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Diabetes Increases Risk for Alzheimer's Disease; Trauma Does Not

Since the early 1990s, nearly 8000 older people in Rotterdam, the Netherlands, have participated in an epidemiologic study of aging. The Rotterdam Study authors have found associations between many risk factors for vascular disease -- including diabetes, atrial fibrillation, dietary fat intake, atherosclerosis, and smoking -- and the occurrence of both vascular dementia (VaD) and Alzheimer's disease (AD). In two new reports, they examine prospectively the effects of diabetes and of head trauma on the incidence of new cases of dementia.

Diabetes nearly doubles the risk for developing dementia (relative risk, 1.9) including both AD (RR, 1.9) and VaD (RR, 2.0). No epidemiologic study is perfect: The authors obtained imaging studies in only one quarter of cases; follow-up averaged only 2.1 years; and patients who developed dementia were a dozen years older than those who did not. After adjustment for all confounding factors, however, this study of new-incident cases makes a strong argument that diabetes is a risk factor for all dementia (AD and VaD), accounting for nearly 9% of cases.

By contrast, mild head trauma with loss of consciousness caused no increase in the incidence of AD or in dementia as a whole; nor did the presence of an APOE-(epsilon)4 allele increase the risk for developing AD in those with head trauma.

Comment: The reported associations between vascular risk factors and AD are generating growing interest in a potential causal relation. The simplest possibility is that a small, asymptomatic stroke may precipitate dementia in patients with subclinical AD pathology (see The Gerontologist 1997; 37:150). But modest head trauma did not increase the incidence of dementia, suggesting that a "straw breaking the camel's back" is probably not the only mechanism by which vascular risk factors may cause dementia.

The association of coronary disease with AD, the finding that apolipoprotein (epsilon)4 is a risk factor for AD, the relation of the lipoprotein receptor-related protein to AD, and the finding of advanced glycation end products in senile plaques and tangles -- all suggest important, still obscure, relations among the vascular system, lipid and glucose metabolism, and AD. We have long accepted that, sans infarcts, vascular compromise produces little objective pathology in the brain. Perhaps it's time to reassess this myth.

— DA Drachman

David A. Drachman, MD, is Professor and Chairman, Department of Neurology, University of Massachusetts Medical School, Worcester, MA.

Published in Journal Watch Neurology March 1, 2000

Citation(s):

Ott A et al. Diabetes mellitus and the risk of dementia: The Rotterdam Study. Neurology 1999 Dec 10 53 1937 -1942.

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Mehta KM et al. Head trauma and risk of dementia and Alzheimer's disease: The Rotterdam Study. Neurology 1999 Dec 10 53 1959 -1962.

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