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DOI: 10.1055/s-0040-1708416
Validation of the Alzheimer’s dementia conversion-related pattern as a biomarker of neurodegeneration within the NIA-AA research framework
Publication History
Publication Date:
08 April 2020 (online)
Ziel/Aim According to the NIA-AA research framework, Alzheimer’s disease (AD) is defined biologically by in vivo biomarkers of Aβ deposition (labeled ‘A’) and pathological tau (labeled ‘T’). The biomarkers group labeled ‘(N)’ indicates neurodegeneration or neuronal injury, e.g., as seen on F-18-FDG PET. Here, we examined whether the pattern expression score (PES) of the Alzheimer’s dementia conversion-related pattern (ADCRP) on F-18-FDG PET is (1) increased in mild cognitive impairment (MCI) patients with biologically defined AD, and (2) a valid predictor for development of AD dementia in this patient group.
Methodik/Methods 269 MCI subjects from the ADNI database with available F-18-FDG PET, F-18-Florbetapir PET, CSF phosphorylated tau (P-tau) CSF total tau (T-tau), and blood plasma neurofilament light chain (NfL) were included. Biomarkers of Aβ load (A) and P-tau (T) were classified as positive if SUVR > 1.3 and P-tau concentration in CSF > 26.6 pg/mL, respectively. Based on this binarization, patients were categorized to A+T+ (AD), A-T-, A+T- and A-T+ groups. PES was compared among groups, and its prognostic value was assessed within the A+T+ group and compared to that of T-tau and NfL.
Ergebnisse/Results 136 subjects were categorized as A+T+ (41 % of whom converted to AD dementia over 5 years). The ADCRP PES was significantly higher in the A+T+ group compared to each of the other groups (all p < 0.05). Within the A+T+ group, PES was a significant predictor of conversion to AD dementia (HR = 2.02 per z-score increase, p < 0.001; T-tau, HR = 1.38, p = 0.003; NfL, HR = 1.48, p = 0.027). Stratification of A+T+ subjects by PES into three equally-sized groups yielded well-separated groups of high, medium or low conversion risk, whereas T-tau and NfL provided only limited (high vs. low) and no significant risk stratification, respectively.
Schlussfolgerungen/Conclusions The PES of the ADCRP is a valuable biomarker of neurodegeneration in subjects with MCI and biologically defined AD. It shows great potential for stratifying the risk and estimating the time to conversion to dementia in MCI patients with underlying AD (A+T+), which is of great interest for clinical practice and future trials.