Syntactic processing deficits are highly variable in individuals with primary progressive aphasia. Damage to left inferior frontal cortex has been associated with syntactic deficits in primary progressive aphasia in a number of structural and functional neuroimaging studies. However, a contrasting picture of a broader syntactic network has emerged from neuropsychological studies in other aphasic cohorts, and functional imaging studies in healthy controls. To reconcile these findings, we used functional magnetic resonance imaging to investigate the functional neuroanatomy of syntactic comprehension in 51 individuals with primary progressive aphasia, composed of all clinical variants and a range of degrees of syntactic processing impairment. We used trial-by-trial reaction time as a proxy for syntactic processing load, to determine which regions were modulated by syntactic processing in each patient, and how the set of regions recruited was related to whether syntactic processing was ultimately successful or unsuccessful. Relationships between functional abnormalities and patterns of cortical atrophy were also investigated. We found that the individual degree of syntactic comprehension impairment was predicted by left frontal atrophy, but also by functional disruption of a broader syntactic processing network, comprising left posterior frontal cortex, left posterior temporal cortex, and the left intraparietal sulcus and adjacent regions. These regions were modulated by syntactic processing in healthy controls and in patients with primary progressive aphasia with relatively spared syntax, but they were modulated to a lesser extent or not at all in primary progressive aphasia patients whose syntax was relatively impaired. Our findings suggest that syntactic comprehension deficits in primary progressive aphasia reflect not only structural and functional changes in left frontal cortex, but also disruption of a wider syntactic processing network.

Introduction

Primary progressive aphasia (PPA) is a neurodegenerative disorder characterized by progressive deterioration of speech and language. A growing body of research supports the utility of speech and language intervention in individuals with PPA, although access to these services remains limited. One potential means of increasing treatment accessibility is the delivery of treatment via telemedicine. Evidence supports the use of teletherapy in stroke-induced aphasia, but research examining the application of teletherapy in PPA is limited. In the current study, a non-randomized group comparison design was used to evaluate the feasibility and utility of treatment delivered via teletherapy relative to treatment administered in person for individuals with PPA.

Methods

Two treatment protocols were administered as part of a larger study investigating treatment for speech and language deficits in PPA. Participants with semantic (n=10) and logopenic (n=11) PPA received lexical retrieval treatment and individuals with nonfluent/agrammatic PPA (n=10) received video-implemented script training for aphasia designed to promote speech production and fluency. Treatment was administered via teletherapy for approximately half of the participants receiving each intervention. Treatment outcomes and performance on standardized tests were assessed at pre-treatment and post-treatment, as well as 3, 6, and 12 months post-treatment.

Results

Overall, both treatment approaches resulted in significant gains for primary outcome measures. Critically, comparison of in-person and teletherapy groups revealed comparable outcomes. Generalization to untrained targets and tasks and maintenance of treatment-induced gains were also comparable for traditional vs teletherapy participants.

Conclusion

Overall, treatment outcomes were largely equivalent for individuals receiving treatment via teletherapy vs traditional, in-person delivery. Results support the application of teletherapy for administering restitutive interventions to individuals with mild-to-moderate PPA. Potential implications for using teletherapy in the treatment of cognitive-linguistic and motoric impairments in other disorders and suggestions for administering treatment via telemedicine are discussed.

Logopenic variant primary progressive aphasia (lvPPA) is a neurodegenerative language disorder primarily characterized by impaired phonological processing. Sentence repetition and comprehension deficits are observed in lvPPA and linked to impaired phonological working memory, but recent evidence also implicates impaired speech perception. Currently, neural encoding of the speech envelope, which forms the scaffolding for perception, is not clearly understood in lvPPA. We leveraged recent analytical advances in electrophysiology to examine speech envelope encoding in lvPPA. We assessed cortical tracking of the speech envelope and in-task comprehension of two spoken narratives in individuals with lvPPA (n = 10) and age-matched (n = 10) controls. Despite markedly reduced narrative comprehension relative to controls, individuals with lvPPA had increased cortical tracking of the speech envelope in theta oscillations, which track low-level features (e.g., syllables), but not delta oscillations, which track speech units that unfold across a longer time scale (e.g., words, phrases, prosody). This neural signature was highly correlated across narratives. Results indicate an increased reliance on acoustic cues during speech encoding. This may reflect inefficient encoding of bottom-up speech cues, likely as a consequence of dysfunctional temporoparietal cortex.

Purpose Of the three currently recognized variants of primary progressive aphasia, behavioral differentiation between the nonfluent/agrammatic (nfvPPA) and logopenic (lvPPA) variants is particularly difficult. The challenge includes uncertainty regarding diagnosis of apraxia of speech, which is subsumed within criteria for variant classification. The purpose of this study was to determine the extent to which a variety of speech articulation and prosody metrics for apraxia of speech differentiate between nfvPPA and lvPPA across diverse speech samples. Method The study involved 25 participants with progressive aphasia (10 with nfvPPA, 10 with lvPPA, and five with the semantic variant). Speech samples included a word repetition task, a picture description task, and a story narrative task. We completed acoustic analyses of temporal prosody and quantitative perceptual analyses based on narrow phonetic transcription and then evaluated the degree of differentiation between nfvPPA and lvPPA participants (with the semantic variant serving as a reference point for minimal speech production impairment). Results Most, but not all, articulatory and prosodic metrics differentiated statistically between the nfvPPA and lvPPA groups. Measures of distortion frequency, syllable duration, syllable scanning, and-to a limited extent-syllable stress and phonemic accuracy showed greater impairment in the nfvPPA group. Contrary to expectations, classification was most accurate in connected speech samples. A customized connected speech metric-the narrative syllable duration-yielded excellent to perfect classification accuracy. Discussion Measures of average syllable duration in multisyllabic utterances are useful diagnostic tools for differentiating between nfvPPA and lvPPA, particularly when based on connected speech samples. As such, they are suitable candidates for automatization, large-scale study, and application to clinical practice. The observation that both speech rate and distortion frequency differentiated more effectively in connected speech than on a motor speech examination suggests that it will be important to evaluate interactions between speech and discourse production in future research.

Objective

To report the clinical, neuropsychological, linguistic, imaging, and neuropathological features of a unique case of sporadic Jakob-Creutzfeldt disease in which the patient presented with a logopenic variant of primary progressive aphasia.

Design

Case report.

Setting

Large referral center for atypical memory and aging disorders, particularly Jakob-Creutzfeldt disease.

Patient

Patient presenting with logopenic variant primary progressive aphasia initially thought to be due to Alzheimer disease.

Results

Despite the long, slow 3.5-year course, the patient was shown to have pathology-proven sporadic Jakob-Creutzfeldt disease.

Conclusions

These findings expand the differential of primary progressive aphasia to include prion disease.

Many patients with primary progressive aphasia (PPA) are impaired in syntactic production. Because most previous studies of expressive syntax in PPA have relied on quantitative analysis of connected speech samples, which is a relatively unconstrained task, it is not well understood which specific syntactic structures are most challenging for these patients. We used an elicited syntactic production task to identify which syntactic structures pose difficulties for 31 patients with three variants of PPA: non-fluent/agrammatic, semantic and logopenic. Neurodegenerative and healthy age-matched participants were included as controls. As expected, non-fluent/agrammatic patients made the most syntactic errors. The structures that resulted in the most errors were constructions involving third person singular present agreement, and constructions involving embedded clauses. Deficits on this elicited production task were associated with atrophy of the left posterior inferior frontal gyrus.

Introduction

The effect of bilingualism on age at onset has yet to be examined within different clinical variants of Alzheimer's disease.

Methods

We reviewed the research charts of 287 well-characterized participants with either amnestic Alzheimer's dementia or logopenic variant primary progressive aphasia (lvPPA) and identified bilingual speakers based on regular use of two or more languages and/or ability to communicate with native speakers in two or more languages. We evaluated whether bilingual speakers demonstrated a delay in age of symptom onset relative to monolingual speakers while controlling for other variables known to influence cognitive reserve.

Results

A 5-year delay in age at symptom onset was observed for bilingual relative to monolingual speakers with lvPPA. This delay in onset was not observed in the amnestic Alzheimer's dementia cohort.

Discussion

Bilingualism may serve as a unique cognitive reserve variable in lvPPA, but not in amnestic Alzheimer's dementia.

Neuroimaging and neuropsychological studies have implicated the anterior temporal lobe (ATL) in sentence-level processing, with syntactic structure-building and/or combinatorial semantic processing suggested as possible roles. A potential challenge to the view that the ATL is involved in syntactic aspects of sentence processing comes from the clinical syndrome of semantic variant primary progressive aphasia (semantic PPA; also known as semantic dementia). In semantic PPA, bilateral neurodegeneration of the ATLs is associated with profound lexical semantic deficits, yet syntax is strikingly spared. The goal of this study was to investigate the neural correlates of syntactic processing in semantic PPA to determine which regions normally involved in syntactic processing are damaged in semantic PPA and whether spared syntactic processing depends on preserved functionality of intact regions, preserved functionality of atrophic regions, or compensatory functional reorganization. We scanned 20 individuals with semantic PPA and 24 age-matched controls using structural MRI and fMRI. Participants performed a sentence comprehension task that emphasized syntactic processing and minimized lexical semantic demands. We found that, in controls, left inferior frontal and left posterior temporal regions were modulated by syntactic processing, whereas anterior temporal regions were not significantly modulated. In the semantic PPA group, atrophy was most severe in the ATLs but extended to the posterior temporal regions involved in syntactic processing. Functional activity for syntactic processing was broadly similar in patients and controls; in particular, whole-brain analyses revealed no significant differences between patients and controls in the regions modulated by syntactic processing. The atrophic left ATL did show abnormal functionality in semantic PPA patients; however, this took the unexpected form of a failure to deactivate. Taken together, our findings indicate that spared syntactic processing in semantic PPA depends on preserved functionality of structurally intact left frontal regions and moderately atrophic left posterior temporal regions, but no functional reorganization was apparent as a consequence of anterior temporal atrophy and dysfunction. These results suggest that the role of the ATL in sentence processing is less likely to relate to syntactic structure-building and more likely to relate to higher-level processes such as combinatorial semantic processing.

We describe a patient with semantic variant of frontotemporal dementia who received longitudinal clinical evaluations and structural MRI scans and subsequently came to autopsy. She presented with early behavior changes and semantic loss for foods and people and ultimately developed a pervasive semantic impairment affecting social-emotional as well as linguistic domains. Imaging revealed predominant atrophy of the right temporal lobe, with later involvement of the left, and pathology confirmed bilateral temporal involvement. Findings support the view that left and right anterior temporal lobes serve as semantic hubs that may be affected differentially in semantic variant by early, relatively unilateral damage.