Patterns of brain activation and hippocampal functional connectivity associated with verbal memory in midlife postmenopausal women

OBJECTIVE: A range of factors may impact cognitive and brain health in postmenopausal women, yet the underlying neural circuitry supporting memory abilities in this population remains unclear. This study characterized normative patterns of brain activation and hippocampal functional connectivity associated with verbal memory performance in cognitively normal, midlife postmenopausal women. METHODS: In the MsBrain I cohort (N = 171, mean age = 59.3 years, mean education = 15.7 years, 87.7% white), participants completed neuropsychological (California Verbal Learning Test) and neuroimaging assessments, including a functional magnetic resonance imaging task of verbal encoding and recognition. We evaluated the associations of verbal memory measures with regional activation and hippocampal functional connectivity during verbal encoding. RESULTS: 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 the California Verbal Learning Test. Functional connectivity from both hippocampi to primarily right prefrontal regions during verbal encoding was also associated with better California Verbal Learning Test performance. In-scanner experimental 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. CONCLUSIONS: Our findings characterize the normative patterns associated with verbal memory abilities in midlife postmenopausal women. The patterns identified here may act as a foundation for better interpreting the effects of risk and resiliency factors on cognition at midlife, and for informing future interventions aimed at sustaining women's memory function.