Tracking the development of agrammatic aphasia: A tensor-based morphometry study

Abstract

Agrammatic aphasia can be observed in neurodegenerative disorders and has been traditionally linked with damage to Broca’s area, although there have been disagreements concerning whether damage to Broca’s area is necessary or sufficient for the development of agrammatism. We aimed to investigate the neuroanatomical correlates of the emergence of agrammatic aphasia utilizing a unique cohort of patients with primary progressive apraxia of speech (PPAOS) that did not have agrammatism at baseline but developed agrammatic aphasia over time. Twenty PPAOS patients were recruited and underwent detailed speech/language assessments and 3T MRI at two visits, approximately two years apart. None of the patients showed evidence of agrammatism in writing or speech at baseline. Eight patients developed aphasia at follow-up (progressors) and 12 did not (non-progressors). Tensor-based morphometry utilizing symmetric normalization was used to assess patterns of grey matter atrophy and voxel-based morphometry was used to assess patterns of grey matter loss at baseline. The progressors were younger at onset and more likely to show distorted sound substitutions or additions compared to non-progressors. Both groups showed change over time in premotor and motor cortices, posterior frontal lobe, basal ganglia, thalamus and midbrain, but the progressors showed greater rates of atrophy in left pars triangularis, thalamus and putamen compared to non-progressors. The progressors also showed greater grey matter loss in pars triangularis and putamen at baseline. This cohort has provided a unique opportunity to assess the anatomical changes that accompany the development of agrammatic aphasia. The results suggest that damage to a network of regions including Broca’s area, thalamus and basal ganglia are responsible for the development of agrammatic aphasia. Clinical and neuroimaging abnormalities were also present before the onset of agrammatism that could help improve prognosis in these subjects.

Clinical and imaging progression over 10 years in a patient with primary progressive apraxia of speech and autopsy-confirmed corticobasal degeneration

“…The fact that Broca’s area showed abnormalities before the development of agrammatic aphasia in DY suggests that involvement of this region could be a useful predictor for the future development of aphasia in PPAOS. We have previously shown this to also be the case in a larger cohort of patients with PPAOS(Whitwell, et al, 2017). Over time we observed progression in these regions but also the gradual involvement of other regions, starting with the motor cortex, lateral temporal lobe and thalamus in 2013, and then with later involvement of sensory cortex and parietal lobes in 2015.…”

“…We have previously reported longitudinal data over a two year interval in patients with PPAOS in order to investigate patterns of disease progression(Whitwell et al, 2017; Zalewski et al, 2014). We showed that some patients maintained an isolated AOS over time, while some developed agrammatic aphasia, and others developed parkinsonian and other features akin to progressive supranuclear palsy and corticobasal syndrome.…”

FTD spectrum: Neuroimaging across the FTD spectrum

“…However, agPPA showed faster rates of atrophy in the inferior frontal lobe compared to PPAOS, reflecting greater decline in agrammatism than the PPAOS patients 11 . Agrammatism can develop over time in some PPAOS patients, although not all, and when it does develop it is associated with atrophy of the left inferior frontal lobe, thalamus and putamen, showing that a network of regions is responsible for the development of agrammatic aphasia 186 .…”

Longitudinal structural and molecular neuroimaging in agrammatic primary progressive aphasia

“…This pattern differs from agPPA, with agPPA showing more widespread involvement of the frontal and temporal lobes (Josephs et al, 2013). Longitudinal neuroimaging has been described in PPAOS, with grey matter atrophy spreading from the initial focal premotor pattern into the prefrontal and motor cortices, in addition to the basal ganglia and midbrain (Josephs et al, 2014;Whitwell et al, 2017). However, it is unknown how these longitudinal patterns of atrophy compare to those observed in agPPA, and whether the syndromes remain relatively distinct on neuroimaging as the diseases progress or whether they converge into similar patterns of progression, especially given that PPAOS subjects can develop agrammatism over time (Josephs et al, 2014;Whitwell et al, 2017).…”