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.

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.

This timely volume reviews current data on the effects of estrogen on the central nervous system, highlighting clinical aspects of this topic. Experts from the fields of psychiatry, pharmacology, neurology, and geriatrics collaborate to clarify the known risks and benefits of hormone therapy and explore questions that remain to be elucidated. Among the topics discussed: " Preclinical data on estrogen's effects on cognitive performance " The short-lived effects of hormone replacement therapy on cognitive function " Structural and functional brain imaging data regarding estrogen's effects on the central nervous system " Preclinical efforts to develop effective NeuroSERMs for the brain " The effects of estrogen on mood Citing the ongoing confusion over the risks and benefits of estrogen therapy, the contributors emphasize the need for additional research on medication, doses, preparations, methods of administration, alternative therapies, and supplements. This volume educates researchers, clinicians, and students on the current knowledge—including the effects of estrogen on mood, cognition, and brain metabolism—and provides guidelines for clinical practice and future research. Contributors: Roberta Diaz Brinton, Ph.D., University of Southern California; Cheri L. Geist, B.A., David Geffen School of Medicine, University of California at Los Angeles; Robert B. Gibbs, Ph.D., University of Pittsburgh School of Pharmacy; Eva Hogervorst, Ph.D., University of Loughborough and University of Oxford; Pauline M. Maki, Ph.D., Neuropsychiatric Institute, University of Illinois–Chicago; Peter J. Schmidt, M.D., National Institute of Mental Health; Daniel H. S. Silverman, M.D., Ph.D., David Geffen School of Medicine, University of California at Los Angeles; Katherine E. Williams, M.D., Stanford University School of Medicine; Kristine Yaffe, M.D., University of California, San Francisco, and San Francisco VA Medical Center; Laurel N. Zappert, B.A., Stanford University School of Medicine; Liqin Zhao, Ph.D., University of Southern California

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.