Replenishing IRAK-M expression in retinal pigment epithelium attenuates outer retinal degeneration.

Chronic inflammation is a constitutive component of many age-related diseases, including age-related macular degeneration (AMD). Here, we identified interleukin-1 receptor-associated kinase M (IRAK-M) as a key immunoregulator in retinal pigment epithelium (RPE) that declines during the aging process. Rare genetic variants of IRAK3, which encodes IRAK-M, were associated with an increased likelihood of developing AMD. In human samples and mouse models, IRAK-M abundance in the RPE declined with advancing age or exposure to oxidative stress and was further reduced in AMD. Irak3-knockout mice exhibited an increased incidence of outer retinal degeneration at earlier ages, which was further exacerbated by oxidative stressors. The absence of IRAK-M led to a disruption in RPE cell homeostasis, characterized by compromised mitochondrial function, cellular senescence, and aberrant cytokine production. IRAK-M overexpression protected RPE cells against oxidative or immune stressors. Subretinal delivery of adeno-associated virus (AAV)-expressing human IRAK3 rescued light-induced outer retinal degeneration in wild-type mice and attenuated age-related spontaneous retinal degeneration in Irak3-knockout mice. Our data show that replenishment of IRAK-M in the RPE may redress dysregulated pro-inflammatory processes in AMD, suggesting a potential treatment for retinal degeneration.

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.

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.).

COS-PPA: protocol to develop a core outcome set for primary progressive aphasia.

INTRODUCTION: The term primary progressive aphasia (PPA) describes a group of language-led dementias. Disease-modifying treatments that delay, slow or reverse progression of PPA are currently lacking, though a number of interventions to manage the symptoms of PPA have been developed in recent years. Unfortunately, studies exploring the effectiveness of these interventions have used a variety of different outcome measures, limiting comparability. There are more constructs, apart from word retrieval, that are important for people with PPA that have not received much attention in the research literature. Existing core outcome sets (COS) for dementia and non-progressive aphasia do not meet the needs of people with PPA, highlighting a need to develop a specific COS for PPA. METHODS AND ANALYSIS: This protocol describes a three-stage study to identify a COS for PPA interventions in research and clinical practice. The stage 1 systematic review will identify existing speech, language and communication measures used to examine the effectiveness of interventions for PPA in the research literature. Employing a nominal group technique, stage 2 will identify the most important outcomes for people with PPA and their families. The data collected in stages 1 and 2 will be jointly analysed with the project PPI group and will inform the stage 2 modified Delphi consensus study to identify a core outcome measurement set for PPA among a range of research disciplines undertaking intervention studies for people with PPA. ETHICS AND DISSEMINATION: Ethical approval for stage 2 of the study has been sought individually in each country at collaborating institutions and is stated in detail in the manuscript. Stage 3 has been granted ethical approval by the Chairs of UCL Language and Cognition Department Ethics, Project ID LCD-2023-06. Work undertaken at stages 1, 2 and 3 will be published in open-access peer-reviewed journal articles and presented at international scientific conferences. PROSPERO REGISTRATION NUMBER: CRD42022367565.

Understanding experiences, unmet needs and priorities related to post-stroke aphasia care: stage one of an experience-based co-design project.

OBJECTIVE: People with post-stroke aphasia (language/communication impairment) and their supporters report mixed satisfaction with stroke and aphasia care. To date, however, their journey of care and the key service interactions that shape their experience have not been comprehensively explored. We aimed to investigate the lived experience of post-stroke aphasia care, across the continuum of care and by geographical location, to establish priorities for service design. DESIGN: This is the first stage of an experience-based co-design study. We purposively sampled people with aphasia (PWA) and significant others (SOs) across 21 hospital and health service sites, community groups and by self-referral. Participants shared experiences of care in online interviews and focus groups. Touchpoints (key moments that shape experience) and unmet needs were identified using qualitative thematic analysis. Priorities for service design were established using an adapted nominal group technique. SETTING: Sites spanned remote, regional and metropolitan areas in Queensland, Australia. PARTICIPANTS: PWA (n=32; mild=56%; moderate=31%; severe=13%) and SOs (n=30) shared 124 experiences of acute, rehabilitation and community-based care in 23 focus groups and 13 interviews. RESULTS: Both positive and negative healthcare experiences occurred most frequently in hospital settings. Negative experiences regularly related to communication with health professionals, while positive experiences related to the interpersonal qualities of healthcare providers (eg, providing hope) for PWA, or witnessing good rapport between a PWA and their health professional for SOs. To improve services, PWA prioritised communicatively accessible education and information and SOs prioritised access to psychological and peer support. CONCLUSIONS: We identified key aspects of post-stroke aphasia care that shape experience. The needs of PWA and SOs may be better met through health professional training in supported communication, increased service availability in regional and remote areas, communication-accessible hospital environments, increased access to psychological and peer support, and meaningful involvement of SOs in rehabilitation.

Hippocampal resting-state connectivity is associated with posterior-cortical cognitive impairment in Parkinson's disease.

AIM: Frontal and posterior-cortical cognitive subtypes in Parkinson's disease (PD) present with executive/attention and memory/visuospatial deficits, respectively. As the posterior-cortical subtype is predicted to progress rapidly toward dementia, the present study aimed to explore biological markers of this group using resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: K-means cluster analysis delineated subtypes (cognitively intact, frontal, posterior-cortical, and globally impaired) among 85 people with PD. A subset of PD participants (N = 42) and 20 healthy controls (HCs) underwent rs-fMRI. Connectivity of bilateral hippocampi with regions of interest was compared between posterior-cortical, cognitively intact, and HC participants using seed-based analysis, controlling for age. Exploratory correlations were performed between areas of interest from the group analysis and a series of cognitive tests. RESULTS: The posterior-cortical subtype (N = 19) showed weaker connectivity between the left hippocampus and right anterior temporal fusiform cortex compared to the cognitively intact (N = 11) group, p-false discovery rate (FDR) = .01, and weaker connectivity between bilateral hippocampi and most fusiform regions compared to HCs (N = 20). No differences were found between HCs and cognitively intact PD. Exploratory analyses revealed strongest associations between connectivity of the right anterior temporal fusiform cortex and left hippocampus with category fluency (p-FDR = .01). CONCLUSION: Results suggest that weakened connectivity between the hippocampus and fusiform region is a unique characteristic of posterior-cortical cognitive deficits in PD. Further exploration of hippocampal and fusiform functional integrity as a marker of cognitive decline in PD is warranted.

Comprehensive quality assessment for aphasia rehabilitation after stroke: protocol for a multicentre, mixed-methods study.

INTRODUCTION: People with aphasia following stroke experience disproportionally poor outcomes, yet there is no comprehensive approach to measuring the quality of aphasia services. The Meaningful Evaluation of Aphasia SeRvicES (MEASuRES) minimum dataset was developed in partnership with people with lived experience of aphasia, clinicians and researchers to address this gap. It comprises sociodemographic characteristics, quality indicators, treatment descriptors and outcome measurement instruments. We present a protocol to pilot the MEASuRES minimum dataset in clinical practice, describe the factors that hinder or support implementation and determine meaningful thresholds of clinical change for core outcome measurement instruments. METHODS AND ANALYSIS: This research aims to deliver a comprehensive quality assessment toolkit for poststroke aphasia services in four studies. A multicentre pilot study (study 1) will test the administration of the MEASuRES minimum dataset within five Australian health services. An embedded mixed-methods process evaluation (study 2) will evaluate the performance of the minimum dataset and explore its clinical applicability. A consensus study (study 3) will establish consumer-informed thresholds of meaningful change on core aphasia outcome constructs, which will then be used to establish minimal important change values for corresponding core outcome measurement instruments (study 4). ETHICS AND DISSEMINATION: Studies 1 and 2 have been registered with the Australian and New Zealand Clinical Trial Registry (ACTRN12623001313628). Ethics approval has been obtained from the Royal Brisbane and Women's Hospital (HREC/2023/MNHB/95293) and The University of Queensland (2022/HE001946 and 2023/HE001175). Study findings will be disseminated through peer-reviewed publications, conference presentations and engagement with relevant stakeholders including healthcare providers, policy-makers, stroke and rehabilitation audit and clinical quality registry custodians, consumer support organisations, and individuals with aphasia and their families.

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.

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.

Does aphasia impact on return to driving after stroke? A scoping review.

PURPOSE: Stroke can affect driving, an important activity of daily living. Little is known about whether aphasia (language impairment) impacts driving post-stroke. This scoping review explores impacts and perceived impacts of aphasia on driving performance, and the process of returning to driving post-stroke. MATERIALS AND METHODS: Scoping review using Arksey and O'Malley's framework, reported using the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). Bibliographic databases were searched and international clinical practice guidelines were sourced online. Full-text articles were independently assessed by two reviewers. Results were tabulated and summarised using narrative synthesis. RESULTS: Forty-three literature sources and 17 clinical practice guidelines were identified. Six studies investigated return to driving with aphasia post-stroke; 37 sources from the broader literature contributed to objectives. It remains unclear whether aphasia impacts fitness-to-drive; however, people with aphasia face barriers in returning to driving due to: (1) uncertainty regarding the role of language in driving; (2) poor awareness and knowledge of aphasia, and (3) communication demands in the patient-journey and assessment. CONCLUSIONS: The current evidence base is limited, inconsistent, and lacking in quality and recency and there is a lack of guidelines to support clinical practice. People with aphasia face barriers in returning to driving; however, it is unclear if aphasia affects fitness-to-drive post-stroke. Implications for rehabilitationPeople with aphasia, their caregivers and clinicians have identified return to driving as a top 10 research priority.We do not know if aphasia affects fitness-to-drive post-stroke, but communication difficulties can make the process of returning to driving more difficult.Speech pathologists have an important role in ensuring that driving is discussed with people with aphasia post-stroke.Speech pathologists should support the multidisciplinary team to understand and meet the communication needs of people with aphasia throughout the driving evaluation process.

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.

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.

Exploring the usability and feasibility of a mobile music listening application for people living in the community with post-stroke aphasia.

PURPOSE: Language and communication disorders can inhibit participation in activities that have potential therapeutic benefits for recovery. This exploratory research examined the usability and feasibility of a purpose-built music listening mobile application for people living in the community with post-stroke aphasia, and examined relationships between useability and participant age, aphasia severity and time post-stroke. METHODS: Nineteen participants with chronic aphasia tested the application for two weeks. Prior to use, music preferences, technology use and confidence, self-efficacy and music engagement questionnaires were completed. System usability scale, music listening data and a satisfaction rating were completed following use. RESULTS: Overall, the application was perceived as being usable and feasible with a high system usability rating and moderate effectiveness, efficiency and satisfaction. The system usability scores were not associated with aphasia severity, age, years post-stroke, self-efficacy or music engagement. Technology confidence was positively associated with system usability. CONCLUSION: The music listening application is a feasible and usable option for listening to music in people with chronic post-stroke aphasia. This study provides a foundation for the rigorous examination of the usability of music listening technology for people with post-stroke aphasia and the potential investigation of use in acute care facilities and other clinical populations.IMPLICATIONS FOR REHABILITATIONMusic listening has potential therapeutic benefits for people with post-stroke aphasia.Applications for music listening require customisation to enable people with post-stroke aphasia opportunity to listen to their preferred music.Music listening applications that are perceived as usable and feasible by people with post-stroke aphasia may have potential application within rehabilitation and community settings.

Acceptability, feasibility and preliminary efficacy of low-moderate intensity Constraint Induced Aphasia Therapy and Multi-Modality Aphasia Therapy in chronic aphasia after stroke.

BACKGROUND: High-intensity Constraint-Induced Aphasia Therapy Plus (CIAT-Plus) and Multi-Modality Aphasia Therapy (M-MAT) are effective interventions for chronic post-stroke aphasia but challenging to provide in clinical practice. Providing these interventions may be more feasible at lower intensities, but comparative evidence is lacking. We therefore explored feasibility, acceptability, and preliminary efficacy of the treatments at a lower intensity. METHODS: A multisite, single-blinded, randomized Phase II trial was conducted within the Phase III COMPARE trial. Groups of participants with chronic aphasia from the usual care arm of the COMPARE trial were randomized to M-MAT or CIAT-Plus, delivered at the same dose as the COMPARE trial but at lower intensity (6 hours/week × 5 weeks rather than 15 hours/week × 2 weeks). Blinded assessors measured aphasia severity (Western Aphasia Battery-Revised Aphasia Quotient), word retrieval, connected speech, multimodal communication, functional communication, and quality of life immediately post interventions and after 12 weeks. Feasibility and acceptability were explored. RESULTS: Of 70 eligible participants, 77% consented to the trial; 78% of randomized participants completed intervention and 98% of assessment visits were conducted. Fatigue and distress ratings were low with no related withdrawals. Adverse events related to the trial (n = 4) were mild in severity. Statistically significant treatment effects were demonstrated on word retrieval and functional communication and both interventions were equally effective. CONCLUSIONS: Low-moderateintensity CIAT-Plus and M-MAT were feasible and acceptable. Both interventions show preliminary efficacy at a low-moderate intensity. These results support a powered trial investigating these interventions at a low-moderate intensity.

To sleep or not to sleep? No effect of sleep on contextual word learning in younger adults.

This study investigated the effect of sleep on novel word learning through reading context. Seventy-four healthy young adults attended two testing sessions, with either overnight sleep (sleep group) or daytime wakefulness (wake group) occurring between the sessions. At the initial learning session, participants identified the hidden meanings of novel words embedded within sentence contexts and were subsequently tested on their recognition of the novel word meanings. A recognition test was also conducted at the delayed session. The analyses revealed comparable recognition of novel word meanings for the sleep and wake group at both the initial and the delayed session, indicating that there was no benefit of sleep compared with wakefulness for novel word learning through context. Overall, this study highlights the critical influence of encoding method on sleep-dependent learning, where not all forms of word learning appear to benefit from sleep for consolidation.

Replenishing Age-Related Decline of IRAK-M Expression in Retinal Pigment Epithelium Attenuates Outer Retinal Degeneration.

Unchecked, chronic inflammation is a constitutive component of age-related diseases, including age-related macular degeneration (AMD). Here we identified interleukin-1 receptor-associated kinase (IRAK)-M as a key immunoregulator in retinal pigment epithelium (RPE) that declines with age. Rare genetic variants of IRAK-M increased the likelihood of AMD. IRAK-M expression in RPE declined with age or oxidative stress and was further reduced in AMD. IRAK-M-deficient mice exhibited increased incidence of outer retinal degeneration at earlier ages, which was further exacerbated by oxidative stressors. The absence of IRAK-M disrupted RPE cell homeostasis, including compromised mitochondrial function, cellular senescence, and aberrant cytokine production. IRAK-M overexpression protected RPE cells against oxidative or immune stressors. Subretinal delivery of AAV-expressing IRAK-M rescued light-induced outer retinal degeneration in wild-type mice and attenuated age-related spontaneous retinal degeneration in IRAK-M-deficient mice. Our data support that replenishment of IRAK-M expression may redress dysregulated pro-inflammatory processes in AMD, thereby treating degeneration.

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.

Phonological and Semantic Fluency in Alzheimer's Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Semantic and Phonological fluency (SF and PF) are routinely evaluated in patients with Alzheimer's disease (AD). There are disagreements in the literature regarding which fluency task is more affected while developing AD. Most studies focus on SF assessment, given its connection with the temporoparietal amnesic system. PF is less reported, it is related to working memory, which is also impaired in probable and diagnosed AD. Differentiating between performance on these tasks might be informative in early AD diagnosis, providing an accurate linguistic profile. OBJECTIVE: Compare SF and PF performance in healthy volunteers, volunteers with probable AD, and patients with AD diagnosis, considering the heterogeneity of age, gender, and educational level variables. METHODS: A total of 8 studies were included for meta-analysis, reaching a sample size of 1,270 individuals (568 patients diagnosed with AD, 340 with probable AD diagnosis, and 362 healthy volunteers). RESULTS: The three groups consistently performed better on SF than PF. When progressing to a diagnosis of AD, we observed a significant difference in SF and PF performance across our 3 groups of interest (p = 0.04). The age variable explained a proportion of this difference in task performance across the groups, and as age increases, both tasks equally worsen. CONCLUSION: The performance of SF and PF might play a differential role in early AD diagnosis. These tasks rely on partially different neural bases of language processing. They are thus worth exploring independently in diagnosing normal aging and its transition to pathological stages, including probable and diagnosed AD.