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-ɛ4 allele was the strongest risk factor, and with increasing survival age, the effect of ɛ4 diminished. Among ɛ4 positives, developmental risk factors such as smaller head circumference (≤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 ɛ4 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.