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NEUROLOGY 2007;69:1850-1858
© 2007 American Academy of Neurology

Vascular factors predict rate of progression in Alzheimer disease

M. M. Mielke, PhD, P. B. Rosenberg, MD, J. Tschanz, PhD, L. Cook, MStat, C. Corcoran, ScD, K. M. Hayden, PhD, M. Norton, PhD, P. V. Rabins, MD, R. C. Green, MD, K. A. Welsh-Bohmer, PhD, J.C.S. Breitner, MD, R. Munger, PhD and C. G. Lyketsos, MD

From The Johns Hopkins University School of Medicine (M.M.M., P.B.R, P.V.R, C.G.L.), Baltimore, MD; Utah State University (J.T., L.C., C.C., M.N., R.M.), Logan; Duke University Medical Center (K.M.H., K.A.W.-B.), Durham, NC; Boston University School of Medicine (R.C.G.), MA; and VA Puget Sound Health Care System and University of Washington School of Medicine (J.C.S.B.), Seattle.

Address correspondence and reprint requests to Dr. Michelle M. Mielke, Johns Hopkins University School of Medicine, Department of Psychiatry, Division of Geriatric Psychiatry and Behavioral Sciences, 550 N. Broadway, Suite 308, Baltimore, MD 21205 mmielke1{at}jhmi.edu

Background: While there is considerable epidemiologic evidence that cardiovascular risk factors increase risk of incident Alzheimer disease (AD), few studies have examined their effect on progression after an established AD diagnosis.

Objective: To examine the effect of vascular factors, and potential age modification, on rate of progression in a longitudinal study of incident dementia.

Methods: A total of 135 individuals with incident AD, identified in a population-based sample of elderly persons in Cache County, UT, were followed with in-home visits for a mean of 3.0 years (range: 0.8 to 9.5) and 2.1 follow-up visits (range: 1 to 5). The Clinical Dementia Rating (CDR) Scale and Mini-Mental State Examination (MMSE) were administered at each visit. Baseline vascular factors were determined by interview and physical examination. Generalized least-squares random-effects regression was performed with CDR Sum of Boxes (CDR-Sum) or MMSE as the outcome, and vascular index or individual vascular factors as independent variables.

Results: Atrial fibrillation, systolic hypertension, and angina were associated with more rapid decline on both the CDR-Sum and MMSE, while history of coronary artery bypass graft surgery, diabetes, and antihypertensive medications were associated with a slower rate of decline. There was an age interaction such that systolic hypertension, angina, and myocardial infarction were associated with greater decline with increasing baseline age.

Conclusion: Atrial fibrillation, hypertension, and angina were associated with a greater rate of decline and may represent modifiable risk factors for secondary prevention in Alzheimer disease. The attenuated decline for diabetes and coronary artery bypass graft surgery may be due to selective survival. Some of these effects appear to vary with age.

GLOSSARY: 3MS = revised Modified Mini-Mental State Examination for epidemiologic studies; AF = atrial fibrillation; CABG = coronary artery bypass graft surgery; CCHS = Copenhagen City Heart Study; CCSMHA = Cache County Study on Memory, Health, and Aging; CDR = Clinical Dementia Rating; CVD = cardiovascular disease; DM = diabetes mellitus; DPS = Dementia Progression Study; MI = myocardial infarction; MMSE = Mini-Mental State Examination; SBP = systolic blood pressure.

Supplemental data at www.neurology.org

Supported in part by R01 AG21136, R01 AG11380, R01 AG18712, and P01 AG05146 from the National Institute of Aging.

Disclosure: The authors report no conflicts of interest.

Presented in part as a poster at the 10th International Conference on AD and Related Disorders; Madrid, Spain; 2006.

Received February 21, 2007. Accepted in final form May 23, 2007.






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