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

JAMA Neurol. 2016 Jun 1;73(6):733-42. 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aphasia, Primary Progressive / complications*
  • Aphasia, Primary Progressive / diagnostic imaging
  • Atrophy / pathology
  • Autopsy
  • Basal Ganglia / diagnostic imaging
  • Basal Ganglia / pathology*
  • Case-Control Studies
  • Cerebral Cortex / diagnostic imaging
  • Cerebral Cortex / pathology*
  • Cognition Disorders / diagnostic imaging
  • Cognition Disorders / etiology
  • Cross-Sectional Studies
  • Female
  • Humans
  • Image Processing, Computer-Assisted
  • Language
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neurodegenerative Diseases / complications*
  • Neurodegenerative Diseases / diagnostic imaging
  • Neuropsychological Tests
  • Retrospective Studies
  • Severity of Illness Index
  • Statistics, Nonparametric
  • Supranuclear Palsy, Progressive / complications*
  • Supranuclear Palsy, Progressive / diagnostic imaging