Assessment of Alzheimer-related pathologies of dementia using machine learning feature selection.

Although a variety of brain lesions may contribute to the pathological assessment of dementia, the relationship of these lesions to dementia, how they interact and how to quantify them remains uncertain. Systematically assessing neuropathological measures by their degree of association with dementia may lead to better diagnostic systems and treatment targets. This study aims to apply machine learning approaches to feature selection in order to identify critical features of Alzheimer-related pathologies associated with dementia. We applied machine learning techniques for feature ranking and classification to objectively compare neuropathological features and their relationship to dementia status during life using a cohort (n=186) from the Cognitive Function and Ageing Study (CFAS). We first tested Alzheimer's Disease and tau markers and then other neuropathologies associated with dementia. Seven feature ranking methods using different information criteria consistently ranked 22 out of the 34 neuropathology features for importance to dementia classification. Although highly correlated, Braak neurofibrillary tangle stage, beta-amyloid and cerebral amyloid angiopathy features were ranked the highest. The best-performing dementia classifier using the top eight neuropathological features achieved 79% sensitivity, 69% specificity and 75% precision. However, when assessing all seven classifiers and the 22 ranked features, a substantial proportion (40.4%) of dementia cases was consistently misclassified. These results highlight the benefits of using machine learning to identify critical indices of plaque, tangle and cerebral amyloid angiopathy burdens that may be useful for classifying dementia.

A Scoping Review of Approaches to Improving Quality of Data Relating to Health Inequalities.

Identifying and monitoring of health inequalities requires good-quality data. The aim of this work is to systematically review the evidence base on approaches taken within the healthcare context to improve the quality of data for the identification and monitoring of health inequalities and describe the evidence base on the effectiveness of such approaches or recommendations. Peer-reviewed scientific journal publications, as well as grey literature, were included in this review if they described approaches and/or made recommendations to improve data quality relating to the identification and monitoring of health inequalities. A thematic analysis was undertaken of included papers to identify themes, and a narrative synthesis approach was used to summarise findings. Fifty-seven papers were included describing a variety of approaches. These approaches were grouped under four themes: policy and legislation, wider actions that enable implementation of policies, data collection instruments and systems, and methodological approaches. Our findings indicate that a variety of mechanisms can be used to improve the quality of data on health inequalities at different stages (prior to, during, and after data collection). These findings can inform us of actions that can be taken by those working in local health and care services on approaches to improving the quality of data on health inequalities.

The relevance of social and commercial determinants for neurological health.

A disconnect has developed over the past two decades between neurological and neuroscientific research, which have seen notable innovation and development, and our increasing understanding of the role of social and commercial determinants of health, including the health of the nervous system. Over the next two decades, grounding neurological research in public health and epidemiological principles can bring about a paradigm shift, away from reductionism, over-medicalisation, and health inequities towards neurological research that reduces inequalities and has true relevance to the populations it aims to serve. People who are involved in neurological and neuroscientific research and practice, as clinicians, researchers, publishers, and funders, can create change by being more aware of the social and commercial determinants of health, reprioritising research funding, and advocating for greater neurological health equity.

A systematic review of the cost-effectiveness of community and population interventions to reduce the modifiable risk factors for dementia.

Dementia is a leading global cause of morbidity and mortality. Evidence suggests that tackling modifiable lifecourse risk factors could prevent or delay a significant proportion of cases. Population- and community-based approaches change societal conditions such that everyone across a given community is more likely to live more healthily. We systematically reviewed economic studies of population- and community-based interventions to reduce modifiable lifecourse risk factors for dementia. We searched Medline, EMBASE, Web of Science, CINAHL, PsycInfo, Scopus, Econlit, ERIC, the British Education Index, and Google, on 03/03/2022. We included cost-effectiveness, cost-benefit, and cost-utility studies, provided that the direct outcome of the intervention was a modifiable risk factor for dementia, and was measured empirically. Quality appraisal was completed using the Consensus on Health Economic Criteria checklist. A narrative synthesis was performed. We included 45 studies, from 22,749 records identified. Included studies targeted smoking (n = 15), education (n = 10), physical inactivity (n = 9), obesity (n = 5), air pollution (n = 2), traumatic brain injury (n = 1), and multiple risk factors (n = 3). Intervention designs included changing the physical/food environment (n = 13), mass media programmes (n = 11), reducing financial barriers or increasing resources (n = 10), whole-community approaches (n = 6), and legislative change (n = 3). Overall, interventions were highly cost-effective and/or cost-saving, particularly those targeting smoking, educational attainment, and physical inactivity. Effects were observed in high- (e.g. USA and UK) and low- and middle-income (e.g. Mexico, Tanzania, Thailand) countries. Further research into the direct effects of targeting these risk factors on future dementia prevalence will have important economic, social and policy implications.

A cohort study of the impact of COVID-19 on the quality of life of people newly diagnosed with dementia and their family carers.

Introduction: COVID-19 has impacted people with dementia and their family carers, yet little is known about effects on overall quality of life. Methods: In a UK cohort study, pre- and post-pandemic data were collected from 114 carers and 93 recently diagnosed people with dementia. Latent growth curve modeling examined change in quality of life. Results: Carers reported significant decline in quality of life, although no change was demonstrated by people with dementia. In multivariable analyses, higher levels of cognitive impairment, deprivation, study site, and lower number of memory clinic contacts were associated with greater decline in carer quality of life. Discussion: Maintaining life quality for people with dementia during the pandemic appears to have come at the expense of their family carers. This inequity has fallen hardest on those caring for people with more severe dementia, in deprived areas, and with least support from memory services. These effects may be prevented or reversed by post-diagnostic care.

Delirium and Delirium Severity Predict the Trajectory of the Hierarchical Assessment of Balance and Mobility in Hospitalized Older People: Findings From the DECIDE Study.

BACKGROUND: Delirium is common, distressing, and associated with poor outcomes. Despite this, delirium remains poorly recognized, resulting in worse outcomes. There is an urgent need for methods to objectively assess for delirium. Physical function has been proposed as a potential surrogate marker, but few studies have monitored physical function in the context of delirium. We examined if trajectories of physical function are affected by the presence and severity of delirium in a representative sample of hospitalized participants older than 65 years. METHOD: During hospital admissions in 2016, we assessed participants from the Delirium and Cognitive Impact in Dementia study daily for delirium and physical function, using the Hierarchical Assessment of Balance and Mobility (HABAM). We used linear mixed models to assess the effect of delirium and delirium severity during admission on HABAM trajectory. RESULTS: Of 178 participants, 58 experienced delirium during admission. Median HABAM scores in those with delirium were significantly higher (indicating worse mobility) than those without delirium. Modeling HABAM trajectories, HABAM scores at first assessment were worse in those with delirium than those without, by 0.76 (95% CI: 0.49-1.04) points. Participants with severe delirium experienced a much greater perturbance in their physical function, with an even lower value at first assessment and slower subsequent improvement. CONCLUSIONS: Physical function was worse in those with delirium compared to without. This supports the assertion that motor disturbances are a core feature of delirium and monitoring physical function, using a tool such as the HABAM, may have clinical utility as a surrogate marker for delirium and its resolution.

Epidemiologic Trends, Social Determinants, and Brain Health: The Role of Life Course Inequalities.

Brain health as expressed in our mental health and occurrence of specific disorders such as dementia and stroke is vitally important to quality of life, functional independence, and risk of institutionalization. Maintaining brain health is, therefore, a societal imperative, and public health challenge, from prevention of acquisition of brain disorders, through protection and risk reduction to supporting those with such disorders through effective societal and system approaches. To identify possible mechanisms that explain the differential effect of potentially modifiable risk factors, and factors that may mitigate risk, a life course approach is needed. This is key to understanding how poor health can accumulate from the earliest life stages. It also allows us to integrate and investigate key material, behavioral, and psychological factors that generate health inequalities within and across communities and societies. This review provides a narrative on how brain health is intimately linked to wider health determinants, thus importance for clinicians and societies alike. There is compelling evidence accumulated from research over decades that socioeconomic status, higher education, and healthy lifestyle extend life and compress major morbidities into later life. Brain health is part of this, but collective action has been limited, partly because of the separation of disciplines and focus on highly reductionist approaches in that clinicians and associated research have focused more on mitigation and early detection of specific diseases. However, clinicians could be part of the drive for better brain health for all society to support life courses that have more protection and less risk. There is evidence of change in such risks for conditions such as stroke and dementia across generations. The evidence points to the importance of starting with parental health and life course inequalities as a central focus.

The limitations of large-scale volunteer databases to address inequalities and global challenges in health and aging.

Large-scale volunteer databanks (LSVD) have emerged from the recognized value of cohorts, attracting substantial funding and promising great scientific value. A major focus is their size, with the implicit and sometimes explicit assumption that large size (thus power) creates generalizability. We contend that this is open to challenge. In the context of aging and age-related disease research, LSVD typically have limitations such as healthy volunteer, white ethnicity and high-education biases, and they omit early and late life stages critical for understanding aging. Their outputs are heavily focused on biomedical pathways of single chronic diseases. LSVD outputs increasingly dominate the funding and the publication landscapes. This Perspective discusses LSVD limitations and calls for more transparent reporting in LSVD research, as well as a greater reflection on the value of LSVD in relation to resources consumed. We invite funders and researchers to examine whether LSVD do actually contribute knowledge needed for our acute global health challenges including inequalities.

Societal and equity challenges for Brain Health Services. A user manual for Brain Health Services-part 6 of 6.

Brain Health Services are a novel approach to the personalized prevention of dementia. In this paper, we consider how such services can best reflect their social, cultural, and economic context and, in doing so, deliver fair and equitable access to risk reduction. We present specific areas of challenge associated with the social context for dementia prevention. The first concentrates on how Brain Health Services engage with the "at-risk" individual, recognizing the range of factors that shape an individual's risk of dementia and the efficacy of risk reduction measures. The second emphasizes the social context of Brain Health Services themselves and their ability to provide equitable access to risk reduction. We then elaborate proposals for meeting or mitigating these challenges. We suggest that considering these challenges will enable Brain Health Services to address two fundamental questions: the balance between an individualized "high-risk" and population focus for public health prevention and the ability of services to meet ethical standards of justice and health equity.

The contribution of multiple long-term conditions to widening inequalities in disability-free life expectancy over two decades: Longitudinal analysis of two cohorts using the Cognitive Function and Ageing Studies.

BACKGROUND: : Disability-free life expectancy (DFLE) inequalities by socioeconomic deprivation are widening, alongside rising prevalence of multiple long-term conditions (MLTCs). We use longitudinal data to assess whether MLTCs contribute to the widening DFLE inequalities by socioeconomic deprivation. METHODS: : The Cognitive Function and Ageing Studies (CFAS I and II) are large population-based studies of those ≥65 years, conducted in three areas in England. Baseline occurred in 1991 (CFAS I, n=7635) and 2011 (CFAS II, n=7762) with two-year follow-up. We defined disability as difficulty in activities of daily living, MLTCs as the presence of at least two of nine health conditions, and socioeconomic deprivation by area-level deprivation tertiles. DFLE and transitions between disability states and death were estimated from multistate models. FINDINGS: : For people with MLTCs, inequalities in DFLE at age 65 between the most and least affluent widened to around 2.5 years (men:2.4 years, 95% confidence interval (95%CI) 0.4-4.4; women:2.6 years, 95%CI 0.7-4.5) by 2011. Incident disability reduced for the most affluent women (Relative Risk Ratio (RRR):0.6, 95%CI 0.4-0.9), and mortality with disability reduced for least affluent men (RRR:0.6, 95%CI 0.5-0.8). MLTCs prevalence increased only for least affluent men (1991: 58.8%, 2011: 66.9%) and women (1991: 60.9%, 2011: 69.1%). However, DFLE inequalities were as large in people without MLTCs (men:2.4 years, 95%CI 0.3-4.5; women:3.1 years, 95% CI 0.8-5.4). INTERPRETATION: : Widening DFLE inequalities were not solely due to MLTCs. Reduced disability incidence with MLTCs is possible but was only achieved in the most affluent.

Assessment of common infections and incident dementia using UK primary and secondary care data: a historical cohort study.

BACKGROUND: Common infections have been associated with dementia risk; however, evidence is scarce. We aimed to investigate the association between common infections and dementia in adults (≥65 years) in a UK population-based cohort study. METHODS: We did a historical cohort study of individuals who were 65 years and older with no history of dementia or cognitive impairment using the Clinical Practice Research Datalink linked to Hospital Episode Statistics between Jan 1, 2004, and Dec 31, 2018. Multivariable Cox proportional hazard regression models were used to estimate the association between time-updated previous common infections (sepsis, pneumonia, other lower respiratory tract infections, urinary tract infections, and skin and soft tissue infections) and incident dementia diagnosis. We also tested for effect modification by diabetes since it is an independent risk factor for dementia and co-occurs with infection. FINDINGS: Between Jan 1, 2004, and Dec 31, 2018, our study included 989 800 individuals (median age 68·6 years [IQR 65·0-77·0]; 537 602 [54·3%] women) of whom 402 204 (40·6%) were diagnosed with at least one infection and 56 802 (5·7%) had incident dementia during a median follow-up of 5·2 years (IQR 2·3-9·0). Dementia risk increased in those with any infection (adjusted hazard ratio [HR] 1·53 [95% CI 1·50-1·55]) compared with those without infection. HRs were highest for sepsis (HR 2·08 [1·89-2·29]) and pneumonia (HR 1·88 [1·77-1·99]) and for infections leading to hospital admission (1·99 [1·94-2·04]). HRs were also higher in individuals with diabetes compared with those without diabetes. INTERPRETATION: Common infections, particularly those resulting in hospitalisation, were associated with an increased risk of dementia persisting over the long term. Whether reducing infections lowers the risk of subsequent dementia warrants evaluation. FUNDING: Alzheimer's Society, Wellcome Trust, and the Royal Society.

Montreal Cognitive Assessment for the detection of dementia.

BACKGROUND: Dementia is a progressive syndrome of global cognitive impairment with significant health and social care costs. Global prevalence is projected to increase, particularly in resource-limited settings. Recent policy changes in Western countries to increase detection mandates a careful examination of the diagnostic accuracy of neuropsychological tests for dementia. OBJECTIVES: To determine the accuracy of the Montreal Cognitive Assessment (MoCA) for the detection of dementia. SEARCH METHODS: We searched MEDLINE, EMBASE, BIOSIS Previews, Science Citation Index, PsycINFO and LILACS databases to August 2012. In addition, we searched specialised sources containing diagnostic studies and reviews, including MEDION (Meta-analyses van Diagnostisch Onderzoek), DARE (Database of Abstracts of Reviews of Effects), HTA (Health Technology Assessment Database), ARIF (Aggressive Research Intelligence Facility) and C-EBLM (International Federation of Clinical Chemistry and Laboratory Medicine Committee for Evidence-based Laboratory Medicine) databases. We also searched ALOIS (Cochrane Dementia and Cognitive Improvement Group specialized register of diagnostic and intervention studies). We identified further relevant studies from the PubMed 'related articles' feature and by tracking key studies in Science Citation Index and Scopus. We also searched for relevant grey literature from the Web of Science Core Collection, including Science Citation Index and Conference Proceedings Citation Index (Thomson Reuters Web of Science), PhD theses and contacted researchers with potential relevant data. SELECTION CRITERIA: Cross-sectional designs where all participants were recruited from the same sample were sought; case-control studies were excluded due to high chance of bias. We searched for studies from memory clinics, hospital clinics, primary care and community populations. We excluded studies of early onset dementia, dementia from a secondary cause, or studies where participants were selected on the basis of a specific disease type such as Parkinson's disease or specific settings such as nursing homes. DATA COLLECTION AND ANALYSIS: We extracted dementia study prevalence and dichotomised test positive/test negative results with thresholds used to diagnose dementia. This allowed calculation of sensitivity and specificity if not already reported in the study. Study authors were contacted where there was insufficient information to complete the 2x2 tables. We performed quality assessment according to the QUADAS-2 criteria. Methodological variation in selected studies precluded quantitative meta-analysis, therefore results from individual studies were presented with a narrative synthesis. MAIN RESULTS: Seven studies were selected: three in memory clinics, two in hospital clinics, none in primary care and two in population-derived samples. There were 9422 participants in total, but most of studies recruited only small samples, with only one having more than 350 participants. The prevalence of dementia was 22% to 54% in the clinic-based studies, and 5% to 10% in population samples. In the four studies that used the recommended threshold score of 26 or over indicating normal cognition, the MoCA had high sensitivity of 0.94 or more but low specificity of 0.60 or less. AUTHORS' CONCLUSIONS: The overall quality and quantity of information is insufficient to make recommendations on the clinical utility of MoCA for detecting dementia in different settings. Further studies that do not recruit participants based on diagnoses already present (case-control design) but apply diagnostic tests and reference standards prospectively are required. Methodological clarity could be improved in subsequent DTA studies of MoCA by reporting findings using recommended guidelines (e.g. STARDdem). Thresholds lower than 26 are likely to be more useful for optimal diagnostic accuracy of MoCA in dementia, but this requires confirmation in further studies.

Transforming health systems to reduce health inequalities.

Never before in history have we had the data to track such a rapid increase in inequalities. With changes imminent in healthcare and public health organisational landscape in England and health inequalities high on the policy agenda, we have an opportunity to redouble efforts to reduce inequalities. In this article, we argue that health inequalities need re-framing to encompass the breadth of disadvantage and difference between healthcare and health outcome inequalities. Second, there needs to be a focus on long-term organisational change to ensure equity is considered in all decisions. Third, actions need to prioritise the fundamental redistribution of resources, funding, workforce, services and power. Reducing inequalities can involve unpopular and difficult decisions. Physicians have a particular role in society and can support evidenced-based change across practice and the system at large. If we do not act now, then when?

The changing health needs of the UK population.

The demographics of the UK population are changing and so is the need for health care. In this Health Policy, we explore the current health of the population, the changing health needs, and future threats to health. Relative to other high-income countries, the UK is lagging on many health outcomes, such as life expectancy and infant mortality, and there is a growing burden of mental illness. Successes exist, such as the striking improvements in oral health, but inequalities in health persist as well. The growth of the ageing population relative to the working-age population, the rise of multimorbidity, and persistent health inequalities, particularly for preventable illness, are all issues that the National Health Service (NHS) will face in the years to come. Meeting the challenges of the future will require an increased focus on health promotion and disease prevention, involving a more concerted effort to understand and tackle the multiple social, environmental, and economic factors that lie at the heart of health inequalities. The immediate priority of the NHS will be to mitigate the wider and long-term health consequences of the COVID-19 pandemic, but it must also strengthen its resilience to reduce the impact of other threats to health, such as the UK leaving the EU, climate change, and antimicrobial resistance.

Health financing for universal health coverage in Sub-Saharan Africa: a systematic review.

BACKGROUND: Universal health coverage (UHC) embedded within the United Nations Sustainable Development Goals, is defined by the World Health Organization as all individuals having access to required health services, of sufficient quality, without suffering financial hardship. Effective strategies for financing healthcare are critical in achieving this goal yet remain a challenge in Sub-Saharan Africa (SSA). This systematic review aims to determine reported health financing mechanisms in SSA within the published literature and summarize potential learnings. METHODS: A systematic review was conducted aligned with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. On 19 to 30 July 2019, MEDLINE, EMBASE, Web of Science, Global Health Database, the Cochrane Library, Scopus and JSTOR were searched for literature published from 2005. Studies describing health financing approaches for UHC in SSA were included. Evidence was synthesised in form of a table and thematic analysis. RESULTS: Of all records, 39 papers were selected for inclusion. Among the included studies, most studies were conducted in Kenya (n = 7), followed by SSA as a whole (n = 6) and Nigeria (n = 5). More than two thirds of the selected studies reported the importance of equitable national health insurance schemes for UHC. The results indicate that a majority of health care revenue in SSA is from direct out-of-pocket payments. Another common financing mechanism was donor funding, which was reported by most of the studies. The average quality score of all studies was 81.6%, indicating a high appraisal score. The interrater reliability Cohen's kappa score, κ=0.43 (p = 0.002), which showed a moderate level of agreement. CONCLUSIONS: Appropriate health financing strategies that safeguard financial risk protection underpin sustainable health services and the attainment of UHC. It is evident from the review that innovative health financing strategies in SSA are needed. Some limitations of this review include potentially skewed interpretations due to publication bias and a higher frequency of publications included from two countries in SSA. Establishing evidence-based and multi-sectoral strategies tailored to country contexts remains imperative.

Healthy ageing for all? Comparisons of socioeconomic inequalities in health expectancies over two decades in the Cognitive Function and Ageing Studies I and II.

BACKGROUND: Despite increasing life expectancy (LE), cross-sectional data show widening inequalities in disability-free LE (DFLE) by socioeconomic status (SES) in many countries. We use longitudinal data to better understand trends in DFLE and years independent (IndLE) by SES, and how underlying transitions contribute. METHODS: The Cognitive Function and Ageing Studies (CFAS I and II) are large population-based studies of those aged ≥65 years in three English centres (Newcastle, Nottingham, Cambridgeshire), with baseline around 1991 (CFAS I, n = 7635) and 2011 (CFAS II, n = 7762) and 2-year follow-up. We defined disability as difficulty in activities of daily living (ADL), dependency by combining ADLs and cognition reflecting care required, and SES by area-level deprivation. Transitions between disability or dependency states and death were estimated from multistate models. RESULTS: Between 1991 and 2011, gains in DFLE at age 65 were greatest for the most advantaged men and women [men: 4.7 years, 95% confidence interval (95% CI) 3.3-6.2; women: 2.8 years, 95% CI 1.3-4.3]. Gains were due to the most advantaged women having a reduced risk of incident disability [relative risk ratio (RRR):0.7, 95% CI 0.5-0.8], whereas the most advantaged men had a greater likelihood of recovery (RRR: 1.8, 95% CI 1.0-3.2) and reduced disability-free mortality risk (RRR: 0.4, 95% CI 0.3-0.6]. Risk of death from disability decreased for least advantaged men (RRR: 0.7, 95% CI 0.6-0.9); least advantaged women showed little improvement in transitions. IndLE patterns across time were similar. CONCLUSIONS: Prevention should target the most disadvantaged areas, to narrow inequalities, with clear indication from the most advantaged that reduction in poor transitions is achievable.