AbstractIntroductionEnvironmental factors are poorly understood in the etiology of Alzheimer's disease (AD) and related dementias. The importance of environmental factors in gene environment interactions (GxE) is suggested by wide individual differences in cognitive loss, even for carriers of AD‐risk genetic variants.Results and DiscussionWe propose the “AD exposome” to comprehensively assess the modifiable environmental factors relevant to genetic underpinnings of cognitive aging and AD. Analysis of endogenous and exogenous environmental factors requires multi‐generational consideration of these interactions over age and time (GxExT). New computational approaches to the multi‐level complexities may identify accessible interventions for individual brain aging. International collaborations on diverse populations are needed to identify the most relevant exposures over the life course for GxE interactions.