Early Life Epidemiology of Alzheimer's Disease - A Critical Review

Abstract

Background: As adult brain structure is primarily established in early life, genetic and environmental exposures in infancy and childhood influence the risk for Alzheimer disease (AD). In this systematic review, we identified several early life risk factors and discussed the evidence and underlying mechanism for each. Summary: Early risk factors for AD may alter brain anatomy, causing vulnerability to AD-related dementia later in life. In the perinatal period, both genes and learning disabilities have been associated with the development of distinct AD phenotypes. During early childhood, education and intellect, as well as body growth, may predispose to AD through alterations in cognitive and brain reserve, though the specific mediators of neural injury are disputed. Childhood socioeconomic status (SES) may predispose to AD by influencing adult SES and cognition. Association of these risk factors with underlying AD pathology (rather than just clinical diagnosis) has not been sufficiently examined. Key Messages: Factors that impede or alter brain growth during early life could render certain brain regions or networks selectively vulnerable to the onset, accumulation or spread of AD-related pathology during later life. Careful life-course epidemiology could provide clues as to why the brain systematically degenerates during AD.