Risk Estimates of Dementia by Apolipoprotein E Genotypes From a Population-Based Incidence Study: The Rotterdam Study

Abstract

ALTHOUGH THE association between the ϵ4 allele of the apolipoprotein E (APOE) gene and Alzheimer disease (AD) is well established, reported risks vary tremendously among studies.^1-7 Most of these investigations are of clinic-based patient series. In some studies, selection bias may have played a role because the ϵ4 frequency in memory clinic patients was found to be increased compared with patients in the general population.^8,9 Furthermore, all but 2 studies^4,5 are based on prevalent cases. Because the APOE genotype may be a determinant of survival in patients with dementia,^10,11 cross-sectional studies are subject to bias. In addition, it is still controversial whether the ϵ2 allele exerts a protective effect,^11,12 whether a family history of dementia further increases the ϵ4-related risk,^2,3 and whether the APOE genotype is a determinant of the patient's age at the onset of dementia.^1,13 Thus, reliable estimates of the risk of dementia associated with the APOE genotypes are currently not available, and it is not yet clear which part of all patients with dementia is attributable to the APOE genotypes.