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Original Investigation
June 2016

Features of Patients With Nonfluent/Agrammatic Primary Progressive Aphasia With Underlying Progressive Supranuclear Palsy Pathology or Corticobasal Degeneration

Author Affiliations
  • 1Department of Neurology, Memory Aging Center, University of California, San Francisco
  • 2Department of Medicine, Autonomous University of Barcelona, Bellaterra, Barcelona, Spain
  • 3Department of Communication Sciences and Disorders, Temple University, Philadelphia, Pennsylvania
  • 4Department of Speech, Language, and Hearing Sciences, University of Arizona, Tucson
  • 5Department of Communication Sciences and Disorders, University of Texas, Austin
  • 6Center for Neurodegenerative Disease Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia
  • 7Department of Pathology, University of California, San Francisco
JAMA Neurol. 2016;73(6):733-742. doi:10.1001/jamaneurol.2016.0412

Importance  We provide novel evidence of specific clinical and neuroimaging features that may help for the in vivo prediction of underlying pathology in patients with nonfluent/agrammatic primary progressive aphasia (nfvPPA) and progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD) proved by autopsy.

Objective  To characterize the neurological, cognitive, and neuroimaging features of patients with nfvPPA—in whom either PSP or CBD was eventually confirmed at autopsy—at initial presentation and at 1-year follow-up.

Design, Setting, and Participants  A prospective longitudinal clinical-pathological study was conducted in a tertiary research clinic that specialized in cognitive disorders. Fourteen patients were evaluated between January 2002 and December 2014. Inclusion criteria for the study were a clinical diagnosis of nfvPPA; the availability of speech, language, and cognitive testing for at least 1 evaluation; magnetic resonance imaging within 6 months of initial evaluation; and a postmortem pathological diagnosis of PSP or CBD. Ten matched healthy control participants were also included.

Main Outcomes and Measures  Clinical, cognitive, and neuroimaging longitudinal data were analyzed to characterize the whole nfvPPA–4-repeat–tau group and identify differences between nfvPPA-PSP and nfvPPA-CBD both at presentation and longitudinally.

Results  Patient groups did not differ significantly in age, sex, or handedness (nfvPPA-PSP group: median [interquartile range (IQR)] age, 74 [67-76] years; 1 of 5 male [20%]; 1 of 5 left-handed [20%]; and nfvPPA-CBD group: mean [IQR] age, 65 [54-81] years; 3 of 9 male [33%]; 0 left-handed). Motor speech impairment and left frontal white matter atrophy were the most prominent common features. At presentation, dysarthria (Motor Speech Examination median [IQR] score: nfvPPA-PSP, 4 [2-7]; nfvPPA-CBD, 0 [0-4]; P = .02), depression (Geriatric Depression Scale median [IQR] score: nfvPPA-PSP, 19 [3-28]; nfvPPA-CBD, 4 [0-16]; P = .04), and relatively selective white matter atrophy were typical of the nfvPPA-PSP group, while greater gray matter atrophy and a trend toward greater sentence comprehension deficits (median [IQR] sentence comprehension correct: nfvPPA-PSP, 98% [80-100]; nfvPPA-CBD, 81% [65-98]; P = .08) were found in the nfvPPA-CBD group. At follow-up after 1 year, we observed no significant differences in any speech or language measures. Furthermore, atrophy in patients with PSP progressed within the subcortical/brainstem motor system generating greater oculomotors deficits and swallowing difficulty; atrophy in patients with CBD spread anteriorly in prefrontal regions consistent with their greater working memory impairment and development of behavioral symptoms.

Conclusions and Relevance  In patients presenting with nfvPPA, presence of early severe dysarthria, relatively selective white matter atrophy at presentation, and a greater rate of change in the brainstem measured by longitudinal imaging may be useful for differentiating underlying PSP from CBD pathology during life.