Dr. Pauline Maki (Department of Psychiatry)

Dr. Leon Tai (Department of Anatomy and Cell Biology)

In the US, 4.1 million women aged 65 or older are living with Alzheimer’s disease (AD) dementia. Under standing risk and protective factors for AD in women is critical as women comprise two-thirds of those living with AD. We must also address sex differences in disease pathology, especially early in the course of disease and recognize the potential variations in pathogenesis. Attempts to identify factors contributing to sex differences in AD have pointed to midlife changes in sex steroid hormones, namely estrogens, during the menopause transi tion. Surprisingly little is known about the brain changes that occur in women in association with changes in estrogen. To address that gap, I have a growing body of innovative research studies showing estrogen-related changes in brain functional connectivity during memory tasks. Broadly, the data shows that estrogens are asso ciated with differences in brain connectivity, particularly in the hippocampus, a brain area critical in AD patho genesis. Importantly, these differences are related to memory performance in midlife women. I propose to extend this work to resting state functional connectivity, and to the field of AD by examining APOE4 carrier status and blood-based AD biomarkers. My research goal is to examine the associations of endogenous estradiol levels with hippocampal functional connectivity during resting state, and to determine the role of APOE4 carrier status, tau, and amyloid-beta levels in those associations. My training goals align with my research goals and focus on neuroimaging techniques; estrogens, cognitive aging, and AD biomarkers; and development of an F32 Post doctoral training grant application.