IN VIVO VISUALIZATION OF [18]F-THK5351 BINDING IN PRIMARY PROGRESSIVE APHASIA

Abstract

The neuropathology underlying primary progressive aphasia (PPA) is highly heterogeneous. 14 PPA patients (three logopenic variants (LV), three non-fluent variants (NFV), five semantic variants (SV) and three mixed variants (MV)) and 17 matched healthy controls received a [18F]-THK5351-PET scan 50–80 min post injection and a T1-weighted structural MRI. Standardized Uptake Value Ratio (SUVR) images were calculated with the subject-specific cerebellar gray matter as reference region. A voxelwise ANOVA (SPM12) was applied to contrast PPA variants against controls and against each other. The significance threshold was set at voxel-level uncorrected p<0.001 and cluster-level family wise error (FWE)-corrected p<0.05. To determine whether an individual patient differed from controls, a voxelwise one-sided modified t test was used, thresholded at uncorrected p<0.001. LV PPA had significantly increased [18F]-THK5351 retention in the temporoparietal junction, inferior temporal gyrus and the inferior parietal lobule bilaterally compared to controls. This pattern was present in 2/3 LV cases. Compared to SV, LV additionally showed increased retention in the precuneus. The NFV PPA showed significantly increased retention compared to controls and SV in subcortical structures including the nucleus dentatus, the midbrain, the left thalamus extending to the left pallidum, but also in the neocortex including the left pars opercularis, precentral gyrus and supplementary motor area. This cortical binding pattern was present in 2/3 NFV cases. The SV PPA showed a significant increase in the anterior temporal poles and in the orbitofrontal gyri bilaterally compared to controls and NFV (Figure1). This retention pattern was consistent across all five SV PPA. The MV PPA did not show significantly elevated retention at the subgroup level.