The Minster Practice, Lichfield

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The apolipoprotein E (APOE) ε4 allele is a well-established risk factor for Alzheimer's disease (AD). However, the underlying pathophysiological connection is unclear, despite observed associations between APOE ε4 and increased serum cholesterol, between lipoprotein(a) and AD, between cardiovascular risk factors and dementia, and between use of statins and lower risk for AD.

Researchers followed a cohort of 1026 participants in the Framingham study who were free of vascular disease and dementia in 1988-1989, had undergone APOE genotyping, and had serial cholesterol determined biennially from 1950 through 2000. AD developed in 77 subjects from 1992 through 2000. Risk for developing AD was not associated with any measured serum cholesterol levels, including lifetime mean total cholesterol level (from baseline in 1948 through 1978), total cholesterol level in 1988, HDL cholesterol level in 1988, or change in cholesterol level between 1978 and 1988. These results were not altered by adjustment for potential confounders such as age, sex, APOE genotype, coronary artery disease, lipid-lowering therapy, and body-mass index.

Comment— Thomas L. Schwenk, MD  Published in Journal Watch May 27, 2003
 The long-term follow-up on this case-control cohort gives considerable credence to the investigators' conclusion: No association exists between serum cholesterol and risk for developing AD. The authors also conclude that the association between statin use and decreased risk for AD probably is not due to reductions in serum cholesterol.

SourceTan ZS et al. Plasma total cholesterol level as a risk factor for Alzheimer disease: The Framingham study. Arch Intern Med 2003 May 12; 163:1053-7.

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