Varying Degrees of Temporoparietal Hypometabolism on FDG-PET Reveal Amyloid-Positive Logopenic Primary Progressive Aphasia is not a Homogeneous Clinical Entity

Abstract

Background: The logopenic variant of primary progressive aphasia (lvPPA) manifests due to a breakdown of the language network with prominent hypometabolism of the left temporoparietal region. LvPPA is strongly associated with amyloid deposition, yet there is question as to whether it is a homogeneous clinical entity.

Objective: This study investigated whether differences in temporoparietal metabolic patterns on 18F fludeoxyglucose positron emission tomography (FDG-PET) could elucidate brain regions preferentially affected in lvPPA.

Method: We used differences in FDG-PET metabolic z-scores relative to controls for means of left lateral temporal, left inferior parietal, and left superior parietal regions to classify 53 amyloid-positive lvPPA patients into temporal, parietal, or temporoparietal predominate groups. Clinical features and FDG-PET regions of hypometabolism outside of the temporoparietal region were then compared across the three groups; the latter using statistical parametric mapping.

Results: Of the 53 lvPPA patients, 15 were classified as temporal, 14 as temporoparietal, and 22 as parietal predominate. There were no significant differences between the groups on demographic measures, language evaluation, or apolipoprotein E genotype. Compared to the other two groups, individuals with the parietal predominate pattern had extensive hypometabolism in left frontal lobe and the precuneus. Furthermore, this group had greater behavioral dyscontrol and deficits in executive function, visuospatial skills, visual memory retention, working memory, and cognitive flexibility (Bonferronip < 0.05).

Conclusions: This study demonstrates that there is clinical heterogeneity within amyloid-positive lvPPA. Patients with lvPPA with predominant parietal hypometabolism, unlike those with temporal or temporoparietal predominant hypometabolism, demonstrated widespread cognitive and behavioral changes.

Keywords: 18F fludeoxyglucose; Amyloid-β; executive function; positron emission tomography; primary progressiveaphasia; visuospatial deficit; working memory.

Figure 1. Patterns of FDG-PET hypometabolism in the three lvPPA groups compared to controls

Glass brain renders showing patterns of FDG-PET hypometabolism in the parietal, temporoparietal, and temporal predominate lvPPA groups compared to controls. Results are shown after correction for multiple comparisons at p<0.001. Red arrows highlight the voxel with the peak t score for each comparison.

Figure 2. Patterns of FDG-PET hypometabolism in the three lvPPA groups compared to each other

Glass brain renders showing a direct comparisons of the three lvPPA groups, uncorrected for multiple comparisons at p<0.001. Red arrows highlight the voxel with the peak t score for each comparison.

Figure 3. Amyloid-β deposition on PiB-PET in both lvPPA groups

Glass brain renders showing amyloid-β deposition on PiB-PET in the parietal, temporoparietal, and temporal predominate lvPPA groups, corrected for multiple comparisons at p<0.001.