Task-Based Activation and Hippocampal Functional Connectivity Supporting Verbal Memory in Midlife Women

Women show declines in verbal memory across the menopause transition that often persist into the postmenopause; however, the underlying neural circuitry that supports performance on validated, sensitive tests of verbal memory in midlife postmenopausal women remains uncharacterized. The goal of this thesis was to identify patterns of brain activation and hippocampal functional connectivity associated with successful verbal memory abilities in midlife women. A sample of cognitively normal midlife postmenopausal women (n = 171, mean age = 59.3 years, mean education = 15.7 years, 87.7% white) from the MsBrain I study at the University of Pittsburgh completed the California Verbal Learning Test (CVLT) and a functional magnetic resonance imaging task of verbal encoding and recognition. Associations between verbal memory measures (CVLT measures [learning, short- and long-delay recall, semantic clustering] and in-scanner recognition accuracy) and eigenvariates of regional brain activation and hippocampal functional connectivity during verbal encoding were tested via linear regression. Models controlled for age, education, and race. During verbal encoding, greater activation of bilateral prefrontal and medial temporal regions, as well as precuneus, cuneus, caudate, and cerebellar regions, was associated with better performance on all CVLT measures. Functional connectivity between bilateral hippocampi and prefrontal regions during verbal encoding also associated with better CVLT performance. In-scanner recognition accuracy was more strongly positively associated with activation of parietal and occipital regions, and with right hippocampal functional connectivity to parietal and temporal areas. These findings demonstrate the typical patterns of brain activation and hippocampal functional connectivity supporting verbal memory performance in midlife women. Our understanding of the effects of hormonal changes and menopausal symptoms (e.g., vasomotor symptoms, sleep and mood disturbances) on cognition relies upon this foundational knowledge. Furthermore, efforts to address menopause-related cognitive difficulties should target these key regions in order to sustain women’s memory abilities at midlife.