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.

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.

Biomarkers associated with cognitive impairment in post-traumatic stress disorder: A systematic review of current evidence.

OBJECTIVE: This systematic review aimed at synthesizing current evidence on biomarkers associated with cognitive impairment (CI) in Post-Traumatic Stress Disorder (PTSD). METHODS: A systematic literature search was conducted for studies assessing biomarkers associated with CI in PTSD. RESULTS: Of the 10,149 titles screened, 8 studies met our inclusion criteria. In a single longitudinal study, MRI volumes, Aß and tau accumulation were not associated with CI in PTSD. Studies on structural imaging reported no significant association between morphological changes and CI. Two studies on diffusion neuroimaging showed abnormalities in white matter tracts which were cross-sectionally associated with CI in PTSD. Similarly, lower resting-state functional connectivity in neocortical networks, and elevated tau in the neocortex were also cross sectionally associated with CI. Two single studies on biochemical biomarkers showed that sixteen novel plasma proteins and lower BDNF, indicative of genetic vulnerabilities associated with neural and synaptic dysfunctions commonly observed in neurodegeneration, were cross-sectionally associated with CI in PTSD. Overall, evidence is of low quality. CONCLUSIONS: Longitudinal research utilizing large representative samples of trauma exposed populations are needed to establish the utility of specific biomarkers in monitoring cognitive decline in PTSD.

The cognitive neuroscience of self-awareness: Current framework, clinical implications, and future research directions.

Self-awareness, the ability to take oneself as the object of awareness, has been an enigma for our species, with different answers to this question being provided by religion, philosophy, and, more recently, science. The current review aims to discuss the neurocognitive mechanisms underlying self-awareness. The multidimensional nature of self-awareness will be explored, suggesting how it can be thought of as an emergent property observed in different cognitive complexity levels, within a predictive coding approach. A presentation of alterations of self-awareness in neuropsychiatric conditions will ground a discussion on alternative frameworks to understand this phenomenon, in health and psychopathology, with future research directions being indicated to fill current gaps in the literature. This article is categorized under: Philosophy > Consciousness Psychology > Brain Function and Dysfunction Neuroscience > Cognition.

Effectiveness of treatments for people living with severe dementia: A systematic review and meta-analysis of randomised controlled clinical trials.

BACKGROUND: Dementia is a progressive neurodegenerative syndrome that has no cure. Although a significant proportion of people with dementia progress into the severe stages of the disease, evidence on the clinical effectiveness of treatments for people with severe dementia remains limited. AIMS: To systematically review the effectiveness of pharmacological and non-pharmacological treatments for people living with severe dementia and assess the quality of the evidence. METHOD: We searched MEDLINE, EMBASE, PsycINFO, CINAHL and online clinical trial registers up to January 2022, for Randomised Controlled Trials (RCT) in people living with severe dementia. Quality and risk of bias were assessed independently by two authors. RESULTS: A total of 30 trials met our inclusion criteria of which 14 evaluated the effectiveness of pharmacological treatments, and 16 evaluated a non-pharmacological intervention. Pharmacological treatments: Meta-analyses indicated that pharmacological treatments (donepezil: 10 mg, 5 mg; galantamine: 24 mg; memantine: 10 mg) are associated with better outcomes compared to placebo for: severity of symptoms (standardized mean difference (SMD) 0.37, 95% CI 0.26-0.48; 4 studies; moderate-certainty evidence), activities of daily living (SMD 0.15, 95% CI 0.04-0.26; 5 studies; moderate-certainty evidence), and clinical impression of change (Relative Risk (RR) 1.34, 95% CI 1.14-1.57; 4 studies; low-certainty evidence). Pharmacological treatments were also more likely to reduce mortality compared to placebo (RR 0.60, 95% CI 0.40-0.89; 6 studies; low-certainty evidence). Non-pharmacological treatments: Five trials were included in the meta-analyses of non-pharmacological interventions (multi-sensory stimulation, needs assessment, and activities-based interventions); results showed that non-pharmacological interventions may reduce neuropsychiatric symptoms of dementia compared to usual care (SMD -0.33, 95% CI -0.59 to -0.06; low certainty evidence). CONCLUSIONS: There is moderate-certainty evidence that pharmacological treatments may decrease disease severity and improve function for people with severe dementia. Non-pharmacological treatments are probably effective in reducing neuropsychiatric symptoms but the quality of evidence remains low. There is an urgent need for high-quality evidence for other outcomes and for developing service-user informed interventions for this under-served group.

What Are the Neural Correlates of Impaired Awareness of Social Cognition and Function in Dementia? A Systematic Review.

Deficits in social cognition and function are characteristic of dementia, commonly accompanied by a loss of awareness of the presence or extent of these deficits. This lack of awareness can impair social relationships, increase patients' and carers' burden, and contribute to increased rates of institutionalization. Despite clinical importance, neural correlates of this complex phenomenon remain unclear. We conducted a systematic search of five electronic databases to identify functional and structural neuroimaging studies investigating the neural correlates of impaired awareness of social cognition and function in any dementia type. We rated study quality and conducted a narrative synthesis of the results of the eight studies that met the predefined eligibility criteria. Across these studies, deficits in awareness of impairments in social cognition and function were associated with structural or functional abnormalities in the frontal pole, orbitofrontal cortex, temporal pole, middle temporal gyrus, inferior temporal gyrus, fusiform gyrus, amygdala, hippocampus, parahippocampal gyrus, and insula. Several identified regions overlap with established neural correlates of social cognition. More research is needed to understand awareness of social cognition and function and how this becomes impaired in dementia to improve neuroscientific understanding, aid the identification of this problematic symptom, and target interventions to reduce burden and improve care.

Mild Traumatic Brain Injuries and Future Risk of Developing Alzheimer's Disease: Systematic Review and Meta-Analysis.

BACKGROUND: Traumatic brain injury (TBI) increases the risk of future dementia and Alzheimer's disease (AD). However, it is unclear whether this is true for mild TBI (mTBI). OBJECTIVE: To explore the association between mTBI and subsequent risk of developing AD. METHOD: We systematically searched four electronic databases from January 1954 to April 2020. We included studies reporting primary data and where mTBI preceded AD by≥5 years. We meta-analyzed included studies for both high quality studies and studies with a follow up of > 10 years. RESULT: We included 5 of the 10,435 results found. Meta-analysis found a history of mTBI increased risk of AD (pooled relative risk = 1.18, 95% CI 1.11-1.25, N = 3,149,740). The sensitivity analysis including only studies in which mTBI preceded AD by > 10 years, excluded two very large studies and resulted in wider confidence intervals (RR = 2.02, 95% CI 0.66-6.21, N = 2307). CONCLUSION: There is an increased risk of AD following mTBI. Our findings of increased risk even with mTBI means it cannot be assumed that mild head injuries from sports are harmless. The sensitivity analysis suggests that we cannot exclude reverse causation, and longer follow up times are needed. Implementation of policy to reduce mTBIs, including in children and sportsmen, are urgently needed. Further research is needed on the effect of frequency and age at injury of mTBIs.

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 awareness in severe Alzheimer's disease.

There is an urgent need to understand the nature of awareness in people with severe Alzheimer's disease (AD) to ensure effective person-centered care. Objective biomarkers of awareness validated in other clinical groups (e.g., anesthesia, minimally conscious states) offer an opportunity to investigate awareness in people with severe AD. In this article we demonstrate the feasibility of using Transcranial magnetic stimulation (TMS) combined with EEG, event related potentials (ERPs) and fMRI to assess awareness in severe AD. TMS-EEG was performed in six healthy older controls and three people with severe AD. The perturbational complexity index (PCIST) was calculated as a measure of capacity for conscious awareness. People with severe AD demonstrated a PCIST around or below the threshold for consciousness, suggesting reduced capacity for consciousness. ERPs were recorded during a visual perception paradigm. In response to viewing faces, two patients with severe AD provisionally demonstrated similar visual awareness negativity to healthy controls. Using a validated fMRI movie-viewing task, independent component analysis in two healthy controls and one patient with severe AD revealed activation in auditory, visual and fronto-parietal networks. Activation patterns in fronto-parietal networks did not significantly correlate between the patient and controls, suggesting potential differences in conscious awareness and engagement with the movie. Although methodological issues remain, these results demonstrate the feasibility of using objective measures of awareness in severe AD. We raise a number of challenges and research questions that should be addressed using these biomarkers of awareness in future studies to improve understanding and care for people with severe AD.

Understanding Alzheimer's disease as a disorder of consciousness.

People with Alzheimer's disease (AD) demonstrate a range of alterations in consciousness. Changes in awareness of cognitive deficit, self-awareness, and introspection are seen early in AD, and dysfunction of awareness and arousal progresses with increasing disease severity. However, heterogeneity of deficits between individuals and a lack of empirical studies in people with severe dementia highlight the importance of identifying and applying biomarkers of awareness in AD. Impairments of awareness in AD are associated with neuropathology in regions that overlap with proposed neural correlates of consciousness. Recent developments in consciousness science provide theoretical frameworks and experimental approaches to help further understand the conscious experience of people with AD. Recognition of AD as a disorder of consciousness is overdue, and important to both understand the lived experience of people with AD and to improve care.

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.

Empathy and its associations with age and sociodemographic characteristics in a large UK population sample.

OBJECTIVES: Empathy is fundamental to social cognition, driving prosocial behaviour and mental health but associations with aging and other socio-demographic characteristics are unclear. We therefore aimed to characterise associations of these characteristics with two main self-reported components of empathy, namely empathic-concern (feeling compassion) and perspective-taking (understanding others' perspective). METHODS: We asked participants in an internet-based survey of UK-dwelling adults aged ≥18 years to complete the Interpersonal Reactivity Index subscales measuring empathic concern and perspective taking, and sociodemographic and personality questionnaires. We weighted the sample to be UK population representative and employed multivariable weighted linear regression models. RESULTS: In 30,033 respondents, mean empathic concern score was 3.86 (95% confidence interval 3.85, 3.88) and perspective taking was 3.57 (3.56. 3.59); the correlation between these sub-scores was 0.45 (p < 0.001). Empathic concern and perspective taking followed an inverse-u shape trajectory in women with peak between 40 and 50 years whereas in men, perspective taking declines with age but empathic concern increases. In fully adjusted models, greater empathic concern was associated with female gender, non-white ethnicity, having more education, working in health, social-care, or childcare professions, and having higher neuroticism, extroversion, openness to experience and agreeableness traits. Perspective taking was associated with younger age, female gender, more education, employment in health or social-care, neuroticism, openness, and agreeableness. CONCLUSIONS: Empathic compassion and understanding are distinct dimensions of empathy with differential demographic associations. Perspective taking may decline due to cognitive inflexibility with older age whereas empathic concern increases in older men suggesting it is socially-driven.

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.

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.

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.

Social connectedness and dementia prevention: Pilot of the APPLE-Tree video-call intervention during the Covid-19 pandemic.

BACKGROUND AND OBJECTIVES: The Covid-19 pandemic reduced access to social activities and routine health care that are central to dementia prevention. We developed a group-based, video-call, cognitive well-being intervention; and investigated its acceptability and feasibility; exploring through participants' accounts how the intervention was experienced and used in the pandemic context. RESEARCH DESIGN AND METHOD: We recruited adults aged 60+ years with memory concerns (without dementia). Participants completed baseline assessments and qualitative interviews/focus groups before and after the 10-week intervention. Qualitative interview data and facilitator notes were integrated in a thematic analysis. RESULTS: 12/17 participants approached completed baseline assessments, attended 100/120 (83.3%) intervention sessions and met 140/170 (82.4%) of goals set. Most had not used video calling before. In the thematic analysis, our overarching theme was social connectedness. Three sub-themes were as follows: Retaining independence and social connectedness: social connectedness could not be at the expense of independence; Adapting social connectedness in the pandemic: participants strived to compensate for previous social connectedness as the pandemic reduced support networks; Managing social connections within and through the intervention: although there were tensions, for example, between sharing of achievements feeling supportive and competitive, participants engaged with various lifestyle changes; social connections supported group attendance and implementation of lifestyle changes. DISCUSSION AND IMPLICATIONS: Our intervention was acceptable and feasible to deliver by group video-call. We argue that dementia prevention is both an individual and societal concern. For more vulnerable populations, messages that lifestyle change can help memory should be communicated alongside supportive, relational approaches to enabling lifestyle changes.

The Association Between Impaired Awareness and Depression, Anxiety, and Apathy in Mild to Moderate Alzheimer's Disease: A Systematic Review.

Objectives: Impaired awareness of cognitive and functional deficits is a common feature of Alzheimer's disease (AD). Although a lack of awareness has been suggested to be a protective factor against experiencing affective symptoms, such as depression, anxiety, and apathy which are common in AD, there is conflicting evidence about the links between them. This systematic review examines the evidence for an association between impaired awareness and depressive, anxiety, and apathy symptoms in mild to moderate AD. Method: We searched four databases (OvidMedline, Embase, PsycInfo, and PsycArticles) using terms encompassing awareness, apathy, depression, anxiety, and mild-moderate AD. We included studies that assessed the relationship between awareness and depressive symptoms, anxiety symptoms, or apathy. We assessed included papers for quality and report results using a narrative approach, prioritizing high quality studies. Results: We identified 1,544 articles, and twenty-seven studies fulfilled inclusion criteria (high-quality = 15; moderate-quality = 12). Most high-quality studies reported that impaired awareness in early-stage AD is cross-sectionally linked with fewer depressive symptoms and anxiety symptoms (correlation ranged from -0.3 to -0.7), but with more apathy. Conclusions: High-quality studies suggested that in people with early AD, impaired awareness is related to fewer depressive and anxiety symptoms and to more apathy. Future research should focus on elucidating causality among impaired awareness and these symptoms in AD.