Imaging markers for Alzheimer disease
Top Cited Papers
- 30 July 2013
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Neurology
- Vol. 81 (5), 487-500
- https://doi.org/10.1212/wnl.0b013e31829d86e8
Abstract
Revised diagnostic criteria for Alzheimer disease (AD) acknowledge a key role of imaging biomarkers for early diagnosis. Diagnostic accuracy depends on which marker (i.e., amyloid imaging, 18F-fluorodeoxyglucose [FDG]-PET, SPECT, MRI) as well as how it is measured (“metric”: visual, manual, semiautomated, or automated segmentation/computation). We evaluated diagnostic accuracy of marker vs metric in separating AD from healthy and prognostic accuracy to predict progression in mild cognitive impairment. The outcome measure was positive (negative) likelihood ratio, LR+ (LR−), defined as the ratio between the probability of positive (negative) test outcome in patients and the probability of positive (negative) test outcome in healthy controls. Diagnostic LR+ of markers was between 4.4 and 9.4 and LR− between 0.25 and 0.08, whereas prognostic LR+ and LR− were between 1.7 and 7.5, and 0.50 and 0.11, respectively. Within metrics, LRs varied up to 100-fold: LR+ from approximately 1 to 100; LR− from approximately 1.00 to 0.01. Markers accounted for 11% and 18% of diagnostic and prognostic variance of LR+ and 16% and 24% of LR−. Across all markers, metrics accounted for an equal or larger amount of variance than markers: 13% and 62% of diagnostic and prognostic variance of LR+, and 29% and 18% of LR−. Within markers, the largest proportion of diagnostic LR+ and LR− variability was within 18F-FDG-PET and MRI metrics, respectively. Diagnostic and prognostic accuracy of imaging AD biomarkers is at least as dependent on how the biomarker is measured as on the biomarker itself. Standard operating procedures are key to biomarker use in the clinical routine and drug trials.Keywords
This publication has 46 references indexed in Scilit:
- Brain Amyloid Imaging — FDA Approval of Florbetapir F18 InjectionThe New England Journal of Medicine, 2012
- Prediction of conversion from mild cognitive impairment to Alzheimer's disease dementia based upon biomarkers and neuropsychological test performanceNeurobiology of Aging, 2012
- Age and diagnostic performance of Alzheimer disease CSF biomarkersNeurology, 2012
- Alliance for Aging Research AD Biomarkers Work Group: structural MRINeurobiology of Aging, 2011
- Effectiveness and Safety of 18F-FDG PET in the Evaluation of Dementia: A Review of the Recent LiteratureJournal of Nuclear Medicine, 2011
- Amyloid imaging in the differential diagnosis of dementia: review and potential clinical applicationsAlzheimer's Research & Therapy, 2011
- Automatic classification of patients with Alzheimer's disease from structural MRI: A comparison of ten methods using the ADNI databaseNeuroImage, 2011
- Characterizing Alzheimer's disease using a hypometabolic convergence indexNeuroImage, 2011
- Validation of a fully automated 3D hippocampal segmentation method using subjects with Alzheimer's disease mild cognitive impairment, and elderly controlsNeuroImage, 2008
- 100 Years and Counting: Prospects for Defeating Alzheimer's DiseaseScience, 2006