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.

Brain Networks, Neurotransmitters and Psychedelics: Towards a Neurochemistry of Self-Awareness.

PURPOSE OF REVIEW: Self-awareness can be defined as the capacity of becoming the object of one's own awareness and, increasingly, it has been the target of scientific inquiry. Self-awareness has important clinical implications, and a better understanding of the neurochemical basis of self-awareness may help clarifying causes and developing interventions for different psychopathological conditions. The current article explores the relationship between neurochemistry and self-awareness, with special attention to the effects of psychedelics. RECENT FINDINGS: The functioning of self-related networks, such as the default-mode network and the salience network, and how these are influenced by different neurotransmitters is discussed. The impact of psychedelics on self-awareness is reviewed in relation to specific processes, such as interoception, body ownership, agency, metacognition, emotional regulation and autobiographical memory, within a framework based on predictive coding. Improved outcomes in emotional regulation and autobiographical memory have been observed in association with the use of psychedelics, suggesting higher-order self-awareness changes, which can be modulated by relaxation of priors and improved coping mechanisms linked to cognitive flexibility. Alterations in bodily self-awareness are less consistent, being potentially impacted by doses employed, differences in acute/long-term effects and the presence of clinical conditions. Future studies investigating the effects of different molecules in rebalancing connectivity between resting-state networks may lead to novel therapeutic approaches and the refinement of existing treatments.

Neural markers of reduced arousal and consciousness in mild cognitive impairment.

OBJECTIVES: People with Alzheimer's Disease (AD) experience changes in their level and content of consciousness, but there is little research on biomarkers of consciousness in pre-clinical AD and Mild Cognitive Impairment (MCI). This study investigated whether levels of consciousness are decreased in people with MCI. METHODS: A multi-site site magnetoencephalography (MEG) dataset, BIOFIND, comprising 83 people with MCI and 83 age matched controls, was analysed. Arousal (and drowsiness) was assessed by computing the theta-alpha ratio (TAR). The Lempel-Ziv algorithm (LZ) was used to quantify the information content of brain activity, with higher LZ values indicating greater complexity and potentially a higher level of consciousness. RESULTS: LZ was lower in the MCI group versus controls, indicating a reduced level of consciousness in MCI. TAR was higher in the MCI group versus controls, indicating a reduced level of arousal (i.e. increased drowsiness) in MCI. LZ was also found to be correlated with mini-mental state examination (MMSE) scores, suggesting an association between cognitive impairment and level of consciousness in people with MCI. CONCLUSIONS: A decline in consciousness and arousal can be seen in MCI. As cognitive impairment worsens, measured by MMSE scores, levels of consciousness and arousal decrease. These findings highlight how monitoring consciousness using biomarkers could help understand and manage impairments found at the preclinical stages of AD. Further research is needed to explore markers of consciousness between people who progress from MCI to dementia and those who do not, and in people with moderate and severe AD, to promote person-centred care.

Social relationships and depression during the COVID-19 lockdown: longitudinal analysis of the COVID-19 Social Study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic led to measures that reduced social contact and support. We explored whether UK residents with more frequent or supportive social contact had fewer depressive symptoms during March-August 2020, and potential factors moderating the relationship. METHODS: A convenience sample of UK dwelling participants aged ⩾18 in the internet-based longitudinal COVID-19 Social Study completed up to 22 weekly questionnaires about face-to-face and phone/video social contact frequency, perceived social support, and depressive symptoms using the PHQ-9. Mixed linear models examined associations between social contact and support, and depressive symptoms. We examined for interaction by empathic concern, perspective taking and pre-COVID social contact frequency. RESULTS: In 71 117 people with mean age 49 years (standard deviation 15), those with high perceived social support scored 1.836 (1.801-1.871) points lower on PHQ-9 than those with low support. Daily face-to-face or phone/video contact was associated with lower depressive symptoms (0.258 (95% confidence interval 0.225-0.290) and 0.117 (0.080-0.154), respectively) compared to no contact. The negative association between social relationships and depressive symptoms was stronger for those with high empathic concern, perspective taking and usual sociability. CONCLUSIONS: We found during lockdown that those with higher quality or more face-to-face or phone/video contact had fewer depressive symptoms. Contact quality was more strongly associated than quantity. People who were usually more sociable or had higher empathy had more depressive symptoms during enforced reduced contact. The results have implications for COVID-19 and potential future pandemic management, and for understanding the relationship between social factors and mental health.

Self-awareness in Dementia: a Taxonomy of Processes, Overview of Findings, and Integrative Framework.

PURPOSE OF REVIEW: Self-awareness, the capacity of becoming the object of one's own awareness, has been a frontier of knowledge, but only recently scientific approaches to the theme have advanced. Self-awareness has important clinical implications, and a finer understanding of this concept may improve the clinical management of people with dementia. The current article aims to explore self-awareness, from a neurobiological perspective, in dementia. RECENT FINDINGS: A taxonomy of self-awareness processes is presented, discussing how these can be structured across different levels of cognitive complexity. Findings on self-awareness in dementia are reviewed, indicating the relative preservation of capacities such as body ownership and agency, despite impairments in higher-level cognitive processes, such as autobiographical memory and emotional regulation. An integrative framework, based on predictive coding and compensatory abilities linked to the resilience of self-awareness in dementia, is discussed, highlighting possible avenues for future research into the topic.

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.

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.

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.

"Falling through the cracks"; Stakeholders' views around the concept and diagnosis of mild cognitive impairment and their understanding of dementia prevention.

OBJECTIVES: Many people live with an awareness of mild cognitive changes that increase their dementia risk. Previous authors describe the uncertainties of this liminal state, between cognitive health and dementia, where being "at risk" can itself be an illness. We ask how services respond to people with memory concerns currently, and how a future, effective and inclusive dementia prevention intervention might be structured for people with memory concerns. METHODS/DESIGN: We conducted qualitative interviews with 18 people aged 60+ years with subjective or objective memory problems, six family members, 10 health and social care professionals and 11 third sector workers. Interviews were audio-recorded, transcribed and analysed using an inductive thematic approach. RESULTS: Three main themes were identified: (1) acknowledging the liminal state, compounded by current, discordant health service responses: medicalising memory concerns yet situating responsibilities for their management with patients and families; (2) enabling change in challenging contexts of physical and cognitive frailty and social disengagement and (3) building on existing values, cultures and routines. CONCLUSIONS: Effective dementia prevention must empower individuals to make lifestyle changes within challenging contexts. Programmes must be evidence based yet sufficiently flexible to allow new activities to be fitted into people's current lives; and mindful of the risks of pathologising memory concerns. Most current memory services are neither commissioned, financially or clinically resourced to support people with memory concerns without dementia. Effective, large scale dementia prevention will require a broad societal response.

APPLE-Tree (Active Prevention in People at risk of dementia: Lifestyle, bEhaviour change and Technology to REducE cognitive and functional decline) programme: Protocol.

BACKGROUND: Observational studies indicate that approximately a third of dementia cases are attributable to modifiable cardiometabolic, physical and mental health, and social and lifestyle risk factors. There is evidence that intensive behaviour change interventions targeting these factors can reduce cognitive decline. [Figure: see text] METHODS AND ANALYSIS: We will design and test a low intensity, secondary dementia-prevention programme (Active Prevention in People at risk of dementia: Lifestyle, bEhaviour change and Technology to REducE cognitive and functional decline, "APPLE-Tree") to slow cognitive decline in people with subjective cognitive decline with or without objective cognitive impairment. We will embed our work within social science research to understand how dementia prevention is currently delivered and structured. We will carry out systematic reviews and around 50 qualitative interviews with stakeholders, using findings to coproduce the APPLE-Tree intervention. We plan a 10-session group intervention, involving personalised goal-setting, with individual sessions for those unable or unwilling to attend groups, delivered by psychology assistants who will be trained and supervised by clinical psychologists. The coproduction group (including public and patient involvement [PPI], academic and clinical/third-sector professional representatives) will use the Behaviour Change Wheel theoretical framework to develop it. We will recruit and randomly allocate 704 participants, 1:1 to the intervention: informational control group. This sample size is sufficient to detect a between-group difference at 2 years of 0.15 on the primary outcome (cognition: modified neuropsychological test battery; 90% power, 5% significance, effect size 0.25, SD 0.6). DISSEMINATION: We will work with Public Health England and third-sector partners to produce an effective national implementation approach, so that if our intervention works, it is used in practice.

High-speed range and velocity measurement using frequency scanning interferometry with adaptive delay lines [Invited].

Range (i.e., absolute distance), displacement, and velocity of a moving target have been measured with a frequency scanning interferometer that incorporates a 100,000scans-1 vertical-cavity surface-emitting laser with 100 nm tuning range. An adaptive delay line in the reference beam, consisting of a chain of switchable exponentially growing optical delays, reduced modulation frequencies to sub-gigahertz levels. Range, displacement, and velocity were determined from the phase of the interference signal; fine alignment and linearization of the scans were achieved from the interferogram of an independent reference interferometer. Sub-nanometer displacement resolution, sub-100-nm range resolution, and velocity resolution of 12µms-1 have been demonstrated over a depth measurement range of 300 mm.

Investigating the relationship between age of onset of depressive disorder and cognitive function.

OBJECTIVES: Depressive disorder is commonly associated with impaired cognitive function; however, it is unclear whether the age of onset of the first episode of depression, current depression severity, or historical severity of depressive episodes are associated with cognitive performance. METHODS: This study examined baseline cross-sectional data from the ongoing online PROTECT study. A total of 7344 participants, 50 years or older, with a history of depression and no diagnosis of dementia were divided into three groups according to age of onset of their first depressive episode: early-onset, midlife-onset, and late-onset. Performance on measures of visuospatial episodic memory, executive function, verbal working, and visual working memory were evaluated. Demographic and clinical characteristics such as age, education, and severity of symptoms during their worst previous depressive episode and current depression severity were included in multivariate regression models. RESULTS: The late-onset depression group scored significantly lower on the verbal reasoning task than the early-onset group while there were no significant differences found on the other tasks. Midlife-onset depression participants performed better in the visual episodic memory task, but worse on the verbal reasoning task, than early-onset depression participants. Current depression severity was negatively correlated with all four cognitive domains, while historical severity score was found to be significantly associated with cognitive performance on the verbal reasoning and spatial working memory tasks. CONCLUSIONS: The most important indicator of cognitive performance in depression appears to be current, rather than historic depression severity; however, late-onset depression may be associated with more executive impairment than an early-onset depression.

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.

Single-shot areal profilometry using hyperspectral interferometry with a microlens array.

We describe a single-shot technique to measure areal profiles on optically smooth and stepped surfaces for applications where rapid data acquisition in non-cooperative environments is essential. It is based on hyperspectral interferometry (HSI), a technique in which the output of a white-light interferometer provides the input to a hyperspectral imaging system. Previous HSI implementations suffered from inefficient utilisation of the available pixels which limited the number of measured coordinates and/or unambiguous depth range. In the current paper a >20-fold increase in pixel utilisation is achieved through the use of a 2-D microlens array, that leads to a 35 × 35 channel system with an unambiguous depth range of 0.88 mm.

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.

The importance of high quality trials of cognitive interventions in Alzheimer's disease.

Currently available treatments for Alzheimer's disease (AD) are disappointing and their modest benefits do not reflect the increased understanding of the condition that has arisen from the last 50 years of research or the huge investments made by the pharmaceutical industry and academia in developing therapies. Cholinesterase inhibitors and memantine are evidence-based symptomatic treatments that offer benefits at the margins of clinical significance, but successive failures in trials of putative disease-modifying drugs have led researchers to investigate the potential efficacy of non-drug interventions. Exercise and cognitive-based interventions have received the most attention, but we are still a long way from understanding whether any can offer real benefit to patients with AD (Huntley et al., 2015).