Predictive value of APOE- 4 allele for progression from MCI to AD-type dementia: a meta-analysis
2011/04/14 by Lyzel S Elias-Sonnenschein, L. S. Elias-Sonnenschein, Wolfgang Viechtbauer +7 · 149 citations
Mathematics · Medicine · #Allele #Alzheimer's disease research and treatments #Apolipoprotein E #Biology #Dementia #Dementia and Cognitive Impairment Research #Disease #Gene #Genetics #Internal medicine #Mathematics #Medicine #Meta-analysis #Oncology #Predictive value #Renin-Angiotensin System Studies #Statistics #Value (mathematics)
paper · open access · doi:10.1136/jnnp.2010.231555
published in Journal of Neurology Neurosurgery & Psychiatry 82(10), 1149-1156 (BMJ)
openalex publication_date 2011/04/14 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
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.
Citations
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