Patterns of Brain Activation and Hippocampal Functional Connectivity Supporting Verbal Memory in Midlife Women

Women show declines in verbal memory across the menopause transition that may persist into the postmenopause. The goal of the present study was to characterize the patterns of brain activity and hippocampal functional connectivity that support verbal memory performance in midlife postmenopausal women. The study sample included 171 midlife postmenopausal women from the MsBrain I study (mean age = 59.3 years, mean education= 15.7 years, 87.7% white). All participants were cognitively normal, native English speakers, not taking menopausal hormone therapy. Participants completed neuropsychological (California Verbal Learning Test [CVLT]) and neuroimaging assessments, including an fMRI task of verbal encoding and recognition. Findings indicated that during verbal encoding, greater activation of bilateral prefrontal and medial temporal regions, as well as the precuneus, cuneus, caudate, and cerebellar regions, was associated with better performance on CVLT measures, including learning, short- and long-delay recall, and semantic clustering. Functional connectivity from both hippocampi to primarily right prefrontal regions during verbal encoding associated with better CVLT performance. In-scanner word recognition accuracy was more strongly associated with activation of parietal and occipital regions, and with functional connectivity between the right hippocampus and bilateral parietal and temporal regions. Our findings characterize the patterns underlying verbal memory abilities in midlife postmenopausal women. The patterns identified here may act as a foundation for better interpreting the effects of hormonal changes and menopausal symptoms on cognition at midlife, and for identifying neural targets for pharmacological and lifestyle interventions aimed at sustaining women's memory function.