Risk Estimates of Dementia by Apolipoprotein E Genotypes from a Population-based Incidence Study: the Rotterdam Study

Objectives: To provide risk estimates of dementia and Alzheimer disease as a function of the apolipoprotein E (APOE) genotypes and to assess the proportion of dementia that is attributable to the APOE genotypes.

Design: Case-control study nested in a population-based cohort study with a mean (SD) follow-up of 2.1 (0.9) years.

Setting: General population in Rotterdam, the Netherlands.

Participants: A total of 134 patients with incident dementia and a random sample of 997 nondemented control subjects. No participant had dementia at baseline.

Main Outcome Measures: Odds ratios for dementia and Alzheimer disease, the fraction of dementia attributable to the APOE epsilon4 allele, and the proportion of the variance in age at the onset of dementia explained by the APOE genotypes.

Results: Persons with the epsilon4/4 genotype had a more than 10-fold higher risk of dementia (odds ratio, 11.2; 95% confidence interval, 3.6-35.2), and subjects with the epsilon3/4 genotype had a 1.7-fold increased risk of dementia (95% confidence interval, 1.0-2.9) as compared with persons with the epsilon3/3 genotype. The proportion of patients with dementia that is attributable to the epsilon4 allele was estimated to be 20%. The APOE genotypes explained up to 10% of the variance in age at the onset of dementia. The association between the epsilon4 allele and dementia was strongest in the youngest age category and in those with a family history of dementia.

Conclusions: The APOE genotype is an important determinant of the risk of dementia. At a population level, however, other factors than the APOE genotype may play an important role in the cause of dementia.