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

Objective: The effect of APOE on dementia may be mediated through dyslipide mia and atherogenesis through its effect on cholesterol metabolism. The aut hors investigated this possibility among aged survivors from the UK Medical Research Council Trial of the Treatment of Hypertension in Older Adults. D esign: A total of 370 of 657 survivors from an initial cohort of 1,088 recr uited into the trial between 1983 and 1985 were traced in 1994 and agreed t o be screened for dementia. Blood samples were analyzed for APOE genotype a nd serum fibrinogen. Cholesterol level, smoking behavior, blood pressure, b ody mass index, and EKG recordings had been measured at recruitment 10 to 1 2 years earlier. Odds ratios (ORs) for the association between APOE epsilon 4/* and both AD and dementia were estimated and adjusted incrementally for the effect of age and premorbid intelligence, cholesterol, other risk fact ors for vascular disease, and EKG evidence of cardiovascular disease. Resul ts: The authors diagnosed 24 cases of National Institute of Neurological an d Communicative Disorders and Stroke AD from 41 cases of dementia. The crud e OR for the association between APOE epsilon 4/* and AD was 3.40 (95% CI 1 .30 to 8.91). APOE genotype was associated with serum cholesterol level, an d there was a nonsignificant trend for an association with smoking behavior . After adjusting for these and all other vascular risk factors and vascula r disease variables listed earlier, the OR for the association between APOE epsilon 4/* and AD increased to 4.81 (1.60 to 14.4). Conclusion: Presence of APOE epsilon 4/* seems to increase the risk for dementia and AD independ ently of its effect on dyslipidemia and atherogenesis.