Cognitive and executive impairments in Parkinson's disease psychosis: a Bayesian meta-analysis.

BACKGROUND: Cognitive and executive deficits lead to worsening of quality of life and are a risk factor for developing dementia in people with Parkinson's disease (PD) with psychosis (PDP). However, which key cognitive domains are differentially affected in PDP compared with those without (PDnP), remains unclear. Here, we examined this using a Bayesian meta-analytical approach. METHODS: Searches were conducted on PubMed, Web of Science, SCOPUS, Medline and PsycINFO. Hedges' g effect-size estimates were extracted from eligible studies as a measure of standard mean differences between PDP and PDnP participants. Meta-analyses were conducted separately for each cognitive domain and subdomain, we examined the effect of age, PD medications, PD duration and severity, depression and psychosis severity for all major domains with meta-regressions. RESULTS: Effect-size estimates suggest worse performance on all major domains (k=105 studies) in PDP compared with PDnP participants, with global cognition (k=103 studies, g=-0.57), processing speed (k=29 studies, g=-0.58), executive functions (k=33, g=-0.56), episodic memory (k=30 studies, g=-0.58) and perception (k=34 studies, g=-0.55) as the most likely affected domains. Age, depression and PD duration had moderating effects on task-related performance across most of the major nine domains. CONCLUSIONS: We report extensive deficits across nine domains as well as subdomains in PD psychosis, with global cognition, processing speed and executive functions as the most likely impaired. The presence of depression may influence task-related performance in PDP, alongside age and PD duration, but not dose of dopamine replacement treatments.

Therapeutic engagement in robot-assisted psychological interventions: A systematic review.

PURPOSE: Therapeutic engagement is a key component of psychological interventions. Robot-assisted psychological interventions appear to have therapeutic benefits for service users that are challenging to engage. However, engagement with robots in robot-assisted psychological interventions is not well understood. The aim of this systematic review is to evaluate the quality of therapeutic engagement in robot-assisted psychological interventions (PROSPERO: 122437). METHODS: Scopus, Web of Science, PsycInfo and Medline were searched until 15 January 2021 for studies which quantitatively evaluated therapeutic engagement in robot-assisted psychological interventions. The Effective Public Health Practice Project (EPHPP) quality assessment tool was used to assess methodological dimensions of studies. RESULTS: 3647 studies were identified through database searching. Thirty studies (N = 1462), published between 2004 and 2020, and from 14 countries, were included. Robots were typically toy animals or humanoids and were used to provide support and improve wellbeing through social interaction. Studies primarily tested robots on older adults with dementia and children with autism and indicated positive therapeutic engagement. Twelve studies included a control group. EPHPP ratings were 'strong' (N = 1), 'moderate' (N = 10) and 'weak' (N = 19). CONCLUSIONS: Therapeutic engagement between service users and robots is generally positive. Methodological limitations of studies, such as small sample sizes, and lack of control groups and longitudinal data, mean that the field is in early stages of its development and conclusions should be drawn with caution. There are important practical and ethical implications for policymakers to consider, such as responsible clinical practice and how service users may understand the therapeutic relationship with robots.

A meta-analysis of randomised controlled trials of physical activity in people with Alzheimer's disease and mild cognitive impairment with a comparison to donepezil.

OBJECTIVES: Physical exercise may benefit people with Alzheimer's disease (AD) and mild cognitive impairment (MCI). However, randomised controlled trials (RCTs) of exercise have shown conflicting findings and it is unclear if positive outcomes are comparable to a commonly used cholinesterase inhibitor, donepezil. METHODS: Embase, Medline, PsycINFO, PsycARTICLES, SCOPUS were searched for RCTs of physical activity compared to a control condition, and donepezil compared to placebo in people with AD and MCI. Effect sizes were calculated from pre- and post-MMSE and ADAS-Cog scores and pooled using a random effects meta-analysis. RESULTS: Ninteen RCTs were included in the exercise meta-analysis (AD, N = 524; MCI, N = 1269). Physical exercise improved MMSE scores in AD (Hedges' g = 0.46) and MCI groups (g = 0.63). For the MCI group, exercise appeared to have a stronger effect for those with lower MMSE scores at baseline (p = 0.022). 18 RCTs were included in the donepezil meta-analysis (AD, N = 2984, MCI, N = 1559). In people with AD, donepezil improved cognition (MMSE g = 0.23; ADAS-Cog, g = -0.17) but there was no evidence of improved cognition in MCI. CONCLUSIONS: Physical exercise improved cognition in both AD and MCI groups. Where comparisons were possible, the effect size for physical exercise was generally comparable to donepezil. These results strengthen the evidence base for exercise as an effective intervention in AD and MCI, and future clinical trials should examine exercise type, intensity and frequency, in addition to cholinesterase inhibitors to determine the most effective interventions for AD and MCI.

Virtual reality-based assessment and treatment of social functioning impairments in psychosis: a systematic review.

People with psychosis can experience social functioning impairments. Virtual reality (VR) has been used to assess and treat these difficulties. This systematic review (Prospero CRD42015026288) provides an evaluation of these VR applications. PsycINFO, MEDLINE, Embase, Web of Science, Cochrane Library, and Scopus were searched until May 2020. The Effective Public Health Practice Project (EPHPP) Quality Assessment Tool was used to assess studies. Database searching identified 3810 titles. Fifty-eight studies (published 2005-2020; N = 2,853), comprising twenty-six head-mounted display studies (20 assessment, 6 treatment) and thirty-two immersive 2D screen studies (23 assessment, 9 treatment), were included. There were forty-eight observational studies and ten randomised controlled trials, with 1570 participants (of which, 185 were at ultra-high risk of psychosis) in VR test groups. Nearly half the studies were published since 2016. Assessments targeted cognitive and behavioural indicators of social functioning, e.g. paranoia, eye gaze, or interpersonal distance. Treatments promoted cognitive-behavioural social skills or job interview training. Studies indicate feasibility, acceptability, and effectiveness of VR for social functioning impairments in psychosis. Limitations of studies include the narrow scope of social functioning, small sample sizes, and limited randomised controlled trials and standardised interventions. Findings suggest VR has potential to be integrated with existing psychological approaches.

Virtual reality relaxation for the general population: a systematic review.

PURPOSE: Relaxation has significant restorative properties and implications for public health. However, modern, busy lives leave limiting time for relaxation. Virtual reality (VR) experiences of pleasant and calming virtual environments, accessed with a head-mounted display (HMD), appear to promote relaxation. This study aimed to provide a systematic review of feasibility, acceptability, and effectiveness of studies that use VR to promote relaxation in the general population (PROSPERO 195,804). METHODS: Web of Science, PsycINFO, Embase, and MEDLINE were searched until 29th June 2020. Studies were included in the review if they used HMD technology to present virtual environments that aimed to promote or measure relaxation, or relaxation-related variables. The Effective Public Health Practice Project (EPHPP) quality assessment tool was used to assess methodological quality of studies. RESULTS: 6403 articles were identified through database searching. Nineteen studies published between 2007 and 2020, with 1278 participants, were included in the review. Of these, thirteen were controlled studies. Studies predominantly used natural audio-visual stimuli to promote relaxation. Findings indicate feasibility, acceptability, and short-term effectiveness of VR to increase relaxation and reduce stress. Six studies received an EPHPP rating of 'strong', seven were 'moderate', and six were 'weak'. CONCLUSIONS: VR may be a useful tool to promote relaxation in the general population, especially during the COVID-19 pandemic, when stress is increasing worldwide. However, methodological limitations, such as limited randomised controlled trials and longer-term evidence, mean that these conclusions should be drawn with caution. More robust studies are needed to support this promising area of VR relaxation.

Parkinson's disease psychosis associated with accelerated multidomain cognitive decline.

BACKGROUND: Cognitive deficits are associated with poor quality of life and increased risk of development of dementia in patients with Parkinson's disease (PD) psychosis. The trajectory of cognitive decline in PD psychosis remains however unclear. OBJECTIVE: We examined this using data from the Parkinson's Progression Markers Initiative study. METHODS: We analysed data from patients with drug-naïve PD (n=676) and healthy controls (HC, n=187) over 5 years, and examined all cognitive measures assessed at each time point. We classified patients with PD into those who developed psychosis over the course of the study (PDP) and those without psychosis throughout (PDnP) using the Movement Disorders Society Unified Parkinson's Disease Rating Scale part I hallucinations/psychosis item. We used linear mixed-effect models with restricted maximum likelihood. Age, sex, ethnicity, education and neuropsychiatric and PD-specific symptoms were entered as covariates of interest. FINDINGS: There were no baseline cognitive differences between PD patient groups. There were differences in cognitive performance between PD and HC across the majority of the assessments.Patients with PDP exhibited greater cognitive decline over 5 years compared with PDnP across most domains even after controlling for sociodemographics, depression, sleepiness, rapid eye movement sleep behaviour disorder and motor symptom severity (immediate recall, b=-0.288, p=0.003; delayed recall, b=-0.146, p=0.003; global cognition, Montreal Cognitive Assessment, b=-0.206, p<0.001; visuospatial, b=-0.178, p=0.012; semantic fluency, b=-0.704, p=0.002; processing speed, b=-0.337, p=0.029). CONCLUSIONS: Patients with PD psychosis exhibited decline in semantic aspects of language, processing speed, global cognition, visuospatial abilities and memory, regardless of sociodemographic characteristics, neuropsychiatric and motor symptoms. These cognitive domains, particularly semantic aspects of language may therefore play an important role in PD psychosis and warrant further investigation. TRIAL REGISTRATION NUMBER: NCT01141023.

Grey matter volume loss in Parkinson's disease psychosis and its relationship with serotonergic gene expression: A meta-analysis.

BACKGROUND: Neuroanatomical alterations underlying psychosis in Parkinson's Disease (PDP) remain unclear. We carried out a meta-analysis of MRI studies investigating the neural correlates of PDP and examined its relation with dopaminergic and serotonergic receptor gene expression. METHODS: PubMed, Web of Science and Embase were searched for MRI studies (k studies = 10) of PDP compared to PD patients without psychosis (PDnP). Seed-based d Mapping with Permutation of Subject Images and multiple linear regression analyses was used to examine the relationship between pooled estimates of grey matter volume (GMV) loss in PDP and D1/D2 and 5-HT1a/5-HT2a receptor gene expression estimates from Allen Human Brain Atlas. RESULTS: We observed lower grey matter volume in parietal-temporo-occipital regions (PDP n = 211, PDnP, n = 298). GMV loss in PDP was associated with local expression of 5-HT1a (b = 0.109, p = 0.012) and 5-HT2a receptors (b= -0.106, p = 0.002) but not dopaminergic receptors. CONCLUSION: Widespread GMV loss in the parieto-temporo-occipital regions may underlie PDP. Association between grey matter volume and local expression of serotonergic receptor genes may suggest a role for serotonergic receptors in PDP.

Safety and Tolerability of Natural and Synthetic Cannabinoids in Older Adults: A Systematic Review and Meta-Analysis of Open-Label Trials and Observational Studies.

BACKGROUND AND OBJECTIVE: Although cannabinoid-based medications are increasingly used by older adults, their safety and tolerability in this age group remain unclear. The purpose of this systematic review was to examine the safety and tolerability of cannabinoid-based medications by conducting a meta-analysis of open-label observational studies of cannabinoid-based medications for all indications in individuals with a mean age of ≥50 years. METHODS: A systematic search was conducted on PubMed, PsycINFO, MEDLINE, EMBASE and CINHAL. Study quality was assessed using an adapted version of the Grading of Recommendations Assessment, Development and Evaluation criteria and Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed. We included studies that (a) were published from 1990 onwards; (b) included older adults (mean age ≥50 years); and (c) provided data on the safety and tolerability of medical cannabinoids. Data were pooled using a random-effects approach. Risk of adverse events, serious adverse events and withdrawals was computed as the incidence rate (IR). Separate analyses were conducted by the cannabinoid-based medication used, for delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD) and a combination of THC and CBD (THC:CBD). RESULTS: Thirty-eight studies were identified (THC = 23; CBD = 6; THC:CBD = 9; N = 2341, mean age: 63.19 ± 8.08 years, men: 53.86%). THC had a very low incidence of all-cause and treatment-related adverse events (IR: 122.18, 95% confidence interval [CI] 38.23-253.56; IR: 84.76, 95% CI 0.13-326.01, respectively) and negligible serious adverse events (IR = 0). Similar IRs for CBD (all cause, IR: 111.91, 95% CI 1.24-495.93; treatment related, IR: 1.76, 95% CI 4.63-23.05) and no serious adverse events (IR = 0). CBD was not associated with a risk of treatment-related withdrawals. THC had a low risk of all-cause and treatment-related withdrawals (IR: 25.18, 95% CI 12.35-42.52; IR: 7.83, 95% CI 3.26-14.38, respectively). The THC:CBD treatment had a low risk of all-cause and treatment-related adverse events (IR: 100.72, 95% CI 0.25-383.00; IR: 55.38, 95% CI 8.61-142.80, respectively), but reported a risk of all-cause and treatment-related serious adverse events (IR: 21.32, 95% CI 0.18-93.26; IR: 3.71, 95% CI 0.21-11.56, respectively), and all-cause and treatment-related withdrawals (IR: 78.63, 95% CI 17.43-183.90; IR: 34.31, 95% CI 6.09-85.52, respectively). Significant heterogeneity (I2 >55%) was present in most analyses. CONCLUSIONS: Although cannabinoid-based medications were generally safe and acceptable to adults aged over 50 years, these estimates are limited by the lack of a control condition and considerable heterogeneity. Nevertheless, they complement and are consistent with comparable evidence from randomised controlled trials.

The relationship between alexithymia and theory of mind: A systematic review.

Theory of Mind (ToM), the ability to represent the mental states of oneself and others, is an essential social skill disrupted across many psychiatric conditions. The transdiagnostic nature of ToM impairment means it is plausible that ToM impairment is related to alexithymia (difficulties identifying and describing one's own emotions), as alexithymia is seen across psychiatric conditions. Whilst many studies have examined links between alexithymia and ToM, results are mixed. Therefore, the purpose of this systematic review is to provide a taxonomy of ToM tests and assess their relationship with alexithymia. Tests are grouped according to whether they assess propensity to engage spontaneously in ToM or accuracy of ToM inferences, with tests further subdivided into those that do, and do not, require emotion recognition. A review of 63 suitable studies suggests that alexithymia is often associated with reduced ToM, and inaccurate ToM when tasks require emotion recognition. This latter finding appears due to impaired emotion recognition, rather than ToM impairment per se. Further directions and considerations for future research are discussed.