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DOI: 10.1055/s-0039-1683502
Predictive value of quantitative F-18-Florbetapir and F-18-FDG PET for conversion from MCI to AD
Publication History
Publication Date:
27 March 2019 (online)
Ziel/Aim:
The present study examines the predictive values of F-18-Florbetapir (AV45), F-18-FDG PET and clinical variables, separately and in combination in a large population.
Methodik/Methods:
319 mild cognitive impairment (MCI) patients from the ADNI database (median follow-up: 47 months) were studied. For FDG PET, we assessed the pattern expression score (PES) of a recently validated Alzheimer's dementia (AD) conversion-related pattern. For assessment of beta-amyloid load, we calculated the SUV ratios in AD-typical regions using the cerebellum as reference. In a training dataset (n = 159), Cox proportional hazards regressions were applied to estimate the prognostic value of candidate predictors (adjusted for age and sex): i) clinical variables (APOE; FAQ), ii) clinical variables combined with PES, and iii) clinical variables combined with beta-amyloid load. For model validation, the results of Cox regressions were applied to a test dataset (n = 160) by calculating the prognostic index and stratifying each subject according to the predicted conversion risk.
Ergebnisse/Results:
PES (HR per two z-scores increase = 2.38), FAQ (HR = 2.12) and beta-amyloid load (HR = 2.09) were found to be significant independent predictors (all p<= 0.001). In the training dataset, combining clinical variables with PES yielded a significantly better (p < 0.001) model fit than combining with beta-amyloid or clinical variables alone (AIC = 318, 327 and 339, respectively); best prediction accuracy was reached combining PES, beta-amyloid and clinical variables into a combined model (AIC = 300). 5-year conversion-free survival rates for the low, medium and high risk groups were 96%, 77% and 19% for PES, 97%, 64% and 44% for beta-amyloid and 100%, 70% and 28% for PES and beta-amyloid (clinical variables always included). Interestingly, 11% of assumed AD converters were amyloid-negative, but PES scores were not different from amyloid-positive converters.
Schlussfolgerungen/Conclusions:
FDG, beta-amyloid and clinical variables represent complementary predictors of conversion from MCI to AD. The present study also supports the proposed NIA-AA research framework towards a biological definition of AD.