Why are patients with progressive nonfluent aphasia nonfluent

Progressive nonfluent aphasia (PNFA) is one clinical presentation of frontotemporal lobar degeneration (FTLD).1,2 PNFA may be a clinical marker of tauopathies such as dementia with Pick bodies, corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP),3,4 and thus it is critical to understand the characteristics of this condition. The hallmark feature of PNFA is reduced speech fluency.5,6 In this study, we investigated 3 potential sources of nonfluent speech attributed to PNFA, including grammatic simplifications and errors,1,5 a motor-related disorder associated with speech-sound errors known as apraxia of speech (AOS),3,7 and executive difficulty that limits mental search for words.8,9 An executive deficit also is seen in patients with FTLD with a disorder of personality and executive functioning known as behavioral-variant frontotemporal dementia (bvFTD).2,10 Since these patients also have reduced speech fluency,11 it is important to distinguish between reduced fluency in bvFTD and PNFA. In PNFA, left inferior frontal cortex (IFC) atrophy is associated with grammatic processing,12 and an fMRI study shows reduced left IFC recruitment during grammatic processing.13 Patients with PNFA also have atrophy in left insula, an area associated with motor-speech errors,7 and in left dorsolateral prefrontal cortex, an area associated with mental search.14,15 In this study, we related fluency, grammar, executive functioning, and speech-sound production to quantitative measures of cortical thickness. We predicted that nonfluent speech would be related to limited grammatic processing in PNFA and reduced executive functioning in bvFTD. Moreover, in PNFA, we expected reduced WPM to be associated with IFC thinning, and that this would overlap with regions implicated in grammatic difficulty.