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.
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: Scott C Neu; Judy Pa; Walter Kukull; Duane Beekly; Amanda Kuzma; Prabhakaran Gangadharan; Li-San Wang; Klaus Romero; Stephen P Arneric; Alberto Redolfi; Daniele Orlandi; Giovanni B Frisoni; Rhoda Au; Sherral Devine; Sanford Auerbach; Ana Espinosa; Mercè Boada; Agustín Ruiz; Sterling C Johnson; Rebecca Koscik; Jiun-Jie Wang; Wen-Chuin Hsu; Yao-Liang Chen; Arthur W Toga Journal: JAMA Neurol Date: 2017-10-01 Impact factor: 18.302
Authors: David W Craig; Robert M Goor; Zhenyuan Wang; Justin Paschall; Jim Ostell; Michael Feolo; Stephen T Sherry; Teri A Manolio Journal: Nat Rev Genet Date: 2011-09-16 Impact factor: 53.242
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Authors: Mary Ganguli; Ching-Wen Lee; Beth E Snitz; Tiffany F Hughes; Eric M McDade; Chung-Chou H Chang Journal: Alzheimer Dis Assoc Disord Date: 2014 Apr-Jun Impact factor: 2.703
Authors: Noll L Campbell; Fred Unverzagt; Michael A LaMantia; Babar A Khan; Malaz A Boustani Journal: Clin Geriatr Med Date: 2013-11 Impact factor: 3.076
Authors: Lei Yu; Patricia Boyle; Julie A Schneider; Eisuke Segawa; Robert S Wilson; Sue Leurgans; David A Bennett Journal: Psychol Aging Date: 2013-05-06