期刊
ALZHEIMERS RESEARCH & THERAPY
卷 7, 期 -, 页码 -出版社
BMC
DOI: 10.1186/s13195-015-0152-z
关键词
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资金
- Canadian Institutes of Health Research [125740, 13129]
- Linda C. Campbell Foundation
- Heart AMP
- Stroke Foundation Canadian Partnership for Stroke Recovery
- L'Oreal Canada for Women in Science Research Excellence Fellowship
- Canadian Vascular Network
- Sunnybrook Health Sciences Centre, Hurvitz Brain Sciences Program at the Sunnybrook Research Institute, Brill Chair Neurology
- University of Toronto
- Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant) [U01 AG024904]
- DOD ADNI (Department of Defense award) [W81XWH-12-2-0012]
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- Alzheimer's Drug Discovery Foundation
- Araclon Biotech
- BioClinica, Inc.
- Biogen
- Bristol-Myers Squibb Company
- CereSpir, Inc.
- Eisai Inc.
- Elan Pharmaceuticals, Inc.
- Eli Lilly and Company
- EuroImmun
- F. Hoffmann-La Roche Ltd
- Fujirebio
- GE Healthcare
- IXICO Ltd.
- Janssen Alzheimer Immunotherapy Research AMP
- Development, LLC.
- Johnson AMP
- Johnson Pharmaceutical Research AMP
- Development LLC.
- Lumosity
- Lundbeck
- Merck Co., Inc.
- Meso Scale Diagnostics, LLC.
- NeuroRx Research
- Neurotrack Technologies
- Novartis Pharmaceuticals Corporation
- Pfizer Inc.
- Piramal Imaging
- Servier
- Takeda Pharmaceutical Company
- Transition Therapeutics
- Canadian Institutes of Health Research
- Northern California Institute for Research and Education
- AbbVie, Alzheimer's Association
- Fonds de recherche du Quebec - Sante
Introduction: The definition of objective cognitive impairment in current criteria for mild cognitive impairment (MCI) varies considerably between research groups and clinics. This study aims to compare different methods of defining memory impairment to improve prediction models for the development of Alzheimer's disease (AD) from baseline to 24 months. Methods: The sensitivity and specificity of six methods of defining episodic memory impairment (< -1, -1.5 or -2 standard deviations [SD] on one or two memory tests) were compared in 494 non-demented seniors from the Alzheimer's Disease Neuroimaging Initiative using the area under the curve (AUC) for receiver operating characteristic analysis. The added value of non-memory measures (language and executive function) and biomarkers (hippocampal and white-matter hyperintensity volume, brain parenchymal fraction [BPF], and APOE epsilon 4 status) was investigated using logistic regression. Results: Baseline scores < -1 SD on two memory tests predicted AD with 75.91 % accuracy (AUC = 0.80). Only APOE epsilon 4 status further improved prediction (B = 1.10, SE = 0.45, p = .016). A < -1.5 SD cut-off on one test had 66.60 % accuracy (AUC = 0.77). Prediction was further improved using Trails B/A ratio (B = 0.27, SE = 0.13, p = .033), BPF (B = -15.97, SE = 7.58, p = .035), and APOEe4 status (B = 1.08, SE = 0.45, p = .017). A cut-off of < -2 SD on one memory test (AUC = 0.77, SE = 0.03, 95 % CI 0.72-0.82) had 76.52 % accuracy in predicting AD. Trails B/A ratio (B = 0.31, SE = 0.13, p = .017) and APOE epsilon 4 status (B = 1.07, SE = 0.46, p = .019) improved predictive accuracy. Conclusions: Episodic memory impairment in MCI should be defined as scores < -1 SD below normative references on at least two measures. Clinicians or researchers who administer a single test should opt for a more stringent cut-off and collect and analyze whole-brain volume. When feasible, ascertaining APOE epsilon 4 status can further improve prediction.
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