Excessive Alcohol Use as a Risk Factor for Alzheimer's Disease: Epidemiological and Preclinical Evidence.

Abstract

Alcohol use has recently emerged as a modifiable risk factor for Alzheimer's disease (AD). However, the neurobiological mechanisms by which alcohol interacts with AD pathogenesis remain poorly understood. In this chapter, we review the epidemiological and preclinical support for the interaction between alcohol use and AD. We hypothesize that alcohol use increases the rate of accumulation of specific AD-relevant pathologies during the prodromal phase and exacerbates dementia onset and progression. We find that alcohol consumption rates are increasing in adolescence, middle age, and aging populations. In tandem, rates of AD are also on the rise, potentially as a result of this increased alcohol use throughout the lifespan. We then review the biological processes in common between alcohol use disorder and AD as a means to uncover potential mechanisms by which they interact; these include oxidative stress, neuroimmune function, metabolism, pathogenic tauopathy development and spread, and neuronal excitatory/inhibitory balance (EIB). Finally, we provide some forward-thinking suggestions we believe this field should consider. In particular, the inclusion of alcohol use assessments in longitudinal studies of AD and more preclinical studies on alcohol's impacts using better animal models of late-onset Alzheimer's disease (LOAD).