Progressive agrammatic aphasia without apraxia of speech as a distinct syndrome

Abstract

Agrammatic aphasia affects grammatical language production and can result from a neurodegenerative disease. Although it typically presents with concomitant apraxia of speech, this is not always the case. Little is known about the clinical course and imaging features of patients that present with agrammatism in the absence of apraxia of speech, which we will refer to as progressive agrammatic aphasia. We aimed to make a detailed description of the longitudinal clinical, linguistic, and neuroimaging features of a cohort of 11 patients with progressive agrammatic aphasia to provide a complete picture of this syndrome. All patients underwent detailed speech and language, neurological and neuropsychological assessments, 3 T structural and diffusion tensor imaging MRI, 18F-fluorodeoxyglucose and Pittsburgh compound B PET. The 11 patients were matched by age and gender to 22 patients who had mixed apraxia of speech and agrammatism. The progressive agrammatic aphasia patients performed abnormally on tests of language, general cognition, executive function, and functional ability at baseline and declined in these measures over time. Only two patients eventually developed apraxia of speech, while parkinsonism was absent-to-mild throughout all visits for all patients. When compared to the patients with mixed apraxia of speech and agrammatism, the patients with progressive agrammatic aphasia performed better on tests of motor speech and parkinsonism but more poorly, and declined faster over time, on tests of general aphasia severity, agrammatism, and naming. The patients with progressive agrammatic aphasia also showed different neuroimaging abnormalities, with greater atrophy, hypometabolism and white matter tract degeneration in the prefrontal and anterior temporal lobes compared to patients with mixed apraxia of speech and agrammatism. These differences were more pronounced as the disease progressed. These results demonstrate that progressive agrammatic aphasia has a different clinical disease course and different underlying neuroanatomical abnormalities than patients with the more common syndrome of mixed agrammatism and apraxia of speech. This supports the distinction of progressive agrammatic aphasia and has implications for the classification of patients with agrammatic aphasia.

Keywords: MRI; agrammatic; aphasia; longitudinal; positron emission tomography.

Figure 1

Longitudinal performance of all PAA patients on select clinical measures. Normal scores are noted with the solid black line. ASRS = Apraxia of Speech Rating Scale; CDR = Clinical Dementia Rating; FAB = Frontal Assessment Battery; FBI = Frontal Behavioral Inventory; MoCA = Montreal Cognitive Assessment; NPI-Q = Neuropsychiatric Inventory Questionnaire.

Figure 2

Voxel-level maps of grey matter loss in PAA and AOS+PAA. The top three rows show 3D surface renderings of the brain showing grey matter volume loss at baseline and follow-up, and grey matter atrophy measured using TBM-SyN, in PAA (red) and AOS+PAA (blue) versus controls. The bottom three rows show regions where volume loss or atrophy is greater in PAA than AOS+PAA. All results are FWE corrected at P < 0.05.

Figure 3

Voxel-level maps of fractional anisotropy (FA) and mean diffusivity (MD) in PAA and AOS+PAA. The top two rows are 3D transparent renders showing decrease in fractional anisotropy in PAA (red) and AOS+PAA (blue) versus controls at baseline and follow-up, respectively. The third and fourth rows show regions where fractional anisotropy is decreased in PAA compared to AOS+PAA at both time points. Rows five and six show increase in mean diffusivity in PAA (red) and AOS+PAA (blue) versus controls at baseline and follow-up, respectively. The bottom two rows show regions of increased mean diffusivity in PAA compared to AOS+PAA at both time points. All results are FWE corrected at P < 0.05.

Figure 4

Voxel-level maps of FDG hypometabolism in PAA and AOS+PAA. The top two rows show 3D surface renderings of the brain showing FDG hypometabolism in PAA (red) and AOS+PAA (blue) versus controls at baseline and follow-up, respectively. The bottom two rows show regions where FDG hypometabolism is greater in PAA than AOS+PAA at both time points. All results are FWE corrected at P < 0.05.

Figure 5

Cortex ID Z-score maps of FDG-PET hypometabolism in individual PAA patients.