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NEUROLOGY 2005;65:545-551
© 2005 American Academy of Neurology

Aggregation of vascular risk factors and risk of incident Alzheimer disease

J. A. Luchsinger, MD, MPH, C. Reitz, MD, L. S. Honig, MD, PhD, M. X. Tang, PhD, Steven Shea, MD, MS and R. Mayeux, MD, MSe

From the Taub Institute for Research of Alzheimer's Disease and the Aging Brain (Drs. Luchsinger, Reitz, Honig, Tang, and Mayeux), Gertrude H. Sergievsky Center (Drs. Luchsinger, Honig, Tang, and Mayeux), Department of Biostatistics (Drs. Tang, and Mayeux), Joseph P. Mailman School of Public Health, Department of Epidemiology (Drs. Shea, and Mayeux), Joseph P. Mailman School of Public Health, Columbia University, and Division of General Medicine (Drs. Luchsinger, Shea, Mayeux), Department of Medicine, Department of Neurology (Drs. Honig and Mayeux), and Department of Psychiatry (Drs. Mayeux), Columbia University College of Physicians and Surgeons, New York, NY.

Address correspondence and reprint requests to Dr Luchsinger, PH9E-105, 630 W. 168 St., New York, NY 10032; e-mail: jal94{at}columbia.edu

Background: The prevalence of Alzheimer disease (AD) is increasing in the elderly, and vascular risk factors may increase its risk.

Objective: To explore the association of the aggregation of vascular risk factors with AD.

Methods: The authors followed 1,138 individuals without dementia at baseline (mean age 76.2) for a mean of 5.5 years. The presence of vascular risk factors was related to incident possible and probable AD.

Results: Four risk factors (diabetes, hypertension, heart disease, and current smoking) were associated with a higher risk of AD (p < 0.10) when analyzed individually. The risk of AD increased with the number of risk factors (diabetes + hypertension + heart disease + current smoking). The adjusted hazards ratio of probable AD for the presence of three or more risk factors was 3.4 (95% CI: 1.8, 6.3; p for trend < 0.0001) compared with no risk factors. Diabetes and current smoking were the strongest risk factors in isolation or in clusters, but hypertension and heart disease were also related to a higher risk of AD when clustered with diabetes, smoking, or each other.

Conclusions: The risk of Alzheimer disease (AD) increased with the number of vascular risk factors. Diabetes and current smoking were the strongest risk factors, but clusters including hypertension and heart disease also increased the risk of AD. These associations are unlikely to be explained by misclassification of the outcome, given strong associations when only probable AD is considered.


Supported by grants from the National Institute of Aging (AG07232, AG07702, 1K08AG20856-01), from the Charles S. Robertson Memorial Gift for Research on Alzheimer's Disease, from the Blanchette Hooker Rockefeller Foundation, and from the New York City Council Speaker's Fund for Public Health Research.

Disclosure: The authors report no conflicts of interest.

Received December 8, 2004. Accepted in final form May 5, 2005.


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