Perspectives on the diagnosis and management of functional cognitive disorder: An international Delphi study.

BACKGROUND: Current proposed criteria for functional cognitive disorder (FCD) have not been externally validated. We sought to analyse the current perspectives of cognitive specialists in the diagnosis and management of FCD in comparison with neurodegenerative conditions. METHODS: International experts in cognitive disorders were invited to assess seven illustrative clinical vignettes containing history and bedside characteristics alone. Participants assigned a probable diagnosis and selected the appropriate investigation and treatment. Qualitative, quantitative and inter-rater agreement analyses were undertaken. RESULTS: Eighteen diagnostic terminologies were assigned by 45 cognitive experts from 12 countries with a median of 13 years of experience, across the seven scenarios. Accurate discrimination between FCD and neurodegeneration was observed, independently of background and years of experience: 100% of the neurodegenerative vignettes were correctly classified and 75%-88% of the FCD diagnoses were attributed to non-neurodegenerative causes. There was <50% agreement in the terminology used for FCD, in comparison with 87%-92% agreement for neurodegenerative syndromes. Blood tests and neuropsychological evaluation were the leading diagnostic modalities for FCD. Diagnostic communication, psychotherapy and psychiatry referral were the main suggested management strategies in FCD. CONCLUSIONS: Our study demonstrates the feasibility of distinguishing between FCD and neurodegeneration based on relevant patient characteristics and history details. These characteristics need further validation and operationalisation. Heterogeneous labelling and framing pose clinical and research challenges reflecting a lack of agreement in the field. Careful consideration of FCD diagnosis is advised, particularly in the presence of comorbidities. This study informs future research on diagnostic tools and evidence-based interventions.

Structural and Functional Imaging Correlates of Visual Hallucinations in Parkinson's Disease.

PURPOSE OF REVIEW: To review recent structural and functional MRI studies of visual hallucinations in Parkinson's disease. RECENT FINDINGS: Previously, neuroimaging had shown inconsistent findings in patients with Parkinson's hallucinations, especially in studies examining grey matter volume. However, recent advances in structural and functional MRI techniques allow better estimates of structural connections, as well as the direction of connectivity in functional MRI. These provide more sensitive measures of changes in structural connectivity and allow models of the changes in directional functional connectivity to be tested. We identified 27 relevant studies and found that grey matter imaging continues to show heterogeneous findings in Parkinson's patients with visual hallucinations. Newer approaches in diffusion imaging and functional MRI are consistent with emerging models of Parkinson's hallucinations, suggesting shifts in attentional networks. In particular, reduced bottom-up, incoming sensory information, and over-weighting of top-down signals appear to be important drivers of visual hallucinations in Parkinson's disease.

Functional cognitive disorder: dementia's blind spot.

An increasing proportion of cognitive difficulties are recognized to have a functional cause, the chief clinical indicator of which is internal inconsistency. When these symptoms are impairing or distressing, and not better explained by other disorders, this can be conceptualized as a cognitive variant of functional neurological disorder, termed functional cognitive disorder (FCD). FCD is likely very common in clinical practice but may be under-diagnosed. Clinicians in many settings make liberal use of the descriptive term mild cognitive impairment (MCI) for those with cognitive difficulties not impairing enough to qualify as dementia. However, MCI is an aetiology-neutral description, which therefore includes patients with a wide range of underlying causes. Consequently, a proportion of MCI cases are due to non-neurodegenerative processes, including FCD. Indeed, significant numbers of patients diagnosed with MCI do not 'convert' to dementia. The lack of diagnostic specificity for MCI 'non-progressors' is a weakness inherent in framing MCI primarily within a deterministic neurodegenerative pathway. It is recognized that depression, anxiety and behavioural changes can represent a prodrome to neurodegeneration; empirical data are required to explore whether the same might hold for subsets of individuals with FCD. Clinicians and researchers can improve study efficacy and patient outcomes by viewing MCI as a descriptive term with a wide differential diagnosis, including potentially reversible components such as FCD. We present a preliminary definition of functional neurological disorder-cognitive subtype, explain its position in relation to other cognitive diagnoses and emerging biomarkers, highlight clinical features that can lead to positive diagnosis (as opposed to a diagnosis of exclusion), and red flags that should prompt consideration of alternative diagnoses. In the research setting, positive identifiers of FCD will enhance our recognition of individuals who are not in a neurodegenerative prodrome, while greater use of this diagnosis in clinical practice will facilitate personalized interventions.

Impact of the COVID-19 pandemic on older adults mental health services: A mixed methods study.

OBJECTIVES: The COVID-19 pandemic has had a significant impact on older adults mental health care. Our study aimed to explore staff perspectives on key challenges and innovations in order to help inform the delivery of older adults mental health care in subsequent waves of the pandemic. METHODS: A mixed methods online questionnaire developed by National Institute for Health Research Mental Health Policy Research Unit was used to gather staff perspectives on their challenges at work, problems faced by service users and their carers, and sources of help and support. Descriptive statistics were used for quantitative analysis and descriptive content analysis for qualitative analysis. RESULTS: 158 participants, working in either community or inpatient settings, and from a range of professional disciplines, were included. For inpatient staff, a significant challenge was infection control. In the community, staff identified a lack of access to physical and social care as well as reduced contact with friends and families as being challenges for patients. Remote working was seen as a positive innovation along with COVID-19 related guidance from various sources and peer support. CONCLUSION: Our study, with a focus on staff and patient well-being, helps to inform service development for future waves of the pandemic. We discuss measures to improve infection control in inpatient settings, the role of voluntary organisations in supporting socially isolated community patients, the need for better integration of physical and mental health services at an organisational level, and the importance of training staff to support patients and their families with end of life planning.

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.

Improving Conversations about Parkinson's Dementia.

BACKGROUND: People with Parkinson's disease (PD) have an increased risk of dementia, yet patients and clinicians frequently avoid talking about it due to associated stigma, and the perception that "nothing can be done about it". However, open conversations about PD dementia may allow people with the condition to access treatment and support, and may increase participation in research aimed at understanding PD dementia. OBJECTIVES: To co-produce information resources for patients and healthcare professionals to improve conversations about PD dementia. METHODS: We worked with people with PD, engagement experts, artists, and a PD charity to open up these conversations. 34 participants (16 PD; 6 PD dementia; 1 Parkinsonism, 11 caregivers) attended creative workshops to examine fears about PD dementia and develop information resources. 25 PD experts contributed to the resources. RESULTS: While most people with PD (70%) and caregivers (81%) shared worries about cognitive changes prior to the workshops, only 38% and 30%, respectively, had raised these concerns with a healthcare professional. 91% of people with PD and 73% of caregivers agreed that PD clinicians should ask about cognitive changes routinely through direct questions and perform cognitive tests at clinic appointments. We used insights from the creative workshops, and input from a network of PD experts to co-develop two open-access resources: one for people with PD and their families, and one for healthcare professionals. CONCLUSION: Using artistic and creative workshops, co-learning and striving for diverse voices, we co-produced relevant resources for a wider audience to improve conversations about PD dementia.

Paranoid and misidentification subtypes of psychosis in dementia.

This study aimed to review the neurobiological and neuropsychological correlates of paranoid (persecutory delusions) and misidentification (misidentification delusions and/or hallucinations) subtypes of psychosis in dementia, to establish if they represent distinct subphenotypes. Nine studies were eligible, all included patients with Alzheimer's disease. Greater global cognitive deficits and an accelerated global cognitive decline were observed in the misidentification subtype. Neuroimaging studies showed more marked volume loss in multiple regions in patients with the misidentification subtype, including those involved in object recognition and the processing of information on spatial and temporal context. A single study found greater impairment in visual sustained attention and object recognition in the misidentification subtype. The small number of studies and methodological heterogeneity limit interpretation of the findings. Nevertheless, these findings would tentatively suggest that there may be additional or accelerated pathological change in functional networks involved in visuoperceptual processing in the misidentification subtype. This should be further explored in prospective studies and the investigation extended to other forms of dementia, to gain a transdiagnostic perspective.

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.

Acute mental health presentations before and during the COVID-19 pandemic.

BACKGROUND: A number of community based surveys have identified an increase in psychological symptoms and distress but there has been no examination of symptoms at the more severe end of the mental health spectrum. AIMS: We aimed to analyse numbers and types of psychiatric presentations to inform planning for future demand on mental health services in light of the COVID-19 pandemic. METHOD: We analysed electronic data between January and April 2020 for 2534 patients referred to acute psychiatric services, and tested for differences in patient demographics, symptom severity and use of the Mental Health Act 1983 (MHA), before and after lockdown. We used interrupted time-series analyses to compare trends in emergency department and psychiatric presentations until December 2020. RESULTS: There were 22% fewer psychiatric presentations the first week and 48% fewer emergency department presentations in the first month after lockdown initiated. A higher proportion of patients were detained under the MHA (22.2 v. 16.1%) and Mental Capacity Act 2005 (2.2 v. 1.1%) (χ2(2) = 16.3, P < 0.0001), and they experienced a longer duration of symptoms before seeking help from mental health services (χ2(3) = 18.6, P < 0.0001). A higher proportion of patients presented with psychotic symptoms (23.3 v. 17.0%) or delirium (7.0 v. 3.6%), and fewer had self-harm behaviour (43.8 v. 52.0%, χ2(7) = 28.7, P < 0.0001). A higher proportion were admitted to psychiatric in-patient units (22.2 v. 18.3%) (χ2(6) = 42.8, P < 0.0001) after lockdown. CONCLUSIONS: UK lockdown resulted in fewer psychiatric presentations, but those who presented were more likely to have severe symptoms, be detained under the MHA and be admitted to hospital. Psychiatric services should ensure provision of care for these patients as well as planning for those affected by future COVID-19 waves.

What are the neural correlates of meta-cognition and anosognosia in Alzheimer's disease? A systematic review.

Awareness of one's own cognitive processes (metacognition) or of one's own illness or deficits (anosognosia) can be impaired in people with Alzheimer's disease (AD). The neural correlates of anosognosia within AD remain inconclusive. Understanding anosognosia is of importance because of its impact on carer burden and increased institutionalization. A systematic review of structural and functional neuroimaging studies was conducted to identify specific brain regions associated with anosognosia within AD. Thirty-two studies were included in the systematic review. Reduced gray matter density, cerebral blood flow, and hypometabolism in 8 key regions were significantly associated with increased anosognosia scores in people with AD. The most frequently associated regions were the inferior frontal gyrus, anterior cingulate cortex, and medial temporal lobe. Other key regions include the superior frontal gyrus, medial frontal gyrus, orbitofrontal cortex, posterior cingulate cortex, and the insula. Identifying brain regions associated with anosognosia can aid understanding and identification of anosognosia in people with AD and potentially facilitate improvements in care.

Effect of computerised cognitive training on cognitive outcomes in mild cognitive impairment: a systematic review and meta-analysis.

OBJECTIVES: To determine the effect of computerised cognitive training (CCT) on improving cognitive function for older adults with mild cognitive impairment (MCI). DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Embase, Web of Science and the Cochrane Library were searched through January 2018. ELIGIBILITY CRITERIA: Randomised controlled trials comparing CCT with control conditions in those with MCI aged 55+ were included. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted data and assessed the risk of bias. Effect sizes (Hedges' g and 95% CIs) were calculated and random-effects meta-analyses were performed where three or more studies investigated a comparable intervention and outcome. Heterogeneity was quantified using the I2 statistic. RESULTS: 18 studies met the inclusion criteria and were included in the analyses, involving 690 participants. Meta-analysis revealed small to moderate positive treatment effects compared with control interventions in four domains as follows: global cognitive function (g=0.23, 95% CI 0.03 to 0.44), memory (g=0.30, 95% CI 0.11 to 0.50), working memory (g=0.39, 95% CI 0.12 to 0.66) and executive function (g=0.20, 95% CI -0.03 to 0.43). Statistical significance was reached in all domains apart from executive function. CONCLUSIONS: This meta-analysis provides evidence that CCT improves cognitive function in older people with MCI. However, the long-term transfer of these improvements and the potential to reduce dementia prevalence remains unknown. Various methodological issues such as heterogeneity in outcome measures, interventions and MCI symptoms and lack of intention-to-treat analyses limit the quality of the literature and represent areas for future research.

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.

Mutations in the Gabrb1 gene promote alcohol consumption through increased tonic inhibition.

Alcohol dependence is a common, complex and debilitating disorder with genetic and environmental influences. Here we show that alcohol consumption increases following mutations to the γ-aminobutyric acidA receptor (GABAAR) ß1 subunit gene (Gabrb1). Using N-ethyl-N-nitrosourea mutagenesis on an alcohol-averse background (F1 BALB/cAnN x C3H/HeH), we develop a mouse model exhibiting strong heritable preference for ethanol resulting from a dominant mutation (L285R) in Gabrb1. The mutation causes spontaneous GABA ion channel opening and increases GABA sensitivity of recombinant GABAARs, coupled to increased tonic currents in the nucleus accumbens, a region long-associated with alcohol reward. Mutant mice work harder to obtain ethanol, and are more sensitive to alcohol intoxication. Another spontaneous mutation (P228H) in Gabrb1 also causes high ethanol consumption accompanied by spontaneous GABA ion channel opening and increased accumbal tonic current. Our results provide a new and important link between GABAAR function and increased alcohol consumption that could underlie some forms of alcohol abuse.

Esophageal adenocarcinoma versus squamous cell carcinoma: retrospective hospital-based analysis of a 12-year temporal trend.

There is a paucity of literature from the Indian subcontinent looking at the prevalence of esophageal cancer by histological type. In our study, we ascertained the relative proportion and location of adenocarcinoma (AC) and squamous cell carcinoma (SCC) of the esophagus at a referral hospital in Mumbai, India over a 12-year period to assess whether a time-trend existed. A retrospective analysis was carried out on patients who were diagnosed with and/or treated for esophageal cancer at the P D Hinduja Hospital and Research Centre in Mumbai between January 1, 2000 and December 31, 2011. Data were procured from histopathology and oncology registers of the institute, the database of the Gastroenterology consultants, the Endoscopy Department records and from the Medical Records Department. Of the 445 cases of esophageal cancer with known histology, 104 (23 %) were AC and 314 (71 %) were SCC. Over the 12-year period, the proportions of AC compared to SCC did not show a statistically significant temporal change (p = 0.145). AC comprised nearly a quarter of esophageal carcinoma in Mumbai. There has been no significant change in the number and proportion of AC and SCC in the 12-year period.

PCR negative cerebral malaria in a traveller returning from Mumbai.

The incidence of imported malaria to the UK is significant. The authors report a case of a healthy young man diagnosed with PCR negative cerebral malaria, a week after returning from Mumbai. The patient presented with acute confusion and vomiting. His condition deteriorated quickly warranting intubation, ventilation and transfer to intensive therapy unit. Extensive investigation did not find an underlying cause. Antimalarial treatment was initiated based on clinical suspicion despite a negative malarial screen. A rapid response to treatment followed such that the patient was extubated within 24 h. This case highlights the need for the UK Health Protection Agency to review its risk classification of malaria for travellers to Mumbai. Additionally, clinicians should promptly initiate antimalarial treatment in an unwell traveller returning from an endemic area when there is a high clinical suspicion even in the absence of a positive initial malaria screen.