The proposed pilot investigation is in response to the call for projects on the """"""""health-related consequences of female reproductive aging."""""""" Cognitive complaints are common, but not ubiquitous during menopause, and it is not known why some women experience cognitive symptoms while others do not. For example, cognitive symptoms may be related to declining estrogen levels or secondary to other menopause-related symptoms, such as hot flushes, fatigue, depression, or anxiety. Recent evidence of gender-specific effects of APOE genotype on memory ability suggests the possibility that APOE may moderate the effects of declining estrogen levels on mnemonic function. The optimal way to examine changes in cognitive functioning associated with menopause would be to prospectively follow a cohort of women from early perimenopause through the menopausal transition, thereby detecting symptoms as they evolve, and permitting the identification of biological and psychological correlates. The proposed pilot study will establish the framework for such a study by identifying the cognitive domains affected during menopause, examining the relationships between cognitive function and estrogen levels, and exploring the relationship between APOE genotype, estrogen, and cognition in a cross-sectional sample of peri- and postmenopausal women. One-hundred healthy peri- and postmenopausal women will be recruited from health care settings. Participants will receive a detailed neuropsychological examination, complete self-report ratings of mood and severity of menopausal symptoms, and have blood drawn to determine estrogen levels and APOE genotype. Women receiving hormone replacement therapy and those experiencing surgical menopause will be excluded. The proposed analyses will (1) establish the specific cognitive abilities that are affected during menopause; (2) examine the relationship between cognitive functioning and circulating estrogen levels, and explore the interaction between estrogen levels and APOE genotype; and (3) examine the relationship of cognitive functioning to other menopausal and mood symptoms. Results from this pilot study will be used as the basis for an R01 application to prospectively investigate cognitive function through the menopausal transition.
