The association between APOE and dementia does not seem to be mediated by vascular factors

The effect of APOE on dementia may be mediated through dyslipidemia and atherogenesis through its effect on cholesterol metabolism. The authors investigated this possibility among aged survivors from the UK Medical Research Council Trial of the Treatment of Hypertension in Older Adults.

A total of 370 of 657 survivors from an initial cohort of 1,088 recruited into the trial between 1983 and 1985 were traced in 1994 and agreed to be screened for dementia. Blood samples were analyzed for APOE genotype and serum fibrinogen. Cholesterol level, smoking behavior, blood pressure, body mass index, and EKG recordings had been measured at recruitment 10 to 12 years earlier. Odds ratios (ORs) for the association between APOE epsilon4/* and both AD and dementia were estimated and adjusted incrementally for the effect of age and premorbid intelligence, cholesterol, other risk factors for vascular disease, and EKG evidence of cardiovascular disease.

The authors diagnosed 24 cases of National Institute of Neurological and Communicative Disorders and Stroke AD from 41 cases of dementia. The crude OR for the association between APOE epsilon4/* and AD was 3.40 (95% CI 1.30 to 8.91). APOE genotype was associated with serum cholesterol level, and there was a nonsignificant trend for an association with smoking behavior. After adjusting for these and all other vascular risk factors and vascular disease variables listed earlier, the OR for the association between APOE epsilon4/* and AD increased to 4.81 (1.60 to 14.4).

Presence of APOE epsilon4/* seems to increase the risk for dementia and AD independently of its effect on dyslipidemia and atherogenesis.