Affiliations: [a] Department of Brain Sciences, Division of Neurology, Faculty of Medicine, Imperial College London, London, UK
| [b]
School of Medicine, Cardiff University, Cardiff, Wales, UK
Correspondence:
[*]
Correspondence to: Prof Paul Edison, MD, PhD, MPhil, FRCP, FRCPI, Professor of Neuroscience, Department of Brain Sciences, Division of Neurology, Faculty of Medicine, Level 2, Commonwealth Building, Imperial College London, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK. Tel.: +44 20 7594 1081; E-mail: paul.edison@imperial.ac.uk.
Abstract: Background:Tau aggregation demonstrates close associations with hypometabolism in Alzheimer’s disease (AD), although differing pathophysiological processes may underlie their development. Objective:To establish whether tau deposition and glucose metabolism have different trajectories in AD progression and evaluate the utility of global measures of these pathological hallmarks in predicting cognitive deficits. Methods:279 participants with amyloid-β (Aβ) status, and T1-weighted MRI scans, were selected from the Alzheimer’s Disease Neuroimaging Initiative (http://adni.loni.usc.edu). We created the standard uptake value ratio images using Statistical Parametric Mapping 12 for [18F]AV1451-PET (tau) and [18F]FDG-PET (glucose metabolism) scans. Voxel-wise group and single-subject level SPM analysis evaluated the relationship between global [18F]FDG-PET and [18F]AV1451-PET depending on the Aβ status. Linear models assessed whether tau deposition or glucose metabolism better predicted clinical progression. Results:There was a dissociation between global cerebral glucose hypometabolism and global tau load in amyloid-positive AD and amyloid-negative mild cognitive impairment (MCI) (p > 0.05). Global hypometabolism was only associated with global cortical tau in amyloid-positive MCI. Voxel-level single subject tau load better predicted neuropsychological performance, Alzheimer’s disease assessment scale-cognitive (ADAS-Cog) 13 score, and one-year change compared with regional and global hypometabolism. Conclusions:A dissociation between tau pathology and glucose metabolism at a global level in AD could imply that other pathological processes influence glucose metabolism. Furthermore, as tau is a better predictor of clinical progression, these processes may have independent trajectories and require independent consideration in the context of therapeutic interventions.
Keywords: Alzheimer’s disease, fluorodeoxyglucose F18, positron-emission tomography, tau proteins
