Differential impact of two risk communications on antipsychotic prescribing to people with dementia in Scotland: segmented regression time series analysis 2001-2011

The two risk communications were associated with reductions in antipsychotic use, in ways which were compatible with marked differences in their content and dissemination. Further research is needed to ensure that the content and dissemination of regulatory risk communications is optimal, and to track their impact on intended and unintended outcomes. Although rates are falling, antipsychotic prescribing in dementia in Scotland remains unacceptably hig

A mixed-methods feasibility study of a goal-focused manualised intervention to support people with dementia to stay living independently at home with support from family carers: NIDUS (New Interventions for Independence in Dementia Study) Family

Objectives: To examine the feasibility and acceptability of NIDUS-Family, a 6–8 session manualised, individually tailored, modular intervention supporting independence at home for people with dementia; and explore participants’ and facilitators’ experiences of the intervention. / Method: In this single group multi-site feasibility study, trained, supervised non-clinically qualified graduates (facilitators) delivered NIDUS-Family to family carer and people living with dementia dyads. We recruited participants from GP practices and memory services in London and Bradford. We completed quantitative outcomes pre- and post-intervention; and conducted qualitative interviews with participants and facilitators. Our pre-specified main outcomes were proportion of potential participants approached who agreed to participate, intervention adherence and acceptability to family carers, and facilitator fidelity to the manual. / Results: We recruited 16 dyads (57% of those approached); 12 (75%) completed the intervention. Of 12 participants rating intervention acceptability, 9 (75%) agreed or strongly agreed that it had helped; 2 (18%) neither agreed nor disagreed and 1 (8%) disagreed. Mean facilitator fidelity was high (81.5%). Dyads set on average 3.9 goals; these most commonly related to getting out and about and increasing activity/hobby participation (n = 10); carer wellbeing (n = 6), managing physical complaints (n = 6); meal preparation/cooking (n = 5); and reducing irritability, frustration or aggression (n = 5). Almost all secondary outcomes changed in a direction indicating improvement. In our qualitative analysis we identified three overarching themes; relationships facilitate change, goal-focused versus manualised approach and balancing the needs of carers and people with dementia. / Conclusion: NIDUS-Family was feasible and acceptable to participants. Following refinements, testing in a pragmatic trial is underway

Social connectedness and dementia prevention: Pilot of the APPLE-Tree video-call intervention during the Covid-19 pandemic

BACKGROUND AND OBJECTIVES: The Covid-19 pandemic reduced access to social activities and routine health care that are central to dementia prevention. We developed a group-based, video-call, cognitive well-being intervention; and investigated its acceptability and feasibility; exploring through participants’ accounts how the intervention was experienced and used in the pandemic context. RESEARCH DESIGN AND METHOD: We recruited adults aged 60+ years with memory concerns (without dementia). Participants completed baseline assessments and qualitative interviews/focus groups before and after the 10-week intervention. Qualitative interview data and facilitator notes were integrated in a thematic analysis. RESULTS: 12/17 participants approached completed baseline assessments, attended 100/120 (83.3%) intervention sessions and met 140/170 (82.4%) of goals set. Most had not used video calling before. In the thematic analysis, our overarching theme was social connectedness. Three sub-themes were as follows: Retaining independence and social connectedness: social connectedness could not be at the expense of independence; Adapting social connectedness in the pandemic: participants strived to compensate for previous social connectedness as the pandemic reduced support networks; Managing social connections within and through the intervention: although there were tensions, for example, between sharing of achievements feeling supportive and competitive, participants engaged with various lifestyle changes; social connections supported group attendance and implementation of lifestyle changes. DISCUSSION AND IMPLICATIONS: Our intervention was acceptable and feasible to deliver by group video-call. We argue that dementia prevention is both an individual and societal concern. For more vulnerable populations, messages that lifestyle change can help memory should be communicated alongside supportive, relational approaches to enabling lifestyle changes

Social connectedness and dementia prevention: Pilot of the APPLE-Tree video-call intervention during the Covid-19 pandemic.

BACKGROUND AND OBJECTIVES: The Covid-19 pandemic reduced access to social activities and routine health care that are central to dementia prevention. We developed a group-based, video-call, cognitive well-being intervention; and investigated its acceptability and feasibility; exploring through participants' accounts how the intervention was experienced and used in the pandemic context. RESEARCH DESIGN AND METHOD: We recruited adults aged 60+ years with memory concerns (without dementia). Participants completed baseline assessments and qualitative interviews/focus groups before and after the 10-week intervention. Qualitative interview data and facilitator notes were integrated in a thematic analysis. RESULTS: 12/17 participants approached completed baseline assessments, attended 100/120 (83.3%) intervention sessions and met 140/170 (82.4%) of goals set. Most had not used video calling before. In the thematic analysis, our overarching theme was social connectedness. Three sub-themes were as follows: Retaining independence and social connectedness: social connectedness could not be at the expense of independence; Adapting social connectedness in the pandemic: participants strived to compensate for previous social connectedness as the pandemic reduced support networks; Managing social connections within and through the intervention: although there were tensions, for example, between sharing of achievements feeling supportive and competitive, participants engaged with various lifestyle changes; social connections supported group attendance and implementation of lifestyle changes. DISCUSSION AND IMPLICATIONS: Our intervention was acceptable and feasible to deliver by group video-call. We argue that dementia prevention is both an individual and societal concern. For more vulnerable populations, messages that lifestyle change can help memory should be communicated alongside supportive, relational approaches to enabling lifestyle changes

Improving recognition of delirium in clinical practice: a call for action

The purpose of this correspondence article is to report opinion amongst experts in the delirium field as to why, despite on-going training for all health professionals, delirium continues to be under recognised. Consensus was obtained by means of two conference workshops and an online survey of members of the European Delirium Association. Major barriers to recognition at an individual level include ignorance about the benefit of treating delirium. At an organisational level, reflecting socio-cultural attitudes, barriers include a low strategic and financial priority and the fact that delirium is an orphan condition falling between specialties

APPLE-Tree (Active Prevention in People at risk of dementia: Lifestyle, bEhaviour change and Technology to REducE cognitive and functional decline) programme: protocol

Background: Observational studies indicate that approximately a third of dementia cases are attributable to modifiable cardiometabolic, physical and mental health, and social and lifestyle risk factors. There is evidence that intensive behaviour change interventions targeting these factors can reduce cognitive decline. / Methods and analysis: We will design and test a low intensity, secondary dementia‐prevention programme (Active Prevention in People at risk of dementia: Lifestyle, bEhaviour change and Technology to REducE cognitive and functional decline, “APPLE‐Tree”) to slow cognitive decline in people with subjective cognitive decline with or without objective cognitive impairment. We will embed our work within social science research to understand how dementia prevention is currently delivered and structured. We will carry out systematic reviews and around 50 qualitative interviews with stakeholders, using findings to coproduce the APPLE‐Tree intervention. We plan a 10‐session group intervention, involving personalised goal‐setting, with individual sessions for those unable or unwilling to attend groups, delivered by psychology assistants who will be trained and supervised by clinical psychologists. The coproduction group (including public and patient involvement [PPI], academic and clinical/third‐sector professional representatives) will use the Behaviour Change Wheel theoretical framework to develop it. We will recruit and randomly allocate 704 participants, 1:1 to the intervention: informational control group. This sample size is sufficient to detect a between‐group difference at 2 years of 0.15 on the primary outcome (cognition: modified neuropsychological test battery; 90% power, 5% significance, effect size 0.25, SD 0.6). / Dissemination: We will work with Public Health England and third‐sector partners to produce an effective national implementation approach, so that if our intervention works, it is used in practice

Functional Diversity and Structural Disorder in the Human Ubiquitination Pathway

The ubiquitin-proteasome system plays a central role in cellular regulation and protein quality control (PQC). The system is built as a pyramid of increasing complexity, with two E1 (ubiquitin activating), few dozen E2 (ubiquitin conjugating) and several hundred E3 (ubiquitin ligase) enzymes. By collecting and analyzing E3 sequences from the KEGG BRITE database and literature, we assembled a coherent dataset of 563 human E3s and analyzed their various physical features. We found an increase in structural disorder of the system with multiple disorder predictors (IUPred - E1: 5.97%, E2: 17.74%, E3: 20.03%). E3s that can bind E2 and substrate simultaneously (single subunit E3, ssE3) have significantly higher disorder (22.98%) than E3s in which E2 binding (multi RING-finger, mRF, 0.62%), scaffolding (6.01%) and substrate binding (adaptor/substrate recognition subunits, 17.33%) functions are separated. In ssE3s, the disorder was localized in the substrate/adaptor binding domains, whereas the E2-binding RING/HECT-domains were structured. To demonstrate the involvement of disorder in E3 function, we applied normal modes and molecular dynamics analyses to show how a disordered and highly flexible linker in human CBL (an E3 that acts as a regulator of several tyrosine kinase-mediated signalling pathways) facilitates long-range conformational changes bringing substrate and E2-binding domains towards each other and thus assisting in ubiquitin transfer. E3s with multiple interaction partners (as evidenced by data in STRING) also possess elevated levels of disorder (hubs, 22.90% vs. non-hubs, 18.36%). Furthermore, a search in PDB uncovered 21 distinct human E3 interactions, in 7 of which the disordered region of E3s undergoes induced folding (or mutual induced folding) in the presence of the partner. In conclusion, our data highlights the primary role of structural disorder in the functions of E3 ligases that manifests itself in the substrate/adaptor binding functions as well as the mechanism of ubiquitin transfer by long-range conformational transitions. © 2013 Bhowmick et al

Efficacy of lifestyle and psychosocial interventions in reducing cognitive decline in older people: Systematic review

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordIt is unclear what non-pharmacological interventions to prevent cognitive decline should comprise. We systematically reviewed lifestyle and psychosocial interventions that aimed to reduce cognitive decline in healthy people aged 50+, and people of any age with Subjective Cognitive Decline or Mild Cognitive Impairment. We narratively synthesised evidence, prioritising results from studies rated as at lower Risk of Bias (ROB) and assigning Centre for Evidence Based Medicine grades. We included 64 papers, describing: psychosocial (n = 12), multi-domain (n = 10), exercise (n = 36), and dietary (n = 6) interventions. We found Grade A evidence that over 4+ months: aerobic exercise twice weekly had a moderate effect on global cognition in people with/ without MCI; and interventions that integrate cognitive and motor challenges (e.g. dance, dumb bell training) had small to moderate effects on memory or global cognition in people with MCI. We found Grade B evidence that 4+ months of creative art or story-telling groups in people with MCI; 6 months of resistance training in people with MCI and a two-year, dietary, exercise, cognitive training and social intervention in people with or without MCI had small, positive effects on global cognition. Effects for some intervention remained up to a year beyond facilitated sessions.Economic and Social Research Council (ESRC)National Institute for Health Research (NIHR

APPLE-Tree (Active Prevention in People at risk of dementia: Lifestyle, bEhaviour change and Technology to REducE cognitive and functional decline) programme: protocol

Background: Observational studies indicate that approximately a third of dementia cases are attributable to modifiable cardiometabolic, physical and mental health, and social and lifestyle risk factors. There is evidence that intensive behaviour change interventions targeting these factors can reduce cognitive decline. (Figure presented.) Our planned intervention [Colour figure can be viewed at wileyonlinelibrary.com]. Methods and analysis: We will design and test a low intensity, secondary dementia-prevention programme (Active Prevention in People at risk of dementia: Lifestyle, bEhaviour change and Technology to REducE cognitive and functional decline, “APPLE-Tree”) to slow cognitive decline in people with subjective cognitive decline with or without objective cognitive impairment. We will embed our work within social science research to understand how dementia prevention is currently delivered and structured. We will carry out systematic reviews and around 50 qualitative interviews with stakeholders, using findings to coproduce the APPLE-Tree intervention. We plan a 10-session group intervention, involving personalised goal-setting, with individual sessions for those unable or unwilling to attend groups, delivered by psychology assistants who will be trained and supervised by clinical psychologists. The coproduction group (including public and patient involvement [PPI], academic and clinical/third-sector professional representatives) will use the Behaviour Change Wheel theoretical framework to develop it. We will recruit and randomly allocate 704 participants, 1:1 to the intervention: informational control group. This sample size is sufficient to detect a between-group difference at 2 years of 0.15 on the primary outcome (cognition: modified neuropsychological test battery; 90% power, 5% significance, effect size 0.25, SD 0.6). Dissemination: We will work with Public Health England and third-sector partners to produce an effective national implementation approach, so that if our intervention works, it is used in practice