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.

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).

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).

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.

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 older people with treatment-resistant generalised anxiety disorder: the FACTOID feasibility study.

BACKGROUND: Generalised anxiety disorder, characterised by excessive anxiety and worry, is the most common anxiety disorder among older people. It is a condition that may persist for decades and is associated with numerous negative outcomes. Front-line treatments include pharmacological and psychological therapy, but many older people do not find these treatments effective. Guidance on managing treatment-resistant generalised anxiety disorder in older people is lacking. OBJECTIVES: To assess whether or not a study to examine the clinical effectiveness and cost-effectiveness of acceptance and commitment therapy for older people with treatment-resistant generalised anxiety disorder is feasible, we developed an intervention based on acceptance and commitment therapy for this population, assessed its acceptability and feasibility in an uncontrolled feasibility study and clarified key study design parameters. DESIGN: Phase 1 involved qualitative interviews to develop and optimise an intervention as well as a survey of service users and clinicians to clarify usual care. Phase 2 involved an uncontrolled feasibility study and qualitative interviews to refine the intervention. SETTING: Participants were recruited from general practices, Improving Access to Psychological Therapies services, Community Mental Health Teams and the community. PARTICIPANTS: Participants were people aged ≥ 65 years with treatment-resistant generalised anxiety disorder. INTERVENTION: Participants received up to 16 one-to-one sessions of acceptance and commitment therapy, adapted for older people with treatment-resistant generalised anxiety disorder, in addition to usual care. Sessions were delivered by therapists based in primary and secondary care services, either in the clinic or at participants' homes. Sessions were weekly for the first 14 sessions and fortnightly thereafter. MAIN OUTCOME MEASURES: The co-primary outcome measures for phase 2 were acceptability (session attendance and satisfaction with therapy) and feasibility (recruitment and retention). Secondary outcome measures included additional measures of acceptability and feasibility and self-reported measures of anxiety, worry, depression and psychological flexibility. Self-reported outcomes were assessed at 0 weeks (baseline) and 20 weeks (follow-up). Health economic outcomes included intervention and resource use costs and health-related quality of life. RESULTS: Fifteen older people with treatment-resistant generalised anxiety disorder participated in phase 1 and 37 participated in phase 2. A high level of feasibility was demonstrated by a recruitment rate of 93% and a retention rate of 81%. A high level of acceptability was found with respect to session attendance (70% of participants attended ≥ 10 sessions) and satisfaction with therapy was adequate (60% of participants scored ≥ 21 out of 30 points on the Satisfaction with Therapy subscale of the Satisfaction with Therapy and Therapist Scale-Revised, although 80% of participants had not finished receiving therapy at the time of rating). Secondary outcome measures and qualitative data further supported the feasibility and acceptability of the intervention. Health economic data supported the feasibility of examining cost-effectiveness in a future randomised controlled trial. Although the study was not powered to examine clinical effectiveness, there was indicative evidence of improvements in scores for anxiety, depression and psychological flexibility. LIMITATIONS: Non-specific therapeutic factors were not controlled for, and recruitment in phase 2 was limited to London. CONCLUSIONS: There was evidence of high levels of feasibility and acceptability and indicative evidence of improvements in symptoms of anxiety, depression and psychological flexibility. The results of this study suggest that a larger-scale randomised controlled trial would be feasible to conduct and is warranted. TRIAL REGISTRATION: Current Controlled Trials ISRCTN12268776. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 54. See the NIHR Journals Library website for further project information.

Generalised anxiety disorder, characterised by a tendency to worry, is the most common anxiety disorder among older people. Those with this condition may experience other difficulties, including increased distress and disability, poorer coping and reduced quality of life. Medication and talking therapy are usually offered as forms of treatment, but many do not find them helpful. Guidance is lacking on how to help older people manage generalised anxiety disorder when it does not respond to such treatments. We developed a 16-session intervention specifically for older people with treatment-resistant generalised anxiety disorder. This was based on acceptance and commitment therapy: a form of talking therapy that helps people to learn how to best live with distressing experiences while still doing things that really matter to them. It may be particularly suited to older people because many older people experience difficulties with chronic ill health and other problems that cannot be easily improved with conventional talking therapies. We developed our intervention by asking 15 older people about their experiences of treatment-resistant generalised anxiety disorder and treatments they have received for it, as well as what might help or hinder their engagement with talking therapy. We combined their guidance with advice from 36 clinicians to ensure that our intervention was tailored to the needs of this population. We then asked the same 15 older people, our Service User Advisory Group and academic clinicians about how we could optimise our intervention. We also conducted an online survey of service users and clinicians to clarify what care older people with generalised anxiety disorder are typically offered and receive. We tested how acceptable our intervention was to 37 older people with treatment-resistant generalised anxiety disorder, and how feasible it was to deliver within the NHS. We found evidence that it was acceptable to participants, that it could be delivered within the NHS and that its value for money could be tested in a larger study. We also found evidence suggestive of improvements in anxiety, depression and coping. There were some limitations of our study. However, overall, our results suggest that we should conduct a larger study to find out whether or not our intervention is helpful for older people with treatment-resistant generalised anxiety 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.

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.

Endocannabinoid system alterations in Alzheimer's disease: A systematic review of human studies.

Studies investigating alterations of the endocannabinoid system (ECS) in Alzheimer's disease (AD) in humans have reported inconsistent findings so far. We performed a systematic review of studies examining alterations of the ECS specifically within humans with AD or mild cognitive impairment (MCI), including neuroimaging studies, studies of serum and cerebrospinal fluid biomarkers, and post-mortem studies. We attempted to identify reported changes in the expression and activity of: cannabinoid receptors 1 and 2; anandamide (AEA); 2-arachidonoylglycerol (2-AG); monoacylglycerol lipase (MAGL); fatty acid amide hydrolase (FAAH); and transient receptor potential cation channel V1 (TRPV1). Twenty-two studies were identified for inclusion. Mixed findings were reported for most aspects of the ECS in AD, making it difficult to identify a particular profile of ECS alterations characterising AD. The included studies tended to be small, methodologically heterogeneous, and frequently did not control for important potential confounders, such as pathological progression of AD. Eight studies correlated ECS alterations with neuropsychometric performance measures, though studies infrequently examined behavioural and neuropsychiatric correlates. PROSPERO database identifier: CRD42018096249.

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.

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.

Multicomponent Frailty Assessment Tools for Older People with Psychiatric Disorders: A Systematic Review.

OBJECTIVE: To review evidence evaluating the use of multicomponent frailty assessment tools in assessing frailty in older adults with psychiatric disorders. METHODS: A systematic literature review was conducted to identify all multicomponent frailty assessment tools (ie, a tool that assesses two or more indicators of frailty). The items of each frailty assessment tool were compared with Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) diagnostic criteria for psychiatric disorders to assess construct overlap. Studies conducted in community, inpatient, and outpatient clinical settings were considered for inclusion. PARTICIPANTS: Adults aged 60 years or older. RESULTS: A total of 5639 records were identified following the removal of duplicates, from which 95 studies were included for review. Of the 48 multicomponent frailty assessment tools identified, no tool had been developed for, or validated in, older adult populations with a psychiatric disorder. Overall, 20 of 48 frailty assessment tools contained a psychological assessment domain, with 17 of 48 tools citing the presence of depressed mood and/or anxiety as a frailty indicator. Common areas of construct overlap in frailty assessment tools and DSM-5 diagnostic criteria included weight loss (29 of 48) and fatigue (21 of 48). CONCLUSIONS: Significant construct overlap exists between the indicators of frailty as conceptualized in existing frailty assessment tools and DSM-5 diagnostic criteria for common psychiatric disorders including major depressive episode and generalized anxiety disorder that has the potential to confound frailty assessment results. Further research is necessary to establish a reliable and valid tool to assess frailty in this population. J Am Geriatr Soc 67:1085-1095, 2019.

Interventions for subjective cognitive decline: systematic review and meta-analysis.

OBJECTIVES: This review provides a broad overview of the effectiveness of interventions for subjective cognitive decline (SCD) in improving psychological well-being, metacognition and objective cognitive performance. METHODS: Databases including PubMed, Web of Science and Cochrane Systematic Reviews were searched up to August 2017 to identify randomised controlled trials evaluating interventions for SCD. Interventions were categorised as psychological, cognitive, lifestyle or pharmacological. Outcomes of interest included psychological well-being, metacognitive ability and objective cognitive performance. To assess the risk of bias, three authors independently rated study validity using criteria based on the Critical Appraisal Skills Programme. Random-effects meta-analyses were undertaken where three or more studies investigated similar interventions and reported comparable outcomes. RESULTS: Twenty studies met inclusion criteria and 16 had sufficient data for inclusion in the meta-analyses. Of these, only seven were rated as being high quality. Group psychological interventions significantly improved psychological well-being (g=0.40, 95% CI 0.03 to 0.76; p=0.03) but the improvement they conferred on metacognitive ability was not statistically significant (g=0.26, 95% CI -0.22 to 0.73; p=0.28). Overall, cognitive training interventions led to a small, statistically significant improvement in objective cognitive performance (g=0.13, 95% CI 0.01 to 0.25; p=0.03). However, the pooled effect sizes of studies using active control groups (g=0.02, 95% CI -0.19 to 0.22; p=0.85) or reporting global cognitive measures (g=0.06, 95% CI -0.19 to 0.31; p=0.66) were non-significant. CONCLUSIONS: There is a lack of high-quality research in this field. Group psychological interventions improve psychological well-being and may also improve metacognition. A large, high-quality study is indicated to investigate this further. There is no evidence to suggest that cognitive interventions improve global cognitive performance and the clinical utility of small improvements in specific cognitive domains is questionable. There is a lack of research considering lifestyle interventions and poor quality evidence for pharmacological interventions. PROSPERO REGISTRATION NUMBER: CRD42017079391.

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 neurochemistry of agitation in Alzheimer's disease: a systematic review.

OBJECTIVE: To provide an up-to-date systematic review of the characteristics, methodology and findings of studies that have investigated the neurochemistry of agitation in Alzheimer's disease (AD). METHODS: Electronic databases were searched for published peer-reviewed articles which provided data on any neurotransmitter system in relation to agitation in AD. Screening of titles and abstracts and data extraction from full texts were conducted in duplicate. RESULTS: Forty-five studies were included. Monoamines (serotonin, dopamine and noradrenaline) were most commonly investigated. A variety of methods were used to investigate the neurochemistry underlying agitation in AD and, although there were several conflicting findings, there was evidence of serotonergic deficit, relatively preserved dopaminergic function and compensatory overactivity of postsynaptic noradrenergic neurons in agitation in AD. CONCLUSIONS: Disruption of the dynamic balance between multiple neurotransmitter systems could impair functional neural networks involved in affective regulation and executive function. Differences in study design and methodology may have contributed to conflicting findings. Future studies that overcome these limitations (e.g. using standardized criteria to define agitation) and employ neuroimaging methods such as MRI/PET to investigate specific neural networks are needed to clarify the role of neurotransmitter alterations in these patients.

Predictors of treatment outcome in depression in later life: A systematic review and meta-analysis.

BACKGROUND: Predictor analyses of late-life depression can be used to identify variables associated with outcomes of treatments, and hence ways of tailoring specific treatments to patients. The aim of this review was to systematically identify, review and meta-analyse predictors of outcomes of any type of treatment for late-life depression. METHODS: Pubmed, Embase, CINAHL, Web of Science and PsycINFO were searched for studies published up to December 2016. Primary and secondary studies reported treatment predictors from randomised controlled trials of any treatment for patients with major depressive disorder aged over 60 were included. Treatment outcomes included response, remission and change in depression score. RESULTS: Sixty-seven studies met the inclusion criteria. Of 65 identified statistically significant predictors, only 7 were reported in at least 3 studies. Of these, 5 were included in meta-analyses, and only 3 were statistically significant. Most studies were rated as being of moderate to strong quality and satisfied key quality criteria for predictor analyses. LIMITATIONS: The searches were limited to randomised controlled trials and most of the included studies were secondary analyses. CONCLUSIONS: Baseline depression severity, co-morbid anxiety, executive dysfunction, current episode duration, early improvement, physical illnesses and age were reported as statistically significant predictors of treatment outcomes. Only the first three were significant in meta-analyses. Subgroup analyses showed differences in predictor effect between biological and psychosocial treatment. However, high heterogeneity and small study numbers suggest a cautious interpretation of results. These predictors were associated with various mechanisms including brain pathophysiology, perceived social support and proposed distinct types of depressive disorder. Further investigation of the clinical utility of these predictors is suggested.