Differentiating primary progressive aphasias in a brief sample of connected speech

From the Department of Neurology (S.A., E.E., J.O., J.P., A.B., D.W., J.H., C.M., D.J.I., K.R., M.G.) and Center for Neurodegenerative Disease Research (D.J.I.), Perelman School of Medicine of the University of Pennsylvania, Philadelphia.
Neurology (Impact Factor: 8.29). 06/2013; 81(4). DOI: 10.1212/WNL.0b013e31829c5d0e
Source: PubMed


A brief speech expression protocol that can be administered and scored without special training would aid in the differential diagnosis of the 3 principal forms of primary progressive aphasia (PPA): nonfluent/agrammatic PPA, logopenic variant PPA, and semantic variant PPA.
We used a picture-description task to elicit a short speech sample, and we evaluated impairments in speech-sound production, speech rate, lexical retrieval, and grammaticality. We compared the results with those obtained by a longer, previously validated protocol and further validated performance with multimodal imaging to assess the neuroanatomical basis of the deficits.
We found different patterns of impaired grammar in each PPA variant, and additional language production features were impaired in each: nonfluent/agrammatic PPA was characterized by speech-sound errors; logopenic variant PPA by dysfluencies (false starts and hesitations); and semantic variant PPA by poor retrieval of nouns. Strong correlations were found between this brief speech sample and a lengthier narrative speech sample. A composite measure of grammaticality and other measures of speech production were correlated with distinct regions of gray matter atrophy and reduced white matter fractional anisotropy in each PPA variant.
These findings provide evidence that large-scale networks are required for fluent, grammatical expression; that these networks can be selectively disrupted in PPA syndromes; and that quantitative analysis of a brief speech sample can reveal the corresponding distinct speech characteristics.

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    • "ROIs that have been linked to fluency and word production in healthy individuals as well as those with stroke aphasia and PPA: the pars opercularis, pars triangularis, and pars orbitalis of the inferior frontal gyrus (IFG), the caudal middle frontal gyrus (cMFG), the precentral gyrus, the middle temporal gyrus (MTG), the superior temporal gyrus (STG), the inferior parietal cortex (IPC), and the supramarginal gyrus (SMG) (Ash et al., 2013; Gunwardena et al., 2010; Indefrey, 2011; Indefrey & Levelt, 2004; Mirman et al., 2015; Rogalski et al., 2011; Schnur, Schwartz, Brecher, & Hodgson, 2006; Schnur et al., 2009; Schwartz et al., 2009; Wilson et al., 2010; de Zubicaray, McMahon, Eastburn, & Wilson, 2002). We hypothesized that pause distribution by word class would predict atrophy in regions supporting lemma retrieval, such as 7 the MTG (Indefrey, 2011; Indefrey & Levelt, 2004; Schwartz et al., 2009; de Zubicaray et al., 2002) and/or the IFG, which has been claimed to exert top-down control over lemma access and selection during word production (Schnur et al., 2006, 2009; Schwartz et al., 2009). "
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    ABSTRACT: Naming and word-retrieval deficits, which are common characteristics of primary progressive aphasia (PPA), differentially affect production across word classes (e.g., nouns, verbs) in some patients. Individuals with the agrammatic variant (PPA-G) often show greater difficulty producing verbs whereas those with the semantic variant (PPA-S) show greater noun deficits and those with logopenic PPA (PPA-L) evince no clear-cut differences in production of the two word classes. To determine the source of these production patterns, the present study examined word-finding pauses as conditioned by lexical variables (i.e., word class, frequency, length) in narrative speech samples of individuals with PPA-S (n=12), PPA-G (n=12), PPA-L (n=11), and cognitively healthy controls (n=12). We also examined the relation between pause distribution and cortical atrophy (i.e., cortical thickness) in nine left hemisphere regions of interest (ROIs) linked to word production. Results showed higher overall pause rates for PPA compared to unimpaired controls; however, greater naming severity was not associated with increased pause rate. Across all groups, more pauses were produced before lower vs. higher frequency words, with no independent effects of word length after controlling for frequency. With regard to word class, the PPA-L group showed a higher rate of pauses prior to production of nouns compared to verbs, consistent with noun-retrieval deficits arising at the lemma level of word production. Those with PPA-G and PPA-S, like controls, produced similar pause rates across word classes; however, lexical simplification (i.e., production of higher-frequency and/or shorter words) was evident in the more-impaired word class: nouns for PPA-S and verbs for PPA-G. These patterns are consistent with conceptual and/or lemma-level impairments for PPA-S, predominantly affecting objects/nouns, and a lemma-level verb-retrieval deficit for PPA-G, with a concomitant impairment in phonological encoding and articulation affecting overall pause rates. The greater tendency to pause before nouns was correlated with atrophy in the left precentral gyrus, inferior frontal gyrus and inferior parietal lobule, whereas the greater tendency to pause before less frequent and longer words was associated with atrophy in left precentral and inferior parietal regions. Copyright © 2015. Published by Elsevier Ltd.
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    ABSTRACT: Logopenic progressive aphasia is the most recently described clinical variant of primary progressive aphasia (PPA), defined by impairment of lexical retrieval and sentence repetition. Unlike other PPA variants, the logopenic variant of PPA (lv-PPA) is commonly associated with Alzheimer's disease (AD), a fact that is relevant to the selection of patients for clinical trials and disease-modifying therapies. Despite the straightforward definition and coherent pathological association, the existence of lv-PPA has been challenged, as its distinction from AD or other PPA variants can be difficult. Despite these issues, lv-PPA patients display characteristic linguistic deficits, a pattern of brain atrophy, and possibly genetic susceptibility, which warrant considering this variant as a discrete AD endophenotype. More specific clinical and anatomical markers can strengthen the consistency of this syndrome.
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