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

• Published in: International journal of geriatric psychiatry Vol. 23; no. 11; pp. 1134 - 1140
• Main Authors: Prasher, V. P., Sajith, S. G., Rees, S. D., Patel, A., Tewari, S., Schupf, N., Zigman, W. B.
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01-11-2008; Wiley; Wiley Subscription Services, Inc
• Subjects: Adult and adolescent clinical studies; Alleles; Alzheimer Disease - genetics; Alzheimer Disease - mortality; Alzheimer's disease; Apolipoprotein E; Apolipoprotein E4 - genetics; Biological and medical sciences; Chromosome aberrations; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dementia; Disease Progression; Down Syndrome; Down Syndrome - genetics; Down Syndrome - mortality; Effects; Female; Gene Frequency - genetics; Genetic Predisposition to Disease - genetics; Genetic Testing; Genotype; Genotype & phenotype; Geriatric psychiatry; Humans; Learning disabilities; Male; Medical genetics; Medical sciences; Middle Aged; Mortality; Neurology; Organic mental disorders. Neuropsychology; Prospective Studies; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Risk Assessment; Risk factors; Survival Analysis; United Kingdom; Europe; Chromosomal aberration; Social environment; Human; Nervous system diseases; Trisomy; Alzheimer disease; Mortality; Mental health; Chromosome G21; Aneuploidy; Genotype; Down syndrome; Genetic determinism; Epidemiology; Cerebral disorder; Apolipoprotein E; Follow up study; Central nervous system disease; Risk factor; Genetics; dementia; Degenerative disease; Alzheimer's disease; Public health
• ISSN: 0885-6230; 1099-1166
• DOI: 10.1002/gps.2039

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.