The clinical Alzheimer's disease spectrum classified in the A/T/N framework with ¹⁸F-Flutemetamol-Centiloid, ¹⁸F-MK-6240-CenTauR, and ¹⁸F-FDG-AD metaROI: a multicenter memory clinic observational study.

Abstract

This study pioneers the ability of semi-quantitative A/T/N classification using combined ¹⁸F-Flutemetamol (A), ¹⁸F-MK-6240 (T) and ¹⁸F-FDG (N) positron emission tomography (PET) tracers with binary classifications and standardised scales for Centiloid (A), CenTauR (T), and AD metaROI (N), to clinically describe subjects with Mild Cognitive Impairment (MCI) or Mild Dementia (MD) in Alzheimer's disease (AD). MCI (n = 45, mean age 71.0 ± 8.8, 40% female, MMSE 26.2) and MD (n = 44, mean age 70.1 ± 7.6, 48% female, MMSE 24.1) participants underwent PET with ¹⁸F-Flutemetamol for amyloid-β, ¹⁸F-MK-6240 tau and/or ¹⁸F-FDG for neurodegeneration. Images were semi-quantified using Centiloid, CenTauR, and AD metaROI. Predefined cut-offs classified scans as positive (+) or negative (-), and standard uptake value ratio (SUVR) values semi-quantified A-burden, T-burden, and N-burden. T+ was more frequent in MD (68%) than in MCI (44%). Among T+ , MD participants were more often A+ (39%) than MCI (27%). T-burden differed significantly between MCI and MD (W = 642, p = 0.004). Increasing A-burden, T-burden, and hypometabolism, reflected by lower N-burden were associated with worse performance in Norwegian validated revised mini-mental state-examination (MMSE-NR3) (p = 0.048, < 0.001, and 0.006, respectively), A-burden and N-burden with CERAD Word List Memory Test for immediate and delayed recall (CERAD) (p = 0.041), T-burden with CERAD Word List Memory Test for recognition (CERAD R) (p < 0.001), and N-burden with Clock-drawing test (CDT) (p = 0.023) and Controlled Oral Word Association Test (COWAT) (p = 0.025). The A/T/N classification was most informative for A (+/-) and T (+/-) PET, with T-PET appearing to distinguish MCI from MD, while N-PET correlated most with cognitive impairment.