Publication Type Review
Authors Frisoni G, Bocchetta M, Chételat G, Rabinovici G, de Leon M, Kaye J, Reiman E, Scheltens P, Barkhof F, Black S, Brooks D, Carrillo M, Fox N, Herholz K, Nordberg A, Jack C, Jagust W, Johnson K, Rowe C, Sperling R, Thies W, Wahlund L, Weiner M, Pasqualetti P, Decarli C
Journal Neurology
Volume 81
Issue 5
Pagination 487-500
Date Published 07/30/2013
ISSN 1526-632X
Keywords Alzheimer Disease
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.
DOI 10.1212/WNL.0b013e31829d86e8
PubMed ID 23897875
PubMed Central ID PMC3776529
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