Work

P2‐555: Heterogeneity in the Increased Risk for Alzheimer's Disease and Related Dementias Associated With Fine Particle Exposure: Exploring the Role of Cognitive Reserve

Year: 2019

Type: article

Abstract: Emerging epidemiologic and neurotoxicological data suggest PM2.5 (particulate matter with aerodynamic diameter <2.5 μm) as a novel environmental risk factor for Alzheimer's disease and related dementias (ADRD), which may disproportionately affect socially disadvantaged individuals (e.g., less educated). Cognitive reserve (CR) may explain discrepancies between severity of neuropathology and cognitive performance. We prospectively investigated whether a statistically-defined measure of CR modifies the association of PM2.5 on ADRD incidence. Subjects were community-dwelling Women's Health Initiative Memory Study participants, ages 65–79 years at baseline and free of dementia at enrollment. Incident centrally-adjudicated (DSM-IV criteria) ADRD was based on annual (1996-2010) cognitive screening, neuropsychiatric evaluation, and clinical data. Three-year moving average PM2.5 residential exposures were aggregated from daily 1999–2010 estimates from nationwide spatiotemporal modeling, integrating local monitoring and atmospheric air predictions. CR was derived via a structural equation model following a Multiple Indicator, Multiple Cause framework, with cognitive scores and educational attainment as reflective indicators and physical activity and occupational attainment as formative latent variables of CR. We examined whether the resulting CR measure (median-split) modified ADRD risk associated with residing in locations exceeding the US National Ambient Air Quality Standard (3-year average PM2.5 >12 vs. ≤12 μg/m), adjusting for potential confounders, with proportional hazards regression. Among 6113 women, 262 were classified as incident cases of ADRD (average follow-up 8.8 years). Residing in locations with high PM2.5 was associated with increased ADRD risk (hazard ratio [HR]=1.70; 95% CI [1.31, 2.22]), adjusting for geographic region, age, socioeconomic characteristics, lifestyle, clinical characteristics, and hormone therapy. This putative neurotoxic effect of PM2.5 was much greater (interaction p=0.01) among older women with lower educational attainment (≤ high school; HR=2.58, [1.66, 4.02]) compared to their counterparts (> high school; HR=1.35; [0.99, 1.85]). Although non-significant, low CR was associated with increased ADRD risk (HR=1.23; [0.90, 1.68]). The adverse effect of PM2.5 was much greater (interaction p=0.02) among women with low CR (HR=2.13; [1.51, 2.99]) than among women with high CR where the association was no longer significant (HR=1.21; [0.82, 1.78]). Our novel findings support the hypothesis that high CR attenuates the PM2.5 neurotoxicity on brain aging.

Source: Alzheimer s & Dementia

DOI: 10.1016/j.jalz.2019.06.2964