Midlife and Late-life Environmental Exposures on Dementia Risk in the Wisconsin Longitudinal Study: The Modifying Effects of ApoE

Introduction: Late-life air pollution exposure is associated with an increased risk for dementia, with this effect exacerbated among apolipoprotein E-4 (ApoE-4) carriers. However, whether midlife occupational exposures likewise influence dementia outcomes, and varies as a function of ApoE-4 status is unknown.

Methods: Using data from 3814 participants in the Wisconsin Longitudinal Study (WLS), we employed weighted logistic regression to evaluate associations between midlife occupational respiratory exposures and late-life air pollution on all-cause dementia risk, stratified by ApoE-4 status.

Results: Midlife occupational exposure was associated with increased odds of all-cause dementia preferentially among ApoE-4 noncarriers (odds ratio [OR] = 1.59, p = 0.01), whereas higher late-life urban air pollution exposure was associated with increased dementia risk among ApoE-4 carriers (OR = 1.258, p = 0.029).

Discussion: Associations between environmental exposures and dementia risk vary based on the timing of exposure and ApoE-4 status. While late-life environmental exposures are associated with dementia among ApoE-4 carriers, for noncarriers midlife environmental exposure confers the greatest risk.

Highlights: The effect of adult environmental respiratory exposures on subsequent dementia risk varies as a function of both ApoE-4 carrier status and exposure timing. Midlife occupational exposure to respiratory hazards is preferentially associated with increased dementia odds among ApoE-4 noncarriers. Late-life exposure to ambient air pollution is associated with dementia risk, but only among ApoE-4 carriers. While higher exposure to PM increases the risk for dementia, higher exposure to ozone was associated with reduced risk for dementia among ApoE-4 carriers.