Warneford Hospital,Oxford Health NHS Foundation Trust

Autistic people are overrepresented among people experiencing homelessness, and better recognition of autism may improve access to homelessness services. This study examined whether staff working in homelessness services identify autism in service users. A total of 203 staff working with people experiencing homelessness in the UK completed an online survey in which they were asked to identify a mental health or neurodevelopmental condition from five vignettes co-developed with experts by experience. Participants were most accurate at identifying more traditional presentations of autism and least accurate at identifying Emotionally Unstable Personality Disorder (EUPD). Personal or professional connection to, and experience with, autism did not predict accuracy or whether participants said they would make adaptations. These findings suggest that recognition of more nuanced presentations of autism needs to improve. Future research should examine how adaptations are implemented in practice and how service users experience those adaptations.

Background Dementia represents a major public health challenge worldwide. Interventions are required to maintain functional ability and prevent crises. Exercise-based therapy may improve activities of daily living and prevent falls. Objective We aimed to systematically develop an intervention, called Promoting Activity, Independence and Stability in Early Dementia and mild cognitive impairment (PrAISED), and evaluate its clinical and cost-effectiveness. Design A mixed-methods study. Literature review, co-design, patient and public involvement and practical experience were used to develop and refine a therapy intervention. We applied principles of behaviour change to promote engagement and motivation. Three-arm feasibility randomised controlled trial to test research procedures, the practicality of intervention, and establish the need for prolonged supervision. Two-arm, multicentre randomised controlled trial, comparing intervention with control, with 15 months’ follow-up. Process and realist evaluations, including quantitative data, interviews and thematic analyses. Health economic evaluations, including a cost-effectiveness analysis using Markov modelling and social return on investment. Implementation study. Setting Therapy and research were undertaken in participants’ homes and local communities across 5 sites in England. Participants People with diagnosed mild dementia or mild cognitive impairment, Montreal Cognitive Assessment score 13–25, living at home and a family member or carer. In the main trial, there were five sites in England, participants were 98% White ethnicity and 20% had mild cognitive impairment. Interventions A specially designed, dementia-specific, rehabilitation programme focusing on strength, balance, physical activity and performance of activities of daily living, which was tailored, progressive and addressed risk, providing up to 50 therapy sessions over 12 months. The control group received usual care plus a falls risk assessment. Main outcome measures The primary trial outcome was the informant-reported Disability Assessment for Dementia 12 months after randomisation. Secondary outcomes were: self-reported activities of daily living, physical activity, quality of life, frailty, balance, functional mobility, cognition, fear of falling, mood, carer strain and service use (at 12 months) and falls (between months 4 and 15). Results Three hundred and sixty-five people were randomised in the multicentre trial, 183 to intervention and 182 to control. Median age of participants was 80 years (range 65–95), median Montreal Cognitive Assessment score was 20/30 (range 13–26) and 58% were men. Participants received a median of 31 (interquartile range = 22–40) therapy sessions out of a possible maximum of 50. Participants reported completing a mean 121 minutes/week of PrAISED activity. Primary outcome data were available for 149 (intervention) and 141 (control) participants. There was no difference in Disability Assessment for Dementia scores between groups: adjusted mean difference −1.3/100, 95% confidence interval (−5.2 to 2.6); Cohen’s d effect size −0.06 (−0.26 to 0.15); p = 0.5. Upper 95% confidence intervals excluded small to moderate effects on any secondary outcome measures. Between months 4 and 15, there were 79 falls in the intervention group and 200 falls in the control group, and adjusted incidence rate ratio was 0.78 (0.5 to 1.3); p = 0.3. Participants and therapists liked the intervention and thought that it produced health benefits. Tailoring, perceiving benefits, professional supervision and family or carer support were important facilitators. Cognitive and physical impairment, risk aversion and tapering the level of support were barriers. Therapeutic relationship between participant and therapist was important. The cost per quality-adjusted life-year gained was £130,000 over a lifetime horizon. Social return on investment was positive before the onset of the COVID-19 pandemic but was negative after the first pandemic lockdown, largely due to unavailability of access to community facilities. Limitations The multicentre randomised controlled trial was disrupted by the COVID-19 pandemic. The first lockdown occurred when 301 participants had been randomised and 64 participants had completed the trial. Recruitment was suspended, and some therapy and data collection were undertaken remotely. The intervention was diminished compared with in-person delivery, but reported fidelity remained reasonable. Our participant population lacked socioeconomic and ethnic diversity – over 30% lived in the least deprived decile of postcodes. The intervention was very popular with participants and therapists, and it is possible that our predominantly biomedical and functionally orientated outcome variables failed to capture intervention benefits. Conclusions The intensive PrAISED programme of exercise and functional activity training did not improve activities of daily living, physical activity, quality of life, reduce falls or improve any other secondary health status outcomes. Due to the pandemic, the population recruited, and the outcomes chosen, some uncertainty remains about the effectiveness of the intervention. Future work Consider: (1) repeating the trial outside of a pandemic; (2) more psychosocial outcomes, such as social participation, affirming personhood and valuing therapeutic relationships; (3) alternative approaches to risk reduction and ability maintenance in dementia; (4) other models of support to manage problems associated with inevitable progression and decline; (5) that conventional randomised controlled trials may not be the best way to evaluate complex intervention for complex and degenerative conditions; interpretative and realist methods should supplement evaluation; and (6) work to include a wider range of ethnicities and socioeconomic circumstances. Study registration This study is registered as ISRCTN10550694, 15320670. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research programme (NIHR award ref: RP-PG-0614-20007) and is published in full in Programme Grants for Applied Research; Vol. 14, No. 1. See the NIHR Funding and Awards website for further award information. Plain language summary Dementia causes deterioration in memory and thinking abilities. The Promoting Activity, Independence and Stability in Early Dementia (PrAISED) programme aimed to develop and test a physical exercise and activity intervention to improve the ability to do daily activities among older people in the early stages of dementia. We developed a therapy programme specifically designed for people with dementia. We paid particular attention to encouraging participation. Therapy was tailored to participants’ goals, preferences and abilities. We confirmed that we could deliver the intervention and do the research to test it in a small-scale feasibility study. We tested PrAISED by recruiting 365 people with dementia and a family member from five English counties. We randomly assigned them to receive PrAISED therapy or to a control group, who were given advice on falls prevention. The PrAISED group received up to 50 therapy sessions, delivered by trained therapists, and were also encouraged to do exercises on their own. At the start and after 12 months, we measured ability to do everyday activities and other aspects of health, including falls, quality of life, activity and National Health Service and social care use. We did interviews and observations to explain the findings. Those receiving PrAISED therapy did no better on any of our measurements than those in the control group. The therapy programme was popular, and participants described benefits to their lives. Professional supervision and family support were important. However, memory and physical health problems often prevented full participation. The study was disrupted by the COVID-19 pandemic. An economic study showed that PrAISED was not cost-effective. A method which values social outcomes suggested that PrAISED gave a good return before the pandemic but not during it. We conclude that it might be more appropriate to help people manage problems associated with the inevitable decline seen in dementia rather than to try to change the course of the disease. Scientific summary Background The prevalence of dementia is increasing with the ageing population and is expected to double in the next 30 years. About 950,000 people live with dementia in the UK. Dementia causes progressive deterioration in a person’s cognitive and functional abilities. People with dementia are often dependent on other people. Dementia results in high levels of demand on health and social care as well as family and other informal carers. We need therapeutic interventions to reduce the decline in functional abilities so people with dementia can remain independent for longer. Exercise-based activities and functional rehabilitation may improve people with dementia’s activities of daily living (ADL). Objectives The Promoting Activity, Independence and Stability in Early Dementia and mild cognitive impairment (PrAISED) programme aimed to develop and evaluate an exercise and activity intervention to increase independence in ADL for older people living with dementia or mild cognitive impairment (MCI). The programme comprised seven work packages (WPs): WP1 – intervention development: develop, manualise and support the delivery of an evidence-based multicomponent therapy intervention. WP2 – adherence and motivation: develop strategies to support engagement with the intervention and achieve long-term adherence. WP3 – feasibility study: test the feasibility and practicality of delivering the intervention and conducting a randomised controlled trial (RCT). WP4 – process evaluation: conduct process and realist evaluations of the trials. WP5 – multicentre RCT: establish the clinical effectiveness of the PrAISED intervention in a multicentre RCT. WP6 – health economics: establish the cost-effectiveness of the intervention and social return on investment (SROI). WP7 – implementation: understand factors that would affect implementation of the intervention in practice. Methods Work package 1 – intervention development The PrAISED intervention was developed by a team of clinical academics, practitioners and patient and public involvement and engagement representatives using evidence and theory from systematic reviews, interviews, focus groups, empirical studies and expert opinion. This followed work in an Alzheimer’s Society PhD fellowship (Dr Vicky Booth) and a National Institute for Health and Care Research (NIHR) Programme Development Grant. We used theory about how to motivate people with dementia to do exercises. The intervention was described in a manual. We developed practitioner training courses. These were refined following experience in the feasibility study and described using the Template for Intervention Description and Replication (TIDieR) checklist. Work package 2 – adherence and motivation We initially used self-determination theory (SDT) to inform intervention development but later developed a new dementia-specific behaviour change model (PHYT-in-dementia), derived from literature reviews, synthesis and empirical evidence from the feasibility study. It was validated using interview data collected during the RCT process evaluation. PHYT-in-dementia identified factors that mediate behaviour change and maintenance in people living with dementia. These were: characteristics of the person with dementia, support, expectations, goals, carer characteristics, progress, social opportunity, self-efficacy, capability, intervention characteristics, autonomy, control, physical infrastructure, personal history, information, knowledge, characteristics of therapists and personal beliefs. Work package 3 – feasibility study We conducted a three-arm randomised feasibility trial to establish that we could recruit and randomise participants at a sufficient rate, deliver the intervention in participants’ homes across two sites, retain and follow up participants; that the intervention was practical and safe; that we could collect trial data and that our sample size assumptions were reasonable. We explored the level of supervision participants would need to undertake 3 hours of PrAISED exercises and activities a week and sustain this over the duration of the trial. We compared the PrAISED intervention with supervision over 12 months to a shorter intervention comprising nine therapy visits and three telephone calls delivered over 12 weeks and a control group who received a falls prevention assessment and advice. Data were collected at baseline and 12-month follow-up, during face-to-face interviews with two researchers. Health status measures comprised disability in ADL [Disability Assessment for Dementia scale (DAD)], habitual physical activity, quality of life (QoL), frailty, cognition, other intermediate outcomes and carer outcomes. Monthly calendars were completed for falls and activity ascertainment. Work package 4 – process evaluation We investigated implementation of the PrAISED intervention during the trials, the mechanisms of impact and context. We adopted a mixed-methods approach investigating fidelity, adaptations, dose and reach, including quantitative data, interviews and thematic analyses. Mechanisms of impact and context were identified through semistructured qualitative interview with a sample of therapists, participants and carers. Interviews were conducted 6 and 12 months into involvement in PrAISED. Interviews were conducted remotely during the COVID-19 lockdown between May 2020 and September 2020. Work package 5 – multicentre randomised controlled trial Participants were recruited from five sites in England via secondary care memory assessment clinics, general practice registers, dementia support groups and the NIHR Join Dementia Research register. Participants were recruited as patient–carer dyads. The RCT was conducted between September 2018 and June 2022. This included the COVID-19 pandemic period, which impacted recruitment, intervention delivery and data collection. Between March 2020 and September 2020, research and intervention contacts were delivered remotely. We included participants aged over 65 years, with a diagnosis of dementia or MCI, a Montreal Cognitive Assessment (MoCA) score of 13–25 (out of 30), a family member or unpaid carer who knew the participant well and who was willing to participate. Participants had to have mental capacity to consent and be willing to take part in an exercise intervention. Separate consent was taken for the carer. Active intervention comprised a specially designed, dementia-specific, rehabilitation programme focusing on strength, balance, physical activity and performance of ADL, which was tailored, progressive and addressed risk, providing up to 50 therapy sessions over 12 months. The control group received usual care plus a falls risk assessment. The primary outcome was ADL, measured at 12 months by the informant-completed DAD scale. Secondary outcomes included self-assessed ADL (Nottingham Extended ADL scale); cognition (MoCA, animal-naming verbal fluency; Cambridge Neuropsychological Test Automated Battery), balance (Berg Balance Scale); mobility and ability in divided attention [Timed Up and Go (TUG), dual-task (TUG)]; hand grip strength; health and social care resource use for patient and carer Client Service Receipt Inventory; fear of falling; frailty, mood; carer strain, carer and self-assessed health-related quality of life (EQ5D DemQoL scales), physical activity; step count by accelerometer; and apathy. Participants were followed up after 12 months. Between months 1 and 15, self-completed calendars were used to record falls and PrAISED exercise undertaken. A brief postal follow-up questionnaire was completed by the patient’s carer/informant after 6 months. A sample of 368 participants (184 per group), with 23% attrition, had 80% statistical power to detect a change in disability outcome (DAD), with a moderate effect size of 0.5. A secure internet-based system based in a Clinical Trials Unit was used to randomise individuals, 1 : 1, stratified by site, presence of a co-resident and history of previous falls. Blinding of participants and therapists was not possible due to the nature of the intervention. Analysis was conducted blind. An analysis of covariance was conducted for the primary outcome (DAD) at the 12-month follow-up, using group, stratification variables and baseline DAD score as covariates. The analysis was conducted on an intention-to-treat basis. Scaled secondary outcome measures were analysed similarly. Adjusted mean differences, Cohen’s d standardised effect size, 95% confidence intervals (CIs) and p-values were reported. Work package 6 – health economics Cost–utility analysis using a Markov-modelled projection over a 15-year time frame, and a SROI analysis. Work package 7 – implementation We undertook four small-scale implementation studies, using the Consolidated Framework for Implementation Research. We investigated adaptation and adoption of a pilot service in routine practice at one site. We interviewed therapists who delivered the PrAISED intervention, commissioners and service leaders. We explored lack of participation by ethnic minority populations through discussions with community groups and leaders. We developed advice on compiling a business case for commissioning the intervention. Results We developed and refined the PrAISED intervention. This comprised a 12-month, home-based, individually tailored rehabilitation programme, focusing on strength, balance, physical activity and performance of ADL. Tailoring took account of individual history, personality and abilities, problems, interests, family and other resources. Fourteen core principles were defined to guide intervention delivery. A logic model was developed. Delivery was by physiotherapists, occupational therapists and rehabilitation support workers. Participants were encouraged to undertake a total of at least 180 minutes of exercise per week. The programme was progressed by therapists following periodic reassessments. Supervised sessions were tapered over the 12 months (twice-weekly visits in the first 3 months, reducing to monthly in the final 3 months) and community activities were signposted. An intervention manual was published. Therapists were supported throughout the intervention delivery period with training and regular clinical support sessions. We reviewed behaviour change frameworks for older people and people living with dementia. We adapted SDT to support the intervention, which posits the importance of autonomy, relatedness and competence, and 12 practical support approaches. Further reviews led to the development of a new behaviour change framework, PHYT-in-dementia, which was adapted, validated and applied to the intervention for the multicentre RCT. We undertook a two-site, three-arm feasibility RCT. We successfully recruited 60 participants, of whom 45 completed the intervention and provided outcome data. There were no serious, related adverse events (AEs). Missing data rates were satisfactory, apart from some scales that were investigating SDT. We made some other minor adjustments to eligibility criteria and outcome scales. We found that participants were unable to adhere to the programme in the absence of supervision and carried forward higher-intensity supervision but developed an algorithm to plan and gradually reduce intensity, considering ability to undertake activities independently. Analysis of outcomes supported the superiority of the higher-intensity programme and suggested moderate to large benefits in balance, gait speed and disability. We undertook a five-site, two-arm RCT, powered to detect a moderate effect size on the DAD scale. We recruited 365 participants, median age 80 years, 42% female, median MoCA score 20/30, predominantly from less-deprived localities. There were no significant differences in characteristics between groups at baseline. A median of 31 therapy sessions were delivered, interquartile range 22–40, 68% face to face. Fidelity judged from (pre pandemic) video-recorded therapy sessions was good. Intervention group participants reported undertaking an additional mean of 121 minutes of exercise per week. Two hundred and ninety (79%) were followed up. There were no significant differences on the primary outcome, the DAD: adjusted mean difference −1.3 (95% CI −5.2 to 2.6); standardised effect size (d) −0.06, 95% CI −0.26 to 0.15; p = 0.5; or on physical activity, balance, QoL, cognition or a range of other measures. There was a statistically significant small difference in favour of the control group, on the dual-task TUG test and on the self-report DemQoL scale. Upper 95% CIs excluded even small benefits on other scales. Rate of falling was reduced by 22%, but this was not statistically significant. Results did not change in a range of sensitivity analyses. Both service delivery and research were disrupted by the COVID-19 pandemic. Recruitment was delayed, some follow-up was undertaken remotely and some intervention sessions were delivered by telephone or video call, which were consequently much less ambitious than intended. Community facilities and activities became unavailable to vulnerable people. Results were no different for those completing the intervention before the COVID-19 pandemic. One hundred and sixty-seven AEs were recorded: 59 in control and 108 in the intervention groups, involving 68 participants. There were 91 serious adverse events: 29 in control and 62 in intervention, involving 60 participants. None was serious and related to intervention. There was no statistically significant difference between the intervention and control groups for AEs. The process evaluation studied implementation of the intervention, mechanisms of impact and context. Eighty-eight interviews were undertaken with participants, carers and staff. The PrAISED intervention was well received among participants and clinicians. Many gave examples of benefits gained as a result of taking part in PrAISED. However, cognitive impairment, physical comorbidity and fear of falls or getting lost prevented independent engagement. Tapered support was ineffective and acted as a barrier to continued engagement. Family members played a major role in supporting participation. A realist evaluation considered mechanisms behind the social benefits and concluded that participants improved social interactions when therapy activities were tailored to their preferences, when therapy support was maintained and when participants perceived improvements as a result of the intervention. The cost-effectiveness study showed a cost/quality-adjusted life-year of £130,000. SROI suggested benefits, but only in the feasibility and pre-COVID phases of the study. Participants completing the trial after the start of the pandemic had a negative social return, predominantly due to lack of availability of community facilities. We introduced PrAISED into routine practice in a socioeconomically deprived part of Nottingham. Eleven participants were referred and completed a shorter version of PrAISED, less than half what was anticipated or provided for. The intervention was well received by those who participated. We investigated reasons behind poor recruitment of participants from ethnic minority groups, finding feelings of mistrust towards health services and research, and stigma against dementia. We interviewed commissioners to provide guidelines on constructing a business case for implementing exercise and post-diagnostic support programmes. Conclusions We delivered an ambitious programme of research to address whether we can intervene to maintain safe activity and independence after a diagnosis of dementia. We systematically designed a new dementia-specific intervention, and used multiple methods to evaluate it, centred around a multicentre RCT. The intervention was about as intensive as it would be possible to deliver in the UK health and cultural context. Despite positive reception and perceived benefits by participants, we measured no benefits from the programme. Our RCT was significantly disrupted by the COVID-19 pandemic. This, a lack of diversity in the participant population and the fact that the outcome measures used might not have captured the impact of the intervention, leave persisting uncertainties about whether a PrAISED-like intervention might be beneficial. However, our findings suggest that a more ‘supportive’ approach to health care after a diagnosis of dementia may be appropriate, helping to manage problems associated with inevitable functional decline, rather than trying to change the course of disease or to maintain abilities. This would involve developing therapeutic relationships, providing support to live with limitations, minimising intervention burden, maintaining personhood, inclusion and occupation, providing psychological and emotional support and support to family and other carers. Study registration This study is registered as ISRCTN10550694, 15320670. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research programme (NIHR award ref: RP-PG-0612-20004) and is published in full in Programme Grants for Applied Research; Vol. 14, No. 1. See the NIHR Funding and Awards website for further award information.

Emotional crying refers to the uniquely human characteristic of producing visible tears in response to emotionally salient experiences. Originating in infancy as a biologically prepared distress signal, emotional crying persists across the lifespan with relatively stable social effects across cultures, appearing to function to recruit the attention and support of others. Although particular to humans, comparative research suggests crying visible emotional tears can be situated in a broader evolutionary pattern. Across a range of other social species, adults strategically redeploy juvenile-typical behaviors that can influence the responses of conspecifics. Recent primatological work has termed this paedomorphic signaling. We suggest this provides a valuable conceptual anchor for understanding the evolutionary origins of emotional tears in humans. We propose that paedomorphic signaling by adults is effective in eliciting care from conspecifics because, in humans and others species that invest in the care of dependent young, adults have evolved predispositions to attend to and respond to juvenile-like signals. Understanding emotional tears as a form of paedomorphic signaling provides a coherent evolutionary account of their potency, context-sensitivity, and developmental persistence and generates novel predictions that may guide future research. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

Glycosphingolipids (GSLs) play major roles in viral infections by mediating viral entry and egress from cells in lipid rafts; however, GSLs are also important in neurodegenerative diseases. The role of GSLs in acute COVID-19 infection is critical but remains less-studied in the sequelae of long COVID (post-COVID condition); because the same enzymes that regulate GSL metabolism are critical for viral entry and exit, neuromuscular junctions, neurological function, and cellular metabolism, it is important to determine whether long COVID may increase the risk of subsequent neurodegeneration. SARS-CoV-2 infection alters lipid metabolism and oxygen use and can bind to and modify the expression of neurotrophic GSLs such as GM1 ganglioside. GM1 (N-acetylneuraminic acid) is human-specific and probably evolved as a result of a pandemic 3-2.5 million years ago that drove its selection. GM1 functions as a coreceptor with angiotensin-converting enzyme 2 for SARS-CoV-2 while also being a neurotrophin. Viral multiplication takes place in the endoplasmic reticulum/Golgi apparatus, where GSLs are synthesized. This review defines the complex interaction between viruses, GSLs, and neurodegeneration, which provides new perspectives on the interlinked metabolic changes. A European working group has been set up to assess the risks of neurodegeneration with long COVID, based on potential GSL-mediated mechanisms. SIGNIFICANCE STATEMENT: The SARS-CoV-2 pandemic has resulted in a large number of subjects living with long-term consequences (long COVID). Glycosphingolipids and gangliosides are involved in both viral infections and neurodegeneration; hence, it is important to evaluate whether long COVID may increase the risk of neurodegeneration via this route. This study is the result of a European consortium formed to evaluate this possibility.

BACKGROUND:Insulin resistance is recognised as a midlife risk factor for cognitive decline, yet the pathways linking metabolic dysfunction to early brain changes remain unclear. METHODS:We cross-sectionally analysed 355 cognitively normal adults from the PREVENT cohort to test associations between insulin sensitivity (Homoeostatic Model Assessment for Insulin Resistance; HOMA-IR), frontal white matter hyperintensities (WMH), cerebral blood flow (CBF), hippocampal volume, and cognition. FINDINGS:Multivariable regression showed higher log-transformed HOMA-IR was associated with greater frontal WMH burden (β = 0.118, p = 0.026) and lower global cognitive performance (β = -0.132, p = 0.012). Decreased insulin sensitivity was not associated with global CBF (β = -0.019, p = 0.74). Adjusting for WMH burden, hippocampal volume, and CBF, lower insulin sensitivity remained associated with lower global cognition (β = -0.123, p = 0.021). Structural equation modelling (n = 328) demonstrated a direct negative association between higher HOMA-IR and cognition (β = -0.055, p = 0.042) and trended toward higher vascular burden (p = 0.06). The indirect pathway through vascular burden was non-significant (p = 0.23), as vascular burden, hippocampal volume, and CBF did not associate with cognition. INTERPRETATION:Decreased insulin sensitivity was linked to early small vessel disease and measurable cognitive differences, suggesting the cognitive association was largely direct rather than explained by vascular injury, hippocampal atrophy, or global perfusion. These findings point toward partially parallel metabolic and vascular pathways rather than a sequential process. These cross-sectional associations suggest that insulin sensitivity warrants investigation as a modifiable midlife factor for cognitive health; interventional studies are needed to determine whether targeting it preserves cognition before neurodegenerative markers emerge. FUNDING:MRC Dementias Platform UK, NIHR, Alzheimer's Society, Alzheimer's Association, Race Against Dementia, and HRB.