Hormone replacement therapy and incidence of Alzheimer disease in older women: the cache county study.
JAMA 2002 Nov 6;288(17):2123-9. 2002 Nov;288(17):2123-9.
CONTEXT: Previous studies have shown a sex-specific increased risk of Alzheimer disease (AD) in women older than 80 years. Basic neuroscience findings suggest that hormone replacement therapy (HRT) could reduce a woman's risk of AD. Epidemiologic findings on AD and HRT are mixed. OBJECTIVE: To examine the relationship between use of HRT and risk of AD among elderly women. DESIGN, SETTING, AND PARTICIPANTS: Prospective study of incident dementia among 1,357 men (mean age, 73.2 years) and 1,889 women (mean age, 74.5 years) residing in a single county in Utah. Participants were first assessed in 1995-1997, with follow-up conducted in 1998-2000. History of women's current and former use of HRT, as well as of calcium and multivitamin supplements, was ascertained at the initial contact. MAIN OUTCOME MEASURE: Diagnosis of incident AD. RESULTS: Thirty-five men (2.6 percent) and 88 women (4.7 percent) developed AD between the initial interview and time of the follow-up (three years). Incidence among women increased after age 80 years and exceeded the risk among men of similar age (adjusted hazard ratio [HR], 2.11; 95 percent confidence interval [CI], 1.22-3.86). Women who used HRT had a reduced risk of AD (26 cases among 1,066 women) compared to non-HRT users (58 cases among 800 women) (adjusted HR, 0.59; 95 percent CI, 0.36-0.96). Risk varied with duration of HRT use, so that a woman's sex-specific increase in risk disappeared entirely with more than 10 years of treatment (seven cases among 427 women). Adjusted HRs were 0.41 (95 percent CI, 0.17-0.86) for HRT users compared to nonusers and 0.77 (95 percent CI, 0.31-1.67) compared with men. No similar effect was seen with calcium or multivitamin use. Almost all of the HRT-related reduction in incidence reflected former use of HRT (nine cases among 490 women; adjusted HR, 0.33 [95 percent CI, 0.15-0.65]). There was no effect with current HRT use (17 cases among 576 women; adjusted HR, 1.08 [95 percent CI, 0.59-1.91]) unless duration of treatment exceeded 10 years (six cases among 344 women; adjusted HR, 0.55 [95 percent CI, 0.21-1.23]). CONCLUSIONS: Prior HRT use is associated with reduced risk of AD, but there is no apparent benefit with current HRT use unless such use has exceeded 10 years.