•
•
•
•
My group investigates the effects of sex and sex hormones as modifiers of cognitive and brain aging. Through our neuroimaging study of elderly participants in the Baltimore Longitudinal Study of Aging (BLSA), we study brain and cognitive changes as early predictors of cognitive impairment and whether sex and sex hormones modify those changes. Based on observational findings from our BLSA studies, we initiated an ancillary study of cognitive change in participants enrolled in the randomized hormone therapy trials of the Women’s Health Initiative (WHI) and the WHI Memory Study (WHIMS). The Women's Health Initiative Study of Cognitive Aging (WHISCA) enrolled 2,302 women aged 66 to 84 years (mean 73.9; standard deviation 3.8) who did not meet criteria for dementia. Women were randomly assigned by the WHI to hormone treatment (unopposed conjugated estrogens (CEE) 0.625 mg/day if they were without a uterus; CEE combined with medroxyprogesterone acetate (MPA) 2.5 mg/day otherwise) or placebo for an average of 3 years before the first WHISCA assessment. WHISCA investigated the effects of hormone therapy on rates of change over time in memory, other aspects of cognition (language, attention, spatial ability), motor function, and mood. Although study medications in the WHI hormone therapy trials have been terminated, follow-up assessments of participants continue in WHI, WHIMS, and WHISCA. Through the interface between these studies, a wealth of information is available to address important questions regarding predictors of age-related changes in specific cognitive functions using data from more than 10,000 evaluations performed through WHISCA. In addition, cross-sectional structural MRI data delineating vascular and atrophic findings will be available through the WHIMS-MRI study (including about 1100 WHISCA participants) to investigate the potential mechanisms underlying variability in cognitive change over time. Given the unexpected WHIMS findings that postmenopausal hormone therapy in older women increased the risk for probable dementia and global cognitive decline, we will investigate whether deleterious effects of hormone therapy on specific aspects of cognitive function are mediated through vascular insults (infarcts and white matter abnormalities). Further, we hypothesize that these deleterious effects on cognition will not be observed in women who do not have vascular abnormalities. We will also test the hypothesis that there may be modest benefits on specific cognitive functions and brain structure (measured by hippocampal and other regional volumes) in women without vascular or other brain abnormalities.
In addition to our WHISCA studies of the effects of hormone therapy on age-related changes in specific cognitive functions, we are conducting a parallel study of Cognition in the Study of Tamoxifen and Raloxifene (CO-STAR) through an ancillary study of more than 1400 women enrolled in the STAR trial (Study of Tamoxifen and Raloxifene), which compares the efficacy of these two selective estrogen receptor modulators in breast cancer prevention. Although the treatment status of participants remains blinded at the present time, data from this study can also be used to investigate predictors of cognitive change.
Through WHISCA and CO-STAR and the large databases of the parent studies, there is a wealth of existing longitudinal data on cognitive function available for a clinical fellow to address predictors of successful aging and cognitive impairment in older women. Findings from these studies will provide essential information that will contribute to the maintenance of women’s cognitive health in the post-reproductive years.
