Clark, Heather M.

This study examined the rate of producing alternating motion rates, sequential motion rates (SMRs), and repeated words in 27 individuals with the semantic variant of Primary Progressive Aphasia (svPPA). Only the rate of producing SMRs was significantly elevated in svPPA compared to controls. This may be associated with concomitant neuropsychiatric symptoms in svPPA, as correlation analysis showed a relationship between increased SMR rate and the Neuropsychiatric Inventory Questionnaire, which documented anxiety and disinhibition. Future studies will assess these findings in a larger cohort and work to better understand if this phenomenon is a manifestation of behavioral and/or motor changes.

Purpose This case series details the clinical progression of patients with primary progressive apraxia of speech (PPAOS) to illustrate, using several methods and supplemental material examples, the changes that occur in speech and language functioning in this patient population. Method Four patients who presented with PPAOS were followed between 5 and 6 years. Two patients had predominant articulatory abnormalities (termed phonetic PPAOS ), 1 had predominant prosodic abnormalities (prosodic PPAOS), and 1 had relatively equal articulatory and prosodic abnormalities (mixed PPAOS). Detailed speech (including acoustics), language, neurologic, and neuropsychological data were collected. Results At initial exam, the patients ranged from 60 to 77 years old, with presenting disease duration of 1.5–10 years. Although all patients presented with an isolated apraxia of speech, all developed varying degrees of aphasia and dysarthria. Patients with phonetic PPAOS developed relatively more severe aphasia than the other 2 patients. All patients eventually had severe functional communication limitations and required alternative or augmentative means of communication, although at varying times postonset of their initial speech problem. Two patients developed dysphagia, 3 showed mild–moderate Parkinsonism, and 2 developed depression. For all patients, simple temporal acoustic measurements documented slowed speech rate over time. Conclusions This case series demonstrates that patients who initially present with PPAOS may develop aphasia and dysarthria, cognitive and behavioral changes, and other neurologic signs. Whether these changes can be predicted by the perceptual characteristics of the apraxia of speech is yet to be determined. The detailed longitudinal profiles provide valuable clinical insight into the progression of disease in people with PPAOS. Supplemental Material https://doi.org/10.23641/asha.7051616

Background: Neuropsychological assessment can add essential information to the characterization of individuals presenting with the logopenic variant of primary progressive aphasia (lvPPA). Objective: This study examined the neuropsychological characteristics of lvPPA patients. We also examined differences in regional and whole brain atrophy based on neuropsychological profiles. Methods: We conducted a hierarchical cluster analysis on memory, executive functioning, and visuospatial neuropsychological test data for 56 individuals with lvPPA. We then compared resultant clusters to left middle temporal, inferior parietal, and superior parietal regions-of-interest using multivariate analysis of covariance. We also performed voxel-level analyses. Results: We identified three clusters characterized as lvPPA with no neurocognitive impairment ( n = 5), lvPPA with mild neurocognitive deficits ( n = 23), and lvPPA with marked cognitive deficits ( n = 28). WAB-AQ was associated with left middle temporal volume. Superior parietal volumes were smaller for the lvPPA group with marked cognitive symptoms compared to the less severe groups. Voxel-level analyses showed greater atrophy in temporal, parietal, lateral occipital, and frontal regions, left worse than right. Age, disease duration, gender, WAB-AQ, and PiB-PET did not account for differences between groups. Conclusions: LvPPA patients without cognitive deficits in other domains were relatively uncommon while 50% of our sample exhibited pronounced neurocognitive deficits outside the language domain. Pronounced cognitive deficits in lvPPA are associated with widespread atrophy, left worse than right. Our study underscores the importance of examining neuropsychological function in addition to language in patients with lvPPA.

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