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- Title
Typical and atypical pathology in primary progressive aphasia variants.
- Authors
Spinelli, Edoardo G.; Mandelli, Maria Luisa; Miller, Zachary A.; Santos‐Santos, Miguel A; Wilson, Stephen M.; Agosta, Federica; Grinberg, Lea T.; Huang, Eric J.; Trojanowski, John Q.; Meyer, Marita; Henry, Maya L.; Comi, Giancarlo; Rabinovici, Gil; Rosen, Howard J.; Filippi, Massimo; Miller, Bruce L.; Seeley, William W.; Gorno‐Tempini, Maria Luisa
- Abstract
<bold>Objective: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Interpretation: </bold>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;81:430-443.
- Publication
Annals of Neurology, 2017, Vol 81, Issue 3, p430
- ISSN
0364-5134
- Publication type
journal article
- DOI
10.1002/ana.24885