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Serum cholesterol and risk of Alzheimer disease

A community-based cohort study

From the Departments of Psychiatry and Behavioral Science (Drs. Li, Peskind, Tsuang, and Breitner, and J.B. Shofer), Epidemiology (Dr. Kukull), Medicine (Drs. McCormick and Larson), Neurology (Dr. Bowen), Psychosocial and Community Health (Dr. Teri), and Geriatrics and Gerontology (Dr. Schellenberg), University of Washington, Seattle; the Mental Illness Research and Education Clinical Center (Drs. Peskind and Tsuang) and Geriatric Research, Education and Clinical Center (Drs. Breitner and Schellenberg), Veterans Affairs Puget Sound Health Care System, Seattle; and the Center for Health Studies (Dr. Larson), Group Health Cooperative, Seattle, WA.

Address correspondence and reprint requests to Dr. Gail Li, VA Puget Sound Health Care System, 1660 S Columbian Way, Mailstop S-116 MIRECC, Seattle, WA 98108; e-mail: gli{at}u.washington.edu

Objectives: To examine the association of serum total cholesterol (TC) and high density lipoprotein (HDL) levels and subsequent incidence of dementia and Alzheimer disease (AD) in a population-based cohort study.

Methods: A cohort of cognitively intact persons, aged 65 and older, was randomly selected from Group Health Cooperative (GHC), a large health maintenance organization, and was assessed biennially for dementia. Premorbid levels of TC and HDL were obtained from a computerized clinical laboratory database at GHC. Cox proportional hazards regression was used to calculate hazard ratios (HR, 95% CI) for dementia and AD associated with quartiles of TC and HDL levels.

Results: Of the 2,356 eligible participants, 2,141 had at least one serum TC measure prior to the initial enrollment. Using the lowest TC quartiles as the reference group, the HR in the highest TC quartiles was not significantly elevated for dementia (1.16, 0.81 to 1.67) or for AD (1.00, 0.61 to 1.62) after adjusting for age, sex, education, baseline cognition, vascular comorbidities, body mass index, and lipid-lowering agent use. Serum HDL showed a similar lack of significant association with risk of dementia or AD. Models that included the presence of one or more APOE-4 alleles showed a typical association of 4 with AD risk. This association was not materially modified by inclusion of TC level.

Conclusion: The data do not support an association between serum total cholesterol or high density lipoprotein in late life and subsequent risk of dementia or Alzheimer disease (AD). The increased risk of AD with APOE-4 is probably not mediated by serum total cholesterol levels.

Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the October 11 issue to find the title link for this article.

Supported in part by grants AG20020, AG06781, AG16976, and AG05136 from the National Institute of Aging, National Institutes of Health, Bethesda, MD.

Disclosure: The authors report no conflicts of interest.

Received April 7, 2005. Accepted in final form June 27, 2005.

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