title: Significant effect of APOE epsilon 4 genotype on the risk of dementia in Alzheimer's disease and mortality in persons with Down syndrome.
abstract: 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 status was confirmed as recommended by the Working Group for the Establishment of Criteria for the Diagnosis of Dementia in Individuals with Intellectual Disability.
  
  
  RESULTS
  APOE genotype results were available for 252 individuals. Participants with APOE epsilon 4 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 epsilon 3 allele (4.2 years vs. 5.4 years, respectively, p = 0.048). In non-demented persons with DS, epsilon 4 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 epsilon 4 allele.
authors.affiliation: The Greenfields, Monyhull Hospital, Birmingham, UK. vprasher@compuserve.com
authors.forename: V P
authors.initials: VP
authors.lastname: Prasher
authors.forename: S G
authors.initials: SG
authors.lastname: Sajith
authors.forename: S D
authors.initials: SD
authors.lastname: Rees
authors.forename: A
authors.initials: A
authors.lastname: Patel
authors.forename: S
authors.initials: S
authors.lastname: Tewari
authors.forename: N
authors.initials: N
authors.lastname: Schupf
authors.forename: W B
authors.initials: WB
authors.lastname: Zigman
mesh_terms: D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics* / Q000401:mortality; D053327:Apolipoprotein E4 / Q000235:genetics*; D018450:Disease Progression; D004314:Down Syndrome / Q000235:genetics* / Q000401:mortality; D005260:Female; D005787:Gene Frequency / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018570:Risk Assessment; D016019:Survival Analysis
chemical_list: D053327:Apolipoprotein E4