Comparison of visual and quantitative florbetapir F 18 positron emission tomography analysis in predicting mild cognitive impairment outcomes
- Author(s): Schreiber, S
- Landau, SM
- Fero, A
- Schreiber, F
- Jagust, WJ
- et al.
Published Web Locationhttp://jamanetwork.com/journals/jamaneurology/fullarticle/2417176
Copyright 2015 American Medical Association. All rights reserved. IMPORTANCE: The applicability of ß-amyloid peptide (Aß) 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 Aß PET assessment seems to be the most feasible approach. OBJECTIVES: To determine the agreement between visual and quantitative Aß 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 a1.6-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. MAINOUTCOMES ANDMEASURES: Sensitivity and specificity of positive and negative [18F] florbetapir PET categorization, which was estimated with cerebrospinal fluid Aß1-42 as the reference standard. Risk for conversion to AD was assessed using Cox proportional hazards regression models. RESULTS: The frequency of Aß 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 e4, concurrent fludeoxyglucose F 18 PET scan, and baseline cognitive status. CONCLUSIONS AND RELEVANCE: Visual and SUVR Aß PET analysis maybe equivalently used to determine Aß status for individuals with MCI participating in clinical trials, and both approaches add significant value for clinical course prognostication.
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