Journal Article

Pick's disease presenting as progressive apraxia of speech: Atypical clinical and neuroimaging features in three autopsy-confirmed cases

Clark, Heather M., Jones, Katherine E., Graff-Radford, Jonathan, Dickson, Dennis W., Botha, Hugo, Duffy, Joseph R., Whitwell, Jennifer L., Josephs, Keith A., Utianski, Rene L., Machulda, Mary M.

2025

Overview

Patients with progressive apraxia of speech (PAOS) often develop atypical parkinsonian features suggestive of corticobasal syndrome (CBS) or progressive supranuclear palsy (PSP), and typically have an underlying 4-repeat tauopathy at autopsy. We describe three cases of PAOS with underlying Pick’s disease, a 3-repeat tauopathy, who lacked CBS or PSP features during life. We reviewed patients enrolled in the Neurodegenerative Research Group’s ongoing studies on speech and language disorders and identified those with PAOS who had autopsy-confirmed Pick’s disease. All patients had comprehensive neurologic, speech-language, and neuropsychological assessments, as well as multimodal neuroimaging, during life. Three female patients presented with phonetic PAOS without parkinsonism. Patient 1 had speech onset at age 54, later developed behavioral variant frontotemporal dementia (bvFTD), and died at 64. Patient 2 had speech onset at 47, early bvFTD features, prominent frontal and temporal involvement, and died at 53. Patient 3 had speech onset at 58, minimal behavioral changes, primarily frontal involvement on imaging, and died at 63. Our findings highlight that Pick's disease can present with PAOS and may be distinguished from 4R-tau PAOS by an absence of motoric CBS/PSP features and, in some cases, by prominent temporal hypometabolism with bvFTD development. These atypical features may prove useful in the antemortem identification of Pick's disease as a cause of PAOS. •Progressive apraxia of speech typically shares features with 4R tauopathies.•We report three autopsy-confirmed cases of PAOS with underlying 3R tau.•Early behavioral changes and lack of parkinsonism may be clinical clues to 3R tau.•Prominent temporal involvement on imaging may be a marker of 3R tau.

• Publisher: Elsevier B.V,Elsevier Limited
• Subject: Age / Aphasia / Apraxia / Apraxias - diagnostic imaging / Apraxias - etiology / Apraxias - pathology / Atypical Parkinsonism / Autopsies / Autopsy / Basal ganglia / Behavioral variant frontotemporal dementia (bvFTD) / Central nervous system diseases / Cognitive ability / Dementia / Dementia disorders / Disease / Female / Frontotemporal dementia / Humans / Impulsivity / Language / Medical imaging / Middle Aged / Movement disorders / Neurodegenerative diseases / Neuroimaging / Neurology / Neuropathology / Neuropsychology / Neurosurgery / Niemann-Pick disease / Parkinson's disease / Patients / Phonetics / Pick Disease of the Brain - complications / Pick Disease of the Brain - diagnosis / Pick Disease of the Brain - diagnostic imaging / Pick Disease of the Brain - pathology / Pick’s disease / Progressive apraxia of speech (PAOS) / Progressive supranuclear palsy / Regulatory approval / Speech / Speech Disorders - etiology / Tau protein / Tauopathy / White people