Acceptance and Commitment Therapy plus usual care for improving quality of life in people with motor neuron disease (COMMEND): a multicentre, parallel, randomised controlled trial in the UK.

BACKGROUND: Motor neuron disease is a progressive, fatal neurodegenerative disease for which there is no cure. Acceptance and Commitment Therapy (ACT) is a psychological therapy incorporating acceptance, mindfulness, and behaviour change techniques. We aimed to evaluate the effectiveness of ACT plus usual care, compared with usual care alone, for improving quality of life in people with motor neuron disease. METHODS: We conducted a parallel, multicentre, two-arm randomised controlled trial in 16 UK motor neuron disease care centres or clinics. Eligible participants were aged 18 years or older with a diagnosis of definite or laboratory-supported probable, clinically probable, or possible familial or sporadic amyotrophic lateral sclerosis; progressive muscular atrophy; or primary lateral sclerosis; which met the World Federation of Neurology's El Escorial diagnostic criteria. Participants were randomly assigned (1:1) to receive up to eight sessions of ACT adapted for people with motor neuron disease plus usual care or usual care alone by a web-based system, stratified by site. Participants were followed up at 6 months and 9 months post-randomisation. Outcome assessors and trial statisticians were masked to treatment allocation. The primary outcome was quality of life using the McGill Quality of Life Questionnaire-Revised (MQOL-R) at 6 months post-randomisation. Primary analyses were multi-level modelling and modified intention to treat among participants with available data. This trial was pre-registered with the ISRCTN Registry (ISRCTN12655391). FINDINGS: Between Sept 18, 2019, and Aug 31, 2022, 435 people with motor neuron disease were approached for the study, of whom 206 (47%) were assessed for eligibility, and 191 were recruited. 97 (51%) participants were randomly assigned to ACT plus usual care and 94 (49%) were assigned to usual care alone. 80 (42%) of 191 participants were female and 111 (58%) were male, and the mean age was 63·1 years (SD 11·0). 155 (81%) participants had primary outcome data at 6 months post-randomisation. After controlling for baseline scores, age, sex, and therapist clustering, ACT plus usual care was superior to usual care alone for quality of life at 6 months (adjusted mean difference on the MQOL-R of 0·66 [95% CI 0·22-1·10]; d=0·46 [0·16-0·77]; p=0·0031). Moderate effect sizes were clinically meaningful. 75 adverse events were reported, 38 of which were serious, but no adverse events were deemed to be associated with the intervention. INTERPRETATION: ACT plus usual care is clinically effective for maintaining or improving quality of life in people with motor neuron disease. As further evidence emerges confirming these findings, health-care providers should consider how access to ACT, adapted for the specific needs of people with motor neuron disease, could be provided within motor neuron disease clinical services. FUNDING: National Institute for Health and Care Research Health Technology Assessment and Motor Neurone Disease Association.

Cost-effectiveness of acceptance and commitment therapy for people living with motor neuron disease, and their health-related quality of life.

BACKGROUND: Given the degenerative nature of the condition, people living with motor neuron disease (MND) experience high levels of psychological distress. The purpose of this research was to investigate the cost-effectiveness of acceptance and commitment therapy (ACT), adapted for the specific needs of this population, for improving quality of life. METHODS: A trial-based cost-utility analysis over a 9-month period was conducted comparing ACT plus usual care (n = 97) versus usual care alone (n = 94) from the perspective of the National Health Service. In the primary analysis, quality-adjusted life years (QALYs) were computed using health utilities generated from the EQ-5D-5L questionnaire. Sensitivity analyses and subgroup analyses were also carried out. RESULTS: Difference in costs was statistically significant between the two arms, driven mainly by the intervention costs. Effects measured by EQ-5D-5L were not statistically significantly different between the two arms. The incremental cost-effectiveness was above the £20,000 to £30,000 per QALY gained threshold used in the UK. However, the difference in effects was statistically significant when measured by the McGill Quality of Life-Revised (MQOL-R) questionnaire. The intervention was cost-effective in a subgroup experiencing medium deterioration in motor neuron symptoms. CONCLUSIONS: Despite the intervention being cost-ineffective in the primary analysis, the significant difference in the effects measured by MQOL-R, the low costs of the intervention, the results in the subgroup analysis, and the fact that ACT was shown to improve the quality of life for people living with MND, suggest that ACT could be incorporated into MND clinical services.

A randomised controlled trial of acceptance and commitment therapy plus usual care compared to usual care alone for improving psychological health in people with motor neuron disease (COMMEND): study protocol.

BACKGROUND: Motor neuron disease (MND) is a rapidly progressive, fatal neurodegenerative disease that predominantly affects motor neurons from the motor cortex to the spinal cord and causes progressive wasting and weakening of bulbar, limb, abdominal and thoracic muscles. Prognosis is poor and median survival is 2-3 years following symptom onset. Psychological distress is relatively common in people living with MND. However, formal psychotherapy is not routinely part of standard care within MND Care Centres/clinics in the UK, and clear evidence-based guidance on improving the psychological health of people living with MND is lacking. Previous research suggests that Acceptance and Commitment Therapy (ACT) may be particularly suitable for people living with MND and may help improve their psychological health. AIMS: To assess the clinical and cost-effectiveness of ACT modified for MND plus usual multidisciplinary care (UC) in comparison to UC alone for improving psychological health in people living with MND. METHODS: The COMMEND trial is a multi-centre, assessor-blind, parallel, two-arm RCT with a 10-month internal pilot phase. 188 individuals aged ≥ 18 years with a diagnosis of definite, laboratory-supported probable, clinically probable, or possible familial or sporadic amyotrophic lateral sclerosis, and additionally the progressive muscular atrophy and primary lateral sclerosis variants, will be recruited from approximately 14 UK-based MND Care Centres/clinics and via self-referral. Participants will be randomly allocated to receive up to eight 1:1 sessions of ACT plus UC or UC alone by an online randomisation system. Participants will complete outcome measures at baseline and at 6- and 9-months post-randomisation. The primary outcome will be quality of life at six months. Secondary outcomes will include depression, anxiety, psychological flexibility, health-related quality of life, adverse events, ALS functioning, survival at nine months, satisfaction with therapy, resource use and quality-adjusted life years. Primary analyses will be by intention to treat and data will be analysed using multi-level modelling. DISCUSSION: This trial will provide definitive evidence on the clinical and cost-effectiveness of ACT plus UC in comparison to UC alone for improving psychological health in people living with MND. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN12655391. Registered 17 July 2017, https://www.isrctn.com/ISRCTN12655391 . PROTOCOL VERSION: 3.1 (10/06/2020).

Assessing frailty indicators in the context of psychiatric disorder: A Delphi consensus study.

OBJECTIVES: Substantial construct overlap exists between indicators of frailty and symptoms of some psychiatric disorders. This study aimed to gain consensus of expert academic opinion on the potential impact of psychiatric illness on frailty assessment and how best to conceptualise and measure frailty indicators in the context of psychiatric symptoms. DESIGN: A classic Delphi approach was employed across two studies to achieve consensus: The first-round questionnaire consisted of open-ended questions, analysed through content analysis. The results informed the development of statements for participants to rate their agreement with in subsequent Delphi rounds. Statements with ≥66% agreement were accepted. Delphi Study 1 recruited experts in frailty assessment (n = 13) and Delphi Study 2 recruited experts in frailty and psychiatric disorder (n = 8). Experts were recruited globally. RESULTS: Overall, 40% of Delphi Study 1 statements and 43% of Delphi Study 2 statements were accepted. Primarily, consensus was reached for statements concerning the influence of depression/anxiety on frailty assessment and potential methods of conceptualising and measuring frailty indicators in the context of psychiatric symptoms. Little consensus was reached concerning the ease and importance of differentiating between frailty indicators and psychiatric assessment criteria with substantial overlap. CONCLUSIONS: The Delphi studies provide a novel exploration and consensus of expert academic opinions concerning the assessment of frailty indicators in the context of psychiatric symptoms. The results will inform future research into the adaptation or development of a frailty assessment tool specifically for use in older adult psychiatric populations.

Acceptance and commitment therapy for late-life treatment-resistant generalised anxiety disorder: a feasibility study.

BACKGROUND: Generalised anxiety disorder (GAD) is the most common anxiety disorder in older people. First-line management includes pharmacological and psychological therapies, but many do not find these effective or acceptable. Little is known about how to manage treatment-resistant generalised anxiety disorder (TR-GAD) in older people. OBJECTIVES: To examine the acceptability, feasibility and preliminary estimates of the effectiveness of acceptance and commitment therapy (ACT) for older people with TR-GAD. PARTICIPANTS: People aged ≥65 years with TR-GAD (defined as not responding to GAD treatment, tolerate it or refused treatment) recruited from primary and secondary care services and the community. INTERVENTION: Participants received up to 16 one-to-one sessions of ACT, developed specifically for older people with TR-GAD, in addition to usual care. MEASUREMENTS: Co-primary outcomes were feasibility (defined as recruitment of ≥32 participants and retention of ≥60% at follow-up) and acceptability (defined as participants attending ≥10 sessions and scoring ≥21/30 on the satisfaction with therapy subscale). Secondary outcomes included measures of anxiety, worry, depression and psychological flexibility (assessed at 0 and 20 weeks). RESULTS: Thirty-seven participants were recruited, 30 (81%) were retained and 26 (70%) attended ≥10 sessions. A total of 18/30 (60%) participants scored ≥21/30 on the satisfaction with therapy subscale. There was preliminary evidence suggesting that ACT may improve anxiety, depression and psychological flexibility. CONCLUSIONS: There was evidence of good feasibility and acceptability, although satisfaction with therapy scores suggested that further refinement of the intervention may be necessary. Results indicate that a larger-scale randomised controlled trial of ACT for TR-GAD is feasible and warranted.

Optimising the acceptability and feasibility of acceptance and commitment therapy for treatment-resistant generalised anxiety disorder in older adults.

BACKGROUND: generalised anxiety disorder (GAD) is common in later life with a prevalence of 3-12%. Many only partially respond to cognitive behavioural therapy or pharmacotherapy and can be classified as treatment resistant. These patients experience poor quality of life, and are at increased risk of comorbid depression, falls and loneliness. Acceptance and commitment therapy (ACT) is an emerging therapy, which may be particularly suited to this population, but has not been tailored to their needs. OBJECTIVES: to optimise the acceptability and feasibility of ACT for older adults with treatment-resistant GAD. DESIGN: a person-based approach to ground the adapted ACT intervention in the perspectives and lives of those who will use it. METHODS: first, we conducted qualitative interviews with 15 older adults with GAD and 36 healthcare professionals to develop guiding principles to inform the intervention. Second, we consulted service users and clinical experts and interviewed the same 15 older adults using 'think aloud' techniques to enhance its acceptability and feasibility. RESULTS: in Stage 1, older adults' concerns and needs were categorised in four themes: 'Expert in one's own condition', 'Deep seated coping strategies', 'Expert in therapy' and 'Support with implementation'. In Stage 2, implications for therapy were identified that included an early focus on values and ACT as a collaborative partnership, examining beliefs around 'self as worrier' and the role of avoidance, validating and accommodating individuals' knowledge and experience and compensating for age-related cognitive changes. DISCUSSION: Our systematic approach combined rigour and transparency to develop a therapeutic intervention tailored to the specific needs of older adults with treatment-resistant GAD.

Clinical presentation and neuropsychological profiles of Functional Cognitive Disorder patients with and without co-morbid depression.

INTRODUCTION: Functional Cognitive Disorder (FCD) is poorly understood. We sought to better characterise FCD in order to inform future diagnostic criteria and evidence based treatments. Additionally, we compared FCD patients with and without co-morbid depression, including their neuropsychological profiles, to determine whether these two disorders are distinct. METHODS: 47 FCD patients (55% female, mean age: 52 years) attending a tertiary neuropsychiatric clinic over a one year period were included. We evaluated sociodemographic characteristics and clinical features including presentation, medications, the presence and nature of co-morbid psychiatric or physical illnesses, and the results of neuropsychometric testing. RESULTS: 23/47 (49%) patients had co-morbid depression. Six had cognitive difficulties greater than expected from their co-morbid conditions suggesting "functional overlay". 34 patients had formal neuropsychological testing; 12 demonstrated less than full subjective effort. 16/22 (73%) of the remaining patients had non-specific cognitive impairment in at least one domain. There were no significant differences between those with and without co-morbid depression. CONCLUSIONS: Our study informs future diagnostic criteria. For example, they should not exclude patients with co-morbid psychiatric illness or abnormal neuropsychometric testing and clinicians should remain open to the possibility of "functional overlay". Furthermore, FCD and depression are distinct disorders that can exist co-morbidly.

Metacognition in functional cognitive disorder- a potential mechanism and treatment target.

Introduction: Functional Cognitive Disorder (FCD) is common. Despite this, there is no evidence-based consensus on how to treat FCD. Poor metacognitive ability has been suggested as a key mechanism underlying the disorder. This paper evaluates the proposal that strategies which improve metacognition could provide a mechanistically plausible translational therapy. Methods: We reviewed the existing literature relating to metacognition in FCD, previous strategies to improve metacognitive ability in FCD and whether metacognitive performance can be modulated. Results: Though limited, there is evidence to suggest that metacognition is impaired in FCD. Converging evidence from neuroimaging studies suggests that metacognitive performance can be modulated. The effectiveness of existing strategies to improve metacognition including cognitive training, psychoeducation and lifestyle interventions have been equivocal. Recently, a potential treatment option has emerged in the form of a computer-based metacognitive training paradigm. Conclusions: There is an urgent need for effective treatments in FCD. Impaired metacognition may be a plausible therapeutic target but, in the first instance, further research is required to demonstrate deficits in "local" metacognitive ability in FCD patients when measured objectively. If so, clinical trials of interventions, such as computerised metacognitive training, are required to evaluate their effectiveness in improving FCD symptoms.

TNF alpha inhibitors in Alzheimer's disease: A systematic review.

OBJECTIVES: The objective of this study was to evaluate the effect of tumour necrosis factor-alpha inhibitors (TNF-αI) on Alzheimer's disease-associated pathology. DESIGN: A literature search of PubMed, Embase, PsychINFO, Web of Science, Scopus, and the Cochrane Library databases for human and animal studies that evaluated the use of TNF-αI was performed on 26 October 2016. RESULTS: The main outcomes assessed were cognition and behaviour, reduction in brain tissue mass, presence of plaques and tangles, and synaptic function. Risk of bias was assessed regarding blinding, statistical model, outcome reporting, and other biases. Sixteen studies were included, 13 of which were animal studies and 3 of which were human. All animal studies found that treatment with TNF-αI leads to an improvement in cognition and behaviour. None of the studies measured change in brain tissue mass. The majority of studies documented a beneficial effect in other areas, including the presence of plaques and tangles and synaptic function. The amount of data from human studies was limited. Two out of 3 studies concluded that TNF-αI are beneficial in Alzheimer's disease patients, with one being an observational study and the latter being a small pilot study, with a high risk of bias. CONCLUSION: It was concluded that a large-scale randomized controlled trial assessing the effectiveness of TNF-αI on humans is warranted.

The importance of sustained attention in early Alzheimer's disease.

INTRODUCTION: There is conflicting evidence regarding impairment of sustained attention in early Alzheimer's disease (AD). We examine whether sustained attention is impaired and predicts deficits in other cognitive domains in early AD. METHODS: Fifty-one patients with early AD (MMSE > 18) and 15 healthy elderly controls were recruited. The sustained attention to response task (SART) was used to assess sustained attention. A subset of 25 patients also performed tasks assessing general cognitive function (ADAS-Cog), episodic memory (Logical memory scale, Paired Associates Learning), executive function (verbal fluency, grammatical reasoning) and working memory (digit and spatial span). RESULTS: AD patients were significantly impaired on the SART compared to healthy controls (total error ß = 19.75, p = 0.027). SART errors significantly correlated with MMSE score (Spearman's rho = -0.338, p = 0.015) and significantly predicted deficits in ADAS-Cog (ß = 0.14, p = 0.004). DISCUSSIONS: Patients with early AD have significant deficits in sustained attention, as measured using the SART. This may impair performance on general cognitive testing, and therefore should be taken into account during clinical assessment, and everyday management of individuals with early AD. Copyright © 2016 John Wiley & Sons, Ltd.

Tests of pattern separation and pattern completion in humans-A systematic review.

To systematically review the characteristics, validity and outcome measures of tasks that have been described in the literature as assessing pattern separation and pattern completion in humans. Electronic databases were searched for articles. Parameters for task validity were obtained from two reviews that described optimal task design factors to evaluate pattern separation and pattern completion processes. These were that pattern separation should be tested during an encoding task using abstract, never-before-seen visual stimuli, and pattern completion during a retrieval task using partial cues; parametric alteration of the degree of interference of stimuli or degradation of cues should be used to generate a corresponding gradient in behavioral output; studies should explicitly identify the specific memory domain under investigation (sensory/perceptual, temporal, spatial, affect, response, or language) and account for the contribution of other potential attributes involved in performance of the task. A systematic, qualitative assessment of validity in relation to these parameters was performed, along with a review of general validity and task outcome measures. Sixty-two studies were included. The majority of studies investigated pattern separation and most tasks were performed on young, healthy adults. Pattern separation and pattern completion were most frequently tested during a retrieval task using familiar or recognizable visual stimuli and cues. Not all studies parametrically altered the degree of stimulus interference or cue degradation, or controlled for potential confounding factors. This review found evidence that some of the parameters for task validity have been followed in some human studies of pattern separation and pattern completion, but no study was judged to have adequately met all the parameters for task validity. The contribution of these parameters and other task design factors towards an optimal behavioral paradigm is discussed and recommendations for future research are made. © 2015 Wiley Periodicals, Inc.

Putting brain training to the test.

'Brain training', or the goal of improved cognitive function through the regular use of computerized tests, is a multimillion-pound industry, yet in our view scientific evidence to support its efficacy is lacking. Modest effects have been reported in some studies of older individuals and preschool children, and video-game players outperform non-players on some tests of visual attention. However, the widely held belief that commercially available computerized brain-training programs improve general cognitive function in the wider population in our opinion lacks empirical support. The central question is not whether performance on cognitive tests can be improved by training, but rather, whether those benefits transfer to other untrained tasks or lead to any general improvement in the level of cognitive functioning. Here we report the results of a six-week online study in which 11,430 participants trained several times each week on cognitive tasks designed to improve reasoning, memory, planning, visuospatial skills and attention. Although improvements were observed in every one of the cognitive tasks that were trained, no evidence was found for transfer effects to untrained tasks, even when those tasks were cognitively closely related.

Psychometric properties of multicomponent tools designed to assess frailty in older adults: A systematic review.

BACKGROUND: Frailty is widely recognised as a distinct multifactorial clinical syndrome that implies vulnerability. The links between frailty and adverse outcomes such as death and institutionalisation have been widely evidenced. There is currently no gold standard frailty assessment tool; optimizing the assessment of frailty in older people therefore remains a research priority. The objective of this systematic review is to identify existing multi-component frailty assessment tools that were specifically developed to assess frailty in adults aged ≥60 years old and to systematically and critically evaluate the reliability and validity of these tools. METHODS: A systematic literature review was conducted using the standardised COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist to assess the methodological quality of included studies. RESULTS: Five thousand sixty-three studies were identified in total: 73 of which were included for review. 38 multi-component frailty assessment tools were identified: Reliability and validity data were available for 21 % (8/38) of tools. Only 5 % (2/38) of the frailty assessment tools had evidence of reliability and validity that was within statistically significant parameters and of fair-excellent methodological quality (the Frailty Index-Comprehensive Geriatric Assessment [FI-CGA] and the Tilburg Frailty Indicator [TFI]). CONCLUSIONS: The TFI has the most robust evidence of reliability and validity and has been the most extensively examined in terms of psychometric properties. However, there is insufficient evidence at present to determine the best tool for use in research and clinical practice. Further in-depth evaluation of the psychometric properties of these tools is required before they can fulfil the criteria for a gold standard assessment tool.

Cognitive phenotype of psychotic symptoms in Alzheimer's disease: evidence for impaired visuoperceptual function in the misidentification subtype.

BACKGROUND: Establishing the cognitive phenotype of psychotic symptoms in Alzheimer's disease (AD) could localise discrete pathology and target symptomatic treatment. This study aimed to establish whether psychotic symptoms would be associated with poorer performance on neuropsychological tests known to correlate with striatal dopaminergic function and to investigate whether these differences would be attributed to the paranoid (persecutory delusions) or misidentification (misidentification phenomena +/- hallucinations) subtype. METHODS: Seventy patients with probable AD (34 psychotic and 36 nonpsychotic) were recruited to the study. Analysis of covariance was used to compare motor speed and the rapid visual processing test of sustained visual attention, after adjusting for potential confounding factors. Multivariate analyses were used to compare performance across other cognitive domains. Significant findings were explored by separating patients on the basis of subtype. RESULTS: Rapid visual processing performance accuracy was reduced in patients with psychotic symptoms (F1,58 = 5.94, p = 0.02) and differed significantly across subtypes (F2,51 = 3.94, p = 0.03), largely because of poorer performance in the misidentification compared with nonpsychotic group. Multivariate analyses (corrected for multiple comparisons) showed poorer performance on the incomplete letters task in psychotic patients (F1,63 = 8.77, p = 0.004) and across subtypes (F2,55 = 10.90, p < 0.001), similarly attributed to the misidentification subtype. CONCLUSIONS: These findings provide further support of the involvement of dopaminergic networks in the psychosis endophenotype in AD and, in addition, implicate the ventral (temporo-occipital) pathway in the misidentification subtype. Future studies should investigate the early trajectory of neuropathological change in vivo across psychosis subtypes.

Interventions for reducing benzodiazepine use in older people: meta-analysis of randomised controlled trials.

BACKGROUND: The use of benzodiazepines has been advised against in older people, but prevalence rates remain high. AIMS: To review the evidence for interventions aimed at reducing benzodiazepine use in older people. METHOD: We conducted a systematic review, assessment of risk of bias and meta-analyses of randomised controlled trials of benzodiazepine withdrawal and prescribing interventions. RESULTS: Ten withdrawal and eight prescribing studies met the inclusion criteria. At post-intervention, significantly higher odds of not using benzodiazepines were found with supervised withdrawal with psychotherapy (odds ratio (OR) = 5.06, 95% CI 2.68-9.57, P<0.00001) and withdrawal with prescribing interventions (OR = 1.43, 95% CI 1.02-2.02, P = 0.04) in comparison with the control interventions treatment as usual (TAU), education placebo, withdrawal with or without drug placebo, or psychotherapy alone. Significantly higher odds of not using benzodiazepines were also found for multifaceted prescribing interventions (OR = 1.37, 95% CI 1.10-1.72, P = 0.006) in comparison with control interventions (TAU and prescribing placebo). CONCLUSIONS: Supervised benzodiazepine withdrawal augmented with psychotherapy should be considered in older people, although pragmatic reasons may necessitate consideration of other strategies such as medication review.

Acceptance and Commitment Therapy for people living with motor neuron disease: an uncontrolled feasibility study.

BACKGROUND: Motor neuron disease (MND) is a fatal, progressive neurodegenerative disease that causes progressive weakening and wasting of limb, bulbar, thoracic and abdominal muscles. Clear evidence-based guidance on how psychological distress should be managed in people living with MND (plwMND) is lacking. Acceptance and Commitment Therapy (ACT) is a form of psychological therapy that may be particularly suitable for this population. However, to the authors' knowledge, no study to date has evaluated ACT for plwMND. Consequently, the primary aim of this uncontrolled feasibility study was to examine the feasibility and acceptability of ACT for improving the psychological health of plwMND. METHODS: PlwMND aged ≥ 18 years were recruited from 10 UK MND Care Centres/Clinics. Participants received up to 8 one-to-one ACT sessions, developed specifically for plwMND, plus usual care. Co-primary feasibility and acceptability outcomes were uptake (≥ 80% of the target sample [N = 28] recruited) and initial engagement with the intervention (≥ 70% completing ≥ 2 sessions). Secondary outcomes included measures of quality of life, anxiety, depression, disease-related functioning, health status and psychological flexibility in plwMND and quality of life and burden in caregivers. Outcomes were assessed at baseline and 6 months. RESULTS: Both a priori indicators of success were met: 29 plwMND (104%) were recruited and 76% (22/29) attended ≥ 2 sessions. Attrition at 6-months was higher than anticipated (8/29, 28%), but only two dropouts were due to lack of acceptability of the intervention. Acceptability was further supported by good satisfaction with therapy and session attendance. Data were possibly suggestive of small improvements in anxiety and psychological quality of life from baseline to 6 months in plwMND, despite a small but expected deterioration in disease-related functioning and health status. CONCLUSIONS: There was good evidence of acceptability and feasibility. Limitations included the lack of a control group and small sample size, which complicate interpretation of findings. A fully powered RCT to evaluate the clinical and cost-effectiveness of ACT for plwMND is underway. TRIAL REGISTRATION: The study was pre-registered with the ISRCTN Registry (ISRCTN12655391).

Improving the measurement of QALYs in dementia: developing patient- and carer-reported health state classification systems using Rasch analysis.

OBJECTIVES: Cost-utility analysis is increasingly used to inform resource allocation. This requires a means of valuing health states before and after intervention. Although generic measures are typically used to generate values, these do not perform well with people with dementia. We report the development of a health state classification system amenable to valuation for use in studies of dementia, derived from the DEMQOL system, measure of health-related quality of life in dementia by patient self-report (DEMQOL) and carer proxy-report (DEMQOL-Proxy). METHODS: Factor analysis was used to determine the dimensional structure of DEMQOL and DEMQOL-Proxy. Rasch analysis was subsequently used to investigate item performance across factors in terms of item-level ordering, functioning across subgroups, model fit, and severity-range coverage. This enabled the selection of one item from each factor for the classification system. A sample of people with a diagnosis of mild/moderate dementia (n = 644) and a sample of carers of those with mild/moderate dementia (n = 683) were used. RESULTS: Factor analysis found different five-factor solutions for DEMQOL and DEMQOL-Proxy. Following item reduction and selection by using Rasch analysis, a five-dimension classification for DEMQOL and a four-dimension classification for DEMQOL-Proxy were developed. Each item contained four health state levels. CONCLUSION: Combining Rasch and classical psychometric analysis is a valid method of selecting items for dementia health state classifications from both the patient and carer perspectives. The next stage is to obtain preference weights so that the measure can be used in the economic evaluation of treatment, care, and support arrangements for dementia.

Metacognition in functional cognitive disorder.

Functional cognitive disorder is common but underlying mechanisms remain poorly understood. Metacognition, an individual's ability to reflect on and monitor cognitive processes, is likely to be relevant. Local metacognition refers to an ability to estimate confidence in cognitive performance on a moment-to-moment basis, whereas global metacognition refers to long-run self-evaluations of overall performance. Using a novel protocol comprising task-based measures and hierarchical Bayesian modelling, we compared local and global metacognitive performance in individuals with functional cognitive disorder. Eighteen participants with functional cognitive disorder (mean age = 49.2 years, 10 males) were recruited to this cross-sectional study. Participants completed computerized tasks that enabled local metacognitive efficiency for perception and memory to be measured using the hierarchical meta-d' model within a signal detection theory framework. Participants also completed the Multifactorial Memory Questionnaire measuring global metacognition, and questionnaires measuring anxiety and depression. Estimates of local metacognitive efficiency were compared with those estimated from two control groups who had undergone comparable metacognitive tasks. Global metacognition scores were compared with the existing normative data. A hierarchical regression model was used to evaluate associations between global metacognition, depression and anxiety and local metacognitive efficiency, whilst simple linear regressions were used to evaluate whether affective symptomatology and local metacognitive confidence were associated with global metacognition. Participants with functional cognitive disorder had intact local metacognition for perception and memory when compared with controls, with the 95% highest density intervals for metacognitive efficiency overlapping with the two control groups in both cognitive domains. Functional cognitive disorder participants had significantly lower global metacognition scores compared with normative data; Multifactorial Memory Questionnaire-Ability subscale (t = 6.54, P < 0.0001) and Multifactorial Memory Questionnaire-Satisfaction subscale (t = 5.04, P < 0.0001). Mood scores, global metacognitive measures and metacognitive bias were not significantly associated with local metacognitive efficiency. Local metacognitive bias [ß = -0.20 (SE = 0.09), q = 0.01] and higher depression scores as measured by the Patient Health Questionnaire-9 [ß = -1.40 (SE = 2.56), q = 0.01] were associated with the lower global metacognition scores. We show that local metacognition is intact, whilst global metacognition is impaired, in functional cognitive disorder, suggesting a decoupling between the two metacognitive processes. In a Bayesian model, an aberrant prior (impaired global metacognition), may override bottom-up sensory input (intact local metacognition), giving rise to the subjective experience of abnormal cognitive processing. Future work should further investigate the interplay between local and global metacognition in functional cognitive disorder.

COVID-19 Deaths in the United States: Shifts in Hot Spots over the Three Phases of the Pandemic and the Spatiotemporally Varying Impact of Pandemic Vulnerability.

The geographic areas most impacted by COVID-19 may not remain static because public health measures/behaviors change dynamically, and the impacts of pandemic vulnerability also may vary geographically and temporally. The nature of the pandemic makes spatiotemporal methods essential to understanding the distribution of COVID-19 deaths and developing interventions. This study examines the spatiotemporal trends in COVID-19 death rates in the United States from March 2020 to May 2021 by performing an emerging hot spot analysis (EHSA). It then investigates the effects of the COVID-19 time-dependent and basic social vulnerability factors on COVID-19 death rates using geographically and temporally weighted regression (GTWR). The EHSA results demonstrate that over the three phases of the pandemic (first wave, second wave, and post-vaccine deployment), hot spots have shifted from densely populated cities and the states with a high percentage of socially vulnerable individuals to the states with relatively relaxed social distancing requirements, and then to the states with low vaccination rates. The GTWR results suggest that local infection and testing rates, social distancing interventions, and other social, environmental, and health risk factors show significant associations with COVID-19 death rates, but these associations vary over time and space. These findings can inform public health planning.