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The Cache County Study

Peter P. Zandi, PhD; Michelle C. Carlson, PhD; Brenda L. Plassman, PhD; Kathleen A. Welsh-Bohmer, PhD; Lawrence S. Mayer, MD; David C. Steffens, MD; John C. S. Breitner, MD; for the Cache County Memory Study Investigators

JAMA. 2002;288:2123-2129.

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 1357 men (mean age, 73.2 years) and 1889 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%) and 88 women (4.7%) developed AD between the initial interview and time of the follow-up (3 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% confidence interval [CI], 1.22-3.86). Women who used HRT had a reduced risk of AD (26 cases among 1066 women) compared with non-HRT users (58 cases among 800 women) (adjusted HR, 0.59; 95% 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 (7 cases among 427 women). Adjusted HRs were 0.41 (95% CI, 0.17-0.86) for HRT users compared with nonusers and 0.77 (95% 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 (9 cases among 490 women; adjusted HR, 0.33 [95% CI, 0.15-0.65]). There was no effect with current HRT use (17 cases among 576 women; adjusted HR, 1.08 [95% CI, 0.59-1.91]) unless duration of treatment exceeded 10 years (6 cases among 344 women; adjusted HR, 0.55 [95% 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.

Author Affiliations: Department of Mental Hygiene, School of Hygiene and Public Health, the Johns Hopkins University, Baltimore, Md (Drs Zandi, Carlson, Mayer, and Breitner); Department of Psychiatry and Behavioral Sciences (Drs Plassman, Welsh-Bohmer, and Steffens), and The Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC (Dr Welsh-Bohmer); Banner Health System, Phoenix, Ariz (Dr Mayer); and VA Puget Sound Health Care System and Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle (Dr Breitner).

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