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

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.

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

CONTEXT: Although postmenopausal hormone replacement (HRT) therapy is widely used, its risks and benefits are not well understood. Some observational data suggest that HRT may reduce the risk of cognitive decline and dementia but results have been conflicting. OBJECTIVE: To review and evaluate studies of HRT for preventing cognitive decline and dementia in healthy postmenopausal women. DATA SOURCES: Studies with English-language abstracts identified in MEDLINE (1966-December 2000), HealthSTAR (1975-December 2000), PsychINFO (1984-December 2000); Cochrane Library databases; and articles listed in reference lists of key articles. STUDY SELECTION: Randomized controlled trials and cohort studies were reviewed for the effects of HRT on cognitive decline; cohort and case-control studies were reviewed for dementia risk. No randomized controlled trials regarding dementia risk were identified. DATA EXTRACTION: Twenty-nine studies met inclusion criteria and were rated. Two reviewers rated study quality independently and 100% agreement was reached on Jadad scores and 80% agreement was reached on U.S. Preventive Services Task Force quality scores. A final score was reached through consensus if reviewers disagreed. DATA SYNTHESIS: Studies of cognition were not combined quantitatively because of heterogeneous study design. Women symptomatic from menopause had improvements in verbal memory, vigilance, reasoning, and motor speed, but no enhancement of other cognitive functions. Generally, no benefits were observed in asymptomatic women. A Bayesian meta-analysis of 12 observational studies suggested that HRT was associated with a decreased risk of dementia (summary odds ratio, 0.66; 95% confidence interval, 0.53-0.82). However, possible biases and lack of control for potential confounders limit interpretation of these studies. Eight studies received a poor quality rating, 3 fair, and 1 good. Studies did not contain enough information to assess adequately the effects of progestin use, various estrogen preparations or doses, or duration of therapy. CONCLUSIONS: In women with menopausal symptoms, HRT may have specific cognitive effects, and future studies should target these effects. The meta-analysis found a decreased risk of dementia in HRT users but most studies had important methodological limitations.

Written by an acknowledged leader in the field, this is a vital clinical reference on the influence of estrogen replacement therapy on Alzheimer's disease, visual dementia, stroke, disorders of movement, epilepsy, migraine headache, and multiple sclerosis. It opens with introductory information and an overview of estrogen and the brain and with coverage of the mechanisms of estrogen action on the brain and the neuroprotective effects of estrogen. Two sections cover the effects of estrogen replacement therapy on mood behavior and cognition and a major section focuses on Alzheimer's disease and other dementias. Another key section covers other neurological disorders, including stroke prevention after menopause, stroke protection in men, neuroprotection after stroke, movement disorders, epilepsy, migraine headache, and multiple sclerosis. Includes color illustrations, bibliographic references and index.