Maternal age and Alzheimer's disease: a collaborative re-analysis of case-control studies. EURODEM Risk Factors Research Group.
Rocca WA., van Duijn CM., Clayton D., Chandra V., Fratiglioni L., Graves AB., Heyman A., Jorm AF., Kokmen E., Kondo K.
To investigate the possible association between Alzheimer's disease and late maternal age at index birth, we conducted a collaborative re-analysis of existing case-control data sets. Of the 11 studies participating in the EURODEM project, four were included in the analyses regarding maternal age. In all four studies, cases were matched to controls by age and gender, and only population controls were considered. Analyses were conducted on the individual data sets, on the pooled sample, and on subgroups defined by gender, age at onset, and familial aggregation of dementia. Maternal age of 40 years and over was found to be suggestively associated with a higher risk of Alzheimer's disease (overall relative risk = 1.7; 95% confidence intervals: 1.0-2.9). In subgroup analyses, the association was statistically significant for women and for sporadic cases. Adjustments for education or analyses restricted to case-control pairs matched by type of respondent did not modify these results noticeably. The association was confirmed by a test of consistency with the Down's syndrome risk model; results of this test were again more definite for sporadic Alzheimer's disease. In addition, three of the four studies also suggested an increased risk for maternal age at index birth between 15 and 19 years (overall relative risk = 1.5; 95% confidence intervals: 0.8-3.0). Although consistency across studies was not always complete, only some of the increased relative risks reached statistical significance, and information regarding maternal age obtained through a next-of-kin interview may have limitations, our study suggests that both early and late maternal age should be further investigated as possible risk factors for Alzheimer's disease.