An effort to mitigate the cumbersome physiological, cognitive, and psychological changes that naturally occur during the menopausal transition has been ongoing for decades. Discrepant findings of symptom presentation and mediation across translational models and among human studies have perplexed researchers for years. Specifically, as an understanding of the role of estrogenic signaling in processes underlying cognition and emotion regulation evolved, researchers speculated that exogenous hormonal therapy might modify disease/symptom onset and course. This chapter describes the variable methodological approaches that likely led to disparities in the literature around hormone therapy use, particularly as it pertains to manipulating symptom onset and course of Alzheimer’s pathology. The authors expound upon current recommendations for exogenous hormone therapy use in aging women and how researchers arrived at these conclusions. Finally, we describe remaining questions regarding hormone therapy use and its long-term impact on cognition and mood, Alzheimer’s disease biomarkers, vascular functioning, and genomic variables.
Longitudinal plasma Alzheimer’s disease biomarkers in an Alzheimer’s disease research center cohort suggest pTau181 as the most reliable plasma biomarker for brain Alzheimer’s pathology
