Cognitive and Neural Mechanisms of Social Communication Dysfunction in Primary Progressive Aphasia

Goldberg, Zoë-Lee; El-Omar, Hashim; Foxe, David; Leyton, Cristian E.; Piguet, Olivier; Irish, Muireann

doi:10.3390/brainsci11121600

Cited by 8 publications

(4 citation statements)

References 86 publications

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“… 108–112 Ultimately, it is unsurprising that a combination of aphasia, poor memory and general cognition, increased apathy and agitation significantly compounds carer burden and caring-related challenges in lvPPA. 110 , 113 , 114 Additional investigations of the inter-dependence between behavioural and mood symptoms, the neural bases of non-linguistic cognitive and behavioural difficulties, and how these changes relate to underlying pathological and genetic changes in lvPPA are required (see Box 1 ). Nevertheless, the extant evidence consistently implicates TPJ/IPL dysfunction as one of the brain regions central to multidimensional cognitive decline in the syndrome.…”

Section: Lvppa Clinical Observations Mirror Cognitive Neurosciencementioning

confidence: 99%

Understanding the multidimensional cognitive deficits of logopenic variant primary progressive aphasia

Ramanan

Irish

Patterson

et al. 2022

Brain

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The logopenic variant of primary progressive aphasia is characterized by early deficits in language production and phonological short-term memory, attributed to left-lateralized temporoparietal, inferior parietal and posterior temporal neurodegeneration. Despite patients primarily complaining of language difficulties, emerging evidence points to performance deficits in non-linguistic domains. Temporoparietal cortex, and functional brain networks anchored to this region, are implicated as putative neural substrates of non-linguistic cognitive deficits in logopenic variant primary progressive aphasia, suggesting that degeneration of a shared set of brain regions may result in co-occurring linguistic and non-linguistic dysfunction early in the disease course. Here, we provide a Review aimed at broadening the understanding of logopenic variant primary progressive aphasia beyond the lens of an exclusive language disorder. By considering behavioural and neuroimaging research on non-linguistic dysfunction in logopenic variant primary progressive aphasia, we propose that a significant portion of multidimensional cognitive features can be explained by degeneration of temporal/inferior parietal cortices and connected regions. Drawing on insights from normative cognitive neuroscience, we propose that these regions underpin a combination of domain-general and domain-selective cognitive processes, whose disruption results in multifaceted cognitive deficits including aphasia. This account explains the common emergence of linguistic and non-linguistic cognitive difficulties in logopenic variant primary progressive aphasia, and predicts phenotypic diversification associated with progression of pathology in posterior neocortex.

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Section: Lvppa Clinical Observations Mirror Cognitive Neurosciencementioning

confidence: 99%

Understanding the multidimensional cognitive deficits of logopenic variant primary progressive aphasia

Ramanan

Irish

Patterson

et al. 2022

Brain

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“…Examples signalled here include syndromic hallmarks such as early binary reversals in nfvPPA and the prominence of auditory and nonverbal behavioural features across PPA syndromes. A staging system for PPA could provide a bridge to the development of bespoke functional scales of daily life communication 77 that could in turn serve as outcome measures for clinical trials in these syndromes and language-led AD clinical phenotypes 78 . Looking forward, we envisage that particular symptoms identified as harbingers of early-stage PPA might inform the development of diagnostic 'cognitive stress tests' based on the analysis of patients' spontaneous conversation [79][80][81] or requiring production and/or understanding of speech in multi-talker environments or other demanding conditions 52,82 .…”

Section: Discussionmentioning

confidence: 99%

Symptom-led staging for primary progressive aphasia

Hardy

Taylor-Rubin

Taylor³

et al. 2023

Preprint

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The primary progressive aphasias (PPA) present complex and diverse challenges of diagnosis, management and prognosis. A clinically-informed, syndromic staging system for PPA would take a substantial step toward meeting these challenges. This study addressed this need using detailed, multi-domain mixed-methods symptom surveys of people with lived experience in a large international PPA cohort. We administered structured online surveys to caregivers of patients with a canonical PPA syndromic variant (nonfluent/agrammatic (nvPPA), semantic (svPPA) or logopenic (lvPPA)). In an exploratory survey, a putative list and ordering of verbal communication and nonverbal functioning (nonverbal thinking, conduct and wellbeing, physical) symptoms was administered to 118 caregiver members of the UK national PPA Support Group. Based on feedback, we expanded the symptom list and created six provisional clinical stages for each PPA subtype. In a consolidation survey, these stages were presented to 110 caregiver members of UK and Australian PPA Support Groups, and refined based on quantitative and qualitative feedback. Symptoms were retained if rated as present by a majority (at least 50%) of respondents representing that PPA syndrome, and assigned to a consolidated stage based on majority consensus; the confidence of assignment was estimated for each symptom as the proportion of respondents in agreement with the final staging for that symptom. Qualitative responses were analysed using framework analysis. For each PPA syndrome, six stages ranging from 1 (Very mild) to 6 (Profound) were identified; earliest stages were distinguished by syndromic hallmark symptoms of communication dysfunction, with increasing trans-syndromic convergence and dependency for basic activities of daily living at later stages. Spelling errors, hearing changes and nonverbal behavioural features were reported at early stages in all syndromes. As the illness evolved, swallowing and mobility problems were reported earlier in nfvPPA than other syndromes, while difficulty recognising familiar people and household items characterised svPPA and visuospatial symptoms were more prominent in lvPPA. Overall confidence of symptom staging was higher for svPPA than other syndromes. Across syndromes, functional milestones were identified as key deficits that predict the sequence of major daily life impacts and associated management needs. Qualitatively, we identified five major themes encompassing 15 subthemes capturing respondents' experiences of PPA and suggestions for staging implementation. This work introduces a prototypical, symptom-led staging scheme for canonical PPA syndromes: the PPA Progression Planning Aid (PPA-squared). Our findings have implications for diagnostic and care pathway guidelines, trial design and personalised prognosis and treatment for people living with these diseases.

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“…69,70 Post mortem data would link clinical symptoms to neuropathology, while genetic cohorts represent an opportunity to unpack earliest disease stages (i.e., "PPA-Squared 0"). 71 Functional illness staging and grading of daily-life symptoms affecting communication and other domains 72 should support care decisions and interactions between clinical teams, as well as providing outcome measures for trials in PPA and other dementias with prominent language features. 73 Further development of the stages and scale will therefore entail collaborative validation and distillation of large datasets.…”

Section: Discussionmentioning

confidence: 99%

Symptom‐led staging for semantic and non‐fluent/agrammatic variants of primary progressive aphasia

Hardy,

Taylor‐Rubin,

Taylor

et al. 2023

Alzheimer's & Dementia

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INTRODUCTIONHere we set out to create a symptom‐led staging system for the canonical semantic and non‐fluent/agrammatic variants of primary progressive aphasia (PPA), which present unique diagnostic and management challenges not well captured by functional scales developed for Alzheimer's disease and other dementias.METHODSAn international PPA caregiver cohort was surveyed on symptom development under six provisional clinical stages and feedback was analyzed using a mixed‐methods sequential explanatory design.RESULTSBoth PPA syndromes were characterized by initial communication dysfunction and non‐verbal behavioral changes, with increasing syndromic convergence and functional dependency at later stages. Milestone symptoms were distilled to create a prototypical progression and severity scale of functional impairment: the PPA Progression Planning Aid (“PPA‐Squared”).DISCUSSIONThis work introduces a symptom‐led staging scheme and functional scale for semantic and non‐fluent/agrammatic variants of PPA. Our findings have implications for diagnostic and care pathway guidelines, trial design, and personalized prognosis and treatment for PPA.Highlights We introduce new symptom‐led perspectives on primary progressive aphasia (PPA). The focus is on non‐fluent/agrammatic (nfvPPA) and semantic (svPPA) variants. Foregrounding of early and non‐verbal features of PPA and clinical trajectories is featured. We introduce a symptom‐led staging scheme for PPA. We propose a prototype for a functional impairment scale, the PPA Progression Planning Aid.

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Cognitive and Neural Mechanisms of Social Communication Dysfunction in Primary Progressive Aphasia

Cited by 8 publications

References 86 publications

Understanding the multidimensional cognitive deficits of logopenic variant primary progressive aphasia

Understanding the multidimensional cognitive deficits of logopenic variant primary progressive aphasia

Symptom-led staging for primary progressive aphasia

Symptom‐led staging for semantic and non‐fluent/agrammatic variants of primary progressive aphasia

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