The role of per- and polyfluoroalkyl substances in cognitive impairment and dementia.

Per- and polyfluoroalkyl substances (PFAS) are ubiquitous persistent organic pollutants. The neurotoxic and cardiometabolic effects of PFAS are well documented, leading to the hypothesis that exposure increases dementia risk. However, empirical data on PFAS in relation to cognitive impairment and dementia are weak, limited, and inconsistent. This report reviews the literature on PFAS and cognitive impairment and provides a rationale and overview of the PFAS VascCog Longitudinal Study, a new study using the population-based Northern Manhattan Study cohort, to prospectively examine serum concentrations of 13 PFAS in relation to lipids, carotid atherosclerosis, cognitive impairment, and dementia. We hypothesize that PFAS deleteriously impact cognition through a pathway involving hyperlipidemia and atherosclerosis. Rigorous examination of PFAS exposure in relation to dementia is needed to inform public health policies on PFAS-containing products, support regulations to reduce community exposure, and provide new avenues to protect cognitive health and impact dementia at the individual and community levels. HIGHLIGHTS: PFAS exposure increases cardiometabolic risk factors and neurotoxicity. Data on PFAS in relation to cognitive health is limited, weak, and controversial. We hypothesize that PFAS exposure increases dementia risk. We hypothesize a mechanistic pathway involving hyperlipidemia and atherosclerosis. Rigorous study of PFAS exposure and dementia risk can inform public health policy.