Effectiveness of Dementia Care Mapping™ to reduce agitation in care home residents with dementia: an open-cohort cluster randomised controlled trial

Objectives: Agitation is common and problematic in care home residents with dementia. This study investigated the (cost)effectiveness of Dementia Care Mapping™ (DCM) for reducing agitation in this population.Method: Pragmatic, cluster randomised controlled trial with cost-effectiveness analysis in 50 care homes, follow-up at 6 and 16 months and stratified randomisation to intervention (n = 31) and control (n = 19). Residents with dementia were recruited at baseline (n = 726) and 16 months (n = 261). Clusters were not blinded to allocation. Three DCM cycles were scheduled, delivered by two trained staff per home. Cycle one was supported by an external DCM expert. Agitation (Cohen-Mansfield Agitation Inventory (CMAI)) at 16 months was the primary outcome.Results: DCM was not superior to control on any outcomes (cross-sectional sample n = 675: 287 control, 388 intervention). The adjusted mean CMAI score difference was -2.11 points (95% CI -4.66 to 0.44, p = 0.104, adjusted ICC control = 0, intervention 0.001). Sensitivity analyses supported the primary analysis. Incremental cost per unit improvement in CMAI and QALYs (intervention vs control) on closed-cohort baseline recruited sample (n = 726, 418 intervention, 308 control) was £289 and £60,627 respectively. Loss to follow-up at 16 months in the original cohort was 312/726 (43·0%) mainly (87·2%) due to deaths. Intervention dose was low with only a quarter of homes completing more than one DCM cycle.Conclusion: No benefits of DCM were evidenced. Low intervention dose indicates standard care homes may be insufficiently resourced to implement DCM. Alternative models of implementation, or other approaches to reducing agitation should be considered.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.This work was supported by the National Institute for Health Research Health Technology Assessment programme (project number 11/15/13). The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the HTA, NIHR, NHS or the Department of Health and Social Care.published version, accepted version (12 month embargo), submitted versio

The mental and physical health of older adults with a genetic predisposition for autism

Autism commonly aggregates in families, with twin studies stimating heritability to be around 80%. Subclinical autism-like characteristics have also been found at elevated rates in relatives of autistic probands. Physical and psychiatric conditions have been reported at elevated rates in autistic children and adults, and also in their relatives. However, to date there has been no exploration of how ageing may affect this pattern. This study examined cross-sectional data from the ongoing online PROTECT study. A total of 20,220 adults aged 50 years and older reported whether they have an autistic first-degree relative. In total, 739 older adults reported having an autistic first-degree relative (AFDR group) and 11,666 were identified as having no family history of any neurodevelopmental disorder (NFD group). The AFDR group demonstrated significantly higher frequencies of self-reported psychiatric diagnoses and a greater total number of co-occurring psychiatric diagnoses than the NFD group. Furthermore, the AFDR group reported elevated current self-report symptoms of depression, anxiety, traumatic experience, and post-traumatic stress than the NFD group. By contrast, few differences between AFDR and NFD groups were observed in physical health conditions, and no differences were observed in the total number of co-occurring physical health diagnoses. These findings suggest that adults who have an autistic first-degree relative may be at greater risk of poor mental, but not physical, health in later life. Older adults with autistic relatives may benefit from close monitoring to mitigate this susceptibility and to provide timely intervention

The mental and physical health profiles of older adults who endorse elevated autistic traits

Objective The mental and physical health profile of autistic people has been studied in adolescence and adulthood, with elevated rates of most conditions being reported. However, this has been little studied taking a dimensional approach to autistic traits, and in older age. Methods A total of 20,220 adults aged 50-81 years from the PROTECT study reported whether they experienced persistent socio-communicative traits characteristic of autism. Approximately 1%, 276 individuals, were identified as endorsing elevated autistic traits in childhood and currently, henceforth the ‘Autism Spectrum Trait’ (AST) group. An age and gender matched comparison group was formed of 10,495 individuals who did not endorse any autistic behavioral traits, henceforth the ‘Control Older Adults’ (COA) group. Differences between AST and COA groups were explored in self-reported psychiatric diagnoses, self-reported symptoms of current depression and anxiety, and self-reported physical health diagnoses. Associations were also examined between autistic traits and health across the whole sample. Results The AST group reported significantly elevated rates of psychiatric diagnoses compared to COAs. Additionally, the AST group showed significantly higher self-reported symptoms of current depression and anxiety than COAs. However, few differences were observed in individual physical health conditions, and no differences in total co-occurring physical diagnoses between groups. Similar associations between autistic traits and health were also found taking a dimensional approach across the whole sample. Discussion These findings suggest that older adults with elevated autistic traits may be at greater risk of poorer mental, but not physical, health in later life. Future studies should incorporate polygenic scores to elucidate the possible genetic links between propensity to autism/high autistic traits and to psychiatric conditions, and to explore whether those with elevated autistic traits experience particular barriers to mental health care

Traumatic life experiences and post-traumatic stress symptoms in middle-aged and older adults with and without autistic traits

Objectives Research with younger adults has begun to explore associations between autism/autistic traits and vulnerability to Post Traumatic Stress Disorder (PTSD). Large scale studies and/or examination of age-effects have not been conducted. Methods Adults aged 50 years+ from the PROTECT study (n = 20,220) completed items about current and childhood socio-communicative difficulties characteristic of autism. Approximately 1% (n = 251) endorsed high autistic traits, henceforth the Autism Spectrum Traits (AST) group. Differences between the AST and an age—and sex-matched “Comparison Older Adults” (COA; n = 9179) group were explored for lifetime traumatic experiences and current symptoms of PTSD, depression, and anxiety. Results Almost 30% of the AST group, compared to less than 8% of the COA, reported severe trauma in childhood/adulthood, including emotional, physical or sexual abuse. Elevated current PTSD symptoms were reported by AST compared to COA. An interaction was observed between autistic traits and trauma severity; the effect of level of trauma on PTSD symptoms was significantly greater for AST versus COA participants. This interaction remained significant when controlling for current depression and anxiety symptoms. Conclusions The findings suggest that high autistic traits may increase the likelihood of experiencing trauma across the lifespan, and the impact of severe trauma on PTSD symptoms. Older adults with high (vs. low) autistic traits may be at greater risk of experiencing PTSD symptoms in latter life. Future research should test whether the pattern of results is similar for diagnosed autistic adults

The development and use of the Assessment of Dementia Awareness and Person-centred Care Training (ADAPT) tool in long-term care

Policy and practice guidelines recommend person-centred care (PCC) to support people to live well with dementia in long-term care (LTC). Therefore, staff working in LTC settings need to be trained in dementia awareness and PCC. However, the access to, content of and reach of training across LTC settings can be varied. Data on current and ongoing access to PCC training can form and important component of data gathered on usual care (UC) in research studies, in particular clinical trials within LTC. However, no suitable assessment tools are available to measure dementia awareness and PCC training availability, content and reach. This paper describes the development of a training audit tool to meet this need for a UC measure of dementia awareness and PCC training. The ‘Assessment of Dementia Awareness and Person-centred care Training’ (ADAPT) tool was based on a review of published PCC literature and consultation with dementia and aged care experts. The ADAPT tool was piloted in 13 LTC facilities the UK and Australia, before being used to assess the content of dementia and PCC awareness training in 50 UK settings in a randomized controlled trial (RCT) as part of a UC recording. Following pilot testing, modifications to the ADAPT tool’s wording were made to enhance item clarity. When implemented in the RCT, pre-baseline training assessment data showed that the ADAPT tool was able to differentiate between LTC and identify settings where further dementia awareness training was required. ADAPT was then used as a method of recording data on dementia awareness and PCC training as part of UC data collection. The ADAPT tool is suitable for use by researchers to establish the availability, content and reach of dementia and PCC awareness training to staff within research studies

Microglial activation, tau and amyloid deposition in TREM2 p.R47H carriers and mild cognitive impairment patients: a multi-modal/multi-tracer PET/MRI imaging study with influenza vaccine immune challenge

BACKGROUND: Microglia are increasingly understood to play an important role in the pathogenesis of Alzheimer's disease. The rs75932628 (p.R47H) TREM2 variant is a well-established risk factor for Alzheimer's disease. TREM2 is a microglial cell surface receptor. In this multi-modal/multi-tracer PET/MRI study we investigated the effect of TREM2 p.R47H carrier status on microglial activation, tau and amyloid deposition, brain structure and cognitive profile. METHODS: We compared TREM2 p.R47H carriers (n = 8; median age = 62.3) and participants with mild cognitive impairment (n = 8; median age = 70.7). Participants underwent two [18F]DPA-714 PET/MRI scans to assess TSPO signal, indicative of microglial activation, before and after receiving the seasonal influenza vaccination, which was used as an immune stimulant. Participants also underwent [18F]florbetapir and [18F]AV1451 PET scans to assess amyloid and tau burden, respectively. Regional tau and TSPO signal were calculated for regions of interest linked to Braak stage. An additional comparison imaging healthy control group (n = 8; median age = 45.5) had a single [18F]DPA-714 PET/MRI. An expanded group of participants underwent neuropsychological testing, to determine if TREM2 status influenced clinical phenotype. RESULTS: Compared to participants with mild cognitive impairment, TREM2 carriers had lower TSPO signal in Braak II (P = 0.04) and Braak III (P = 0.046) regions, despite having a similar burden of tau and amyloid. There were trends to suggest reduced microglial activation following influenza vaccine in TREM2 carriers. Tau deposition in the Braak VI region was higher in TREM2 carriers (P = 0.04). Furthermore, compared to healthy controls TREM2 carriers had smaller caudate (P = 0.02), total brain (P = 0.049) and white matter volumes (P = 0.02); and neuropsychological assessment revealed worse ADAS-Cog13 (P = 0.03) and Delayed Matching to Sample (P = 0.007) scores. CONCLUSIONS: TREM2 p.R47H carriers had reduced levels of microglial activation in brain regions affected early in the Alzheimer's disease course and differences in brain structure and cognition. Changes in microglial response may underlie the increased Alzheimer's disease risk in TREM2 p.R47H carriers. Future therapeutic agents in Alzheimer's disease should aim to enhance protective microglial actions

Genetic associations with psychosis and affective disturbance in Alzheimer's disease

INTRODUCTION Individuals with Alzheimer's disease (AD) commonly experience neuropsychiatric symptoms of psychosis (AD+P) and/or affective disturbance (depression, anxiety, and/or irritability, AD+A). This study's goal was to identify the genetic architecture of AD+P and AD+A, as well as their genetically correlated phenotypes. METHODS Genome-wide association meta-analysis of 9988 AD participants from six source studies with participants characterized for AD+P AD+A, and a joint phenotype (AD+A+P). RESULTS AD+P and AD+A were genetically correlated. However, AD+P and AD+A diverged in their genetic correlations with psychiatric phenotypes in individuals without AD. AD+P was negatively genetically correlated with bipolar disorder and positively with depressive symptoms. AD+A was positively correlated with anxiety disorder and more strongly correlated than AD+P with depressive symptoms. AD+P and AD+A+P had significant estimated heritability, whereas AD+A did not. Examination of the loci most strongly associated with the three phenotypes revealed overlapping and unique associations. DISCUSSION AD+P, AD+A, and AD+A+P have both shared and divergent genetic associations pointing to the importance of incorporating genetic insights into future treatment development.publishedVersio

Evaluating the effectiveness and cost-effectiveness of Dementia Care Mapping™ to enable person-centred care for people with dementia and their carers (DCM-EPIC) in care homes: study protocol for a randomised controlled trial

Background Up to 90 % of people living with dementia in care homes experience one or more behaviours that staff may describe as challenging to support (BSC). Of these agitation is the most common and difficult to manage. The presence of agitation is associated with fewer visits from relatives, poorer quality of life and social isolation. It is recommended that agitation is treated through psychosocial interventions. Dementia Care Mapping™ (DCM™) is an established, widely used observational tool and practice development cycle, for ensuring a systematic approach to providing person-centred care. There is a body of practice-based literature and experience to suggests that DCM™ is potentially effective but limited robust evidence for its effectiveness, and no examination of its cost-effectiveness, as a UK health care intervention. Therefore, a definitive randomised controlled trial (RCT) of DCM™ in the UK is urgently needed. Methods/design A pragmatic, multi-centre, cluster-randomised controlled trial of Dementia Care Mapping (DCM™) plus Usual Care (UC) versus UC alone, where UC is the normal care delivered within the care home following a minimum level of dementia awareness training. The trial will take place in residential, nursing and dementia-specialist care homes across West Yorkshire, Oxfordshire and London, with residents with dementia. A random sample of 50 care homes will be selected within which a minimum of 750 residents will be registered. Care homes will be randomised in an allocation ratio of 3:2 to receive either intervention or control. Outcome measures will be obtained at 6 and 16 months following randomisation. The primary outcome is agitation as measured by the Cohen-Mansfield Agitation Inventory, at 16 months post randomisation. Key secondary outcomes are other BSC and quality of life. There will be an integral cost-effectiveness analysis and a process evaluation. Discussion The protocol was refined following a pilot of trial procedures. Changes include replacement of a questionnaire, whose wording caused some residents distress, to an adapted version specifically designed for use in care homes, a change to the randomisation stratification factors, adaption in how the staff measures are collected to encourage greater compliance, and additional reminders to intervention homes of when mapping cycles are due, via text message. Trial registration Current Controlled Trials ISRCTN82288852. Registered on 16 January 2014. Full protocol version and date: v7.1: 18 December 2015

Mild behavioral impairment: measurement and clinical correlates of a novel marker of preclinical Alzheimer’s disease

Abstract Background Late-life onset neuropsychiatric symptoms are established risk factors for dementia. The mild behavioral impairment (MBI) diagnostic framework was designed to standardize assessment to determine dementia risk better. In this Mini Review, we summarize the emerging clinical and biomarker evidence, which suggests that for some, MBI is a marker of preclinical Alzheimer’s disease. Main MBI is generally more common in those with greater cognitive impairment. In community and clinical samples, frequency is around 10–15%. Mounting evidence in cognitively normal samples links MBI symptoms with known AD biomarkers for amyloid, tau, and neurodegeneration, as well as AD risk genes. Clinical studies have found detectable differences in cognition associated with MBI in cognitively unimpaired people. Conclusion The emerging evidence from biomarker and clinical studies suggests MBI can be an early manifestation of underlying neurodegenerative disease. Future research must now further validate MBI to improve identification of those at the very earliest stages of disease