High-Intensity Aphasia Therapy Is Cost-Effective in People With Poststroke Aphasia: Evidence From the COMPARE Trial.

BACKGROUND: Evidence from systematic reviews confirms that speech and language interventions for people with aphasia during the chronic phase after stroke (>6 months) improve word retrieval, functional communication, and communication-related quality of life. However, there is limited evidence of their cost-effectiveness. We aimed to estimate the cost per quality-adjusted life year gained from 2 speech and language therapies compared with usual care in people with aphasia during the chronic phase (median, 2.9 years) after stroke. METHODS: A 3-arm, randomized controlled trial compared constraint-induced aphasia therapy plus (CIAT-Plus) and multimodality aphasia therapy (M-MAT) with usual care in 216 people with chronic aphasia. Participants were administered a standardized questionnaire before intervention and at 12 weeks after the 2-week intervention/control period to ascertain health service utilization, employment changes, and informal caregiver burden. Unit prices from Australian sources were used to estimate costs in 2020. Quality-adjusted life years were estimated using responses to the EuroQol-5 Dimension-3 Level questionnaire. To test uncertainty around the differences in costs and outcomes between groups, bootstrapping was used with the cohorts resampled 1000 times. RESULTS: Overall 201/216 participants were included (mean age, 63 years, 29% moderate or severe aphasia, 61 usual care, 70 CIAT-Plus, 70 M-MAT). There were no statistically significant differences in mean total costs ($13 797 usual care, $17 478 CIAT-Plus, $11 113 M-MAT) and quality-adjusted life years (0.19 usual care, 0.20 CIAT-Plus, 0.20 M-MAT) between groups. In bootstrapped analysis of CIAT-Plus, 21.5% of iterations were likely to result in better outcomes and be cost saving (dominant) compared with usual care. In contrast, 72.4% of iterations were more favorable for M-MAT than usual care. CONCLUSIONS: We observed that both treatments, but especially M-MAT, may result in better outcomes at an acceptable additional cost, or potentially with cost savings. These findings are relevant in advocating for the use of these therapies for chronic aphasia after stroke.

High-Intensity Aphasia Intervention Is Minimally Fatiguing in Chronic Aphasia: An Analysis of Participant Self-Ratings From a Large Randomized Controlled Trial.

BACKGROUND: High-intensity therapy is recommended in current treatment guidelines for chronic poststroke aphasia. Yet, little is known about fatigue levels induced by treatment, which could interfere with rehabilitation outcomes. We analyzed fatigue experienced by people with chronic aphasia (>6 months) during high-dose interventions at 2 intensities. METHODS: A retrospective observational analysis was conducted on self-rated fatigue levels of people with chronic aphasia (N=173) collected during a previously published large randomized controlled trial of 2 treatments: constraint-induced aphasia therapy plus and multi-modality aphasia therapy. Interventions were administered at a higher intensity (30 hours over 2 weeks) or lower intensity (30 hours over 5 weeks). Participants rated their fatigue on an 11-point scale before and after each day of therapy. Data were analyzed using Bayesian ordinal multilevel models. Specifically, we considered changes in self-rated participant fatigue across a therapy day and over the intervention period. RESULTS: Data from 144 participants was analyzed. Participants were English speakers from Australia or New Zealand (mean age, 62 [range, 18-88] years) with 102 men and 42 women. Most had mild (n=115) or moderate (n=52) poststroke aphasia. Median ratings of the level of fatigue by people with aphasia were low (1 on a 0-10-point scale) at the beginning of the day. Ratings increased slightly (+1.0) each day after intervention, with marginally lower increases in the lower intensity schedule. There was no evidence of accumulating fatigue over the 2- or 5-week interventions. CONCLUSIONS: Findings suggest that intensive intervention was not associated with large increases in fatigue for people with chronic aphasia enrolled in the COMPARE trial (Constraint-Induced or Multimodality Personalised Aphasia Rehabilitation). Fatigue did not change across the course of the intervention. This study provides evidence that intensive treatment was minimally fatiguing for stroke survivors with chronic aphasia, suggesting that fatigue is not a barrier to high-intensity treatment.

Structural brain networks correlating with poststroke cognition.

Cognitive deficits are a common and debilitating consequence of stroke, yet our understanding of the structural neurobiological biomarkers predicting recovery of cognition after stroke remains limited. In this longitudinal observational study, we set out to investigate the effect of both focal lesions and structural connectivity on poststroke cognition. Sixty-two patients with stroke underwent advanced brain imaging and cognitive assessment, utilizing the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE), at 3-month and 12-month poststroke. We first evaluated the relationship between lesions and cognition at 3 months using voxel-based lesion-symptom mapping. Next, a novel correlational tractography approach, using multi-shell diffusion-weighted magnetic resonance imaging (MRI) data collected at both time points, was used to evaluate the relationship between the white matter connectome and cognition cross-sectionally at 3 months, and longitudinally (12 minus 3 months). Lesion-symptom mapping did not yield significant findings. In turn, correlational tractography analyses revealed positive associations between both MoCA and MMSE scores and bilateral cingulum and the corpus callosum, both cross-sectionally at the 3-month stage, and longitudinally. These results demonstrate that rather than focal neural structures, a consistent structural connectome underpins the performance of two frequently used cognitive screening tools, the MoCA and the MMSE, in people after stroke. This finding should encourage clinicians and researchers to not only suspect cognitive decline when lesions affect these tracts, but also to refine their investigation of novel approaches to differentially diagnosing pathology associated with cognitive decline, regardless of the aetiology.

Heparanase inhibition as a systemic approach to protect the endothelial glycocalyx and prevent microvascular complications in diabetes.

BACKGROUND: Diabetes mellitus is a chronic disease which is detrimental to cardiovascular health, often leading to secondary microvascular complications, with huge global health implications. Therapeutic interventions that can be applied to multiple vascular beds are urgently needed. Diabetic retinopathy (DR) and diabetic kidney disease (DKD) are characterised by early microvascular permeability changes which, if left untreated, lead to visual impairment and renal failure, respectively. The heparan sulphate cleaving enzyme, heparanase, has previously been shown to contribute to diabetic microvascular complications, but the common underlying mechanism which results in microvascular dysfunction in conditions such as DR and DKD has not been determined. METHODS: In this study, two mouse models of heparan sulphate depletion (enzymatic removal and genetic ablation by endothelial specific Exotosin-1 knock down) were utilized to investigate the impact of endothelial cell surface (i.e., endothelial glycocalyx) heparan sulphate loss on microvascular barrier function. Endothelial glycocalyx changes were measured using fluorescence microscopy or transmission electron microscopy. To measure the impact on barrier function, we used sodium fluorescein angiography in the eye and a glomerular albumin permeability assay in the kidney. A type 2 diabetic (T2D, db/db) mouse model was used to determine the therapeutic potential of preventing heparan sulphate damage using treatment with a novel heparanase inhibitor, OVZ/HS-1638. Endothelial glycocalyx changes were measured as above, and microvascular barrier function assessed by albumin extravasation in the eye and a glomerular permeability assay in the kidney. RESULTS: In both models of heparan sulphate depletion, endothelial glycocalyx depth was reduced and retinal solute flux and glomerular albumin permeability was increased. T2D mice treated with OVZ/HS-1638 had improved endothelial glycocalyx measurements compared to vehicle treated T2D mice and were simultaneously protected from microvascular permeability changes associated with DR and DKD. CONCLUSION: We demonstrate that endothelial glycocalyx heparan sulphate plays a common mechanistic role in microvascular barrier function in the eye and kidney. Protecting the endothelial glycocalyx damage in diabetes, using the novel heparanase inhibitor OVZ/HS-1638, effectively prevents microvascular permeability changes associated with DR and DKD, demonstrating a novel systemic approach to address diabetic microvascular complications.

Qualitative Exploration of Speech Pathologists' Experiences and Priorities for Aphasia Service Design: Initial Stage of an Experience-Based Co-Design Project to Improve Aphasia Services.

INTRODUCTION AND AIMS: Stroke survivors with aphasia (impaired language/communication) have poor outcomes and gaps in the clinical implementation of best practice contribute to this. Little is known, however, about speech pathologist perspectives on the touchpoints (key moments shaping experiences) in the clinical care pathway that have the greatest impact on service delivery nor how this varies by geographical location. We explored the experiences of speech pathologists who provide aphasia services to establish priorities for improvement and design. METHODS AND ANALYSIS: This is the initial experience gathering and priority identification stage of an experience-based co-design (EBCD) project. Speech pathologists were recruited from 21 geographically diverse Hospital and Health Services in Queensland, Australia. Speech pathologists working in acute, rehabilitation and community services shared positive and negative experiences of delivering aphasia care in interviews and focus groups. Experiential data were analysed using qualitative thematic analysis to determine touchpoints. Priorities for service design were identified using an adapted nominal group technique. RESULTS: Speech pathologists (n = 62) participated in 16 focus groups and nine interviews and shared 132 experiences of delivering aphasia care. Providing care in teams with poor awareness of the impacts of aphasia was identified as a key challenge, as poor patient-provider communication was perceived to increase risk of adverse outcomes for patients. Speech pathologists identified areas for improvement related to their own professional needs (e.g., greater access to clinical supervision); collaborative health care (e.g., better coordination and interdisciplinary care to increase therapy time); and the service context and environment (e.g., psychological services able to support diverse communication needs). CONCLUSIONS: Speech pathologist delivery of aphasia services could be improved through increased access to clinical supervision, opportunities for peer debriefing and interdisciplinary care. Priorities for service design varied by geographical location and included: education to support care transitions (remote areas), improved referral pathways and service linkage (regional areas) and dedicated aphasia staffing (metropolitan areas). PATIENT OR PUBLIC CONTRIBUTION: A consumer advisory committee comprising people with aphasia (n = 3, authors K.M., K.D. and B.A.), their significant others (n = 2, authors J.D. and P.M.), and a Cultural Capability Officer (author G.B.) guided this research. The team: (1) reviewed participant information; (2) co-designed surveys and workshop resources; (3) copresented research outcomes and contributed to publications. Research questions and study design (e.g., analysis methods and assessment measures) were developed by the research team (authors L.A., V.J.P., D.A.C. and S.J.W.).

An exploratory study of longitudinal trajectory of language, swallowing and cognition post endovascular clot retrieval.

BACKGROUND: Endovascular clot retrieval (ECR) is known to reduce global disability at 3 months post stroke however limited research exists regarding the trajectory of specific clinical impairments including language, swallowing and cognitive deficits between onset and 3 months. AIMS: To assess language, swallowing, and cognitive performance following ECR and explore whether impairment severity is correlated with modified Thrombolysis in Cerebral Infarction score (mTICI), stroke severity or quality of life (QoL). METHODS: Assessment was completed within 7 days (T1), 1 month (T2) and 3 months (T3) post-stroke. Performance was measured with the Functional Oral Intake Scale (FOIS), Repeatable Battery for Assessment of Neuropsychological Status (RBANS), Trail Making Test (TMT A and B) and Brixton Spatial Awareness Test. The Western Aphasia Battery (WAB) was used for left hemisphere stroke. QoL was measured with the Stroke and Aphasia Quality of Life Scale. RESULTS: Twenty-five participants (median 72 years; 64% male) were prospectively recruited following ECR. High reperfusion success (68% mTICI 3) and low stroke severity post ECR (median 24 h NIHSS = 3, IQR 7-18) were noted. At T1, 10 participants presented with aphasia, eight required a modified diet and 20 had impaired cognition. At T3 all had recovered to a normal oral diet, 39% had persistent cognitive impairment and 45% of patients with left hemisphere stroke remained aphasic. Performance on the WAB, FOIS, RBANS and TMT changed significantly over time (all p < 0.05). The severity score at T1 for all measures, excluding TMT B and Brixton, was significantly correlated with 24 h NIHSS. WAB scores at T3 were correlated with QoL (r = 0.618; p = 0.043). CONCLUSION: This exploratory study found the longitudinal performance of language, swallowing and cognition significantly improved over time and severity in the first-week post-ECR was correlated with 24 h NIHSS rather than the degree of reperfusion. WHAT THIS PAPER ADDS: What is already known on the subject Randomised control trials have demonstrated the benefit of ECR in patients with ischemic stroke using global measures of disability and function. Limited research exists regarding the trajectory of specific clinical impairments including language, swallowing and cognitive deficits. There is also a reliance on screening assessments and a lack of consideration of the influence of co-occurring impairments. What this paper adds to existing knowledge This prospective study is amongst the first to explore the longitudinal trajectory of language, swallowing and cognitive impairment using a standardised assessment battery. Twenty-four-hour NIHSS was significantly correlated with language, swallowing, global cognition and some measures of executive function. Language performance post ECR was correlated with domain-specific cognitive assessment of attention, immediate memory and delayed memory, which differed from swallowing performance post ECR that correlated with measures of executive function. What are the potential or actual clinical implications of this work? It is important for speech-language pathologists and the wider medical team to monitor language, swallowing and cognitive performance post ECR regardless of treatment success. Stroke severity at 24 h post-ECR influences the severity of language, swallowing and cognitive impairments.

Early within therapy naming probes as a clinically-feasible predictor of anomia treatment response.

This study investigated the relationship between early within-therapy probe naming performance and anomia therapy outcomes in individuals with aphasia. Thirty-four adults with chronic, post-stroke aphasia participated in the Aphasia Language Impairment and Functioning Therapy (Aphasia LIFT) programme, comprised of 48 h of comprehensive aphasia therapy. Sets of 30 treated and 30 untreated items identified at baseline were probed during impairment therapy which targeted word retrieval using a combined semantic feature analysis and phonological component analysis approach. Multiple regression models were computed to determine the relationship between baseline language and demographic variables, early within-therapy probe naming performance (measured after 3 h of impairment therapy) and anomia treatment outcomes. Early within-therapy probe naming performance emerged as the strongest predictor of anomia therapy gains at post-therapy and at 1-month follow-up. These findings have important clinical implications, as they suggest that an individual's performance after a brief period of anomia therapy may predict response to intervention. As such, early within-therapy probe naming may provide a quick and accessible tool for clinicians to identify potential response to anomia treatment.

Right hemispheric structural connectivity and poststroke language recovery.

Poststroke aphasia typically results from brain damage to the left-lateralized language network. The contribution of the right-lateralized homologues in aphasia recovery remains equivocal. In this longitudinal observational study, we specifically investigated the role of right hemisphere structural connectome in aphasia recovery. Twenty-two patients with aphasia after a left hemispheric stroke underwent comprehensive language assessment at the early subacute and chronic stages. A novel structural connectometry approach, using multi-shell diffusion-weighted MRI data collected at the early subacute stage, was used to evaluate the relationship between right hemisphere white matter connectome and language production and comprehension abilities at early subacute stage. Moreover, we evaluated the relationship between early subacute right hemisphere white matter connectome and longitudinal change in language production and comprehension abilities. All results were corrected for multiple comparisons. Connectometry analyses revealed negative associations between early subacute stage right hemisphere structural connectivity and language production, both cross-sectionally and longitudinally (pFDR < .0125). In turn, only positive associations between right hemisphere structural connectivity and language comprehension were observed, both cross-sectionally and longitudinally (pFDR < .0125). Interhemispheric connectivity was highly associated with comprehension scores. Our results shed light on the discordant interpretations of previous findings, by providing evidence that while some right hemisphere white matter pathways may make a maladaptive contribution to the recovery of language, other pathways support the recovery of language, especially comprehension abilities.

Global assessment, cognitive profile, and characteristics of mild cognitive impairment in Parkinson's disease.

BACKGROUND: Cognitive deficits are evident throughout the course of Parkinson's disease (PD), with 24% of patients experiencing subtle cognitive disturbances at the time of diagnosis, and with up to 80% of patients developing PD dementia (PDD) at advanced stages of the disease PD patients with mild cognitive impairment (MCI), an at-risk phenotype of PDD, present with heterogeneous clinical characteristics that complicate the management of PD. OBJECTIVES: This study aims to examine the characteristics of PD-MCI by using the Movement Disorder Society (MDS) diagnostic criteria and evaluate the validity of global cognitive scales in identifying PD-MCI. METHODS: Seventy-nine (79) PD patients completed neuropsychological assessments and a comprehensive cognitive battery. PD-MCI was classified according to the level 2 MDS task force criteria. Mini-Mental State Examination (sMMSE), Montreal Cognitive Assessment (MoCA) and Parkinson's Disease Cognitive Rating Scale (PDCRS) were examined against a level 2 dichotomised PD-MCI diagnosis. Characteristics of PD-MCI were evaluated using logistic regression analysis. RESULTS: Twenty-seven patients met criteria for PD-MCI (34%). The MoCA and PDCRS demonstrated high validity to screen for PD-MCI. Impairments in multiple cognitive domains were observed in 77.8% of PD-MCI patients. There were significantly more males in the PD-MCI group compared to PD patients without MCI (p < 0.01). CONCLUSIONS: PD patients with MCI exhibited impairments in the attention/working memory, executive function and memory domains. Heterogeneous cognitive characteristics in PD warrant further investigation into specific cognitive subtypes to advance understanding and effective evaluation of PD-MCI.

Allied Health Clinicians' Uptake of Evidence in Stroke Rehabilitation: A Systematic Review of Determinants Targeted in Implementation Studies.

OBJECTIVE: This study aimed to determine whether targeting specific implementation determinants is associated with allied health clinicians' uptake of evidence when implemented within stroke rehabilitation settings. DATA SOURCES: 7 key databases were searched to identify articles published between 1990 and 2022 for inclusion. Reference lists of relevant articles were hand searched. STUDY SELECTION: Studies were independently screened by 2 authors and included if the implementation intervention targeted allied health clinical practice in any stroke rehabilitation context and reported at least 1 quantitative measure of evidence uptake. Thirty studies met inclusion criteria. DATA EXTRACTION: Data were independently extracted by the first and second author. Implementation outcomes for each study were categorized as either mostly successful, partially successful, or not successful based on the degree of evidence uptake achieved. Determinants targeted were categorized using the Consolidated Framework for Implementation Research (CFIR). DATA SYNTHESIS: Patterns between the degree of evidence uptake and determinants targeted across studies were analyzed by the first and second authors in 1 of 3 groups: A (pre-post statistical analysis), B (pre-post descriptive analysis), or C (post-only descriptive analysis). Patterns between evidence uptake and determinants targeted were first identified within groups A and B, with group C consulted to support findings. All studies categorized as "mostly successful" targeted facilitation in combination with establishing face-to-face networks and communication strategies. Conversely, no studies rated "not successful" targeted either of these determinants. Studies rated "partially successful" targeted either 1, but seldom both, of these determinants. CONCLUSIONS: This review has provided descriptive evidence of determinants which may be important to target for allied health clinicians' uptake of evidence within stroke rehabilitation settings.

Examining Dose Frameworks to Improve Aphasia Rehabilitation Research.

The effect of treatment dose on recovery of post-stroke aphasia is not well understood. Inconsistent conceptualization, measurement, and reporting of the multiple dimensions of dose hinders efforts to evaluate dose-response relations in aphasia rehabilitation research. We review the state of dose conceptualization in aphasia rehabilitation and compare the applicability of 3 existing dose frameworks to aphasia rehabilitation research-the Frequency, Intensity, Time, and Type (FITT) principle, the Cumulative Intervention Intensity (CII) framework, and the Multidimensional Dose Articulation Framework (MDAF). The MDAF specifies dose in greater detail than the CII framework and the FITT principle. On this basis, we selected the MDAF to be applied to 3 diverse examples of aphasia rehabilitation research. We next critically examined applicability of the MDAF to aphasia rehabilitation research and identified the next steps needed to systematically conceptualize, measure, and report the multiple dimensions of dose, which together can progress understanding of the effect of treatment dose on outcomes for people with aphasia after stroke. Further consideration is required to enable application of this framework to aphasia interventions that focus on participation, personal, and environmental interventions and to understand how the construct of episode difficulty applies across therapeutic activities used in aphasia interventions.

The effect of sleep and semantic information on associative novel word learning.

This study investigated the effect of overnight sleep on associative novel word learning and examined whether the effects of sleep on word learning are modulated by the provision of semantic information. Seventy-five healthy young adults attended an initial word-learning session followed by a delayed testing session. An interval of overnight sleep (sleep group) or daytime wakefulness (wake group) separated the two sessions. At the initial learning session, participants learned three-word names of 20 novel objects, where half the names comprised a novel word and two semantic attributes (semantic condition), and half comprised a novel word and two meaningless proper names (name condition). Novel word cued-recall was measured at both the initial and the delayed session. Although both groups demonstrated similar cued-recall accuracy at the first session, by the delayed session the sleep group demonstrated superior cued-recall accuracy compared to the wake group. There was no influence of semantics on the sleep-dependent consolidation of the novel words. Overall, these findings suggest that novel words encoded with or without the provision of semantic information can benefit from an overnight sleep period for consolidation.

Measuring communication as a core outcome in aphasia trials: Results of the ROMA-2 international core outcome set development meeting.

BACKGROUND: Evidence-based recommendations for a core outcome set (COS; minimum set of outcomes) for aphasia treatment research have been developed (the Research Outcome Measurement in Aphasia-ROMA, COS). Five recommended core outcome constructs: communication, language, quality of life, emotional well-being and patient-reported satisfaction/impact of treatment, were identified through three international consensus studies. Constructs were paired with outcome measurement instruments (OMIs) during an international consensus meeting (ROMA-1). Before the current study (ROMA-2), agreement had not been reached on OMIs for the constructs of communication or patient-reported satisfaction/impact of treatment. AIM: To establish consensus on a communication OMI for inclusion in the ROMA COS. METHODS & PROCEDURES: Research methods were based on recommendations from the Core Outcome Measures in Effectiveness Trials (COMET) Initiative. Participants with expertise in design and conduct of aphasia trials, measurement instrument development/testing and/or communication outcome measurement were recruited through an open call. Before the consensus meeting, participants agreed on a definition of communication, identified appropriate OMIs, extracted their measurement properties and established criteria for their quality assessment. During the consensus meeting they short-listed OMIs and participants without conflicts of interest voted on the two most highly ranked instruments. Consensus was defined a priori as agreement by ≥ 70% of participants. OUTCOMES & RESULTS: In total, 40 researchers from nine countries participated in ROMA-2 (including four facilitators and three-panel members who participated in pre-meeting activities only). A total of 20 OMIs were identified and evaluated. Eight short-listed communication measures were further evaluated for their measurement properties and ranked. Participants in the consensus meeting (n = 33) who did not have conflicts of interest (n = 29) voted on the top two ranked OMIs: The Scenario Test (TST) and the Communication Activities of Daily Living-3 (CADL-3). TST received 72% (n = 21) of 'yes' votes and the CADL-3 received 28% (n = 8) of 'yes' votes. CONCLUSIONS & IMPLICATIONS: Consensus was achieved that TST was the preferred communication OMI for inclusion in the ROMA COS. It is currently available in the original Dutch version and has been adapted into English, German and Greek. Further consideration must be given to the best way to measure communication in people with mild aphasia. Development of a patient-reported measure for satisfaction with/impact of treatment and multilingual versions of all OMIs of the COS is still required. Implementation of the ROMA COS would improve research outcome measurement and the quality, relevance, transparency, replicability and efficiency of aphasia treatment research. WHAT THIS PAPER ADDS: What is already known on this subject International consensus has been reached on five core constructs to be routinely measured in aphasia treatment studies. International consensus has also been established for OMIs for the three constructs of language, quality of life and emotional well-being. Before this study, OMIs for the constructs of communication and patient-reported satisfaction/impact of treatment were not established. What this paper adds to existing knowledge We gained international consensus on an OMI for the construct of communication. TST is recommended for inclusion in the ROMA COS for routine use in aphasia treatment research. What are the potential or actual clinical implications of this work? The ROMA COS recommends OMIs for a minimum set of outcomes for adults with post-stroke aphasia within phases I-IV aphasia treatment research. Although not intended for clinical use, clinicians may employ the instruments of the ROMA COS, considering the quality of their measurement properties. The systematic inclusion of a measure of communication, such as TST, in clinical practice could ultimately support the implementation of research evidence and best practices.

Prognostication in post-stroke aphasia: Perspectives of people with aphasia on receiving information about recovery.

Many people with aphasia (language impairment post-stroke) want to know their prognosis for recovery, yet current understanding of their experience of receiving prognoses is limited. Such insight is necessary to inform clinical practice in formulating and delivering aphasia prognoses, especially given the psycho-emotional distress and secondary adverse effects on recovery associated with conversations about prognosis. We sought an in-depth understanding of the perspectives of people with aphasia in relation to receiving prognoses post-stroke, with the aim of informing an evidence-based approach to aphasia prognostication in clinical practice. Semi-structured interviews, facilitated by communication support strategies, were conducted one-to-one with eight people with aphasia (ranging from mild to very severe) 3-12 months post-stroke. Reflexive thematic analysis was used to analyse the qualitative data, yielding two over-arching themes: (1) How would you know without knowing me?; (2) I need to know, but I don't want to know. Our findings illustrate issues of mistrust within the patient-clinician relationship, and complex emotions relating to hope and post-stroke adjustment. The present insight into the lived experience of receiving aphasia prognoses highlights the need for focused consideration of personal definitions of normalcy, measures for fostering trust, and the role of prognostic uncertainty.

Systematic Review and Meta-Analyses of Word Production Abilities in Dysfunction of the Basal Ganglia: Stroke, Small Vessel Disease, Parkinson's Disease, and Huntington's Disease.

Clinical populations with basal ganglia pathologies may present with language production impairments, which are often described in combination with comprehension measures or attributed to motor, memory, or processing-speed problems. In this systematic review and meta-analysis, we studied word production in four (vascular and non-vascular) pathologies of the basal ganglia: stroke affecting the basal ganglia, small vessel disease, Parkinson's disease, and Huntington's disease. We compared scores of these clinical populations with those of matched cognitively unimpaired adults on four well-established production tasks, namely picture naming, category fluency, letter fluency, and past-tense verb inflection. We conducted a systematic search in PubMed and PsycINFO with terms for basal ganglia structures, basal ganglia disorders and language production tasks. A total of 114 studies were included, containing results for one or more of the tasks of interest. For each pathology and task combination, effect sizes (Hedges' g) were extracted comparing patient versus control groups. For all four populations, performance was consistently worse than that of cognitively unimpaired adults across the four language production tasks (p-values < 0.010). Given that performance in picture naming and verb inflection across all pathologies was quantified in terms of accuracy, our results suggest that production impairments cannot be fully explained by motor or processing-speed deficits. Our review shows that while language production difficulties in these clinical populations are not negligible, more evidence is necessary to determine the exact mechanism that leads to these deficits and whether this mechanism is the same across different pathologies.

Results of the COMPARE trial of Constraint-induced or Multimodality Aphasia Therapy compared with usual care in chronic post-stroke aphasia.

BACKGROUND: While meta-analyses confirm treatment for chronic post-stroke aphasia is effective, a lack of comparative evidence for different interventions limits prescription accuracy. We investigated whether Constraint-Induced Aphasia Therapy Plus (CIAT-plus) and/or Multimodality Aphasia Therapy (M-MAT) provided greater therapeutic benefit compared with usual community care and were differentially effective according to baseline aphasia severity. METHODS: We conducted a three-arm, multicentre, parallel group, open-label, blinded endpoint, phase III, randomised-controlled trial. We stratified eligible participants by baseline aphasia on the Western Aphasia Battery-Revised Aphasia Quotient (WAB-R-AQ). Groups of three participants were randomly assigned (1:1:1) to 30 hours of CIAT-Plus or M-MAT or to usual care (UC). Primary outcome was change in aphasia severity (WAB-R-AQ) from baseline to therapy completion analysed in the intention-to-treat population. Secondary outcomes included word retrieval, connected speech, functional communication, multimodal communication, quality of life and costs. RESULTS: We analysed 201 participants (70 in CIAT-Plus, 70 in M-MAT and 61 in UC). Aphasia severity was not significantly different between groups at postintervention: 1.05 points (95% CI -0.78 to 2.88; p=0.36) UC group vs CIAT-Plus; 1.06 points (95% CI -0.78 to 2.89; p=0.36) UC group vs M-MAT; 0.004 points (95% CI -1.76 to 1.77; p=1.00) CIAT-Plus vs M-MAT. Word retrieval, functional communication and communication-related quality of life were significantly improved following CIAT-Plus and M-MAT. Word retrieval benefits were maintained at 12-week follow-up. CONCLUSIONS: CIAT-Plus and M-MAT were effective for word retrieval, functional communication, and quality of life, while UC was not. Future studies should explore predictive characteristics of responders and impacts of maintenance doses. TRIAL REGISTRATION NUMBER: ACTRN 2615000618550.

The Attention Network Test in Parkinson and Lewy Body Disease: A Systematic Review.

BACKGROUND: The Attention Network Test (ANT) is a well-established measure of efficiency for the alerting, orienting, and executive attentional networks. However, its novel application in Parkinson disease (PD) and Lewy body dementia (LBD) research more broadly has yet to be evaluated systematically. OBJECTIVE: To compare and consolidate the outcomes of studies reporting use of the ANT in PD and LBD groups and to identify the methodological considerations for the conduct of such studies. METHOD: We performed a systematic literature search for articles exploring attention in PD and LBD groups using the ANT. We excluded articles on the basis of irrelevant scope, non-English, and groups other than PD and LBD. Once the full text articles were identified, we extracted the data and assessed the studies' quality. RESULTS: The final sample included 16 articles ranging from low to moderate quality. Behavioral findings suggested a general slowing of responses yet preserved accuracy from the PD group compared with controls. Overall, the evidence was inconclusive regarding the state of the alerting network in the PD and LBD groups, mostly supportive of an intact orienting network, and strongly suggestive of an impaired executive network. Differences in sample stratification, patient symptomatology, and dopaminergic medication levels were identified as influential factors in the attentional results across studies. CONCLUSION: Although sparse, the existing evidence indicates that the ANT is a viable option for measuring attention in PD; it can also be harnessed to explore the impact of symptoms and medications on attentional networks in PD and LBD groups.

Effects of emotional cues on novel word learning in typically developing children in relation to broader autism traits.

Emotion can influence various cognitive processes. Communication with children often involves exaggerated emotional expressions and emotive language. Children with autism spectrum disorder often show a reduced tendency to attend to emotional information. Typically developing children aged 7 to 9 years who varied in their level of autism-like traits learned the nonsense word names of nine novel toys, which were presented with either happy, fearful, or neutral emotional cues. Emotional cues had no influence on word recognition or recall performance. Eye-tracking data showed differences in visual attention depending on the type of emotional cues and level of autism-like traits. The findings suggest that the influence of emotion on attention during word learning differs according to whether the children have lower or higher levels of autism-like traits, but this influence does not affect word learning outcomes.

Advancing Stroke Recovery Through Improved Articulation of Nonpharmacological Intervention Dose.

Dose articulation is a universal issue of intervention development and testing. In stroke recovery, dose of a nonpharmaceutical intervention appears to influence outcome but is often poorly reported. The challenges of articulating dose in nonpharmacological stroke recovery research include: (1) the absence of specific internationally agreed dose reporting guidelines; (2) inadequate conceptualization of dose, which is multidimensional; and (3) unclear and inconsistent terminology that incorporates the multiple dose dimensions. To address these challenges, we need a well-conceptualized and consistent approach to dose articulation that can be applied across stroke recovery domains to stimulate critical thinking about dose during intervention development, as well as promote reporting of planned intervention dose versus actually delivered dose. We followed the Design Research Paradigm to develop a framework that guides how to articulate dose, conceptualizes the multidimensional nature and systemic linkages between dose dimensions, and provides reference terminology for the field. Our framework recognizes that dose is multidimensional and comprised of a duration of days that contain individual sessions and episodes that can be active (time on task) or inactive (time off task), and each individual episode can be made up of information about length, intensity, and difficulty. Clinical utility of this framework was demonstrated via hypothetical application to preclinical and clinical domains of stroke recovery. The suitability of the framework to address dose articulation challenges was confirmed with an international expert advisory group. This novel framework provides a pathway for better articulation of nonpharmacological dose that will enable transparent and accurate description, implementation, monitoring, and reporting, in stroke recovery research.

Cellular senescence in the aging retina and developments of senotherapies for age-related macular degeneration.

Age-related macular degeneration (AMD), a degenerative disease in the central macula area of the neuroretina and the supporting retinal pigment epithelium, is the most common cause of vision loss in the elderly. Although advances have been made, treatment to prevent the progressive degeneration is lacking. Besides the association of innate immune pathway genes with AMD susceptibility, environmental stress- and cellular senescence-induced alterations in pathways such as metabolic functions and inflammatory responses are also implicated in the pathophysiology of AMD. Cellular senescence is an adaptive cell process in response to noxious stimuli in both mitotic and postmitotic cells, activated by tumor suppressor proteins and prosecuted via an inflammatory secretome. In addition to physiological roles in embryogenesis and tissue regeneration, cellular senescence is augmented with age and contributes to a variety of age-related chronic conditions. Accumulation of senescent cells accompanied by an impairment in the immune-mediated elimination mechanisms results in increased frequency of senescent cells, termed "chronic" senescence. Age-associated senescent cells exhibit abnormal metabolism, increased generation of reactive oxygen species, and a heightened senescence-associated secretory phenotype that nurture a proinflammatory milieu detrimental to neighboring cells. Senescent changes in various retinal and choroidal tissue cells including the retinal pigment epithelium, microglia, neurons, and endothelial cells, contemporaneous with systemic immune aging in both innate and adaptive cells, have emerged as important contributors to the onset and development of AMD. The repertoire of senotherapeutic strategies such as senolytics, senomorphics, cell cycle regulation, and restoring cell homeostasis targeted both at tissue and systemic levels is expanding with the potential to treat a spectrum of age-related diseases, including AMD.