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

IMPORTANCE The applicability of beta-amyloid peptide (A beta) 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 A beta PET assessment seems to be the most feasible approach. OBJECTIVES To determine the agreement between visual and quantitative A beta 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 [F-18] 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 [F-18] florbetapir PET categorization, which was estimated with cerebrospinal fluid A beta 1-42 as the reference standard. Risk for conversion to AD was assessed using Cox proportional hazards regression models. RESULTS The frequency of A beta 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 (kappa = 0.74) and between all methods (Fleiss kappa = 0.71). For approximately 10% of the 401 participants in whom visual and SUVR data disagreed, interrater reliability was moderate (kappa = 0.44), but it was very high if visual and quantitative results agreed (kappa = 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 [F-18] 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 epsilon 4, concurrent fludeoxyglucose F 18 PET scan, and baseline cognitive status. CONCLUSIONS AND RELEVANCE Visual and SUVR A beta PET analysis may be equivalently used to determine A beta status for individuals with MCI participating in clinical trials, and both approaches add significant value for clinical course prognostication.