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.

Alzheimer’s Disease: Dawn of a New Era?

“…While Apo E4 is the top gene associated with late onset-AD gene, other genes that may modulate the risk of late-onset AD include CLU, CR1, PICALM, BIN1, SORL1, GAB2, ABCA7, MS4A4/MS4A6E, CD2AP, CD33, APHA1, and HLA-DRB1/5. Other risk factors for AD include head trauma, female gender, learning disabilities, education level, homocysteine levels, socioeconomic status, and previous depression (12). Importantly, vascular risk factors including diabetes and hyperlipidemia are additional risk factors for AD (13,14).…”

“…At the cellular level, AD is characterized by a progressive loss of cortical neurons most notable in the entorhinal cortex, hippocampus and posterior cingulate cortex (12). The neuronal damage is believed to be related to the deposition of abnormal proteins, which are the hallmark pathological lesions of AD known as the "plaques", found in the extracellular space, and "tangles", inside the cells.…”

Insights on the Early-Life Origins of Alzheimer's Disease: Relevance for Primary Prevention?

“…Yet consideration of early-life risk factors in AD is important, as an increasing number of studies suggest that many of the diseases of later life are associated with early-life risk factors. As Seifan et al [2] point out, exposure to adverse childhood events increases the risk of heart disease, stroke and diabetes. Loss of a parent has also been associated with risk of cancer before 40 years of age [5] .…”

“…Thus, the review of the 'early-life epidemiology' of AD by Seifan et al [2] is welcome. If the factors identified in this review are truly relevant to risk of AD, it may be possible to expand candidates for secondary prevention and even think about 'lifespan primary prevention', that is, interventions designed for entire populations offered early in life.In a careful retrieval and review of nearly 35 years of research, Seifan et al [2] identified 43 papers that examined early-life factors …”

“…Identifying these early-life risk factors may suggest new prevention targets. Thus, the review of the 'early-life epidemiology' of AD by Seifan et al [2] is welcome. If the factors identified in this review are truly relevant to risk of AD, it may be possible to expand candidates for secondary prevention and even think about 'lifespan primary prevention', that is, interventions designed for entire populations offered early in life.…”