Typical and atypical pathology in primary progressive aphasia variants.
Ann Neurol
; 81(3): 430-443, 2017 Mar.
Article
en En
| MEDLINE
| ID: mdl-28133816
ABSTRACT
OBJECTIVE:
To characterize in vivo signatures of pathological diagnosis in a large cohort of patients with primary progressive aphasia (PPA) variants defined by current diagnostic classification.METHODS:
Extensive clinical, cognitive, neuroimaging, and neuropathological data were collected from 69 patients with sporadic PPA, divided into 29 semantic (svPPA), 25 nonfluent (nfvPPA), 11 logopenic (lvPPA), and 4 mixed PPA. Patterns of gray matter (GM) and white matter (WM) atrophy at presentation were assessed and tested as predictors of pathological diagnosis using support vector machine (SVM) algorithms.RESULTS:
A clinical diagnosis of PPA was associated with frontotemporal lobar degeneration (FTLD) with transactive response DNA-binding protein (TDP) inclusions in 40.5%, FTLD-tau in 40.5%, and Alzheimer disease (AD) pathology in 19% of cases. Each variant was associated with 1 typical pathology; 24 of 29 (83%) svPPA showed FTLD-TDP type C, 22 of 25 (88%) nfvPPA showed FTLD-tau, and all 11 lvPPA had AD. Within FTLD-tau, 4R-tau pathology was commonly associated with nfvPPA, whereas Pick disease was observed in a minority of subjects across all variants except for lvPPA. Compared with pathologically typical cases, svPPA-tau showed significant extrapyramidal signs, greater executive impairment, and severe striatal and frontal GM and WM atrophy. nfvPPA-TDP patients lacked general motor symptoms or significant WM atrophy. Combining GM and WM volumes, SVM analysis showed 92.7% accuracy to distinguish FTLD-tau and FTLD-TDP pathologies across variants.INTERPRETATION:
Each PPA clinical variant is associated with a typical and most frequent cognitive, neuroimaging, and neuropathological profile. Specific clinical and early anatomical features may suggest rare and atypical pathological diagnosis in vivo. Ann Neurol 2017;81430-443.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Afasia Progresiva Primaria
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Degeneración Lobar Frontotemporal
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Enfermedad de Alzheimer
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Sustancia Gris
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Sustancia Blanca
Límite:
Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Ann Neurol
Año:
2017
Tipo del documento:
Article
País de afiliación:
Canadá