Victoria, Victoria, British Columbia, Canada
Serhiy Dekhtyar
Affiliation: Department of Clinical Neuroscience, Division of Psychology, Karolinska Institutet, Stockholm, Sweden
ORCID http://orcid.org/0000-0002-3062-4848
Laura Fratiglioni
Affiliations Aging Research Center, Department of Neurobiology, Caring Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden, Stockholm Gerontology Research Center, Stockholm, SwedenAbstract
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 ([gamma] = 0.9), whereas early-late ([gamma] = 0.27) and adult-late ([gamma] = 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) [epsilon]4 allele. A reduced risk of dementia was associated...