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 diseas e 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 popu lation in Rotterdam, the Netherlands. Participants: A total of 134 pat ients with incident dementia and a random sample of 997 nondemented co ntrol 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 propor tion 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 m ore than 10-fold higher risk of dementia (odds ratio, 11.2; 95% confid ence interval, 3.6-35.2), and subjects with the epsilon 3/4 genotype h ad 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 prop ortion 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 bet ween the epsilon 4 allele and dementia was strongest in the youngest a ge category and in those with a family history of dementia. Conclusion s: The APOE genotype is an important determinant of the risk of dement ia. At a population level, however, other factors than the APOE genoty pe may play an important role in the cause of dementia.