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Zandi PP, Carlson MC, Plassman BL, et al. Hormone Replacement Therapy and Incidence of Alzheimer Disease in Older Women: The Cache County Study. JAMA. 2002;288(17):2123–2129. doi:10.1001/jama.288.17.2123
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).
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
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.
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