Syndromes dominated by apraxia of speech show distinct characteristics from agrammatic PPA

Abstract

Objective: We assessed whether clinical and imaging features of subjects with apraxia of speech (AOS) more severe than aphasia (dominant AOS) are more similar to agrammatic primary progressive aphasia (agPPA) or to primary progressive AOS (PPAOS).

Methods: Sixty-seven subjects (PPAOS = 18, dominant AOS = 10, agPPA = 9, age-matched controls = 30) who all had volumetric MRI, diffusion tensor imaging, F18-fluorodeoxyglucose and C11-labeled Pittsburgh compound B (PiB)-PET scanning, as well as neurologic and speech and language assessments, were included in this case-control study. AOS was classified as either type 1, predominated by sound distortions and distorted sound substitutions, or type 2, predominated by syllabically segmented prosodic speech patterns.

Results: The dominant AOS subjects most often had AOS type 2, similar to PPAOS. In contrast, agPPA subjects most often had type 1 (p = 0.01). Both dominant AOS and PPAOS showed focal imaging abnormalities in premotor cortex, whereas agPPA showed widespread involvement affecting premotor, prefrontal, temporal and parietal lobes, caudate, and insula. Only the dominant AOS and PPAOS groups showed midbrain atrophy compared with controls. No differences were observed in PiB binding across all 3 groups, with the majority being PiB negative.

Conclusion: These results suggest that dominant AOS is more similar to PPAOS than agPPA, with dominant AOS and PPAOS exhibiting a clinically distinguishable subtype of progressive AOS compared with agPPA.

Figure 1. Three-dimensional renderings showing patterns of gray (in red) and white matter (in green) loss and FDG-PET hypometabolism (in blue) in each group compared with controls

Gray and white matter results are shown after correction for multiple comparisons using the FDR at p < 0.005. No regions of FDG-PET hypometabolism survived correction at FDR p < 0.005 for PPAOS and dominant AOS, and therefore FDG-PET results are shown uncorrected for multiple comparisons at p < 0.001. agPPA = agrammatic primary progressive aphasia; AOS = apraxia of speech; FDG = F18-fluorodeoxyglucose; FDR = false discovery rate; PPAOS = primary progressive AOS.

Figure 2. Results of the TBSS analysis of FA

The mean FA skeleton is shown in green with red representing regions of reduced FA in PPAOS, dominant AOS, and agPPA compared with controls. Results were corrected for multiple comparisons at p < 0.05. agPPA = agrammatic primary progressive aphasia; AOS = apraxia of speech; FA = fractional anisotropy; PPAOS = primary progressive AOS; TBSS = Tract-Based Spatial Statistics.

Figure 3. Flow chart illustrating the proposed 2-level classification scheme for subjects with AOS, agrammatic aphasia, or both

Subjects with agrammatic aphasia, AOS, or both should be first separated into those with PPA and those with PAOS. The diagnosis of PPA (specifically agPPA) should be made in those with either isolated agrammatic aphasia or dominant agrammatic aphasia, i.e., if AOS is present, it must be less severe than the aphasia. Similarly, the diagnosis of PAOS should be made in those with either isolated AOS or dominant AOS, i.e., if aphasia is present, it must be less severe than the AOS. agPPA and PAOS can then be further subdivided. Specifically, for agPPA, those with isolated agrammatic aphasia can be separated from those in which the aphasia is more severe than the AOS, and for PAOS, those with isolated AOS (PPAOS) can be separated from those in which the AOS is more severe than the aphasia (dominant AOS). agPPA = agrammatic PPA; AOS = apraxia of speech; PPAOS = primary progressive AOS.