In vivo signatures of nonfluent/agrammatic primary progressive aphasia caused by FTLD pathology

Francesca Caso, Maria Luisa Mandelli, Maya Henry, Benno Gesierich, Brianne M. Bettcher, Jennifer Ogar, Massimo Filippi, Giancarlo Comi, Giuseppe Magnani, Manu Sidhu, John Q. Trojanowski, Eric J. Huang, Lea T. Grinberg, Bruce L. Miller, Nina Dronkers, William W. Seeley, Maria Luisa Gorno-Tempini

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: To identify early cognitive and neuroimaging features of sporadic nonfluent/agrammatic variant of primary progressive aphasia (nfvPPA) caused by frontotemporal lobar degeneration (FTLD) subtypes. Methods: We prospectively collected clinical, neuroimaging, and neuropathologic data in 11 patients with sporadic nfvPPA with FTLD-tau (nfvPPA-tau, n5 9) or FTLD-transactive response DNA binding protein pathology of 43 kD type A (nfvPPA-TDP, n = 2). We analyzed patterns of cognitive and gray matter (GM) and white matter (WM) atrophy at presentation in the whole group and in each pathologic subtype separately. We also considered longitudinal clinical data. Results: At first evaluation, regardless of pathologic FTLD subtype, apraxia of speech (AOS) was the most common cognitive feature and atrophy involved the left posterior frontal lobe. Each pathologic subtype showed few distinctive features. At presentation, patients with nfvPPA-tau presented with mild to moderate AOS, mixed dysarthria with prominent hypokinetic features, clear agrammatism, and atrophy in the GM of the left posterior frontal regions and in left frontal WM. While speech and language deficits were prominent early, within 3 years of symptom onset, all patients with nfvPPA-tau developed significant extrapyramidal motor signs. At presentation, patients with nfvPPA-TDP had severe AOS, dysarthria with spastic features, mild agrammatism, and atrophy in left posterior frontal GM only. Selective mutism occurred early, when general neurologic examination only showed mild decrease in finger dexterity in the right hand. Conclusions: Clinical features in sporadic nfvPPA caused by FTLD subtypes relate to neurodegeneration of GMandWMin frontal motor speech and language networks. We propose that earlyWM atrophy in nfvPPA is suggestive of FTLD-tau pathology while early selective GM loss might be indicative of FTLD-TDP.

Original languageEnglish
Pages (from-to)239-247
Number of pages9
JournalNeurology
Volume82
Issue number3
DOIs
Publication statusPublished - Jan 21 2014

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)
  • Medicine(all)

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