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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.
Santos‐Santos et al. (Mon,) studied this question.