title: Predictive value of APOE-ε4 allele for progression from MCI to AD-type dementia: a meta-analysis.
abstract: BACKGROUND
  The identification of subjects with mild cognitive impairment (MCI) at high risk for Alzheimer's disease (AD) is important for prognosis and early intervention. The APOE-ε4 allele is the strongest known genetic risk factor for AD. The authors performed a meta-analysis to establish the predictive accuracy of the APOE-ε4 allele for progression from MCI to AD-type dementia.
  
  
  METHODS
  The authors included 35 prospective cohort studies of subjects with MCI, including 6095 subjects, of whom 1236 progressed to AD-type dementia after 2.9 years of follow-up. Pooled estimates of the OR, sensitivity, specificity, positive and negative predictive values (PPV and NPV), and positive and negative likelihood ratios (LR+ and LR-) were obtained using random-effects models.
  
  
  RESULTS
  The OR for subjects with MCI who are carriers of APOE-ε4 allele to progress to AD-type dementia was 2.29 (95% CI 1.88 to 2.80), the sensitivity was 0.53 (95% CI 0.46 to 0.61), the specificity was 0.67 (95% CI 0.62 to 0.71), the PPV was 0.57 (95% CI 0.48 to 0.66), the NPV was 0.75 (95% CI 0.70 to 0.80), the LR+ was 1.60 (95% CI 1.48 to 1.72), and the LR- was 0.75 (95% CI 0.67 to 0.82). Meta-regression showed that sensitivity, specificity and NPV were dependent on age, APOE-ε4 allele background prevalence or follow-up length.
  
  
  CONCLUSIONS
  The APOE-ε4 allele is associated with a moderately increased risk for progression from MCI to AD-type dementia. The low sensitivity and PPV makes genotyping of limited value for predicting AD-type dementia in clinical practice. For trials aiming to prevent progression from MCI to AD-type dementia, APOE genotyping may be useful in selecting subjects with a higher risk for progression to AD-type dementia.
authors.affiliation: School of Mental Health and Neuroscience, Alzheimer Center Limburg, Department of Psychiatry and Neuropsychology, Maastricht University Medical Center, Maastricht, The Netherlands. lyzel.elias@maastrichtuniversity.nl
authors.forename: Lyzel S
authors.initials: LS
authors.lastname: Elias-Sonnenschein
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Viechtbauer
authors.forename: Inez H G B
authors.initials: IH
authors.lastname: Ramakers
authors.forename: Frans R J
authors.initials: FR
authors.lastname: Verhey
authors.forename: Pieter Jelle
authors.initials: PJ
authors.lastname: Visser
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics*; D003072:Cognition Disorders / Q000175:diagnosis / Q000235:genetics*; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D016013:Likelihood Functions; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D053327:Apolipoprotein E4