Basic and clinical research on sex steroids, ageing, and cognition to integrate existing findings with emerging data.

D., University of Southern California--Julie A. Dumas "Sex Roles"

In this systematic evidence review, we evaluate data on the use of hormone replacement therapy (HRT) to prevent cognitive decline and dementia in healthy postmenopausal women. Specifically, we reviewed the literature reporting effects of HRT on cognitive function in women without dementia. In addition, we conducted a review and meta-analysis of studies of HRT and dementia, focusing on Alzheimer disease. Results of this review have been recently published. This report is part of a larger project on the risks and benefits of HRT prepared for the U.S. Preventive Services Task Force to assist them in making recommendations. Between 3 and 8 million people in the United States have dementia. The most common type of dementia is Alzheimer disease, which affects 3 to 4 million people and is the fourth leading cause of death in the United States. The incidence of dementia is 1 percent per year in older individuals, although in the most elderly populations this rate may be as high as 2 to 3 percent. One community-based prevalence study in east Boston estimated that almost 50 percent of those aged 85 and over suffered from dementia. Most studies report that after accounting for differences in life expectancy, women have a 1.4 to 3-fold higher risk of Alzheimer disease than men. The life expectancy of demented patients is greatly reduced. Those with early-onset (before age 60) Alzheimer disease have a median survival of 6.7 to 8.1 years, while survival in those with late-onset disease is 4.8 to 6.0 years. In 1991, the annual cost of Alzheimer disease was estimated to be $67.3 billion. Given the expected growth of the elderly population, this financial cost, as well as the emotional and physical costs of caring for demented patients, will continue to increase. Observational data suggest a possible but inconsistent relationship between endogenous estrogen exposure and cognition. Women in the high estrogen phase of the menstrual cycle have been shown to perform better on tests of motor skills compared to when they are in the low estrogen phase of the cycle. Bone mineral density, hypothesized to be a marker of cumulative estrogen exposure, has been correlated with risk of cognitive deterioration. Because of the association between endogenous estrogen exposure and cognition, it can be hypothesized that hormone replacement therapy (HRT) after menopause may prevent cognitive decline and the development of dementia.

Hormone replacement therapy (HRT) has been studied as a protective factor for cognitive decline and dementia. However, study findings have been inconsistent. Variation in study findings may be due to differences in study designs, small sample size, exposure ascertainment, diagnostic procedures, and inclusion of relevant risk and confounding factors. Moreover, there may be significant differences between the characteristics of women choosing to use HRT and those opting not to use the therapy. Using a large-scale, population-based, cohort study, we examined the relationship between HRT and cognition while paying particular attention to moderating and confounding factors. The main outcomes of interest were to assess differences in risk for cognitive impairments and dementia between HRT user and never user groups; examine HRTs impact on age of onset of dementia; and explore the relationship between duration of HRT and cognitive decline. Logistic regression and Cox Proportional Hazards models were used to test HRT as a predictor for cognitive impairments, Alzheimers disease and vascular dementia, as well as to assess the effect of duration. Linear regression was used to consider the putative relationship between age at onset of dementia and HRT status. HRT use was found to be a statistically significant predictor for Alzheimers disease and vascular dementia. Overall, HRT use did not significantly predict for milder cognitive impairments, although significant interaction effects indicate that HRT may be protective at least for specific sub-groups of women. No durational effect was found for any of the outcomes. Neither did HRT appear to predict for age at onset of dementia. Notably, a large proportion of women in the current study reported using estrogen-only hormone supplements, and therefore generalizations regarding the findings are likely limited to estrogen-only preparations, not combination estrogen-progestin therapies. These findings must be considered within the c.