Primary progressive aphasia: Linguistic patterns and clinical variants
Introduction
Since Mesulam, 1982, Mesulam, 2001 seminal observations, an increasing number of studies have suggested the existence of distinguishable clinical forms of primary language disorders. Classification of the primary progressive aphasias (PPA) into clinical variants (Gorno-Tempini et al., 2011) is primarily based on the characteristics of speech production and single-word and sentence processing. By using high-resolution MRI with group-level, voxel-wise statistical analyses of grey matter volumes and cortical thickness (Gorno-Tempini et al., 2004, Grossman, 2010, Mesulam et al., 2009, Wilson et al., 2009), previous studies were able to correlate three different syndromic variants of PPA (semantic – S, logopenic – L and nonfluent – NF) with distinct patterns of regional cortical atrophy. Atrophic changes in the anterior and lateral temporal lobe were correlated with the S variant, in the anterior perisylvian regions with the NF variant and in the posterior perisylvian regions with the L variant (Grossman, 2010). These atrophic patterns were found to be lateralized in the left hemisphere (Mesulam et al., 2009).
But, thanks to the fine-grained descriptions of the patterns of language disorders that emerge when explored using the sophisticated tools of cognitive neuropsychology, it is clear that the boundaries between the various subtypes of aphasia blend into each other and a virtually unlimited number of intermediate forms can be observed. Thus, although the classification of language disorders into main syndromes has clinical value, from a theoretical point of view the question of aphasia classification is still open. In fact, two issues are still being discussed in this regard: the basis on which combinations of symptoms supposed to represent the core feature of an aphasic syndrome should be predicted (Kohn & Smith, 1992) and whether patients’ symptoms are sufficiently homogeneous to allow separating them into well-defined types of aphasia (Schwartz & Dell, 2010). Confirmation that degeneration in the left perisylvian regions gives rise to definable patterns of linguistic disorders would support the hypothesis that the emergence of different types of aphasia reflects the functional organization of language in the brain and not an assembly of symptoms generated by a random distribution of neural damage. In fact, patterns of symptoms might reflect involution of specific neural networks that have specific functions in language organization. In this perspective, PPA could provide information complementary to that provided by the vascular forms of aphasia to define the neural networks exposed to selective neurodegenerative changes that can lead to distinct language impairments.
Pathological and genetic markers have sometimes been reported in association with defined patterns of neurodegeneration correlated with different diseases and language disorders (Caso et al., 2012, Rohrer et al., 2010a). This supports the hypothesis that different aphasia variants-phenotypes might represent stable patterns of symptoms subtended by specific underlying diseases with predictable histopathological and genetic patterns (Grossman, 2010). This multimodal approach to aphasia is promising; thus far, however, consistent correspondence between aphasia variants and specific pathological entities has not been found (Drachman, 2011).
However, aphasia is not just a clinical entity. From a psycholinguistic point of view it reflects the degradation of different dimensions of the functional organization of language (Crystal, 1988), namely, the sublexical, lexical semantic and syntactic dimensions; each of these could be subtended by dedicated neural subsystems. A linguistic approach to PPA could bypass the limitation of the a priori grouping of patients into discrete clinical entities and could allow to identify (in each patient) patterns that reflect degradation along various dimensions of language supported by networks that might present different sensitivity to different brain pathologies.
Forty-two patients with PPA were studied. We tried to classify them into the principal variants of aphasia according to current standard criteria (Gorno-Tempini et al., 2011), namely, non-fluent, semantic and logopenic. The concept of “nonfluent” production is, however, multidimensional (see Hillis, 2007) and includes features that go beyond agrammatism and apraxia of speech (which are the main features of the so-called nonfluent/agrammatic variant of PPA according to Gorno-Tempini et al., 2011) such as, reduced speech rate or decreased phrase length and word-finding difficulty. On the basis of this evidence we reasoned that nonfluent forms of primary aphasia might not necessarily correspond to apraxia of speech/agrammatism, which is a well-defined clinical syndrome (Harris et al., 2013, Josephs and Duffy, 2008). Thus, apraxia of speech associated with agrammatism was considered a clinical variant, separate from other nonfluent language disorders.
Besides clinical classification, we also defined the pattern of each patient’s language disorder according to prevalent involvement of the sublexical, lexical semantic and syntactic levels, respectively. For this purpose, we used a battery of tests devised to explore the status of the different components of the linguistic systems with a cognitive neuropsychological approach (Capasso & Miceli, 2001).
The first aim of the study was to confirm (in a population of Italian-speaking aphasic patients) whether primary disorders of language can actually be classified in the proposed discrete clinical entities and then to test whether the corresponding expected brain atrophy patterns can be radiologically detected using visually-assessed scales that are feasible during routine MRI examinations. Second, we investigated whether the disorganization of language in degenerative pathology reflects nonrandom degradation of language dimensions (Crystal, 1988, Jakobson, 1980), that is, sublexical, lexical semantic and syntactic, and to what extent this degradation contributes (if at all) to the emergence of the main clinical variants of PPA.
Section snippets
Participants
We recruited 42 patients at the Centre for the Medicine of the Aging of the Department of Geriatrics, Neurology and Orthopedics of the Catholic University of Rome, from January 2007 to June 2012. They fulfilled the criteria for PPA (Mesulam, 2001) and underwent a brain MRI scan within a maximum interval of two months from the neuropsychological examination (i.e., either before or after). Patients were included only if they had at least 5 years of formal education, did not express themselves in
Language: main features of the clinical variants
Table 1 shows the distribution of the 42 aphasic patients in the different clinical variants. The table also reports demographic and clinical data. The MMSE score is also reported, even though it is not fully appropriate for quantifying mental deterioration in subjects with language disorders. Table 2 reports the performance (adjusted scores) (type of errors is not considered) obtained by the patients of each variant in the various tasks of the ENPA battery.
Table 3 shows type and severity of
Clinical variant of PPA
Thirty-five out of 42 patients could be clinically classified as having the S, L and NF variants (Gorno-Tempini et al., 2011); four had AOS/aph; three patients could not be placed in any recognizable syndrome. Patients in all groups were formally hypofluent compared to controls if we consider MLU and speech rate. However, the S patients had a significantly longer speech rate compared to the L and NF patients and produced fewer fragments. Patients with the S variant presented a relatively
Conclusion
Our main conclusion is that the clinical variants of PPA can only be partially predicted by linguistic analysis. Indeed, it is likely that only the selective semantic deficit and, to a lesser extent, agrammatic production with apraxia of speech present identifiable patterns that might correspond to definable clinical syndromes and possibly diseases which selectively affect specific neural substrates (semantic dementia and corticobasal degeneration respectively). There is a large group of
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2016, Journal of NeurolinguisticsCitation Excerpt :To a certain extent, connected speech can sound quite normal (Sajjadi et al., 2012) but patients tend to lose their differentiated vocabulary over time and use more general and more frequent instead of semantically precise words (Ash et al., 2006; Bird, Lambon Ralph, Patterson, & Hodges, 2000; Bozeat et al., 2003; Fraser et al., 2014; Laisney et al., 2011). Apart from the changes in vocabulary, errors of syntax and morphology may also occur in the spoken language of individuals with svPPA, as has – somewhat contrary to initial expectations – been pointed out recently (Auclair-Ouellet, 2015; Benedet, Patterson, Gomez-Pastor, & la Rocha, 2006; Gorno-Tempini et al., 2011; Kavé, Leonard, Cupit, & Rochon, 2007; Leyton & Hodges, 2014; Meteyard & Patterson, 2009; Meteyard, Quain, & Patterson, 2014; Silveri et al., 2014; Thompson et al., 2012; Wilson et al., 2010, 2014). Individuals with svPPA seem to show syntactic abnormalities in the sense of paragrammatic constructions such as sentence inversions or duplications and substitutions on the morphological level.
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2015, CortexCitation Excerpt :We recently proposed recognizing PAOS, consisting of cases that have apraxia of speech alone or as a dominant feature in the setting of aphasia, as a separate group from PPA altogether based on clinical, radiological and pathological grounds (Harris et al., 2013; Josephs et al., 2010, 2013, 2012; Josephs, Duffy, et al., 2006; Mesulam, 2013). Data driven approaches have also supported viewing patients with apraxia of speech as a distinct group (Leyton, Ballard, Piguet, & Hodges, 2014; Silveri et al., 2014). Recent longitudinal data showed that many subjects with primary progressive AOS develop a devastating progressive supranuclear palsy-like syndrome approximately 5 years after onset, further highlighting the importance of recognizing this group as distinct from the agrammatic group (Josephs, Duffy, Strand, Machulda, Senjem, et al., 2014).
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Present address: Neurocenter of Southern Switzerland, Department of Neuroradiology, Via Tesserete 46 – 6900, Lugano, Switzerland.