Developmental and vascular risk factors for Alzheimer's disease

To investigate developmental and vascular risk factors for Alzheimer's disease (AD), we examined 90 incident cases of probable AD in a cohort of 1859 individuals followed prospectively for six years. The presence of the APOE-epsilon4 allele was the strongest risk factor, and with increasing survival age, the effect of epsilon4 diminished. Among epsilon4 positives, developmental risk factors such as smaller head circumference ( less than or equal to 54.4 cm) and having more than four children in the household at age 2-3 were independently associated with incident AD (hazard ratio (HR) = 2.6 (95% CI 1.04-6.3) and 3.3 (1.2-9.2), respectively). Among epsilon4 negatives, vascular risk factors were related to AD risk (self-reported diagnoses of transient ischemic attack and diabetes (HR = 5.1, 95% CI 1.7-15.5; HR 3.3,95% CI 1.4-8.1)). These findings indicate that clinical AD is a result of early life as well as later life risk factors, and that genetic predisposition to the disease may modify the constellation of predictors. (C) 2004 Elsevier Inc. All rights reserved.