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August 17, 2010; 75 (7) Articles

Syndromes of nonfluent primary progressive aphasia

A clinical and neurolinguistic analysis

Jonathan D. Rohrer, Martin N. Rossor, Jason D. Warren
First published August 16, 2010, DOI: https://doi.org/10.1212/WNL.0b013e3181ed9c6b
Jonathan D. Rohrer
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Martin N. Rossor
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Jason D. Warren
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Syndromes of nonfluent primary progressive aphasia
A clinical and neurolinguistic analysis
Jonathan D. Rohrer, Martin N. Rossor, Jason D. Warren
Neurology Aug 2010, 75 (7) 603-610; DOI: 10.1212/WNL.0b013e3181ed9c6b

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Abstract

Background: Despite recent work, the nosology of nonfluent primary progressive aphasia (PPA) remains unresolved.

Methods: We describe a clinical and neurolinguistic cross-sectional analysis of a cohort of 24 patients with nonfluent PPA. Patients were initially classified based on analysis of spontaneous speech into 4 groups: apraxia of speech (AOS)/agrammatism (10 patients); AOS/no agrammatism (4 patients); no AOS/agrammatism (3 patients); no AOS/no agrammatism (7 patients). These groups were further characterized using a detailed neurolinguistic and neuropsychological battery. Parkinsonism was present in 3/10 patients in the AOS/agrammatism group. All patients in the no AOS/agrammatism group had mutations in the progranulin (GRN) gene, while 5/7 cases in the no AOS/no agrammatism group had CSF findings compatible with Alzheimer disease.

Results: The groups without AOS showed more severe neurolinguistic impairments for a given disease stage, and sentence comprehension, speech repetition, and reading were impaired in all groups. Prolonged word-finding pauses and impaired single word comprehension were salient features in the no AOS/agrammatism group. Additional impairments of executive function and praxis were present in both groups with agrammatism, and impaired episodic memory was a feature of the no AOS/no agrammatism group.

Conclusion: PPA with AOS is aligned with the syndrome previously designated progressive nonfluent aphasia; agrammatism may emerge as the syndrome evolves, or alternatively, the pure AOS group may be pathophysiologically distinct. PPA without AOS resembles the syndrome designated logopenic/phonologic aphasia; however, there is evidence for a distinct subsyndrome of GRN-associated aphasia. The findings provide a rationale for further longitudinal studies with pathologic correlation.

Footnotes

  • Editorial, page 582

    See pages 588 and 595

    Supplemental data at www.neurology.org

    Study funding: This work was undertaken at UCLH/UCL, which received a proportion of funding from the Department of Health's NIHR Biomedical Research Centres funding scheme. The Dementia Research Centre is an Alzheimer's Research Trust Coordinating Centre. This work was also funded by the Medical Research Council UK and the Wellcome Trust.

    Disclosure: Author disclosures are provided at the end of the article.

    Received October 21, 2009. Accepted in final form March 29, 2010.

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