OBJECTIVE: To investigate the associations between midlife work-related stress and mild cognitive impairment (MCI), dementia, and Alzheimer's disease later in life, in a large representative population.

METHOD: Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study participants were randomly selected from independent population-based surveys (mean age 50 years). A random sample of 2,000 individuals was invited for two reexaminations including cognitive tests (at mean age 71 and mean age 78), and 1,511 subjects participated in at least one reexamination (mean follow-up 28.5 years). Work-related stress was measured using two questions on work demands that were administered in midlife. Analyses adjusted for important confounders.

RESULTS: Higher levels of midlife work-related stress were associated with higher risk of MCI (odds ratio [OR], 1.38; 95% confidence interval [CI], 1.08-1.76), dementia (OR, 1.53; CI, 1.13-2.07), and Alzheimer's disease (OR, 1.55; CI, 1.19-2.36) at the first follow-up among the CAIDE participants. Results remained significant after adjusting for several possible confounders. Work-related stress was not associated with MCI and dementia during the extended follow-up.

DISCUSSION: Midlife work-related stress increases the risk for MCI, dementia, and Alzheimer's disease in later life. The association was not seen after the extended follow-up possibly reflecting selective survival/participation, heterogeneity in dementia among the oldest old, and a critical time window for the effects of midlife stress.