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Arjen J. C. Slooter, MD; Marc Cruts, PhD; Sandra Kalmijn, MD, MSc; Albert Hofman, MD, PhD; Monique M. B. Breteler, MD, PhD; Christine Van Broeckhoven, PhD; Cornelia M. van Duijn, PhD

Arch Neurol. 1998;55:964-968.

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 4 allele, and the proportion of the variance in age at the onset of dementia explained by the APOE genotypes.

Results  Persons with the 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 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 3/3 genotype. The proportion of patients with dementia that is attributable to the 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 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.

From the Department of Epidemiology and Biostatistics, Erasmus University Medical School, Rotterdam, the Netherlands (Drs Slooter, Kalmijn, Hofman, Breteler, and van Duijn); and the Neurogenetics Laboratory, Flanders Interuniversity Institute for Biotechnology, Born-Bunge Foundation, Department of Biochemistry, University of Antwerpen, Antwerpen, Belgium (Drs Cruts and Van Broeckhoven).

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