Epigenetics as a link between environmental factors and dementia risk.

Dementia encompasses a broad spectrum of neuropsychiatric disease states marked by cognitive impairments that interfere with day-to-day functioning. Most dementias are complex phenotypes that result from a genome-environment interplay. Epigenetic regulation has emerged as a candidate mechanism for studying this interplay. In this narrative review, we discuss state-of-the-art evidence on environmental exposures relevant to dementia, including nutrition, physical exercise, psychosocial stress, and environmental toxins, and highlight epigenetic mechanisms that have been reported as a putative link between each exposure and dementia risk. We then discuss the clinical implications and future directions of this line of research. An improved understanding of the epigenetic mechanisms involved in dementia pathogenesis can promote the development of novel biomarkers for predicting outcomes but also targeted therapies to intervene early in the course of the disease.