18F-Flortaucipir (AV1451) imaging identifies grey matter atrophy in retired athletes

Abstract

Background: The long-term consequences of concussions may include pathological neurodegeneration as seen in Alzheimer's disease (AD) and chronic traumatic encephalopathy (CTE). Tau-PET showed promise as a method to detect tau pathology of CTE, but more studies are needed OBJECTIVE: This study aimed (1) to assess the association of imaging evidence of tau pathology with brain volumes in retired athletes and (2) to examine the relationship between tau-PET and neuropsychological functioning.

Methods: Former contact sport athletes were recruited through the Canadian Football League Alumni Association or the Canadian Concussion Centre clinic. Athletes completed MRI, [¹⁸F]flortaucipir tau-PET, and a neuropsychological battery. Memory composite was created by averaging the Rey Auditory Verbal Learning Test and Rey Visual Design Learning Test z-scores. Grey matter (GM) volumes were age/intracranial volume corrected using normal control MRIs. Tau-PET % positivity in GM was calculated as the number of positive voxels (≥ 1.3 standardized uptake value ratio (SUVR)/total voxels).

Results: 47 retired contact sport athletes negative for AD (age:51 ± 14; concussions/athlete:15 ± 2) and 54 normal controls (age:50 ± 13) were included. Tau-PET positive voxels had significantly lower GM volumes, compared to tau-PET negative voxels (- 0.37 ± 0.41 vs. - 0.31 ± 0.37, paired p = .006). There was a significant relationship between GM tau-PET % positivity and memory composite score (r = - .366, p = .02), controlled for age, PET scanner, and PET scan duration. There was no relationship between tau-PET measures and concussion number, or years of sport played.

Conclusion: A higher tau-PET signal was associated with reduced GM volumes and lower memory scores. Tau-PET may be useful for identifying those at risk for neurodegeneration.

Keywords: Athletes; Chronic traumatic encephalopathy; Concussion; Neurodegeneration; Pet; Tau.

Fig. 1

A neuroimaging approach to extract mean grey matter volumes from tau-PET positive and negative voxels of each participant. Illustration of the steps required to extract the mean standardized grey matter volumes (VBM w-scores) from tau-PET positive and negative voxels for each participant. First, motion and partial volume effect corrected SUVR images are created using inferior cerebellar grey matter as a reference region. The SUVR image is then co-registered to the MRI image that is preprocessed using the standard CAT12 VBM pipeline. Next, the deformation fields from MRI are used on the SUVR image to bring it into standard space, followed by masking using a grey matter mask created from LONI Probabilistic Atlas (LPBA40) and smoothing. Different smoothing kernels were applied depending on the PET scanner used: subjects scanned on the HRRT scanner had a smoothing kernel of FWHM: 7.37 × 7.37 × 7.91; subjects scanned on the PET/CT scanner had a smoothing kernel of FWHM: 6.55 × 6.55 × 7.75. Finally, the smoothed SUVR images were threshold at ≥ 1.30 to create a mask with tau-PET positive voxels, and < 1.30 to create a mask with tau-PET negative voxels. The participant-specific positive and negative tau-PET masks were overlaid over the VBM w-score images and mean GM w-score values were extracted for each participant. SUVR Standardized uptake value ratios, VBM voxel-based morphometry, GM grey matter

Fig. 2

Example of the flortaucipir tau-PET signal and distribution of low grey matter volume in a single former athlete. Spatial maps of the flortaucipir tau-PET SUVR (top) and the reduced grey matter volumes showed in blue and defined as voxels with a w-score of > 1.5 below the mean (bottom) in a single former athlete

Fig. 3

Mean tau-PET SUVR values across quartiles