27 research outputs found
Visuospatial Functioning In The Primary Progressive Aphasias
Objectives: The aim of this study was to identify whether the three main primary progressive aphasia (PPA) variants would show differential profiles on measures of visuospatial cognition. We hypothesized that the logopenic variant would have the most difficulty across tasks requiring visuospatial and visual memory abilities. Methods: PPA patients (n = 156), diagnosed using current criteria, and controls were tested on a battery of tests tapping different aspects of visuospatial cognition. We compared the groups on an overall visuospatial factor; construction, immediate recall, delayed recall, and executive functioning composites; and on individual tests. Cross-sectional and longitudinal comparisons were made, adjusted for disease severity, age, and education. Results: The logopenic variant had significantly lower scores on the visuospatial factor and the most impaired scores on all composites. The nonfluent variant had significant difficulty on all visuospatial composites except the delayed recall, which differentiated them from the logopenic variant. In contrast, the semantic variants performed poorly only on delayed recall of visual information. The logopenic and nonfluent variants showed decline in figure copying performance over time, whereas in the semantic variant, this skill was remarkably preserved. Conclusions: This extensive examination of performance on visuospatial tasks in the PPA variants solidifies some previous findings, for example, delayed recall of visual stimuli adds value in differential diagnosis between logopenic variant PPA and nonfluent variant PPA variants, and illuminates the possibility of common mechanisms that underlie both linguistic and non-linguistic deficits in the variants. Furthermore, this is the first study that has investigated visuospatial functioning over time in the PPA variants
Altered topology of the functional speech production network in non-fluent/agrammatic variant of PPA
Non-fluent/agrammatic primary progressive aphasia (nfvPPA) is caused by neuro-degeneration within the left fronto-insular speech and language production network (SPN). Graph theory is a branch of mathematics that studies network architecture (topology) by quantifying features based on its elements (nodes and connections). This approach has been recently applied to neuroimaging data to explore the complex architecture of the brain connectome, though few studies have exploited this technique in PPA. Here, we used graph theory on functional MRI resting state data from a group of 20 nfvPPA patients and 20 matched controls to investigate topological changes in response to focal neuro-degeneration. We hypothesized that changes in the network architecture would be specific to the affected SPN in nfvPPA, while preserved in the spared default mode network (DMN). Topological configuration was quantified by hub location and global network metrics. Our findings showed a less efficiently wired and less optimally clustered SPN, while no changes were detected in the DMN. The SPN in the nfvPPA group showed a loss of hubs in the left fronto-parietal-temporal area and new critical nodes in the anterior left inferior-frontal and right frontal regions. Behaviorally, speech production score and rule violation errors correlated with the strength of functional connectivity of the left (lost) and right (new) regions respectively. This study shows that focal neurodegeneration within the SPN in nfvPPA is associated with network-specific topological alterations, with the loss and gain of crucial hubs and decreased global efficiency that were better accounted for through functional rather than structural changes. These findings support the hypothesis of selective network vulnerability in nfvPPA and may offer biomarkers for future behavioral intervention
Emergence of methicillin resistance predates the clinical use of antibiotics
The discovery of antibiotics more than 80 years ago has led to considerable improvements in human and animal health. Although antibiotic resistance in environmental bacteria is ancient, resistance in human pathogens is thought to be a modern phenomenon that is driven by the clinical use of antibiotics(1). Here we show that particular lineages of methicillin-resistant Staphylococcus aureus-a notorious human pathogen-appeared in European hedgehogs in the pre-antibiotic era. Subsequently, these lineages spread within the local hedgehog populations and between hedgehogs and secondary hosts, including livestock and humans. We also demonstrate that the hedgehog dermatophyte Trichophyton erinacei produces two beta-lactam antibiotics that provide a natural selective environment in which methicillin-resistant S. aureus isolates have an advantage over susceptible isolates. Together, these results suggest that methicillin resistance emerged in the pre-antibiotic era as a co-evolutionary adaptation of S. aureus to the colonization of dermatophyte-infected hedgehogs. The evolution of clinically relevant antibiotic-resistance genes in wild animals and the connectivity of natural, agricultural and human ecosystems demonstrate that the use of a One Health approach is critical for our understanding and management of antibiotic resistance, which is one of the biggest threats to global health, food security and development
Four-Repeat Tauopathies: Current Management and Future Treatments
Four-repeat tauopathies are a neurodegenerative disease characterized by brain parenchymal accumulation of a specific isoform of the protein tau, which gives rise to a wide breadth of clinical syndromes encompassing diverse symptomatology, with the most common syndromes being progressive supranuclear palsy-Richardson's and corticobasal syndrome. Despite the lack of effective disease-modifying therapies, targeted treatment of symptoms can improve quality of life for patients with 4-repeat tauopathies. However, managing these symptoms can be a daunting task, even for those familiar with the diseases, as they span motor, sensory, cognitive, affective, autonomic, and behavioral domains. This review describes current approaches to symptomatic management of common clinical symptoms in 4-repeat tauopathies with a focus on practical patient management, including pharmacologic and nonpharmacologic strategies, and concludes with a discussion of the history and future of disease-modifying therapeutics and clinical trials in this population
Connected speech markers of amyloid burden in primary progressive aphasia
INTRODUCTION
Positron emission tomography (PET) amyloid imaging has become an important part of the diagnostic workup for patients with primary progressive aphasia (PPA) and uncertain underlying pathology. Here, we employ a semi-automated analysis of connected speech (CS) with a twofold objective. First, to determine if quantitative CS features can help select primary progressive aphasia (PPA) patients with a higher probability of a positive PET amyloid imaging result. Second, to examine the relevant group differences from a clinical perspective.
METHODS
117 CS samples from a well-characterised cohort of PPA patients who underwent PET amyloid imaging were collected. Expert consensus established PET amyloid status for each patient, and 40% of the sample was amyloid positive.
RESULTS
Leave-one-out cross-validation yields 77% classification accuracy (sensitivity: 74%, specificity: 79%).
DISCUSSION
Our results confirm the potential of CS analysis as a screening tool. Discriminant CS features from lexical, syntactic, pragmatic, and semantic domains are discussed
Diagnostic Assessment in Primary Progressive Aphasia: An Illustrative Case Example
Purpose
Diagnosis and classification of primary progressive aphasia (PPA) requires confirmation of specific speech and language symptoms, highlighting the important role of speech-language pathologists (SLPs) in the evaluation process. The purpose of this case report is to inform SLPs regarding current practices for diagnostic assessment in PPA, describing standard approaches as well as complementary, state-of-the-art procedures that may improve diagnostic precision.
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Method
We describe the diagnostic evaluation of a 49-year old female with complaints of progressive word-finding difficulty. She completed standard neurological, neuropsychological, and speech-language evaluations, as well as magnetic resonance and positron emission tomography imaging of her brain. In addition, a history of developmental speech, language, and learning abilities was obtained, as well as genetic testing, and assessment of cerebrospinal fluid biomarkers. We discuss the evaluation results in the context of the most current research related to PPA diagnosis.
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Conclusion
Detailed behavioral assessment, thorough intake of symptom history and neurodevelopmental differences, multimodal neuroimaging, and comprehensive examination of genes and biomarkers are of paramount importance for detecting and characterizing PPA, with ramifications for early behavioral and/or pharmacological intervention
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Diagnostic Assessment in Primary Progressive Aphasia: An Illustrative Case Example
Purpose
Diagnosis and classification of primary progressive aphasia (PPA) requires confirmation of specific speech and language symptoms, highlighting the important role of speech-language pathologists (SLPs) in the evaluation process. The purpose of this case report is to inform SLPs regarding current practices for diagnostic assessment in PPA, describing standard approaches as well as complementary, state-of-the-art procedures that may improve diagnostic precision.
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Method
We describe the diagnostic evaluation of a 49-year old female with complaints of progressive word-finding difficulty. She completed standard neurological, neuropsychological, and speech-language evaluations, as well as magnetic resonance and positron emission tomography imaging of her brain. In addition, a history of developmental speech, language, and learning abilities was obtained, as well as genetic testing, and assessment of cerebrospinal fluid biomarkers. We discuss the evaluation results in the context of the most current research related to PPA diagnosis.
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Conclusion
Detailed behavioral assessment, thorough intake of symptom history and neurodevelopmental differences, multimodal neuroimaging, and comprehensive examination of genes and biomarkers are of paramount importance for detecting and characterizing PPA, with ramifications for early behavioral and/or pharmacological intervention
Auditory Verb Generation Performance Patterns Dissociate Variants of Primary Progressive Aphasia.
Primary progressive aphasia (PPA) is a clinical syndrome in which patients progressively lose speech and language abilities. Three variants are recognized: logopenic (lvPPA), associated with phonology and/or short-term verbal memory deficits accompanied by left temporo-parietal atrophy; semantic (svPPA), associated with semantic deficits and anterior temporal lobe (ATL) atrophy; non-fluent (nfvPPA) associated with grammar and/or speech-motor deficits and inferior frontal gyrus (IFG) atrophy. Here, we set out to investigate whether the three variants of PPA can be dissociated based on error patterns in a single language task. We recruited 21 lvPPA, 28 svPPA, and 24 nfvPPA patients, together with 31 healthy controls, and analyzed their performance on an auditory noun-to-verb generation task, which requires auditory analysis of the input, access to and selection of relevant lexical and semantic knowledge, as well as preparation and execution of speech. Task accuracy differed across the three variants and controls, with lvPPA and nfvPPA having the lowest and highest accuracy, respectively. Critically, machine learning analysis of the different error types yielded above-chance classification of patients into their corresponding group. An analysis of the error types revealed clear variant-specific effects: lvPPA patients produced the highest percentage of "not-a-verb" responses and the highest number of semantically related nouns (production of baseball instead of throw to noun ball); in contrast, svPPA patients produced the highest percentage of "unrelated verb" responses and the highest number of light verbs (production of take instead of throw to noun ball). Taken together, our findings indicate that error patterns in an auditory verb generation task are associated with the breakdown of different neurocognitive mechanisms across PPA variants. Specifically, they corroborate the link between temporo-parietal regions with lexical processing, as well as ATL with semantic processes. These findings illustrate how the analysis of pattern of responses can help PPA phenotyping and heighten diagnostic sensitivity, while providing insights on the neural correlates of different components of language
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Discriminating nonfluent/agrammatic and logopenic PPA variants with automatically extracted morphosyntactic measures from connected speech
Morphosyntactic assessments are important for characterizing individuals with nonfluent/agrammatic variant primary progressive aphasia (nfvPPA). Yet, standard tests are subject to examiner bias and often fail to differentiate between nfvPPA and logopenic variant PPA (lvPPA). Moreover, relevant neural signatures remain underexplored. Here, we leverage natural language processing tools to automatically capture morphosyntactic disturbances and their neuroanatomical correlates in 35 individuals with nfvPPA relative to 10 healthy controls (HC) and 26 individuals with lvPPA. Participants described a picture, and ensuing transcripts were analyzed via part-of-speech tagging to extract sentence-related features (e.g., subordinating and coordinating conjunctions), verbal-related features (e.g., tense markers), and nominal-related features (e.g., subjective and possessive pronouns). Gradient boosting machines were used to classify between groups using all features. We identified the most discriminant morphosyntactic marker via a feature importance algorithm and examined its neural correlates via voxel-based morphometry. Individuals with nfvPPA produced fewer morphosyntactic elements than the other two groups. Such features robustly discriminated them from both individuals with lvPPA and HCs with an AUC of .95 and .82, respectively. The most discriminatory feature corresponded to subordinating conjunctions was correlated with cortical atrophy within the left posterior inferior frontal gyrus across groups (pFWE < .05). Automated morphosyntactic analysis can efficiently differentiate nfvPPA from lvPPA. Also, the most sensitive morphosyntactic markers correlate with a core atrophy region of nfvPPA. Our approach, thus, can contribute to a key challenge in PPA diagnosis
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Speech production differences in English and Italian speakers with nonfluent variant PPA.
OBJECTIVE:To understand whether the clinical phenotype of nonfluent/agrammatic primary progressive aphasia (nfvPPA) could present differences depending on the patient's native language. METHODS:In this cross-sectional study, we analyzed connected speech samples in monolingual English (nfvPPA-E) and Italian speakers (nfvPPA-I) who were diagnosed with nfvPPA and matched for age, sex, and Mini-Mental State Examination scores. Patients also received a comprehensive neuropsychological battery. All patients and 2 groups of age-matched healthy controls underwent an MRI scan with 3D T1-weighted sequences. Connected speech measures and the other cognitive features were compared between patient groups. MRI variables, in terms of gray matter volume, were compared between each patient group and the corresponding controls. RESULTS:Compared to nfvPPA-E, nfvPPA-I had fewer years of education and shorter reported disease duration. The 2 groups showed similar regional atrophy compatible with clinical diagnosis. Patients did not differ in nonlanguage domains, comprising executive scores. Connected speech sample analysis showed that nfvPPA-E had significantly more distortions than nfvPPA-I, while nfvPPA-I showed reduced scores in some measures of syntactic complexity. On language measures, Italian speakers performed more poorly on syntactic comprehension. CONCLUSIONS:nfvPPA-E showed greater motor speech impairment than nfvPPA-I despite higher level of education and comparable disease severity and atrophy changes. The data also suggest greater grammatical impairment in nfvPPA-I. This study illustrates the need to take into account the possible effect of the individual's spoken language on the phenotype and clinical presentation of primary progressive aphasia variants