Katrine L Rasmussen, Anne Tybjærg-Hansen, Børge G Nordestgaard, Ruth Frikke-Schmidt

Dementia is a major cause of disability, and risk-factor reduction may have the potential to delay or prevent the disease. Our aim was to determine the absolute 10-year risk of dementia, by age, sex and apolipoprotein E (APOE) genotype. We obtained data from the Copenhagen General Population Study (from 2003 to 2014) and the Copenhagen City Heart Study (from 1991 to 1994 and 2001 to 2003). Participants underwent a questionnaire, physical examination and blood sampling at baseline. Diagnoses of dementia and cerebrovascular disease were obtained from the Danish National Patient Registry up to Nov. 10, 2014. Among 104 537 individuals, the absolute 10-year risk of Alzheimer disease in 3017 women and men who were carriers of the APOE ɛ44 genotype was, respectively, 7% and 6% at age 60-69 years, 16% and 12% at age 70-79 years, and 24% and 19% at age 80 years and older. Corresponding values for all dementia were 10% and 8%, 22% and 19%, and 38% and 33%, respectively. Adjusted hazard ratios (HRs) for all dementia increased by genotype, from genotype ɛ22 to ɛ32 to ɛ33 to ɛ42 to ɛ43 to ɛ44 (p for trend < 0.001). Compared with ɛ33 carriers, ɛ44 carriers were more likely to develop Alzheimer disease (adjusted HR 8.74, 95% confidence interval [CI] 7.08-10.79), vascular dementia (adjusted HR 2.87, 95% CI 1.54-5.33), unspecified dementia (adjusted HR 4.68, 95% CI 3.74-5.85) and all dementia (adjusted HR 5.77, 95% CI 4.89-6.81). Age, sex and APOE genotype robustly identify high-risk groups for Alzheimer disease and all dementia. These groups can potentially be targeted for preventive interventions.