Validation of the Alzheimer Disease Dementia Conversion-Related Pattern as an ATN Biomarker of Neurodegeneration

Objective To determine whether the Alzheimer disease (AD) dementia conversion-related pattern (ADCRP) on [F-18]FDG PET can serve as a valid predictor for the development of AD dementia, the individual expression of the ADCRP (subject score) and its prognostic value were examined in patients with mild cognitive impairment (MCI) and biologically defined AD. Methods A total of 269 patients with available [F-18]FDG PET, [F-18]AV-45 PET, phosphorylated and total tau in CSF, and neurofilament light chain in plasma were included. Following the AT(N) classification scheme, where AD is defined biologically by in vivo biomarkers of beta-amyloid (A beta) deposition ("A") and pathologic tau ("T"), patients were categorized to the A-T-, A+T-, A+T+ (AD), and A-T+ groups. Results The mean subject score of the ADCRP was significantly higher in the A+T+ group compared to each of the other group (all p < 0.05) but was similar among the latter (all p > 0.1). Within the A+T+ group, the subject score of ADCRP was a significant predictor of conversion to dementia (hazard ratio, 2.02 per z score increase; p < 0.001), with higher predictive value than of alternative biomarkers of neurodegeneration (total tau and neurofilament light chain). Stratification of A+T+ patients by the subject score of ADCRP yielded well-separated groups of high, medium, and low conversion risks. Conclusions The ADCRP is a valuable biomarker of neurodegeneration in patients with MCI and biologically defined AD. It shows great potential for stratifying the risk and estimating the time to conversion to dementia in patients with MCI and underlying AD (A+T+). Classification of Evidence This study provides Class I evidence that [F-18]FDG PET predicts the development of AD dementia in individuals with MCI and underlying AD as defined by the AT(N) framework.