Relationships between [18F]-THK5351 Retention and Language Functions in Primary Progressive Aphasia

Background and Purpose There are three distinct subtypes of primary progressive aphasia (PPA): the nonfluent/agrammatic variant (nfvPPA), the semantic variant (svPPA), and the logopenic variant (lvPPA). We sought to characterize the pattern of [F-18]-THK5351 retention across all three subtypes and determine the topography of [F-18]-THK5351 retention correlated with each neurolinguistic score. Methods We enrolled 50 participants, comprising 13 PPA patients (3 nfvPPA, 5 svPPA, and 5 lvPPA) and 37 subjects with normal cognition (NC) who underwent 3.0-tesla magnetic resonance imaging, [F-18]-THK5351 positron-emission tomography scans, and detailed neuropsychological tests. The PPA patients additionally participated in extensive neurolinguistic tests. Voxel-wise and region-of-interest-based analyses were performed to analyze [F-18]-THK5351 retention. Results The nfvPPA patients exhibited higher [F-18]-THK5351 retention in the the left inferior frontal and precentral gyri. In svPPA patients, [F-18]-THK5351 retention was elevated in the anteroinferior and lateral temporal cortices compared to the NC group (left>right). The lvPPA patients exhibited predominant [F-18]-THK5351 retention in the inferior parietal, lateral temporal, and dorsolateral prefrontal cortices, and the precuneus (left>right). [F-18]-THK5351 retention in the left inferior frontal area was associated with lower fluency scores. Comprehension was correlated with [F-18]-THK5351 retention in the left temporal cortices. Repetition was associated with [F-18]-THK5351 retention in the left inferior parietal and posterior temporal areas, while naming difficulty was correlated with retention in the left fusiform and temporal cortices. Conclusions The pattern of [F-18]-THK5351 retention was well matched with clinical and radiological findings for each PPA subtype, in agreement with the anatomical and functional location of each language domain.