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


OBJECTIVE
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.


METHODS
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.


METHODS
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
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.
Helen Wills Neuroscience Institute, University of California, Berkeley2Department of Neurology, Otto-von-Guericke University, Magdeburg, Germany3German Center for Neurodegenerative Diseases, Magdeburg.
Stefanie
S
Schreiber
Helen Wills Neuroscience Institute, University of California, Berkeley4Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California.
Susan M
SM
Landau
Helen Wills Neuroscience Institute, University of California, Berkeley4Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California.
Allison
A
Fero
Institute of Control Engineering, Technische Universität Braunschweig, Braunschweig, Germany.
Frank
F
Schreiber
Helen Wills Neuroscience Institute, University of California, Berkeley4Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California.
William J
WJ
Jagust
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000175:diagnosis / Q000628:therapy; D016229:Amyloid beta-Peptides / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis; D060825:Cognitive Dysfunction / Q000150:complications / Q000000981:diagnostic imaging* / Q000628:therapy; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods; D011237:Predictive Value of Tests; D016896:Treatment Outcome
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D019788:Fluorodeoxyglucose F18