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Abstract
Background: Cellular and animal studies suggest that hypercholesterolemia contributes to Alzheimer disease (AD). However, the relationship between cholesterol and dementia at the population level is less clear and may vary over the lifespan.
Methods: The Prospective Population Study of Women, consisting of 1,462 women without dementia aged 38–60 years, was initiated in 1968–1969 in Gothenburg, Sweden. Follow-ups were conducted in 1974–1975, 1980–1981, 1992–1993, and 2000–2001. All-cause dementia was diagnosed according to DSM-III-R criteria and AD according to National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer's Disease and Related Disorders Association criteria. Cox proportional hazards regression examined baseline, time-dependent, and change in cholesterol levels in relation to incident dementia and AD among all participants. Analyses were repeated among participants who survived to the age of 70 years or older and participated in the 2000–2001 examination.
Results: Higher cholesterol level in 1968 was not associated with an increased risk of AD (highest vs lowest quartile: hazard ratio [HR] 2.82, 95% confidence interval [CI] 0.94–8.43) among those who survived to and participated in the 2000–2001 examination. While there was no association between cholesterol level and dementia when considering all participants over 32 years, a time-dependent decrease in cholesterol over the follow-up was associated with an increased risk of dementia (HR 2.35, 95% CI 1.22–4.58).
Conclusion: These data suggest that midlife cholesterol level is not associated with an increased risk of AD. However, there may be a slight risk among those surviving to an age at risk for dementia. Declining cholesterol levels from midlife to late life may better predict AD risk than levels obtained at one timepoint prior to dementia onset. Analytic strategies examining this and other risk factors across the lifespan may affect interpretation of results.
Footnotes
Study funding: Supported by the NIH (NIA 1R03AG026098-01A1, NIA 1R21AG028754, and NINDS R21NS060271-01), the Swedish Research Council (11267 and 2005-8460), the Swedish Brain Power Project, EU FP7 project LipiDiDiet (211696), Swedish Council for Working Life and Social Research (1154), FAS EpiLife (2006–1506), Swedish Alzheimer Association, Stiftelsen Söderström-Königska Sjukhemmet, Stiftelsen för Gamla Tjänarinnor, Hjalmar Svenssons Foundation, The Swedish Society of Medicine, The Göteborg Medical Society, the Lions Foundation, the Dr. Felix Neubergh Foundation, the Wilhelm and Martina Lundgren Foundation, the Elsa and Eivind Kison Sylvan Foundation, and the Alzheimer's Association Zenith Award (ZEN-01-3151).
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- AD
- Alzheimer disease
- BMI
- body mass index
- CI
- confidence interval
- DBP
- diastolic blood pressure
- DSM-III-R
- Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, revised
- HR
- hazard ratio
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Editorial, page 1862.
Supplemental data at www.neurology.org.
- Received April 18, 2010.
- Accepted July 20, 2010.
- Copyright © 2010 by AAN Enterprises, Inc.
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