title: Imaging markers for Alzheimer disease: which vs how.
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.
authors.affiliation: LENITEM-Laboratory of Epidemiology, Neuroimaging and Telemedicine, IRCCS, S. Giovanni di Dio, Fatebenefratelli Brescia, Italy. gfrisoni@fatebenefratelli.it
authors.forename: Giovanni B
authors.initials: GB
authors.lastname: Frisoni
authors.forename: Martina
authors.initials: M
authors.lastname: Bocchetta
authors.forename: Gael
authors.initials: G
authors.lastname: Chételat
authors.forename: Gil D
authors.initials: GD
authors.lastname: Rabinovici
authors.forename: Mony J
authors.initials: MJ
authors.lastname: de Leon
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Kaye
authors.forename: Eric M
authors.initials: EM
authors.lastname: Reiman
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Black
authors.forename: David J
authors.initials: DJ
authors.lastname: Brooks
authors.forename: Maria C
authors.initials: MC
authors.lastname: Carrillo
authors.forename: Nick C
authors.initials: NC
authors.lastname: Fox
authors.forename: Karl
authors.initials: K
authors.lastname: Herholz
authors.forename: Agneta
authors.initials: A
authors.lastname: Nordberg
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Jack
authors.forename: William J
authors.initials: WJ
authors.lastname: Jagust
authors.forename: Keith A
authors.initials: KA
authors.lastname: Johnson
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Rowe
authors.forename: Reisa A
authors.initials: RA
authors.lastname: Sperling
authors.forename: William
authors.initials: W
authors.lastname: Thies
authors.forename: Lars-Olof
authors.initials: LO
authors.lastname: Wahlund
authors.forename: Michael W
authors.initials: MW
authors.lastname: Weiner
authors.forename: Patrizio
authors.initials: P
authors.lastname: Pasqualetti
authors.forename: Charles
authors.initials: C
authors.lastname: Decarli
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D011859:Radiography; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
chemical_list: D015415:Biomarkers; D019788:Fluorodeoxyglucose F18
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