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 CSD) 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 epsilon 4 allele, and the proportion of the variance in age at the onset of dementia explained by the APOE genotypes. Results: Persons with the epsilon 4/4 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 epsilon 3/4 genotype had a 1.7-fold increased risk of dementia (95% confidence interval, 1.0-2.9) as compared with persons with the epsilon 3/3 genotype. The proportion of patients with dementia that is attributable to the epsilon 4 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 epsilon 4 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.