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

Objective: To determine whether the Alzheimer’s disease dementia conversion-related pattern (ADCRP) on [18F]FDG PET can serve as a valid predictor for the development of Alzheimer’s disease dementia, the individual expression of the ADCRP (subject score) and its prognostic value were examined in subjects with mild cognitive impairment and biologically defined Alzheimer’s disease. Methods: 269 subjects with available [18F]FDG PET, [18F]AV-45 PET, phosphorylated and total tau in CSF, and neurofilament light chain in plasma were included. Following the AT(N) classification scheme, where Alzheimer’s disease is defined biologically by in vivo biomarkers of Aβ deposition (“A”) and pathological tau (“T”), subjects were categorized to the A-T-, A+T-, A+T+ (Alzheimer’s disease), 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 0.1). Within the A+T+ group, the subject score of ADCRP was a significant predictor of conversion to dementia (HR = 2.02 per z-score increase, p Conclusions: The ADCRP is a valuable biomarker of neurodegeneration in subjects with mild cognitive impairment and biologically defined Alzheimer’s disease. It shows great potential for stratifying the risk and estimating the time to conversion to dementia in subjects with mild cognitive impairment and underlying Alzheimer’s disease (A+T+). Classification of Evidence: This study provides Class I evidence that [18F]FDG PET predicts the development of AD dementia in individuals with MCI and underlying AD as defined by the AT(N) framework.