Hearing and vision rehabilitation for people with dementia in five European countries (SENSE-Cog): a randomised controlled trial.

BACKGROUND: The effect of hearing and vision difficulties on the risk of developing dementia and worsening outcomes in people already living with dementia is well established. We evaluated the clinical impact of a hearing and vision rehabilitation and support programme on quality of life in people with mild-to-moderate dementia and concurrent sensory difficulties. METHODS: We conducted a parallel-group, multicentre, observer-blind, superiority randomised controlled trial in seven older adult clinics in five European countries (Cyprus, France, Greece, Ireland, and the UK). People with mild-to-moderate dementia with adult-acquired hearing difficulties, vision difficulties, or both were randomly assigned (1:1) along with their care partner to an 18-week home-basedsensory support intervention (SSI) of tailored hearing and vision rehabilitation and support, or to care as usual. Randomisation was blocked (block size of four, six, or eight) and stratified by country, with allocation assigned via a remote web-based system. The SSI included: full hearing assessment, vision assessment, or both; fitting of hearing aids, glasses, or other sensory aids; and home-based support from a sensory support therapist to assist adherence and uptake of sensory aids, foster social networking, and optimise the home sensory environment. Care as usual involved no additional intervention beyond services normally available to people with dementia at the respective sites. The primary outcome was health-related quality of life (Dementia Quality of Life Instrument [DEMQoL]) score at 36 weeks, reported as an adjusted mean difference. Analyses were done according to the intention-to-treat principle. This trial is registered with the ISRCTN Registry, ISRCTN17056211. FINDINGS: Between May 4, 2018, and May 6, 2021, 252 people with mild-to-moderate dementia were randomly assigned, of whom 251 (n=126 in the SSI group and n=125 in the care as usual group) were included in the analysis. The mean age of participants was 79·6 years (SD 5·8), and 132 (53%) were women. After a median follow-up time of 37·7 weeks (IQR 36·2-39·0), the mean DEMQoL score was 92·8 (SD 15·2) in the SSI group and 92·8 (14·0) in the care as usual group (adjusted difference 0·18, 95% CI -2·13 to 2·30, p=0·87). Among 114 adverse events reported for 56 (44%) participants in the SSI group, ten events in nine participants were related or possibly related to the intervention (medical device pain or discomfort n=6, ear pain n=1, scratch to the ear n=1, sore eye n=1, redness n=1; all of grade 1). Serious adverse events were reported for 25 (20%) participants in the SSI group and 16 (13%) in the care as usual group. Six (5%) participants in the SSI group and five (4%) in the care as usual group died. None of the serious adverse events or deaths were related to the study intervention or procedures. INTERPRETATION: This study showed no improvement in quality in life in participants who received the intervention in the longer term. Sensory difficulties are common in people with dementia and interventions aimed at improving sensory-cognitive health should be explored further. FUNDING: EU Horizon 2020.

A cross-cultural study of the Montreal Cognitive Assessment for people with hearing impairment.

BACKGROUND: Cognitive screening tools enable the detection of cognitive impairment, facilitate timely intervention, inform clinical care, and allow long-term planning. The Montreal Cognitive Assessment for people with hearing impairment (MoCA-H) was developed as a reliable cognitive screening tool for people with hearing loss. Using the same methodology across four languages, this study examined whether cultural or linguistic factors affect the performance of the MoCA-H. METHODS: The current study investigated the performance of the MoCA-H across English, German, French, and Greek language groups (n = 385) controlling for demographic factors known to affect the performance of the MoCA-H. RESULTS: In a multiple regression model accounting for age, sex, and education, cultural-linguistic group accounted for 6.89% of variance in the total MoCA-H score. Differences between languages in mean score of up to 2.6 points were observed. CONCLUSIONS: Cultural or linguistic factors have a clinically significant impact on the performance of the MoCA-H such that optimal performance cut points for identification of cognitive impairment derived in English-speaking populations are likely inappropriate for use in non-English speaking populations. To ensure reliable identification of cognitive impairment, it is essential that locally appropriate performance cut points are established for each translation of the MoCA-H.

Assessing the pool activity level (PAL) checklist for use with people with hearing and vision loss.

BACKGROUND: The PAL is a career-completed assessment that indexes cognitive functional ability to inform individualised support. As hearing and vision loss are prevalent, we assessed the PAL for potential bias with hearing or vision impairment. METHODS: We collected PAL responses for 333 adults aged over 60 years in the UK, France, Canada, Greece and Cyprus. All participants had normal cognition based on self-reported status and normal range scores on a cognitive screening test. Using a Kruskal-Wallis test, we compared PAL item response distributions for people with assessed hearing or vision loss compared to those with normal sensory function. RESULTS: There were no differences in response distributions between hearing or vision impaired groups versus those with normal sensory function on any PAL item. CONCLUSION: The PAL reliably indexes cognitive functional ability and may be used to inform support tailored to individual cognitive level amongst older adults with prevalent hearing and vision impairments.

Development and validation of the Montreal cognitive assessment for people with hearing impairment (MoCA-H).

BACKGROUND: Hearing impairment is common among older adults and affects cognitive assessments for identification of dementia which rely on good hearing function. We developed and validated a version of the Montreal Cognitive Assessment (MoCA) for people with hearing impairment. METHODS: We adapted existing MoCA 8.1 items for people with hearing impairment by presenting instructions and stimuli in written rather than spoken format. One Attention domain and two Language domain items required substitution by alternative items. Three and four candidate items respectively were constructed and field-tested along with the items adapted to written form. We used a combination of individual item analysis and item substitution to select the set of alternative items to be included in the final form of the MoCA-H in place of the excluded original items. We then evaluated the performance and reliability of the final tool, including making any required adjustments for demographic factors. RESULTS: One hundred and fifty-nine hearing-impaired participants, including 76 with normal cognition and 83 with dementia, completed the adapted version of the MoCA. A further 97 participants with normal hearing completed the standard MoCA as well as the novel items developed for the MoCA-H to assess score equivalence between the existing and alternative MoCA items and for independence from hearing impairment. Twenty-eight participants were retested between 2-4 weeks after initial testing. After the selection of optimal item set, the final MoCA-H had an area under the curve of 0.973 (95% CI 0.952-0.994). At a cut-point of 24 points or less sensitivity and specificity for dementia was 92.8% and 90.8%, respectively. The intraclass correlation for test-retest reliability was 0.92 (95%CI 0.78-0.97). CONCLUSION: The MoCA-H is a sensitive and reliable means of identifying dementia among adults with acquired hearing impairment.

Dietary Stimuli, Intestinal Bacteria and Peptide Hormones Regulate Female Drosophila Defecation Rate.

Peptide hormones control Drosophila gut motility, but the intestinal stimuli and the gene networks coordinating this trait remain poorly defined. Here, we customized an assay to quantify female Drosophila defecation rate as a proxy of intestinal motility. We found that bacterial infection with the human opportunistic bacterial pathogen Pseudomonas aeruginosa (strain PA14) increases defecation rate in wild-type female flies, and we identified specific bacteria of the fly microbiota able to increase defecation rate. In contrast, dietary stress, imposed by either water-only feeding or high ethanol consumption, decreased defecation rate and the expression of enteroendocrine-produced hormones in the fly midgut, such as Diuretic hormone 31 (Dh31). The decrease in defecation due to dietary stress was proportional to the impact of each stressor on fly survival. Furthermore, we exploited the Drosophila Genetic Reference Panel wild type strain collection and identified strains displaying high and low defecation rates. We calculated the narrow-sense heritability of defecation rate to be 91%, indicating that the genetic variance observed using our assay is mostly additive and polygenic in nature. Accordingly, we performed a genome-wide association (GWA) analysis revealing 17 candidate genes linked to defecation rate. Downregulation of four of them (Pmp70, CG11307, meso18E and mub) in either the midgut enteroendocrine cells or in neurons reduced defecation rate and altered the midgut expression of Dh31, that in turn regulates defecation rate via signaling to the visceral muscle. Hence, microbial and dietary stimuli, and Dh31-controlling genes, regulate defecation rate involving signaling within and among neuronal, enteroendocrine, and visceral muscle cells.

Web- and app-based tools for remote hearing assessment: a scoping review.

OBJECTIVE: Remote hearing screening and assessment may improve access to, and uptake of, hearing care. This review, the most comprehensive to date, aimed to (i) identify and assess functionality of remote hearing assessment tools on smartphones and online platforms, (ii) determine if assessed tools were also evaluated in peer-reviewed publications and (iii) report accuracy of existing validation data. DESIGN: Protocol was registered in INPLASY and reported according to PRISMA-Extension for Scoping Reviews. STUDY SAMPLE: In total, 187 remote hearing assessment tools (using tones, speech, self-report or a combination) and 101 validation studies met the inclusion criteria. Quality, functionality, bias and applicability of each app were assessed by at least two authors. RESULTS: Assessed tools showed considerable variability in functionality. Twenty-two (12%) tools were peer-reviewed and 14 had acceptable functionality. The validation results and their quality varied greatly, largely depending on the category of the tool. CONCLUSION: The accuracy and reliability of most tools are unknown. Tone-producing tools provide approximate hearing thresholds but have calibration and background noise issues. Speech and self-report tools are less affected by these issues but mostly do not provide an estimated pure tone audiogram. Predicting audiograms using filtered language-independent materials could be a universal solution.

Proteobacteria and Firmicutes Secreted Factors Exert Distinct Effects on Pseudomonas aeruginosa Infection under Normoxia or Mild Hypoxia.

Microbiota may alter a pathogen's virulence potential at polymicrobial infection sites. Here, we developed a multi-modal Drosophila assay, amenable to the assessment of human bacterial interactions using fly survival or midgut regeneration as a readout, under normoxia or mild hypoxia. Deploying a matrix of 12 by 33 one-to-one Drosophila co-infections via feeding, we classified bacterial interactions as neutral, synergistic, or antagonistic, based on fly survival. Twenty six percent of these interactions were antagonistic, mainly occurring between Proteobacteria. Specifically, Pseudomonas aeruginosa infection was antagonized by various Klebsiella strains, Acinetobacter baumannii, and Escherichia coli. We validated these interactions in a second screen of 7 by 34 one-to-one Drosophila co-infections based on assessments of midgut regeneration, and in bacterial co-culture test tube assays, where antagonistic interactions depended on secreted factors produced upon high sugar availability. Moreover, Enterococci interacted synergistically with P. aeruginosa in flies and in test tubes, enhancing the virulence and pyocyanin production by P. aeruginosa. However, neither lactic acid bacteria nor their severely hypoxic culture supernatants provided a survival benefit upon P. aeruginosa infection of flies or mice, respectively. We propose that at normoxic or mildly hypoxic sites, Firmicutes may exacerbate, whereas Proteobacteria secreted factors may ameliorate, P. aeruginosa infections.

Cardiac Output Measurement in Neonates and Children Using Noninvasive Electrical Bioimpedance Compared With Standard Methods: A Systematic Review and Meta-Analysis.

OBJECTIVE: To systematically review and meta-analyze the validity of electrical bioimpedance-based noninvasive cardiac output monitoring in pediatrics compared with standard methods such as thermodilution and echocardiography. DATA SOURCES: Systematic searches were conducted in MEDLINE and EMBASE (2000-2019). STUDY SELECTION: Method-comparison studies of transthoracic electrical velocimetry or whole body electrical bioimpedance versus standard cardiac output monitoring methods in children (0-18 yr old) were included. DATA EXTRACTION: Two reviewers independently performed study selection, data extraction, and risk of bias assessment. Mean differences of cardiac output, stroke volume, or cardiac index measurements were pooled using a random-effects model (R Core Team, R Foundation for Statistical Computing, Vienna, Austria, 2019). Bland-Altman statistics assessing agreement between devices and author conclusions about inferiority/noninferiority were extracted. DATA SYNTHESIS: Twenty-nine of 649 identified studies were included in the qualitative analysis, and 25 studies in the meta-analyses. No significant difference was found between means of cardiac output, stroke volume, and cardiac index measurements, except in exclusively neonatal/infant studies reporting stroke volume (mean difference, 1.00 mL; 95% CI, 0.23-1.77). Median percentage error in child/adolescent studies approached acceptability (percentage error less than or equal to 30%) for cardiac output in L/min (31%; range, 13-158%) and stroke volume in mL (26%; range, 14-27%), but not in neonatal/infant studies (45%; range, 29-53% and 45%; range, 28-70%, respectively). Twenty of 29 studies concluded that transthoracic electrical velocimetry/whole body electrical bioimpedance was noninferior. Transthoracic electrical velocimetry was considered inferior in six of nine studies with heterogeneous congenital heart disease populations. CONCLUSIONS: The meta-analyses demonstrated no significant difference between means of compared devices (except in neonatal stroke volume studies). The wide range of percentage error reported may be due to heterogeneity of study designs, devices, and populations included. Transthoracic electrical velocimetry/whole body electrical bioimpedance may be acceptable for use in child/adolescent populations, but validity in neonates and congenital heart disease patients remains uncertain. Larger studies in specific clinical contexts with standardized methodologies are required.

Support care needs of people with hearing and vision impairment in dementia: a European cross-national perspective.

PURPOSE: Aging-related sensory impairments are among the most common and disabling comorbidities in people with dementia (PwD). This study explored the unmet support care needs (SCNs) from the perspectives of people with hearing and/or vision impairment in dementia (PwD), and their care partners in Europe. METHODS: This was a two-phase mixed methods study. We administered standardized questionnaires of SCNs and quality of life (QoL) to PwD with hearing and/or vision impairment (n = 97), and their care partners (n = 97) in the UK, France, and Cyprus. Next, a purposive sub-sample of 34 participants (PwD and care partners) participated as focus groups (FGs) or semi-structured interviews to explore their SCNs in depth. RESULTS: Over 94% of the participants reported unmet SCNs (median, 13 (range 5-23)). Nearly three-quarters reported SCNs in the moderate to high range, with the most prevalent unmet SCNs for PwD being in the psychological (>60%) and physical domains (>56%), followed by the need for health information (>46%). Emergent qualitative themes were: (1) the need for tailored support care interventions; (2) care burden, social isolation, and loneliness arising from the combined problems; (3) the need for adequate support from professionals from the different fields, including education around the use of sensory aids. Both study phases revealed that SCNs were highly individualized. CONCLUSIONS: This cross-national study revealed that PwD with sensory impairment and their care partners experience a wide range of unmet SCNs, the interactions between sensory impairments, SCNs and QoL are also complex. A tailored intervention could address these unmet SCNs, including additional support with sensory aids, psychological support, more information about concurrent impairments, and joined up health systems providing care.Implications for rehabilitationA majority of participants with combined age-related hearing, vision, and cognitive impairment had unmet SCNs.The needs of care partners including the risk of loneliness and social isolation, need to be considered.Individually tailored, specific interventions for hearing, vision, and cognitive impairment should incorporate physical and psychological support, as well as education.

FAK displacement from focal adhesions: a promising strategy to target processes implicated in cancer progression and metastasis.

BACKGROUND: Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that is overexpressed or activated in several advanced-stage solid cancers. It is known to play both kinase-dependent and -independent roles in promoting tumor progression and metastasis. Numerous inhibitors, targeting either the enzymatic or scaffolding activities of FAK have been generated, with varying degree of success. Here, we describe a novel approach to site-specifically target both kinase-dependent and -independent FAK functions at focal adhesions (FAs), the primary sites at which the kinase exerts its activity. METHODS: We took advantage of the well-characterized interactions between the paxillin LD motifs and the FAK FAT domain and generated a polypeptide (LD2-LD3-LD4) expected to compete with interactions with paxillin. Co-immunoprecipitation experiments were performed to examine the interaction between the LD2-LD3-LD4 polypeptide and FAK. The effects of LD2-LD3-LD4 in the localization and functions of FAK, as well as FA composition, were evaluated using quantitative immunofluorescence, cell fractionation, FA isolation and Western Blot analysis. Live cell imaging, as well as 2-D migration and cell invasion assays were used to examine the effects on FA turnover and tumor cell migration and invasion. RESULTS: Expression of the LD2-LD3-LD4 polypeptide prevents FAK localization at FAs, in a controlled and dose-dependent manner, by competing with endogenous paxillin for FAK binding. Importantly, the LD2-LD3-LD4 peptide did not otherwise affect FA composition or integrin activation. LD2-LD3-LD4 inhibited FAK-dependent downstream integrin signaling and, unlike existing inhibitors, also blocked FAK's scaffolding functions. We further show that LD2-LD3-LD4 expression markedly reduces FA turnover and inhibits tumor cell migration and invasion. Finally, we show that dimers of a single motif, linked through a flexible linker of the proper size, are sufficient for the displacement of FAK from FAs and for inhibition of tumor cell migration. This work raises the possibility of using a synthetic peptide as an antimetastatic agent, given that effective displacement of FAK from FAs only requires dimers of a single LD motif linked by a short flexible linker. CONCLUSION: In conclusion, these results suggest that FAK displacement from FAs is a promising new strategy to target critical processes implicated in cancer progression and metastasis. Video abstract.

Tools for App- and Web-Based Self-Testing of Cognitive Impairment: Systematic Search and Evaluation.

BACKGROUND: Tools for app- and Web-based self-testing for identification of cognitive impairment are widely available but are of uncertain quality. OBJECTIVE: The objective of this study was to undertake a scoping review of app- and Web-based self-tests for cognitive impairment and determine the validity of these tests. METHODS: We conducted systematic searches in electronic databases, including Google search, Google Play Store, and iPhone Operating System App Store, using the search terms "Online OR Internet-based AND Memory OR Brain OR Dementia OR mild cognitive impairment OR MCI AND Test OR Screen OR Check." RESULTS: We identified 3057 tools, of which 25 were included in the review. Most tools meeting the inclusion criteria assessed multiple cognitive domains. The most frequently assessed domains were memory, attention, and executive function. We then conducted an electronic survey with the developers of the tools to identify data relating to development and validation of each tool. If no response to the survey was received, Google (to identify gray literature), Google Scholar, and Medical Literature Analysis and Retrieval System Online were searched using key terms "(name of developer, if available)" AND "(the name of the tool)" to identify any additional data. Only 7 tools had any information concerning psychometric quality, and only 1 tool reported data on performance norms, reliability, validity, sensitivity, and specificity for the detection of cognitive impairment. CONCLUSIONS: The number of cognitive self-assessment electronic health tools for cognitive impairment is increasing, but most are of uncertain quality. There is a need for well-validated tools and guidance for users concerning which tools provide reliable information about possible cognitive impairment that could warrant further investigation.

Impact of an intervention to support hearing and vision in dementia: The SENSE-Cog Field Trial.

OBJECTIVES: Hearing, vision, and cognitive impairment commonly co-occur in older adults. Improving sensory function may positively impact outcomes in people with dementia (PwD). We developed a "sensory intervention" (SI) to support hearing and vision in PwD. Here, we report the findings of an international open-label field trial, and nested case series, to explore the impact of the SI on dementia-related outcomes. METHODS: This was a home-based trial conducted in France, England, and Cyprus. Participants were people with mild-to-moderate dementia and hearing and/or vision impairment (n = 19) and their study partners (unpaid carers; n = 19). The "basic" SI included a hearing and vision assessment and provision of glasses and/or hearing aids. A subsample received the "extended" SI with additional weekly visits from a sensory support therapist (SST). Exploratory analyses of dementia-related, health utility and resource utilisation outcomes were performed. RESULTS: Quality of life (QoL) and sensory functional ability improved. Change in QoL exceeded the threshold for a minimum clinically important difference. There was a modest improvement (in absolute terms) post intervention in behavioural disturbance, self-efficacy, and relationship satisfaction. Study partner time assisting instrumental activities of daily living (iADL) and supervision decreased by about 22 and 38 hours per month, respectively, although time for personal ADL support increased. Qualitative data supported effectiveness of the intervention: PwD were more socially engaged, less isolated, less dependent on study partners, and had improved functional ability and communication. CONCLUSIONS: These findings support the need for a definitive randomised controlled trial (RCT) to evaluate the effectiveness of the intervention.

The need for improved cognitive, hearing and vision assessments for older people with cognitive impairment: a qualitative study.

BACKGROUND: Hearing and vision (sensory) impairments are highly prevalent in people with dementia (PwD) and exacerbate the impact of living with dementia. Assessment of sensory or cognitive function may be difficult if people have concurrent dual or triple impairments. Most standard cognitive assessment tests are heavily dependent on having intact hearing and vision, and impairments in these domains may render the assessments unreliable or even invalid. Likewise, dementia may impede on the accurate reporting of symptoms that is required for most hearing and vision assessments. Thus, there is an urgent need for hearing, vision and cognitive assessment strategies to be adapted to ensure that appropriate management and support can be provided. OBJECTIVE: To explore the perspectives of PwD and the care partners regarding the need for accurate hearing, vision and cognitive assessments. METHODS: We conducted focus groups and semi-structured interviews regarding the clinical assessment for cognitive, hearing and visual impairment. Participants (n = 18) were older adults with mild to moderate dementia and a sensory impairment as well as their care partners (e.g. a family member) (n = 15) at three European sites. The qualitative material was analysed according to Mayring's summative content analysis approach. RESULTS: Participants reported that hearing, vision and cognitive assessments were not appropriate to the complex needs of PwD and sensory comorbidity and that challenges in communication with professionals and conveying unmet needs and concerns by PwD were common in all three types of clinical assessments. They felt that information about and guidance regarding support for the condition was not adequate in the assessments and that information sharing among the professionals regarding the concurrent problems was limited. Professionals were reported as being concerned only with problems related to their own discipline and had limited regard for problems in other domains which might impact on their own assessments. CONCLUSIONS: The optimal assessment and support for PwD with multiple impairments, more comprehensive, yet easy to understand, information regarding these linked to conditions and corrective device use is needed. Communication among health care professionals relevant to hearing, vision and cognition needs to be improved.

Erratum: Author Correction: eHealth tools for the self-testing of visual acuity: a scoping review.

[This corrects the article DOI: 10.1038/s41746-019-0154-5.].

Feasibility of an Intervention to Support Hearing and Vision in Dementia: The SENSE-Cog Field Trial.

OBJECTIVES: People with dementia (PwD) frequently experience hearing and vision impairment that is underrecognized and undertreated, resulting in reduced quality of life. Managing these impairments may be an important strategy to improve outcomes in PwD. Our objective was to field-trial a multifaceted sensory intervention (SI) to enhance hearing and vision in PwD. DESIGN: An international single-arm open-label feasibility, acceptability, and tolerability study. SETTING: Home-based setting in the United Kingdom, France, and Cyprus. PARTICIPANTS: Adults aged 60 years and older with mild-to-moderate dementia and uncorrected or suboptimally corrected hearing and/or vision impairment, and their study partners (n = 19 dyads). INTERVENTION: A sensory intervention (SI), comprising assessment of hearing and vision, fitting of corrective devices (glasses, hearing aids), and home-based support from a sensory support therapist for device adherence and maintenance, communication training, referral to support services, environmental sensory modification, and optimization of social inclusion. MEASUREMENTS: Ratings of study procedure feasibility, and intervention acceptability/tolerability, ascertained through questionnaires, participant diaries, therapist logbooks, and semistructured interviews. RESULTS: We successfully delivered all intervention components, and these were received and enacted as intended in all those who completed the intervention. No serious adverse events were reported. Acceptability (ie, understanding, motivation, sense of achievement) and tolerability (ie, effort, fatigue) ratings of the intervention were within a priori target ranges. We met recruitment and retention (93.8%) targets in two of the three sites. Participants completed more than 95% of diary entries, representing minimal missing data. Delays in the logistics circuit for the assessment and delivery of hearing aids and glasses were identified, requiring modification. The need for minor modifications to some outcome measures and the inclusion criteria were identified. CONCLUSION: This is the first study combining home-based hearing and vision remediation in PwD. The positive feasibility, acceptability, and tolerability findings suggest that a full-scale efficacy trial, with certain modifications, is achievable.

Protocol for the development of versions of the Montreal Cognitive Assessment (MoCA) for people with hearing or vision impairment.

INTRODUCTION: Hearing and vision impairments are highly prevalent among older adults and impact commonly used cognitive assessment tools for the identification of dementia. Adaptations of such tests for people with hearing or vision impairment have not been adequately validated among populations with such sensory impairment. METHODS AND ANALYSIS: We will develop two versions of the Montreal Cognitive Assessment (MoCA) for people with acquired hearing impairment (MoCA-H) or vision impairment (MoCA-V). The MoCA-H and MoCA-V will exclude the existing MoCA items that are presented in spoken or visual format, respectively, and include new suitably adapted items. Participants (n=792) with combinations of hearing, vision and cognitive impairment will complete standard or adapted versions of the MoCA across three language sites (English, French and Greek). Development of the MoCA-H and the MoCA-V will be based on analysis of adapted and standard MoCA items following model-based development to select the combination of items for the MoCA-H and MoCA-V that provide optimal sensitivity and specificity for detection of dementia. ETHICS AND DISSEMINATION: The study has received ethical approval from respective centres in the UK, France, Greece and Cyprus. The results of the study will be disseminated through peer-reviewed publication, conference presentations, the study website (https://www.sense-cog.eu/), the SENSE-Cog Twitter account (@sense_cog) and the MoCA test website (https://www.mocatest.org/). The main outputs of the study will be versions of the MoCA that are appropriate for use with adults with acquired hearing or vision impairment and will contribute significantly to the clinical care of older people.

Determining Temporal and Spatial Expression of Calpains in Amphibians.

Calpains are a family of calcium-dependent intracellular cysteine proteases that regulate important physiological processes by substrate cleavage. Despite the fact that Calpains have been identified in the Xenopus genome, their expression patterns and role have not been characterized. Therefore, herein, we describe two methods to determine temporal and spatial expression of Calpain 2 during Xenopus development, namely, RT-PCR and whole-mount in situ hybridization (WISH). In addition, indirect immunofluorescence (IF) is described to determine translocation to the plasma membrane, which correlates with activity levels of Calpain 2.

Methods of Calpain Inhibition to Determine the Role of Calpains in Embryo Development in Amphibians.

Calpains are a family of calcium-dependent intracellular cysteine proteases that regulate important physiological processes by substrate cleavage. Despite the fact that the role of calpains in cell migration and other processes has been extensively studied in vitro, the same does not apply to cell migration and morphogenetic events during embryogenesis, in vivo. Herein, we describe the use of three different methods to selectively block calpain activity in vivo in order to investigate the impact on Xenopus gastrulation and neurulation, namely, a calpain inhibitor, a dominant negative, and a morpholino antisense oligonucleotide (MO). We also provide methods to determine the effectiveness of the calpain inhibition and effect on cell fate specification and morphogenetic movements, during embryogenesis in vivo.

Assessing and managing concurrent hearing, vision and cognitive impairments in older people: an international perspective from healthcare professionals.

BACKGROUND: there is a significant gap in the understanding, assessment and management of people with dementia and concurrent hearing and vision impairments. OBJECTIVE: from the perspective of professionals in dementia, hearing and vision care, we aimed to: (1) explore the perceptions of gaps in assessment and service provision in ageing-related hearing, vision and cognitive impairment; (2) consider potential solutions regarding this overlap and (3) ascertain the attitudes, awareness and practice, with a view to implementing change. METHODS: our two-part investigation with hearing, vision, and dementia care professionals involved: (1) an in-depth, interdisciplinary, international Expert Reference Group (ERG; n = 17) and (2) a wide-scale knowledge, attitudes and practice survey (n = 653). The ERG involved consensus discussions around prototypic clinical vignettes drawn from a memory centre, an audiology clinic, and an optometry clinic, analysed using an applied content approach. RESULTS: the ERG revealed several gaps in assessment and service provision, including a lack of validated assessment tools for concurrent impairments, poor interdisciplinary communication and care pathways, and a lack of evidence-based interventions. Consensus centred on the need for flexible, individualised, patient-centred solutions, using an interdisciplinary approach. The survey data validated these findings, highlighting the need for clear guidelines for assessing and managing concurrent impairments. CONCLUSIONS: this is the first international study exploring professionals' views of the assessment and care of individuals with age-related hearing, vision and hearing impairment. The findings will inform the adaptation of assessments, the development of supportive interventions, and the new provision of services.

Research protocol for a complex intervention to support hearing and vision function to improve the lives of people with dementia.

BACKGROUND: Hearing and vision impairments are among the most common and disabling comorbidities in people living with dementia. Intervening to improve sensory function could be a means by which the lives of people living with dementia may be improved. However, very few studies have tried to ameliorate outcomes in dementia by improving sensory function. This paper describes the multi-step development of a new intervention designed to support hearing and vision function in people living with dementia in their own homes. At the end of the development programme, it is anticipated that a 'sensory support' package will be ready for testing in a full scale randomised controlled trial. METHODS: This programme is based on the process of 'intervention mapping' and comprises four integrated steps, designed to address the following: (1) scoping the gaps in understanding, awareness and service provision for the hearing and/or vision impairment care needs of people with dementia using a systematic literature review and Expert Reference Group; (2) investigating the support care needs through a literature search, stakeholder surveys, focus groups, semi-structured interviews and an Expert Reference Group, leading to a prototype sensory support package; (3) refining the prototype by additional input from stakeholders using focus groups and semi-structured interviews; and (4) field testing the draft intervention using an open-labelled, non-randomised feasibility study, integrating feedback from people with dementia and their significant others to develop the final intervention ready for full scale definitive trialling. Input from the 'patient and public voice' is a cornerstone of the work and will interlink with each step of the development process. The programme will take place in study centres in Manchester, Nicosia and Bordeaux. DISCUSSION: Quantitative and qualitative data analyses will be employed, dependent upon the sub-studies in question. Data from the steps will be integrated with consideration given to weighting of evidence for each step of the programme. This programme represents the logical development of a complex intervention to fulfil an unmet need. It is based on a theoretical framework and will lead to a subsequent full scale efficacy trial. The challenges in integrating the data and addressing the contextual issues across study sites will be scrutinised.