Significant effect of APOE epsilon 4 genotype on the risk of dementia in Alzheimer's disease and mortality in persons with Down Syndrome

Objective Virtually all adults with Down syndrome (DS) have neuropathological manifestations of Dementia in Alzheimer's disease (DAD) but not all develop clinical psychopathology. The effect of allelic variants of Apolipoprotein (APOE) gene in development and progression of DAD and mortality in persons with DS is examined. Methods Recruited participants with DS underwent two to 14 sequential assessments over a follow up period of 6 years on average and their APOE genotype determined. Dementia statuswas confirmed as recommended by the Working Group for the Establishment of Criteria forthe Diagnosis of Dementia in Individuals with Intellectual Disability. Results APOE genotype results were available for 252 individuals. Participants with APOE ε4 allele had significantly higher risk of developing DAD (HR = 1.8, 95% CI: 1.12–2.79), had an earlier onset of DAD (55.0 vs 57.0 years; p = 0.0027) and a more rapid progression to death compared with participants with ε3 allele (4.2 years vs. 5.4 years, respectively, p = 0.048). In non‐demented persons with DS, ε4 allele was associated with earlier death by 17 years (mean survival age, 55.7 vs. 72.7 years; HR = 5.9, 95% CI: 1.7–21.3). Conclusions This study highlights the relationship of APOE genotype to morbidity and mortality in persons with DS which has important clinical implications. We recommend screening for APOE genotype in persons with DS to identify those at risk of DAD and premature death. Further research is required to investigate the underlying reasons for the early mortality in non‐demented DS persons with an ε4 allele. Copyright © 2008 John Wiley & Sons, Ltd.