Longitudinal flortaucipir ([¹⁸F]AV-1451) PET imaging in primary progressive apraxia of speech

Primary progressive apraxia of speech (PPAOS) is a term used to describe a neurodegenerative condition in which apraxia of speech (AOS; a planning and/or programming deficit) occurs in the absence of aphasia (a language deficit). PPAOS is strongly associated with 4-repeat tau pathology. Elevated flortaucipir ([¹⁸F]AV-1451; FTP) uptake has been observed cross-sectionally in patients with PPAOS and those with aphasia. Here, we evaluated longitudinal changes in previously-identified regions of uptake and their relationship with clinical presentation. Thirteen patients who were diagnosed with PPAOS (5 female) at presentation underwent FTP PET imaging at two visits (mean 1 year interval). Median age was 72, with a median of 4 years disease duration at initial testing. Beta-amyloid status was assessed with Pittsburgh Compound B (PiB), where a global PiB ratio>1.48 was deemed amyloid positive (n = 4). FTP uptake was assessed as cortical to cerebellar crus ratios (SUVr) in cortical regions of interest. A single hierarchical linear model (HLM) compared PPAOS patients to 52 cognitively unimpaired controls of similar age and sex. Annualized SUVr change was the outcome, predicted by region, clinical status, and age. Person-specific effects accounted for intra-patient correlations and contralateral regions were included as repeated measures. Changes in clinical measures were assessed using Wilcoxon signed-rank tests; statistically significant changes in the Montreal Cognitive Assessment, MDS-UPDRS, motor section, and PSP Rating Scale were noted between visits. Changes in FTP SUVr were greater for patients than controls. The strongest changes in PPAOS patients were in the precentral gyrus, pallidum, and mid and superior frontal gyri, per the HLM. Qualitatively, larger changes were seen in patients who had developed aphasia by the time of their baseline scan (n = 5). While the biological mechanisms of FTP signal in non-AD tauopathies are unknown, this study demonstrates the utility of FTP in tracking disease progression in 4R tauopathies.