Single-word comprehension deficits in the nonfluent variant of primary progressive aphasia

Abstract

BackgroundA subset of patients with the nonfluent variant of primary progressive aphasia (PPA) exhibit concomitant single-word comprehension problems, constituting a ‘mixed variant’ phenotype. This phenotype is rare and currently not fully characterized. The aim of this study was twofold: to assess the prevalence and nature of single-word comprehension problems in the nonfluent variant and to study multimodal imaging characteristics of atrophy, tau, and amyloid burden associated with this mixed phenotype.MethodsA consecutive memory-clinic recruited series of 20 PPA patients (12 nonfluent, five semantic, and three logopenic variants) were studied on neurolinguistic and neuropsychological domains relative to 64 cognitively intact healthy older control subjects. The neuroimaging battery included high-resolution volumetric magnetic resonance imaging processed with voxel-based morphometry, and positron emission tomography with the tau-tracer [18F]-THK5351 and amyloid-tracer [11C]-Pittsburgh Compound B.ResultsSeven out of 12 subjects who had been classified a priori with nonfluent variant PPA showed deficits on conventional single-word comprehension tasks along with speech apraxia and agrammatism, corresponding to a mixed variant phenotype. These mixed variant cases included three females and four males, with a mean age at onset of 65 years (range 44–77 years). Object knowledge and object recognition were additionally affected, although less severely compared with the semantic variant. The mixed variant was characterized by a distributed atrophy pattern in frontal and temporoparietal regions. A more focal pattern of elevated [18F]-THK5351 binding was present in the supplementary motor area, the left premotor cortex, midbrain, and basal ganglia. This pattern was closely similar to that seen in pure nonfluent variant PPA. At the individual patient level, elevated [18F]-THK5351 binding in the supplementary motor area and premotor cortex was present in six out of seven mixed variant cases and in five and four of these cases, respectively, in the thalamus and midbrain. Amyloid biomarker positivity was present in two out of seven mixed variant cases, compared with none of the five pure nonfluent cases.ConclusionsA substantial proportion of PPA patients with speech apraxia and agrammatism also have single-word comprehension deficits. At the neurobiological level, the mixed variant shows a high degree of similarity with the pure nonfluent variant of PPA.Trial registrationEudraCT, 2014–002976-10. Registered on 13-01-2015.Electronic supplementary materialThe online version of this article (10.1186/s13195-018-0393-8) contains supplementary material, which is available to authorized users.

Primary Progressive Aphasia: Toward a Pathophysiological Synthesis

“…In logopenic variant PPA, research has identified three different subvariants based on core deficits of (i) single-word comprehension, (ii) repetition, and (iii) confrontation naming, each associated with specific atrophy profiles [14•]. Moreover, vocabulary loss (a core feature of svPPA) may be relatively common in nfvPPA [15]. A lack of understanding of the underlying pathophysiology in PPA syndromes is a common theme that makes principled diagnostic classification difficult.…”

Multivariate analysis reveals anatomical correlates of naming errors in primary progressive aphasia

“…In MV, object recognition and comprehension deficits exist in combination with distorted speech or agrammatism (Mesulam et al, 2014(Mesulam et al, , 2012. In SV and MV, semantic distractors related to the more dominant meaning of a homonym were the prime source of errors during single-word comprehension (Schaeverbeke et al, 2018), suggesting a shared mechanism. When directly comparing between PPA subtypes, semantic errors were common in all subtypes, whereas circumlocutions were more frequent in LV and SV versus speech production errors in NFV (Budd et al, 2010).…”

“…were included in previously published work (Grube et al, 2016;Nelissen et al, 2011;Schaeverbeke et al, 2018). Twenty-four healthy controls (HC), matched for age, gender and education (…”

Left frontal white matter links to rhythmic processing relevant to speech production

“…), in combination with neurolinguistics assessment and clinical MRI, as well as, where available, will not be discussed further because of the smaller sample size compared to the NFV and SV groups. Of the 12 NFV cases, all exhibited AOS on clinical examination and 5 patients (case 20-23 and 31) also displayed single-word comprehension deficits upon testing and would also fit the more recently described criteria for the "mixed variant" 2,29 . All patients received a volumetric MRI scan and 7 NFV and 7 SV DTI imaging.…”

“…The LV group will not be discussed because of the smaller sample size compared to the NFV and SV groups. All NFV cases clinically exhibited AOS (“effortful speech”) and 5 patients (case 20-23 and 31) also displayed clinically relevant single-word comprehension deficits early in the disease and would also fit the more recently described criteria for the “mixed variant” (Mesulam et al, 2014; Schaeverbeke et al, 2018). It is of note that this subtype was described after enrollment for our study started.…”