Longitudinal flortaucipir, metabolism and volume differ between phonetic and prosodic speech apraxia.

Progressive apraxia of speech is a neurodegenerative motor-speech disorder that most commonly arises from a 4-repeat tauopathy. Recent studies have established that progressive apraxia of speech is not a homogenous disease, but rather there are distinct subtypes: the phonetic subtype is characterized by distorted sound substitutions, the prosodic subtype by slow and segmented speech, and the mixed subtype by a combination of both but lack of predominance of either. There is some evidence that cross-sectional patterns of neurodegeneration differ across subtypes, although it is unknown whether longitudinal patterns of neurodegeneration differ. We examined longitudinal patterns of atrophy on MRI, hypometabolism on 18F-fluorodeoxyglucose-PET, and tau uptake on flortaucipir-PET in a large cohort of subjects with progressive apraxia of speech that had been followed for many years. Ninety-one subjects with progressive apraxia of speech (51 phonetic, 40 prosodic) were recruited by the Neurodegenerative Research Group. Of these, 54 (27 phonetic, 27 prosodic) returned for annual follow-up, with up to seven longitudinal visits (total visits analyzed = 217). Volumes, metabolism, and flortaucipir uptake was measured for subcortical and cortical regions, for all scans. Bayesian hierarchical models were used to model longitudinal change across imaging modalities with progressive apraxia of speech subtypes being compared at baseline, four years from baseline, and in terms of rates of change. The phonetic group showed smaller volumes and worse metabolism in Broca's area and the striatum at baseline and after four years, and faster rates of change in these regions, compared to the prosodic group. There was also evidence of faster spread of hypometabolism and flortaucipir uptake into the temporal and parietal lobes in the phonetic group. In contrast, the prosodic group showed smaller cerebellar dentate, midbrain, substantia nigra, and thalamus volumes at baseline and after four years, and faster rates of atrophy, than the phonetic group. Greater hypometabolism and flortaucipir uptake were also observed in the cerebellar dentate and substantia nigra in the prosodic group. Mixed findings were observed in the SMA and precentral cortex, with no clear differences observed across phonetic and prosodic groups. These findings support different patterns of disease spread in progressive apraxia of speech subtypes, with corticostriatal patterns in the phonetic subtype and brainstem and thalamic patterns in the prosodic subtype, providing insight into the pathophysiology and heterogeneity of progressive apraxia of speech.

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