Electronic versions

  • Miguel A Santos-Santos
    University of California, San Francisco
  • Maria Luisa Mandelli
    University of California, San Francisco
  • Richard J Binney
    University of California, San Francisco
  • Jennifer Ogar
    University of California, San Francisco
  • Stephen M Wilson
    University of Arizona, Tucson
  • Maya L Henry
    University of Texas, Austin
  • H Isabel Hubbard
    University of California, San Francisco
  • Minerva Meese
    University of California, San Francisco
  • Suneth Attygalle
    University of California, San Francisco
  • Lynne Rosenberg
    University of California, San Francisco
  • Mikhail Pakvasa
    University of California, San Francisco
  • John Q Trojanowski
    University of Pennsylvania, Philadelphia
  • Lea T Grinberg
    University of California, San Francisco
  • Howie Rosen
    University of California, San Francisco
  • Adam L Boxer
    University of California, San Francisco
  • Bruce L Miller
    University of California, San Francisco
  • William W Seeley
    University of California, San Francisco
  • Maria Luisa Gorno-Tempini
    University of California, San Francisco

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.

Keywords

  • primary progressive aphasia, nonfluent/agrammatic variant, voxel based morphometry, corticobasal degeneration, progressive supranuclear palsy
Original languageEnglish
Pages (from-to)733-42
Number of pages10
JournalJAMA neurology
Volume73
Issue number6
Early online date25 Apr 2016
DOIs
Publication statusPublished - 1 Jun 2016
Externally publishedYes
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