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 datawere 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 imagingmay be useful for differentiating underlying PSP from CBD pathology during life.
|Number of pages||10|
|State||Published - Jun 2016|
Bibliographical noteFunding Information:
This work was supported by grants R01 NS050915, P01 AG019724, P50 AG023501, K24 AG045333-01, R01 AG032306, U54NS092089, and R01 AG038791 from the National Institute of Neurological Disorders and Stroke of the NIH; grant DHS 04-35516 from the State of California; grant 09-11410 DHS/ADP/ARCC from the Alzheimer Disease Research Center of California; the Larry L. Hillblom Foundation; the Koret Family Foundation; the Consortium for Frontotemporal Dementia Research; the McBean Family Foundation; and the Alfonso Martin Escudero Foundation. Dr Wilson is funded by grant R01 DC013270 from the NIH. Dr Rosen is funded by grants K24 AG045333 and R01 AG032306 from the NIH. Dr Seeley is funded by grant P50 AG1657303 from the NIH. Dr Miller is funded by grants P50AG023501, P01AG019724, and P50 AG1657303 from the NIH. Dr Gorno-Tempini is funded by grant NINDS R01 NS050915 from the NIH.
Copyright 2016 American Medical Association. All rights reserved.
ASJC Scopus subject areas
- Clinical Neurology