Article Text

Download PDFPDF
Predictive value of APOE-ε4 allele for progression from MCI to AD-type dementia: a meta-analysis
  1. Lyzel S Elias-Sonnenschein1,
  2. Wolfgang Viechtbauer2,
  3. Inez H G B Ramakers1,
  4. Frans R J Verhey1,
  5. Pieter Jelle Visser1,3
  1. 1School of Mental Health and Neuroscience, Alzheimer Center Limburg, Department of Psychiatry and Neuropsychology, Maastricht University Medical Center, Maastricht, The Netherlands
  2. 2Department of Methodology and Statistics, School for Public Health and Primary Care, Maastricht University, Maastricht, The Netherlands
  3. 3Department of Neurology, Vrije Universiteit University Medical Center, Amsterdam, The Netherlands
  1. Correspondence to L S Elias-Sonnenschein, Department of Psychiatry and Neuropsychology, Maastricht University Medical Center, PO Box 616, 6200 MD (Drt. 12), Maastricht, The Netherlands; lyzel.elias{at}


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.

  • Apolipoprotein E
  • Alzheimer's disease
  • mild cognitive impairment
  • cohort studies, meta-analysis
  • apolipoproteins
  • dementia
  • genetics
  • meta-analysis

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Competing interests None.

  • Provenance and peer review Not commissioned; externally peer reviewed.