Citations

Purpose The aims of the study were to assess and compare grammatical deficits in written and spoken language production in subjects with agrammatic primary progressive aphasia (agPPA) and in subjects with agrammatism in the context of dominant apraxia of speech (DAOS) and to investigate neuroanatomical correlates. Method Eight agPPA and 21 DAOS subjects performed the picture description task of the Western Aphasia Battery (WAB) both in writing and orally. Responses were transcribed and coded for linguistic analysis. agPPA and DAOS were compared to 13 subjects with primary progressive apraxia of speech (PPAOS) who did not have agrammatism. Spearman correlations were performed between the written and spoken variables. Patterns of atrophy in each group were compared, and relationships between the different linguistic measures and integrity of Broca's area were assessed. Results agPPA and DAOS both showed lower mean length of utterance, fewer grammatical utterances, more nonutterances, more syntactic and semantic errors, and fewer complex utterances than PPAOS in writing and speech, as well as fewer correct verbs and nouns in speech. Only verb ratio and proportion of grammatical utterances correlated between modalities. agPPA and DAOS both showed greater involvement of Broca's area than PPAOS, and atrophy of Broca's area correlated with proportion of grammatical and ungrammatical utterances and semantic errors in writing and speech. Conclusions agPPA and DAOS subjects showed similar patterns of agrammatism, although subjects performed differently when speaking versus writing. Integrity of Broca's area correlates with agrammatism.

Background and purposeThe non‐fluent/agrammatic variant of primary progressive aphasia (agPPA) is a heterogeneous diagnosis wherein some individuals have apraxia of speech (AOS). When agPPA includes AOS, a tauopathy is the likely underlying pathology. Recently, [18F]AV‐1451 was developed for the in‐vivo assessment of tau. In this study, we compared patterns of tau tracer uptake in patients with agPPA with and without AOS.MethodsNine patients with agPPA (four without AOS) underwent tau positron emission tomography imaging with [18F]AV‐1451. Uptake of [18F]AV‐1451 was assessed as cortical to cerebellar crus ratio (standard uptake value ratio) in cortical regions of interest measured using the MCALT atlas and compared voxel‐wise in SPM12. Each patient was age‐ and sex‐matched to three controls.ResultsThe agPPA without AOS showed uptake in the left frontal and temporal lobes, whereas agPPA with AOS showed uptake in the bilateral supplementary motor areas, frontal lobes, precuneus and precentral gyrus relative to controls. The left precentral gyrus had uptake in agPPA with AOS relative to those without AOS.ConclusionsThis cross‐sectional study suggests that [18F]AV‐1451 uptake in the precentral gyrus is implicated in AOS in agPPA.

Background: Despite common pathology, Alzheimer’s disease (AD) can have multiple clinical presentations which pathological studies suggest result from differences in the regional distribution of tau pathology. Positron emission tomography (PET) ligands are now available that can detect tau proteins in vivo and hence can be used to investigate the biological mechanisms underlying atypical AD. Objective: To assess regional patterns of tau uptake on PET imaging in two atypical AD variants, posterior cortical atrophy (PCA) and logopenic progressive aphasia (lvPPA). Methods: Eighteen PCA and 19 lvPPA subjects that showed amyloid-β deposition on PET underwent tau-PET imaging with [ 18 F]AV-1451. Group comparisons of tau uptake in PCA and lvPPA were performed using voxel-level and regional-level analyses. We also assessed the degree of lobar tau asymmetry and correlated regional tau uptake to age and performance on clinical evaluations. Results: Both syndromes showed diffuse tau uptake throughout all cortical regions, although PCA showed greater uptake in occipital regions compared to lvPPA, and lvPPA showed greater uptake in left frontal and temporal regions compared to PCA. While lvPPA showed predominant left-asymmetric tau deposition, PCA was more bilateral. Younger subjects showed greater tau uptake bilaterally in frontal and parietal lobes than older subjects, and sentence repetition, Boston naming test, simultanagnosia, and visuoperceptual function showed specific regional tau correlates. Conclusion: Tau deposition is closely related to clinical presentation in atypical AD with age playing a role in determining the degree of cortical tau deposition.

ObjectivesTo assess [18F]AV‐1451 tau‐PET (positron emission tomography) uptake patterns across the primary progressive aphasia (PPA) variants (logopenic, semantic, and agrammatic), examine regional uptake patterns of [18F]AV‐1451 independent of clinical diagnosis, and compare the diagnostic utility of [18F]AV‐1451, [18F]‐fluorodeoxygluclose (FDG)‐PET and MRI (magnetic resonance imaging) to differentiate the PPA variants.MethodsWe performed statistical parametric mapping of [18F]AV‐1451 across 40 PPA patients (logopenic‐PPA = 14, semantic‐PPA = 13, and agrammatic‐PPA = 13) compared to 80 cognitively normal, Pittsburgh compound B–negative controls, age and gender matched 2:1. Principal component analysis of regional [18F]AV‐1451 tau‐PET standard uptake value ratio was performed to understand underlying patterns of [18F]AV‐1451 uptake independent of clinical diagnosis. Penalized multinomial regression analyses were utilized to assess diagnostic utility.ResultsLogopenic‐PPA showed striking uptake throughout neocortex, particularly temporoparietal, compared to controls, semantic‐PPA, and agrammatic‐PPA. Semantic‐PPA and agrammatic‐PPA showed milder patterns of focal [18F]AV‐1451 uptake. Semantic‐PPA showed elevated uptake (left>right) in anteromedial temporal lobes, compared to controls and agrammatic‐PPA. Agrammatic‐PPA showed elevated uptake (left>right) throughout prefrontal white matter and in subcortical gray matter structures, compared to controls and semantic‐PPA. The principal component analysis of regional [18F]AV‐1451 indicated two primary dimensions, a severity dimension that distinguished logopenic‐PPA from agrammatic‐PPA and semantic‐PPA, and a frontal versus temporal contrast that distinguishes agrammatic‐PPA and semantic‐PPA cases. Diagnostic utility of [18F]AV‐1451was superior to MRI and at least equal to FDG‐PET.Interpretation[18F]AV‐1451binding characteristics differ across the PPA variants and were excellent at distinguishing between the variants. [18F]AV‐1451binding characteristics were as good or better than other brain imaging modalities utilized in clinical practice, suggesting that [18F]AV‐1451 may have clinical diagnostic utility in PPA. Ann Neurol 2018 Ann Neurol 2018;83:599–611

Purpose This study compared orofacial strength between adults with dysarthria and neurologically normal (NN) matched controls. In addition, orofacial muscle weakness was examined for potential relationships to speech impairments in adults with dysarthria. Method Matched groups of 55 adults with dysarthria and 55 NN adults generated maximum pressure (P max ) against an air-filled bulb during lingual elevation, protrusion and lateralization, and buccodental and labial compressions. These orofacial strength measures were compared with speech intelligibility, perceptual ratings of speech, articulation rate, and fast syllable-repetition rate. Results The dysarthria group demonstrated significantly lower orofacial strength than the NN group on all tasks. Lingual strength correlated moderately and buccal strength correlated weakly with most ratings of speech deficits. Speech intelligibility was not sensitive to dysarthria severity. Individuals with severely reduced anterior lingual elevation P max (< 18 kPa) had normal to profoundly impaired sentence intelligibility (99%–6%) and moderately to severely impaired speech (26%–94% articulatory imprecision; 33%–94% overall severity). Conclusions Results support the presence of orofacial muscle weakness in adults with dysarthrias of varying etiologies but reinforce tenuous links between orofacial strength and speech production disorders. By examining individual data, preliminary evidence emerges to suggest that speech, but not necessarily intelligibility, is likely to be impaired when lingual weakness is severe.

PurposeQuantification of tissue stiffness may facilitate identification of abnormalities in orofacial muscle tone and thus contribute to differential diagnosis of dysarthria. Tissue stiffness is affected by muscle tone as well as age-related changes in muscle and connective tissue.MethodThe Myoton-3 measured tissue stiffness in 40 healthy adults, including equal numbers of men and women in each of two age groups: 18–40 years and 60+ years. Data were collected from relaxed muscles at the masseter, cheek, and lateral tongue surfaces in two positions: reclined on the side and seated with head tilted.ResultsTissue stiffness differed across age, sex, and measurement site with multiple interaction effects. Overall, older subjects exhibited higher stiffness coefficients and oscillation frequency measures than younger subjects whereas sex differences varied by tissue site. Effects of body position were inconsistent across tissue site and measurement.ConclusionsAlthough older subjects were expected to have lower muscle tone, age-related nonmuscular tissue changes may have contributed to yield a net effect of higher stiffness. These data raise several considerations for the development of accurate normative data and for future diagnostic applications of tissue stiffness assessment.