Neurobiology of the Menopausal Transition

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DESCRIPTION (provided by applicant): The menopausal transition is an important life process, significantly impacting the cognitive and psychological health of women. Postmenopausal neuroimaging studies of hormone therapy indicate that estrogen levels have significant effects on brain neural circuitry. However, mechanistic studies of the neurobiology of the menopausal transition are lacking. This proposal combines the rich historical data from and access to a uniquely well-characterized population of women, transitioning the menopause, with neuropsychological testing and state-of-the-art neuroimaging techniques, to characterize the neurobiology of the menopausal transition. To test hypotheses concerning mechanisms of menopausal cognitive and affective changes, we will recruit from a well-characterized population of women at the mid-life who have been participants in a bone health and metabolism study involving extensive hormone and cycle monitoring since 1992. Recruits will be women aged 40-55 years, stratified into panels representing premenopause, early perimenopause, late perimenopause and natural postmenopause defined by follicle-stimulating hormone levels and menstrual bleeding patterns. This collaboration will involve extensive neuropsychological testing combined with a validated functional magnetic resonance (fMRI) imaging paradigm to determine brain activation patterns during cognitive and emotional tasks among women of each panel. The Specific Aims include: 1. Identify if specific stages or characteristics of the menopausal transition are associated with alterations in brain functioning as manifested either by fMRI-BOLD activation during cognitive and emotional tasks or by neuropsychological testing. 2. Delineate the relative contribution of ovarian aging vs. chronological aging in brain functioning as manifested either by fMRI-BOLD activation during cognitive and emotional tasks or by neuropsychological testing. 3. Demonstrate whether cognitive processing changes noted on fMRI-BOLD precede, occur concurrent, or follow observable changes in neuropsychological testing. These studies will determine the contributions of hormones and aging to changes in cognitive and emotional processing. A better understanding of the areas and sequence of brain processing changes will allow the health community to plan interventions which most effectively preserve cognitive and emotional health for women.