Year: 2013
Type: article
Study design: Observational Study
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.
Source: Neurology
Authors: Giovanni B. Frisoni, Martina Bocchetta, Gael Chételat, Gil D. Rabinovici, Mony J. de Leon, Jeffrey Kaye, Eric M. Reiman, Philip Scheltens, Frederik Barkhof, Sandra E. Black, David J. Brooks, Maria C. Carrillo, Nick C. Fox, Karl Herholz, Agneta Nordberg, Clifford R. Jack, William J. Jagust, Keith A. Johnson, Christopher C. Rowe, Reisa A. Sperling, William Thies, Lars-Olof Wahlund, Michael W. Weiner, Patrizio Pasqualetti, Charles DeCarli, For ISTAART's NeuroImaging Professional Interest Area
Institutions: Inserm, University of California, San Francisco, Centre Hospitalier Universitaire de Caen Normandie, Centro San Giovanni di Dio Fatebenefratelli, Université de Caen Normandie, Portland VA Medical Center, Banner Alzheimer’s Institute, Vrije Universiteit Amsterdam, Imperial College London, Karolinska Institutet, Mayo Clinic, United States Department of Veterans Affairs
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: U.S. Department of Veterans Affairs, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, AstraZeneca, GlaxoSmithKline, Heart and Stroke Foundation of Canada, Fondation Brain Canada, Sunnybrook Research Institute, National Institute for Health and Care Research, NOMIS Stiftung, H. Lundbeck A/S, National Institutes of Health, Canadian Institutes of Health Research, Department of Medicine, University of Toronto, National Institute on Aging
OpenAlex ID: W1965618373