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JAMA Neurol. 2015 Oct;72(10):1183-90. doi: 10.1001/jamaneurol.2015.1633.

Comparison of Visual and Quantitative Florbetapir F 18 Positron Emission Tomography Analysis in Predicting Mild Cognitive Impairment Outcomes.

Collaborators (198)

Aisen P, Jack CR Jr, Toga AW, Beckett L, Gamst A, Soares H, Green RC, Montine T, Thomas RG, Donohue M, Walter S, Dale A, Bernstein M, Felmlee J, Fox N, Thompson P, Schuff N, Alexander G, DeCarli C, Bandy D, Chen K, Morris J, Lee VM, Korecka M, Crawford K, Neu S, Harvey D, Kornak J, Saykin AJ, Foroud TM, Potkin S, Shen L, Buckholtz N, Kaye J, Dolen S, Quinn J, Schneider L, Pawluczyk S, Spann BM, Brewer J, Vanderswag H, Heidebrink JL, Lord JL, Petersen R, Johnson K, Doody RS, Villanueva-Meyer J, Chowdhury M, Stern Y, Honig LS, Bell KL, Morris JC, Mintun MA, Schneider S, Marson D, Griffith R, Clark D, Grossman H, Tang C, Marzloff G, deToledo-Morrell L, Shah RC, Duara R, Varon D, Roberts P, Albert MS, Pedroso J, Toroney J, Rusinek H, de Leon MJ, De Santi SM, Doraiswamy P, Petrella JR, Aiello M, Clark CM, Pham C, Nunez J, Smith CD, Given CA 2nd, Hardy P, Lopez OL, Oakley M, Simpson DM, Ismail M, Brand C, BA JR, Mulnard RA, Thai G, Mc-Adams-Ortiz C, Diaz-Arrastia R, Martin-Cook K, DeVous M, Levey AI, Lah JJ, Cellar JS, Burns JM, Anderson HS, Laubinger MM, Bartzokis G, Silverman DH, Lu PH, Graff-Radford NR, Parfitt F, Johnson H, Farlow M, Herring S, Hake AM, van Dyck CH, MacAvoy MG, Benincasa AL, Chertkow H, Bergman H, Hosein C, Black S, Graham S, Caldwell C, Hsiung GY, Feldman H, Assaly M, Kertesz A, Rogers J, Trost D, Bernick C, Munic D, Wu CK, Johnson N, Mesulam M, Sadowsky C, Martinez W, Villena T, Turner S, Johnson KB, Behan KE, Sperling RA, Rentz DM, Johnson KA, Rosen A, Tinklenberg J, Ashford W, Sabbagh M, Connor D, Jacobson S, Killiany R, Norbash A, Nair A, Obisesan TO, Jayam-Trouth A, Wang P, Lerner A, Hudson L, Ogrocki P, DeCarli C, Fletcher E, Carmichael O, Kittur S, Mirje S, Borrie M, Lee TY, Bartha R, Johnson S, Asthana S, Carlsson CM, Potkin SG, Preda A, Nguyen D, Tariot P, Fleisher A, Reeder S, Bates V, Capote H, Rainka M, Hendin BA, Scharre DW, Kataki M, Zimmerman EA, Celmins D, Brown AD, Gandy S, Marenberg ME, Rovner BW, Pearlson G, Blank K, Anderson K, Saykin AJ, Santulli RB, Englert J, Williamson JD, Sink KM, Watkins F, Ott BR, Wu CK, Cohen R, Salloway S, Malloy P, Correia S, Rosen HJ, Miller BL, Mintzer J.

Abstract

IMPORTANCE:

The applicability of β-amyloid peptide (Aβ) positron emission tomography (PET) as a biomarker in clinical settings to aid in selection of individuals at preclinical and prodromal Alzheimer disease (AD) will depend on the practicality of PET image analysis. In this context, visual-based Aβ PET assessment seems to be the most feasible approach.

OBJECTIVES:

To determine the agreement between visual and quantitative Aβ PET analysis and to assess the ability of both techniques to predict conversion from mild cognitive impairment (MCI) to AD.

DESIGN, SETTING, AND PARTICIPANTS:

A longitudinal study was conducted among the Alzheimer's Disease Neuroimaging Initiative (ADNI) sites in the United States and Canada during a 1.6-year mean follow-up period. The study was performed from September 21, 2010, to August 11, 2014; data analysis was conducted from September 21, 2014, to May 26, 2015. Participants included 401 individuals with MCI receiving care at a specialty clinic (219 [54.6%] men; mean [SD] age, 71.6 [7.5] years; 16.2 [2.7] years of education). All participants were studied with florbetapir F 18 [18F] PET. The standardized uptake value ratio (SUVR) positivity threshold was 1.11, and one reader rated all images, with a subset of 125 scans rated by a second reader.

MAIN OUTCOMES AND MEASURES:

Sensitivity and specificity of positive and negative [18F] florbetapir PET categorization, which was estimated with cerebrospinal fluid Aβ1-42 as the reference standard. Risk for conversion to AD was assessed using Cox proportional hazards regression models.

RESULTS:

The frequency of Aβ positivity was 48.9% (196 patients; visual analysis), 55.1% (221 patients; SUVR), and 64.8% (166 patients; cerebrospinal fluid), yielding substantial agreement between visual and SUVR data (κ = 0.74) and between all methods (Fleiss κ = 0.71). For approximately 10% of the 401 participants in whom visual and SUVR data disagreed, interrater reliability was moderate (κ = 0.44), but it was very high if visual and quantitative results agreed (κ = 0.92). Visual analysis had a lower sensitivity (79% vs 85%) but higher specificity (96% vs 90%), respectively, compared with SUVR. The conversion rate was 15.2% within a mean of 1.6 years, and a positive [18F] florbetapir baseline scan was associated with a 6.91-fold (SUVR) or 11.38-fold (visual) greater hazard for AD conversion, which changed only modestly after covariate adjustment for apolipoprotein ε4, concurrent fludeoxyglucose F 18 PET scan, and baseline cognitive status.

CONCLUSIONS AND RELEVANCE:

Visual and SUVR Aβ PET analysis may be equivalently used to determine Aβ status for individuals with MCI participating in clinical trials, and both approaches add significant value for clinical course prognostication.

PMID:
26280102
DOI:
10.1001/jamaneurol.2015.1633
[PubMed - indexed for MEDLINE]
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