Implementing Arts on Prescription at Home for People Living With Dementia: A Hybrid-Effectiveness Feasibility Study.

Arts on prescription at home (AoP@Home) is a participatory art-based approach involving a professional artist engaging a person with dementia (and their family carer) in art-making in their own home. This study evaluated the implementation of AoP@Home within a real-world community aged care context. A hybrid effectiveness-implementation design was used to simultaneously test both the AoP@Home intervention and the implementation process. AoP@Home program outcomes included person with dementia and family carer (dyad) health and wellbeing, and personal goal attainment. Implementation outcomes were evaluated according to feasibility, fidelity, acceptability, uptake, and costs via routinely collected data, artist notes, and interviews with program managers, artists, and participant dyads. Four dyads completed an AoP@Home program during the study period. All participants with dementia reported improvements in their overall health and wellbeing, and wellbeing scores improved for all carers from baseline to post-program. Implementation was feasible using existing government funding mechanisms, and programs were acceptable to all stakeholders. It is possible to deliver participatory arts programs for community-dwelling people with dementia and their family, in their home, using sustainable and available funding models. Programs such as AoP@Home should be made more accessible alongside broader allied health and care services.

Specialised residential care for older people subject to homelessness: experiences of residents and staff of a new aged care home in Australia.

BACKGROUND: The number of older people experiencing homelessness in Australia is rising, yet there is a lack of specialised residential care for older people subject to homelessness with high care and palliative needs. To address this significant gap, a purpose-built care home was recently opened in Sydney, Australia. METHODS: This qualitative study explores the experiences of both residents and staff who were living and working in the home over the first twelve months since its opening. Residents were interviewed at baseline (n = 32) and after six months (n = 22), while staff (n = 13) were interviewed after twelve months. Interviews were analysed using a reflexive thematic analysis approach informed by grounded theory. RESULTS: Three main themes emerged: (1) Challenges in providing care for older people subject to homelessness with high care needs; (2) Defining a residential care service that supports older people subject to homelessness with high care needs, and (3) Perception of the impact of living and working in a purpose-built care home after six months (residents) and twelve months (staff) since its opening. A key finding was that of the complex interplay between resident dependency and behaviours, referral pathways and stakeholder engagement, government funding models and requirements, staff training and wellbeing, and the need to meet operational viability. CONCLUSION: This study provides novel insights into how the lives of older people subject to homelessness with high care needs are affected by living in a specifically designed care home, and on some of the challenges faced and solved by staff working in the care home. A significant gap in the healthcare system remains when it comes to the effective provision of high care for older people subject to homelessness.

The Right to Rehabilitation for People With Dementia: A Codesign Approach to Barriers and Solutions.

INTRODUCTION: People with dementia of all ages have a human right to equal access to quality health care. Despite evidence regarding its effectiveness, many people living with dementia are unable to access rehabilitation for promoting function and quality of life. Conducted in Australia, this study was designed to (1) explore barriers to access to dementia rehabilitation and (2) identify solutions that improve access to rehabilitation. METHODS: People living with dementia (n = 5) and care partners (n = 8) and health professionals (n = 13) were recruited nationally. Experience-based codesign across three virtual workshops was used to understand barriers and design solutions to improve access to rehabilitation treatments. Socio-ecological analyses, using the Levesque Access to Health care framework, were applied to findings regarding barriers and to aid selection of solutions. RESULTS: There was high attendance (92.3%) across the three workshops. Barriers were identified at a user level (including lack of knowledge, transport, cost and difficulty navigating the health, aged care and disability sectors) and health service level (including health professional low dementia knowledge and negative attitudes, inequitable funding models and non-existent or fragmented services). Solutions focused on widespread dementia education and training, including ensuring that people with dementia and their care partners know about rehabilitation therapies and that health professionals, aged care and disability co-ordinators know how to refer to and deliver rehabilitation interventions. Dementia care navigators, changes to Australia's public funding models and specific dementia rehabilitation programmes were also recommended. CONCLUSIONS: Barriers to accessing rehabilitation for people with dementia exist at multiple levels and will require a whole-community and systems approach to ensure change. PATIENT OR PUBLIC CONTRIBUTION: People with living experience (preferred term by those involved) were involved at two levels within this research. A Chief Investigator living with dementia was involved in the design of the study and writing of the manuscript. People with living experience, care partners and service providers were participants in the codesign process to identify barriers and design potential solutions.

Cost modelling rehabilitation in the home for reconditioning in the Australian context.

BACKGROUND: Inpatient rehabilitation services are challenged by increasing demand. Where appropriate, a shift in service models towards more community-oriented approaches may improve efficiency. We aimed to estimate the hypothetical cost of delivering a consensus-based rehabilitation in the home (RITH) model as hospital substitution for patients requiring reconditioning following medical illness, surgery or treatment for cancer, compared to the cost of inpatient rehabilitation. METHODS: Data were drawn from the following sources: the results of a Delphi survey with health professionals working in the field of rehabilitation in Australia; publicly available data and reports; and the expert opinion of the project team. Delphi survey data were analysed descriptively. The costing model was developed using assumptions based on the sources described above and was restricted to the Australian National Subacute and Non-Acute Patient Classification (AN-SNAP) classes 4AR1 to 4AR4, which comprise around 73% of all reconditioning episodes in Australia. RITH cost modelling estimates were compared to the known cost of inpatient rehabilitation. Where weighted averages are provided, these were determined based on the modelled number of inpatient reconditioning episodes per annum that might be substitutable by RITH. RESULTS: The cost modelling estimated the weighted average cost of a RITH reconditioning episode (which mirrors an inpatient reconditioning episode in intensity and duration) for AN-SNAP classes 4AR1 to 4AR4, to be A$11,371, which is 28.1% less than the equivalent weighted average public inpatient cost (of A$15,820). This represents hypothetical savings of A$4,449 per RITH reconditioning substituted episode of care. CONCLUSIONS: The hypothetical cost of a model of RITH which would provide patients with as comprehensive a rehabilitation service as received in inpatient rehabilitation, has been determined. Findings suggest potential cost savings to the public hospital sector. Future research should focus on trials which compare actual clinical and cost outcomes of RITH for patients in the reconditioning impairment category, to inpatient rehabilitation.

Promoting evidence-based practice and nursing excellence: How involvement in a Magnet4Europe® research study led to development of critically appraised topics sessions for health care staff.

BACKGROUND: Gloucestershire Hospitals NHS Foundation Trust (GHNHSFT) is actively participating in the Magnet4Europe® research study, which aims to advance nursing excellence and promote evidence-based practice. OBJECTIVES: As part of this initiative, the Nursing, Allied Health Professional and Midwifery Research Council at GHNHSFT has been actively engaging colleagues in evidence-based practice and research. METHODS: This has been achieved through the development of sessions using the Critically Appraised Topics (CATs) framework, where clinical questions and relevant research articles are discussed. RESULTS AND DISCUSSION: This article describes the collaborative approach between the Lead Nurse for Continual Professional Development and the Deputy Manager of the Library and Knowledge Services to develop and run the sessions. CONCLUSION: Collaboration between clinical staff and library and knowledge teams can be useful in encouraging healthcare professionals' engagement with the evidence base in order to consider changes to practice.

Implementation of an Arts at Home program for people living with dementia: Learnings from key stakeholders.

ISSUE ADDRESSED: This study explores experiences of people with dementia and family carers who participated in an Arts on Prescription at Home (AoP@Home) program, artists who delivered the AoP@Home program and the managers who coordinated the AoP@Home programs. METHODS: Semi structured interviews were conducted with the three stakeholder groups to explore experiences around implementation of AoP@Home. Interview questions were specific to each stakeholder group, and designed to capture the varied experiences around coordinating, delivering and participating in AoP@Home programs when delivered as a standard service offering. Qualitative content analysis was applied to evaluate the transcripts. RESULTS: A total of 13 stakeholders participated in interviews: four people living with dementia and four family carers, three artists and two AoP program managers. Three overarching themes emerged across the stakeholder groups: 'what worked well', 'challenges' and 'moving forward'. CONCLUSIONS: AoP@Home has potential as an important offering for community-dwelling people with dementia who may no longer be able to access group-based community programs. As AoP@Home is expanded, ongoing implementation monitoring and quality improvement will be essential to ensure maximal applicability of the program across the community aged care sector. SO WHAT?: The implementation of a new AoP@home service has been examined, and finds consumer satisfaction (person with dementia and their carer), and support from staff (artists and program managers). The novel nature of the service, however, requires considerable work to educate service referrers about the service and its benefits.

Steps to implementation: Understanding barriers and enablers for implementing Arts on Prescription at Home for people impacted by dementia.

ISSUE ADDRESSED: Arts on Prescription at Home (AoP@Home) involves a professional artist visiting a person with dementia and their informal carer(s) in their own home to engage them in participatory art making. While there is evidence for the use of these programs, more work is needed to facilitate effective implementation. This study explored contextual barriers and enablers to implementation of AoP@Home within a real-world community aged care service. METHODS: Two remote focus groups were conducted at a community aged care provider in Sydney, Australia. Key stakeholders (n = 14) were recruited, representing: people with dementia, informal (family) carers, AoP artists, service referrers and community service managers. Focus group transcripts were analysed using qualitative content analysis and mapped onto the Consolidated Framework for Implementation Research (CFIR). Outcomes were reviewed against the Expert Recommendations for Implementing Change (ERIC) strategy compilation to inform development of a tailored implementation strategy. RESULTS: Four overarching themes described the range of barriers and enablers to AoP@Home implementation: (1) "I don't know enough about it" (awareness and engagement within the sector), (2) artists delivering programs, (3) awareness and engagement of people impacted by dementia, (4) practicalities of implementation. All five domains of the CFIR were represented across the four themes. The ERIC compilation provided a list of practical strategies for implementation of AoP@Home. CONCLUSIONS: The implementation of psychosocial interventions for people living with dementia within a community aged care service is complex and multifactorial. So what?: Organisations planning implementation should consider conducting their own pre-implementation analysis to identify context-specific strategies.

The Acceptability and Usefulness of Positive Behaviour Support Education for Family Carers of People With Frontotemporal Dementia: A Pilot Study.

AIM: This pilot study investigated the acceptability and usefulness of 4 weekly Positive Behaviour Support (PBS) education sessions (delivered face-to-face and online) for family carers of individuals diagnosed with behavioural-variant frontotemporal dementia (bvFTD). These sessions were adapted from the Family-directed Approach to Brain injury (FAB)-PBS program to the FTD population. METHODS: A pre-test post-test mixed-methods design was utilized. Primary outcome measures included a Carer Confidence questionnaire and post-intervention Feedback Questionnaire. Assessments were conducted prior to the 4-week education program, immediately following the final session and a 3 months follow-up. RESULTS: Ten family carers completed the 4 PBS education sessions and indicated that the program was helpful in providing behaviour support. No significant changes in confidence ratings were found before and following the education sessions. A majority of participants, however, reported positive changes to their approach in providing behaviour support, with key themes including 'recognising the function of behaviour', 'changing their own behaviour' and 'promoting a calmer approach'. CONCLUSIONS: The FAB-PBS education sessions demonstrate to be an acceptable approach to increasing the capability of family carers in providing behaviour support to individuals with FTD, which will need to be confirmed in a larger feasibility study.

An Australian aged care home for people subject to homelessness: health, wellbeing and cost-benefit.

BACKGROUND: Older people subject to homelessness face many challenges including poor health status, geriatric syndromes, and depression, coupled with barriers in accessing health and aged care services. Many are in need of formal aged care at a younger age than the general population, yet, in Australia, specialised aged-care services to support this vulnerable cohort are limited. METHODS: This study was an evaluation of a new purpose-built aged care home for people with high care needs and who are homeless or at risk of homelessness. Over the first 12 months post-admission, the study examined: (1) changes in residents' physical, mental, psychological and social health, and (2) the costs incurred by the study cohort, including any cost benefit derived. RESULTS: Thirty-five residents enrolled in the study between March 2020 - April 2021. At admission, almost half of residents were within the range for dementia, the majority were frail, at high risk for falls, and had scores indicative of depression. Over time, linear mixed-effect models showed significant improvement in personal wellbeing scores, with clinically significant improvements in overall health related quality of life. Levels of physical functional independence, frailty, and global cognition were stable, but cognitive functional ability declined over time. Comparison of 12 month pre- and post- admission cost utility data for a smaller cohort (n = 13) for whom complete data were available, suggested an average per resident saving of approximately AU$32,000, while the QALY indicators remained stable post-admission. CONCLUSION: While this was a small study with no control group, these preliminary positive outcomes add to the growing body of evidence that supports the need for dedicated services to support older people subject to homelessness.

Developing a model for rehabilitation in the home as hospital substitution for patients requiring reconditioning: a Delphi survey in Australia.

BACKGROUND: Reconditioning for patients who have experienced functional decline following medical illness, surgery or treatment for cancer accounts for approximately 26% of all reported inpatient rehabilitation episodes in Australia. Rehabilitation in the home (RITH) has the potential to offer a cost-effective, high-quality alternative for appropriate patients, helping to reduce pressure on the acute care sector. This study sought to gain consensus on a model for RITH as hospital substitution for patients requiring reconditioning. METHODS: A multidisciplinary group of health professionals working in the rehabilitation field was identified from across Australia and invited to participate in a three-round online Delphi survey. Survey items followed the patient journey, and also included items on practitioner roles, clinical governance, and budgetary considerations. Survey items mostly comprised statements seeking agreement on 5-point Likert scales (strongly agree to strongly disagree). Free text boxes allowed participants to qualify item answers or make comments. Analysis of quantitative data used descriptive statistics; qualitative data informed question content in subsequent survey rounds or were used in understanding item responses. RESULTS: One-hundred and ninety-eight health professionals received an invitation to participate. Of these, 131/198 (66%) completed round 1, 101/131 (77%) completed round 2, and 78/101 (77%) completed round 3. Consensus (defined as ≥ 70% agreement or disagreement) was achieved on over 130 statements. These related to the RITH patient journey (including patient assessment and development of the care plan, case management and program provision, and patient and program outcomes); clinical governance and budgetary considerations; and included items for initial patient screening, patient eligibility and case manager roles. A consensus-based model for RITH was developed, comprising five key steps and the actions within each. CONCLUSIONS: Strong support amongst survey participants was found for RITH as hospital substitution to be widely available for appropriate patients needing reconditioning. Supportive legislative and payment systems, mechanisms that allow for the integration of primary care, and appropriate clinical governance frameworks for RITH are required, if broad implementation is to be achieved. Studies comparing clinical outcomes and cost-benefit of RITH to inpatient rehabilitation for patients requiring reconditioning are also needed.

Barriers and enablers to the delivery and implementation of the tailored activity programme in Australia: Perspectives of occupational therapists and their managers.

BACKGROUND: Prior to implementing new programmes or practices, it is essential to understand the context, barriers and enablers to support successful use. The tailored activity programme (TAP) is an evidence-based intervention provided by occupational therapists to support community-dwelling people living with dementia and their carers. The programme was developed in the United States, and although it is not currently available for routine use in Australia, its implementation would address the needs of many Australians with dementia and their carers. AIM: The aim of the study is to understand the perspectives of occupational therapists and their managers regarding barriers and enablers to the delivery and implementation of the TAP in Queensland, Australia. METHODS: A qualitative descriptive methodology was employed. Semistructured interviews were undertaken with occupational therapists (n = 18) who work with community-dwelling people with dementia and their carers, and their managers (n = 10). Participants were recruited from a range of organisations across Queensland, and they were asked about potential barriers and enablers to implementing TAP. Interviews were recorded and transcribed verbatim. Data were mapped using framework analysis whilst remaining open to other themes. FINDINGS: Themes were identified, and facilitating factors included the close alignment of TAP with occupational therapists' scope of practice; their acceptance of, and optimism about the programme and its perceived benefits including improved client outcomes; and an opportunity for occupational therapists to further develop their skills. Managerial support and carers' readiness and willingness to participate were also identified as important factors for success, whereas barriers were cost to clients and the capacity of the occupational therapy workforce to provide TAP. CONCLUSION: Occupational therapists and their managers expressed enthusiasm for TAP and awareness of its likely benefits, while also identifying barriers that will need to be addressed if implementation of the programme is to be successful in Australia.

Supporting behaviour change in younger-onset dementia: mapping the needs of family carers in the community.

OBJECTIVES: Almost 10% of people with dementia experience a younger-onset of disease (before 65 years). Changes in behaviour are common, as are delays in diagnosis and limited access to appropriate support and services. This study aimed to explore the specific behaviour support needs of families living with younger-onset dementia. METHODS: Seventy-one families of people with younger-onset dementia were surveyed to understand the experience of family carers regarding difficult-to-manage behaviour changes, confidence in identifying and implementing behaviour support strategies, use of specific behaviour support strategies, and use of formal and informal support services regarding behaviour changes. RESULTS: Survey responses were received from family members of people living with behavioural variant frontotemporal dementia (n = 28), semantic dementia (n = 17), and Alzheimer's disease (n = 23). Over 90% of family carers reported difficult-to-manage behaviours which fell into four main domains: (1) aggression, (2) compulsive behaviour, (3) disinhibition and inappropriate social behaviour, and (4) apathy. A range of preventative and responsive strategies, with an emphasis on de-escalation strategies were identified and carers reported variable confidence in managing behaviour changes or in accessing formal support strategies. CONCLUSIONS: Difficult-to-manage behaviour changes in community-dwelling people with younger-onset dementia are common. The existing agency of families should be recognised and built upon with better access to specific behaviour support services to increase competence and confidence in providing behaviour support and ultimately improve quality of life for them and their family member with dementia.

Positive behaviour support in frontotemporal dementia: A pilot study.

Frontotemporal dementia (FTD) is a progressive neurodegenerative brain condition clinically characterized by marked changes in behaviour that impact the individuals' relationships and community participation, and present challenges for families. Family carers of individuals with FTD find apathy and disinhibition particularly challenging leading to high levels of stress and burden. Positive behaviour support (PBS) as a behaviour intervention framework has never been trialled in FTD. This pilot study examined the functional basis of apathetic and disinhibited behaviours in four FTD dyads and explored the acceptability of a PBS intervention. The PBS programme was provided by an occupational therapist in the participants' homes. Measures collected at baseline and post-intervention (M = 3.9 months) assessed: function of behaviours, challenging behaviours, and qualitative outcomes pertaining to the acceptability of the PBS approach. PBS was an acceptable intervention for all four dyads. "Sensory" and "tangible" were the most common functions contributing to the maintenance of behaviour changes, and aspects of apathetic and disinhibited behaviours improved following intervention. This study demonstrates the acceptability and potential benefit of a PBS programme to provide support in FTD. A more rigorous trial will be an important next step in developing improved services tailored to the needs of this unique population.

Understanding in the Australian aged care sector of reablement interventions for people living with dementia: a qualitative content analysis.

BACKGROUND: Reablement has potential for enhancing function and independence in people with dementia. In order to enhance the use of evidence-based reablement in this population, this study sought to understand the current practices and needs of the sector around these interventions. METHODS: A purposive sample of 22 Australian aged and community-care providers participated in a semi-structured interview. Qualitative content analysis was applied to the data, with key themes interpreted within the context of the study aims: to explore (1) what reablement interventions are currently being offered to people living with dementia in Australia, and (2) what are key factors that will contribute to enhanced uptake of reablement interventions in dementia practice. RESULTS: Four themes emerged: (1) 'what reablement interventions are being offered', outlined a range of exercise and cognitive/social interventions, with only a proportion generated from a clear evidence-base, (2) 'what's in a name', illustrated the range of terms used to describe reablement, (3) 'whose role is it', highlighted the confusion around the range of health professionals involved in providing reablement interventions, and (4) 'perceived barriers and enablers to providing reablement to people living with dementia', described a range of factors that both hinder and support current reablement practice. CONCLUSIONS: Reablement interventions currently provided for people living with dementia in Australia are variable, with confusion around the definition of reablement, and apparently limited use of evidence-informed interventions. A multifaceted approach involving an evidence-informed and freely-accessible resource, and taking into account the varied levels of influence within the aged care sector would support uptake and implementation of reablement interventions for people living with dementia.

The Relationship between Behavioural Changes, Cognitive Symptoms, and Functional Disability in Primary Progressive Aphasia: A Longitudinal Study.

BACKGROUND: The contribution of behavioural changes to functional decline is yet to be explored in primary progressive aphasia (PPA). OBJECTIVES: (1) investigate functional changes in two PPA variants [semantic (svPPA) and non-fluent (nfvPPA)], at baseline and after 12 months; (2) investigate baseline differences in behavioural changes between groups, and (3) explore predictors of functional decline after a 12-month period. METHODS: A longitudinal study involving 29 people with PPA (18 svPPA; 11 nfvPPA) seen annually in Sydney/Australia was conducted. A total of 114 functional and behavioural assessments were included for within-group (repeated-measures ANOVA; annual rate of change; multiple regression analyses) and between-group analyses (pairwise comparisons). RESULTS: Functional profiles in svPPA and nfvPPA were similar in people with up to 5 years of disease duration. Behavioural changes were marked in svPPA patients (stereotypical behaviour and apathy) but did not predict annual rate of change of functional abilities; global cognitive scores at baseline did. Despite mild behavioural changes in nfvPPA (disinhibition, apathy), these were significant predictors of annual rate of functional change. CONCLUSIONS: The presentation and interplay of behavioural changes and functional disability differ in svPPA and nfvPPA. These varying factors should be taken into account when considering prognosis, disease management, and selection of outcome measures for interventions.

"It's Opened My Eyes to a Whole New World": Positive Behaviour Support Training for Staff and Family Members Supporting Residents With Dementia in Aged Care Settings.

OBJECTIVES: This study examined the acceptability and usefulness of Positive Behaviour Support (PBS) training in enhancing the capabilities of support staff and family members providing behaviour support to residents with dementia in residential aged care (RAC). METHODS: A mixed-methods pilot study was conducted across 3 RAC organisations, involving pre- and post-training questionnaire assessments for clinical leaders (n = 8), support staff (n = 37) and family members (n = 18). RESULTS: Findings indicated increased confidence among support staff and family members in providing behaviour support, with 96% indicating it would support their practices across settings. Key training benefits included identifying and addressing underlying causes of challenging behaviours. A majority (89%) expressed the need for further behaviour support training. CONCLUSION: Recommendations focus on developing systems to enable effective and collaborative behaviour support practices. Further research is needed to examine application of PBS principles and planning for residents living with dementia.

Re/connecting with "home": a mixed methods study of service provider and patient perspectives to facilitate implementing rehabilitation in the home for reconditioning.

PURPOSE: To explore the views of healthcare professionals and patients about the advantages and disadvantages of rehabilitation in the home (RITH) for reconditioning, and identify factors that should contribute to the successful implementation of a consensus-based RITH model for reconditioning. MATERIALS AND METHODS: Interviews with 24 healthcare professionals and 21 surveys (comprising Likert scale and free text responses) of inpatients undergoing rehabilitation for reconditioning provided study data. Interpretive thematic analysis was used to analyse interview data; descriptive statistics analysed Likert scale responses; patient written responses assisted with the interpretation of themes developed from the interview data. RESULTS: Two major themes were elicited in this study: the home is a physical setting and the home is a lived space. Advantages and disadvantages of RITH for patients, carers and healthcare professionals were identified within these themes. Appropriate patient selection; effective communication with patients and carers, and within RITH teams; adequate patient and carer support; ensuring the safety of patients and staff; and education of patients, carers and healthcare professionals are essential for the satisfactory implementation of RITH. CONCLUSION: The concept of home shapes the delivery of RITH. Recognising the advantages and disadvantages of RITH highlights important considerations needed to successfully implement RITH for reconditioning.

The home setting facilitates a person-centred approach to care, especially when staff consider patients to be equal partners in their care.Home offers an opportunity to negotiate contextually relevant rehabilitation goals with patients.Effective communication between patients, their local doctor, family, and rehabilitation staff is essential for the successful delivery of rehabilitation in the home.Safety concerns (for patients and staff) and the shift in the burden of care from hospital staff to family must be adequately addressed prior to the commencement of rehabilitation in the home.

Mosaic deletion of claudin-5 reveals rapid non-cell-autonomous consequences of blood-brain barrier leakage.

Claudin-5 (CLDN5) is an endothelial tight junction protein essential for blood-brain barrier (BBB) formation. Abnormal CLDN5 expression is common in brain disease, and knockdown of Cldn5 at the BBB has been proposed to facilitate drug delivery to the brain. To study the consequences of CLDN5 loss in the mature brain, we induced mosaic endothelial-specific Cldn5 gene ablation in adult mice (Cldn5iECKO). These mice displayed increased BBB permeability to tracers up to 10 kDa in size from 6 days post induction (dpi) and ensuing lethality from 10 dpi. Single-cell RNA sequencing at 11 dpi revealed profound transcriptomic differences in brain endothelial cells regardless of their Cldn5 status in mosaic mice, suggesting major non-cell-autonomous responses. Reactive microglia and astrocytes suggested rapid cellular responses to BBB leakage. Our study demonstrates a critical role for CLDN5 in the adult BBB and provides molecular insight into the consequences and risks associated with CLDN5 inhibition.