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Risk Factors for Dementia in the Cardiovascular Health Cognition Study

Kuller L.H.a · Lopez O.L.b · Newman A.c · Beauchamp N.J.d · Burke G.f · Dulberg C.g · Fitzpatrick A.h · Fried L.e · Haan M.N.i
aDepartment of Epidemiology, University of Pittsburgh Graduate School of Public Health, and bDepartment of Neurology and cDivision of Geriatric Medicine, University of Pittsburgh, Pittsburgh, Pa.; dNeuroradiology Division, Johns Hopkins Radiology, and eThe Johns Hopkins Medical Institutions, Baltimore, Md.; fDepartment of Public Health Sciences, WFU School of Medicine, Winston-Salem, N.C.; Departments of gBiostatistics and hEpidemiology, University of Washington, Seattle, Wash., and iDepartment of Epidemiology, University of Michigan School of Public Health, Ann Arbor, Mich., USA Neuroepidemiology 2003;22:13–22 (DOI:10.1159/000067109)


Background: The Cardiovascular Health Cognition Study has evaluated the determinants of dementia among 3,608 participants that had a magnetic resonance imaging (MRI) of the brain in 1991 and were followed to 1998–1999. Methods: There were 480 incident dementia cases, 330 (69%) were classified as Alzheimer’s disease (AD). Results: In univariate analysis, low scores on the Modified Mini-Mental State Examination (3MSE) and on the Digit Symbol Substitution Test as well as declines in scores over time prior to the development of dementia were significant predictors of dementia. A high ventricular grade on the MRI (atrophy) as well as high white matter grade, a number of brain infarcts on the MRI were all determinants of dementia. Apolipoprotein E ε4 (ApoE-4) was also a powerful predictor of dementia. In a multivariate Cox proportional hazards model controlling for race, gender and grade, the hazard ratios for age (1.1), 3MSE score (0.9), ventricular size (1.4), white matter grade (1.8), presence of large infarcts >3 mm (1.3) and ApoE-4 (2.1) were significant predictors of dementia. The combination of an ApoE-4 genotype, 3MSE score <90, ≧5 ventricular grade, ≧3 white matter grade at the time of the MRI were associated with a 17-fold increased risk (95% CI: 8.6–34.9) of dementia as compared to individuals with none of the above attributes. Conclusions: Measures of cognition, ApoE-4 and MRI of the brain are strong predictors of both dementia and of AD.


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