@article{b134a994418a46959bc475a63c10c4da,
title = "Susceptibility of the conventional criteria for mild cognitive impairment to false-positive diagnostic errors",
abstract = "Background We assessed whether mild cognitive impairment (MCI) subtypes could be empirically derived within the Alzheimer's Disease Neuroimaging Initiative (ADNI) MCI cohort and examined associated biomarkers and clinical outcomes. Methods Cluster analysis was performed on neuropsychological data from 825 MCI ADNI participants. Results Four subtypes emerged: (1) dysnomic (n = 153), (2) dysexecutive (n = 102), (3) amnestic (n = 288), and (4) cluster-derived normal (n = 282) who performed within normal limits on cognitive testing. The cluster-derived normal group had significantly fewer APOE ε4 carriers and fewer who progressed to dementia compared with the other subtypes; they also evidenced cerebrospinal fluid Alzheimer's disease biomarker profiles that did not differ from the normative reference group. Conclusions Identification of empirically derived MCI subtypes demonstrates heterogeneity in MCI cognitive profiles that is not captured by conventional criteria. The large cluster-derived normal group suggests that conventional diagnostic criteria are susceptible to false-positive errors, with the result that prior MCI studies may be diluting important biomarker relationships.",
author = "Edmonds, {Emily C.} and Lisa Delano-Wood and Clark, {Lindsay R.} and Jak, {Amy J.} and Nation, {Daniel A.} and McDonald, {Carrie R.} and Libon, {David J.} and Rhoda Au and Douglas Galasko and Salmon, {David P.} and Bondi, {Mark W.}",
note = "Funding Information: This work was supported by NIH grants R01 AG012674 (M.W.B.), K24 AG026431 (M.W.B.), P50 AG05131 (D.G.), R01 AG16495 (R.A.), and an Alzheimer's Association grant NIRG-13-281806 (C.R.M.). Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) ( National Institutes of Health Grant U01 AG024904 ) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012 ). ADNI is funded by the National Institute on Aging , the National Institute of Biomedical Imaging and Bioengineering , and through generous contributions from the following: Alzheimer's Association ; Alzheimer Drug Discovery Foundation ; BioClinica, Inc ; Biogen Idec ; Bristol-Myers Squibb ; Eisai Inc ; Elan Pharmaceuticals, Inc ; Eli Lilly and Company ; F. Hoffmann-La Roche Ltd and its affiliated company Genentech ; GE ; Innogenetics, N.V. ; IXICO Ltd ; Janssen Alzheimer Immunotherapy Research & Development, LLC ; Johnson & Johnson Pharmaceutical Research & Development LLC ; Medpace, Inc ; Merck & Co., Inc. ; Meso Scale Diagnostics, LLC ; NeuroRx Research ; Novartis ; Pfizer ; Piramal Imaging ; Servier ; Synarc Inc ; and Takeda Pharmaceuticals North America . The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health ( www.fnih.org ). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. This research was also supported by NIH grants P30 AG010129 and K01 AG030514 . Publisher Copyright: {\textcopyright} 2015 The Alzheimer's Association.",
year = "2015",
month = apr,
day = "1",
doi = "10.1016/j.jalz.2014.03.005",
language = "English (US)",
volume = "11",
pages = "415--424",
journal = "Alzheimer's and Dementia",
issn = "1552-5260",
publisher = "Elsevier Inc.",
number = "4",
}