Adolescent Alcohol and the Spectrum of Cognitive Dysfunction in Aging.

Among the many changes associated with aging, inflammation in the central nervous system (CNS) and throughout the body likely contributes to the constellation of health-related maladies associated with aging. Genetics, lifestyle factors, and environmental experiences shape the trajectory of aging-associated inflammation, including the developmental timing, frequency, and intensity of alcohol consumption. This chapter posits that neuroinflammatory processes form a critical link between alcohol exposure and the trajectory of healthy aging, at least in part through direct or indirect interactions with cholinergic circuits that are crucial to cognitive integrity. In this chapter, we begin with a discussion of how inflammation changes from early development through late aging; discuss the role of inflammation and alcohol in the emergence of mild cognitive impairment (MCI); elaborate on critical findings on the contribution of alcohol-related thiamine deficiency to the loss of cholinergic function and subsequent development of Wernicke-Korsakoff syndrome (WKS); and present emerging findings at the intersection of alcohol and Alzheimer's disease and related dementias (ADRD). In doing so, our analysis points toward inflammation-mediated compromise of basal forebrain cholinergic function as a key culprit in cognitive dysfunction associated with chronic alcohol exposure, effects that may be rescuable through either pharmacological or behavioral approaches. Furthermore, our chapter reveals an interesting dichotomy in the effects of alcohol on neuropathological markers of ADRD that depend upon both biological sex and genetic vulnerability.