Using census data and birth certificates to reconstruct the early-life socioeconomic environment and the relation to the development of Alzheimer's disease

The early-life environment and its effect on growth and maturation of children and adolescents are associated with several adult chronic diseases, including Alzheimer's disease. Because it is not feasible to collect information prospectively over the average life span, methods to reconstruct the early-life environment of the aged are necessary to evaluate these associations. In a community-based case-control study conducted in the United States, we collected U.S. census records and birth certificates to reconstruct the early-life socioeconomic environment of each elderly subject. Information was found on 82% of the available Alzheimer's disease cases (239 of 292) and 87% of the available controls (245 of 282). We investigated risk of Alzheimer's disease associated with father's occupation, parental age, household size, sibship size, and birth order. Subjects whose fathers were unskilled manual workers or laborers were at higher risk for Alzheimer's disease (odds ratio = 1.80, 95% confidence interval = 1.19-2.73). The risk of Alzheimer's disease was increased with increasing number of people in the household. We also evaluated whether subjects with the apolipoprotein ε4 allele (APOE ε4), a strong genetic risk factor that is not a necessary cause or a sufficient cause by itself for the development of Alzheimer's disease, were at higher risk than subjects who did not carry this allele. Among subjects with the APOE ε4 allele whose fathers held lower-socioeconomic level occupations, the odds of developing Alzheimer's disease were higher (odds ratio = 2.35, 95% confidence interval = 1.07-5.16) compared with subjects without the allele (odds ratio = 1.40, 95% confidence interval = 0.78-2.52). Subjects carrying the APOE ε4 allele alone have a threefold increased risk of Alzheimer's disease (odds ratio = 3.17, 95% confidence interval = 1.99-5.04). Compared with subjects with neither risk factor, subjects with both the genetic and the environmental risk factors (household size of seven or more and father's occupation being manual) had a relatively high risk of Alzheimer's disease (odds ratio = 14.8, 95% confidence interval = 4.9-46). The data suggest that APOE ε4 may modify the associations between father's occupation, other early-life environmental factors, and development of Alzheimer's disease in late life.