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October 24, 2012Article

Hormone therapy and Alzheimer disease dementia

New findings from the Cache County Study

Huibo Shao, John C.S. Breitner, Rachel A. Whitmer, Junmin Wang, Kathleen Hayden, Heidi Wengreen, Chris Corcoran, JoAnn Tschanz, Maria Norton, Ron Munger, Kathleen Welsh-Bohmer, Peter P. Zandi
First published October 24, 2012, DOI: https://doi.org/10.1212/WNL.0b013e318271f823
Huibo Shao
From the Department of Public Health (H.S.), Weill Cornell Medical College, New York, NY; Department of Psychiatry (J.C.S.B.), McGill University Faculty of Medicine, Montreal, Canada; Division of Research (R.A.W.), Kaiser Permanente Northern California, Oakland; Department of Sociology (J.W.), University of Memphis, Memphis, TN; Department of Psychiatry and Behavioral Sciences (K.H., K.W.-B.), Duke University School of Medicine, Durham, NC; Departments of Nutrition and Food Sciences (H.W.), Mathematics and Statistics (C.C.), Psychology (J.T.), and Family Consumer & Human Development (M.N.), and Center for Epidemiologic Studies (C.C., J.T., M.N., R.M.), Utah State University, Logan; and Department of Mental Health (P.P.Z.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
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John C.S. Breitner
From the Department of Public Health (H.S.), Weill Cornell Medical College, New York, NY; Department of Psychiatry (J.C.S.B.), McGill University Faculty of Medicine, Montreal, Canada; Division of Research (R.A.W.), Kaiser Permanente Northern California, Oakland; Department of Sociology (J.W.), University of Memphis, Memphis, TN; Department of Psychiatry and Behavioral Sciences (K.H., K.W.-B.), Duke University School of Medicine, Durham, NC; Departments of Nutrition and Food Sciences (H.W.), Mathematics and Statistics (C.C.), Psychology (J.T.), and Family Consumer & Human Development (M.N.), and Center for Epidemiologic Studies (C.C., J.T., M.N., R.M.), Utah State University, Logan; and Department of Mental Health (P.P.Z.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
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Rachel A. Whitmer
From the Department of Public Health (H.S.), Weill Cornell Medical College, New York, NY; Department of Psychiatry (J.C.S.B.), McGill University Faculty of Medicine, Montreal, Canada; Division of Research (R.A.W.), Kaiser Permanente Northern California, Oakland; Department of Sociology (J.W.), University of Memphis, Memphis, TN; Department of Psychiatry and Behavioral Sciences (K.H., K.W.-B.), Duke University School of Medicine, Durham, NC; Departments of Nutrition and Food Sciences (H.W.), Mathematics and Statistics (C.C.), Psychology (J.T.), and Family Consumer & Human Development (M.N.), and Center for Epidemiologic Studies (C.C., J.T., M.N., R.M.), Utah State University, Logan; and Department of Mental Health (P.P.Z.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
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Junmin Wang
From the Department of Public Health (H.S.), Weill Cornell Medical College, New York, NY; Department of Psychiatry (J.C.S.B.), McGill University Faculty of Medicine, Montreal, Canada; Division of Research (R.A.W.), Kaiser Permanente Northern California, Oakland; Department of Sociology (J.W.), University of Memphis, Memphis, TN; Department of Psychiatry and Behavioral Sciences (K.H., K.W.-B.), Duke University School of Medicine, Durham, NC; Departments of Nutrition and Food Sciences (H.W.), Mathematics and Statistics (C.C.), Psychology (J.T.), and Family Consumer & Human Development (M.N.), and Center for Epidemiologic Studies (C.C., J.T., M.N., R.M.), Utah State University, Logan; and Department of Mental Health (P.P.Z.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
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Kathleen Hayden
From the Department of Public Health (H.S.), Weill Cornell Medical College, New York, NY; Department of Psychiatry (J.C.S.B.), McGill University Faculty of Medicine, Montreal, Canada; Division of Research (R.A.W.), Kaiser Permanente Northern California, Oakland; Department of Sociology (J.W.), University of Memphis, Memphis, TN; Department of Psychiatry and Behavioral Sciences (K.H., K.W.-B.), Duke University School of Medicine, Durham, NC; Departments of Nutrition and Food Sciences (H.W.), Mathematics and Statistics (C.C.), Psychology (J.T.), and Family Consumer & Human Development (M.N.), and Center for Epidemiologic Studies (C.C., J.T., M.N., R.M.), Utah State University, Logan; and Department of Mental Health (P.P.Z.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
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Heidi Wengreen
From the Department of Public Health (H.S.), Weill Cornell Medical College, New York, NY; Department of Psychiatry (J.C.S.B.), McGill University Faculty of Medicine, Montreal, Canada; Division of Research (R.A.W.), Kaiser Permanente Northern California, Oakland; Department of Sociology (J.W.), University of Memphis, Memphis, TN; Department of Psychiatry and Behavioral Sciences (K.H., K.W.-B.), Duke University School of Medicine, Durham, NC; Departments of Nutrition and Food Sciences (H.W.), Mathematics and Statistics (C.C.), Psychology (J.T.), and Family Consumer & Human Development (M.N.), and Center for Epidemiologic Studies (C.C., J.T., M.N., R.M.), Utah State University, Logan; and Department of Mental Health (P.P.Z.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
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Chris Corcoran
From the Department of Public Health (H.S.), Weill Cornell Medical College, New York, NY; Department of Psychiatry (J.C.S.B.), McGill University Faculty of Medicine, Montreal, Canada; Division of Research (R.A.W.), Kaiser Permanente Northern California, Oakland; Department of Sociology (J.W.), University of Memphis, Memphis, TN; Department of Psychiatry and Behavioral Sciences (K.H., K.W.-B.), Duke University School of Medicine, Durham, NC; Departments of Nutrition and Food Sciences (H.W.), Mathematics and Statistics (C.C.), Psychology (J.T.), and Family Consumer & Human Development (M.N.), and Center for Epidemiologic Studies (C.C., J.T., M.N., R.M.), Utah State University, Logan; and Department of Mental Health (P.P.Z.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
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JoAnn Tschanz
From the Department of Public Health (H.S.), Weill Cornell Medical College, New York, NY; Department of Psychiatry (J.C.S.B.), McGill University Faculty of Medicine, Montreal, Canada; Division of Research (R.A.W.), Kaiser Permanente Northern California, Oakland; Department of Sociology (J.W.), University of Memphis, Memphis, TN; Department of Psychiatry and Behavioral Sciences (K.H., K.W.-B.), Duke University School of Medicine, Durham, NC; Departments of Nutrition and Food Sciences (H.W.), Mathematics and Statistics (C.C.), Psychology (J.T.), and Family Consumer & Human Development (M.N.), and Center for Epidemiologic Studies (C.C., J.T., M.N., R.M.), Utah State University, Logan; and Department of Mental Health (P.P.Z.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
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Maria Norton
From the Department of Public Health (H.S.), Weill Cornell Medical College, New York, NY; Department of Psychiatry (J.C.S.B.), McGill University Faculty of Medicine, Montreal, Canada; Division of Research (R.A.W.), Kaiser Permanente Northern California, Oakland; Department of Sociology (J.W.), University of Memphis, Memphis, TN; Department of Psychiatry and Behavioral Sciences (K.H., K.W.-B.), Duke University School of Medicine, Durham, NC; Departments of Nutrition and Food Sciences (H.W.), Mathematics and Statistics (C.C.), Psychology (J.T.), and Family Consumer & Human Development (M.N.), and Center for Epidemiologic Studies (C.C., J.T., M.N., R.M.), Utah State University, Logan; and Department of Mental Health (P.P.Z.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
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Ron Munger
From the Department of Public Health (H.S.), Weill Cornell Medical College, New York, NY; Department of Psychiatry (J.C.S.B.), McGill University Faculty of Medicine, Montreal, Canada; Division of Research (R.A.W.), Kaiser Permanente Northern California, Oakland; Department of Sociology (J.W.), University of Memphis, Memphis, TN; Department of Psychiatry and Behavioral Sciences (K.H., K.W.-B.), Duke University School of Medicine, Durham, NC; Departments of Nutrition and Food Sciences (H.W.), Mathematics and Statistics (C.C.), Psychology (J.T.), and Family Consumer & Human Development (M.N.), and Center for Epidemiologic Studies (C.C., J.T., M.N., R.M.), Utah State University, Logan; and Department of Mental Health (P.P.Z.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
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Kathleen Welsh-Bohmer
From the Department of Public Health (H.S.), Weill Cornell Medical College, New York, NY; Department of Psychiatry (J.C.S.B.), McGill University Faculty of Medicine, Montreal, Canada; Division of Research (R.A.W.), Kaiser Permanente Northern California, Oakland; Department of Sociology (J.W.), University of Memphis, Memphis, TN; Department of Psychiatry and Behavioral Sciences (K.H., K.W.-B.), Duke University School of Medicine, Durham, NC; Departments of Nutrition and Food Sciences (H.W.), Mathematics and Statistics (C.C.), Psychology (J.T.), and Family Consumer & Human Development (M.N.), and Center for Epidemiologic Studies (C.C., J.T., M.N., R.M.), Utah State University, Logan; and Department of Mental Health (P.P.Z.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
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Peter P. Zandi
From the Department of Public Health (H.S.), Weill Cornell Medical College, New York, NY; Department of Psychiatry (J.C.S.B.), McGill University Faculty of Medicine, Montreal, Canada; Division of Research (R.A.W.), Kaiser Permanente Northern California, Oakland; Department of Sociology (J.W.), University of Memphis, Memphis, TN; Department of Psychiatry and Behavioral Sciences (K.H., K.W.-B.), Duke University School of Medicine, Durham, NC; Departments of Nutrition and Food Sciences (H.W.), Mathematics and Statistics (C.C.), Psychology (J.T.), and Family Consumer & Human Development (M.N.), and Center for Epidemiologic Studies (C.C., J.T., M.N., R.M.), Utah State University, Logan; and Department of Mental Health (P.P.Z.), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
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Full PDF
Citation
Hormone therapy and Alzheimer disease dementia
New findings from the Cache County Study
Huibo Shao, John C.S. Breitner, Rachel A. Whitmer, Junmin Wang, Kathleen Hayden, Heidi Wengreen, Chris Corcoran, JoAnn Tschanz, Maria Norton, Ron Munger, Kathleen Welsh-Bohmer, Peter P. Zandi
Neurology Oct 2012, WNL.0b013e318271f823; DOI: 10.1212/WNL.0b013e318271f823

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Abstract

Objectives: Observational studies suggest reduced risk of Alzheimer disease (AD) in users of hormone therapy (HT), but trials show higher risk. We examined whether the association of HT with AD varies with timing or type of HT use.

Methods: Between 1995 and 2006, the population-based Cache County Study followed 1,768 women who had provided a detailed history on age at menopause and use of HT. During this interval, 176 women developed incident AD. Cox proportional hazard models evaluated the association of HT use with AD, overall and in relation to timing, duration of use, and type (opposed vs unopposed) of HT.

Results: Women who used any type of HT within 5 years of menopause had 30% less risk of AD (95% confidence interval 0.49–0.99), especially if use was for 10 or more years. By contrast, AD risk was not reduced among those who had initiated HT 5 or more years after menopause. Instead, rates were increased among those who began “opposed” estrogen-progestin compounds within the 3 years preceding the Cache County Study baseline (adjusted hazard ratio 1.93; 95% confidence interval 0.94–3.96). This last hazard ratio was similar to the ratio of 2.05 reported in randomized trial participants assigned to opposed HT.

Conclusions: Association of HT use and risk of AD may depend on timing of use. Although possibly beneficial if taken during a critical window near menopause, HT (especially opposed compounds) initiated in later life may be associated with increased risk. The relation of AD risk to timing and type of HT deserves further study.

  • Received February 22, 2012.
  • Accepted June 11, 2012.
  • Copyright © 2012 by AAN Enterprises, Inc.

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