Are Population-Level Approaches to Dementia Risk Reduction Under-Researched? A Rapid Review of the Dementia Prevention Literature.

Dementia is forecast to become increasingly prevalent, particularly in low- and middle-income countries, and is associated with high human and economic costs. Primary prevention of dementia -preventing risk factors leading to disease development - is an emerging global public health priority. Primary prevention can be achieved in two ways: individual-level or population-level. In this rapid review, we quantify the proportion of contributing interventional evidence to the dementia primary prevention literature that is concerned with either approach. We searched Medline, the National Institute for Health and Care Excellence, Cochrane, the World Health Organization, and Google to identify systematic reviews that described primary prevention interventions for dementia. We used search terms related to dementia risk reduction, intervention/policy, and review. We analysed reference lists of included dementia prevention reviews to identify contributing primary prevention evidence, and categorised these as either individual-level or population-level. Additionally, we examined search strategies to investigate the likelihood of reviews identifying available population-level interventions. We included twelve of the 527 articles retrieved. Population-level evidence was summarised by only two reviews. In these two reviews, <2.5% of the interventions described where population-level interventions. Most search strategies were weighted towards identifying individual-level evidence. Existing systematic reviews of dementia primary prevention interventions include almost no population-level evidence. Correction of this imbalance is needed to ensure that dementia prevention policies can achieve meaningful reductions in the prevalence of, and inequalities in, dementia.

What is a population-level approach to prevention, and how could we apply it to dementia risk reduction?

The World Health Organisation's 2022 'blueprint for dementia research' highlights the need for more research into population-level risk reduction. However, definitions of population-level prevention vary, and application to dementia is challenging because of its multi-factorial aetiology and a maturing prevention evidence base. This paper compares and contrasts key concepts of 'population-level prevention' from the literature, explores related theoretical models and policy frameworks, and applies this to dementia risk reduction. We reach a proposed definition of population-level risk reduction of dementia, which focusses on the need to change societal conditions such that the population is less likely to develop modifiable risk factors known to be associated with dementia, without the need for high-agency behaviour change by individuals. This definition, alongside identified policy frameworks, can inform synthesis of existing evidence and help to co-ordinate the generation of new evidence.

Community interventions for improving adult mental health: mapping local policy and practice in England.

BACKGROUND: Public mental health (PMH) aims to improve wellbeing and prevent poor mental health at the population level. It is a global challenge and a UK priority area for action. Communities play an important role in the provision of PMH interventions. However, the evidence base concerning community-based PMH interventions is limited, meaning it is challenging to compare service provision to need. Without this, the efficient and equitable provision of services is hindered. Here, we sought to map the current range of community-based interventions for improving mental health and wellbeing currently provided in England to inform priority areas for policy and service intervention. METHOD: We adopted an established mapping exercise methodology, comparing service provision with demographic and deprivation statistics. Five local authority areas of England were selected based on differing demographics, mental health needs and wider challenging circumstances (i.e. high deprivation). Community-based interventions were identified through: 1) desk-based research 2) established professional networks 3) chain-referral sampling of individuals involved in local mental health promotion and prevention and 4) peer researchers' insight. We included all community-based, non-clinical interventions aimed at adult residents operating between July 2019 and May 2020. RESULTS: 407 interventions were identified across the five areas addressing 16 risk/protective factors for PMH. Interventions for social isolation and loneliness were most prevalent, most commonly through social activities and/or befriending services. The most common subpopulations targeted were older adults and people from minority ethnic backgrounds. Interventions focusing on broader structural and environmental determinants were uncommon. There was some evidence of service provision being tailored to local need, though this was inconsistent, meaning some at-risk groups such as men or LGBTQ+ people from minority ethnic backgrounds were missed. Interventions were not consistently evaluated. CONCLUSIONS: There was evidence of partial responsiveness to national and local prioritising. Provision was geared mainly towards addressing social and individual determinants of PMH, suggesting more integration is needed to engage wider service providers and policy-makers in PMH strategy and delivery at the community level. The lack of comprehensive evaluation of services to improve PMH needs to be urgently addressed to determine the extent of their effectiveness in communities they serve.

Community exchange and time currencies: a systematic and in-depth thematic review of impact on public health outcomes.

OBJECTIVES: Austerity in government funding, and public service reform, has heightened expectations on UK communities to develop activities and resources supportive of population health and become part of a transformed place-based system of community health and social care. As non-monetary place-based approaches, Community Exchange/Time Currencies could improve social contact and cohesion, and help mobilise families, neighbourhoods, communities and their assets in beneficial ways for health. Despite this interest, the evidence base for health outcomes resulting from such initiatives is underdeveloped. STUDY DESIGN: A systematic review. METHODS: A literature review was conducted to identify evidence gaps and advance understanding of the potential of Community Exchange System. Studies were quality assessed, and evidence was synthesised on 'typology', population targeted and health-related and wider community outcomes. RESULTS: The overall study quality was low, with few using objective measures of impact on health or well-being, and none reporting costs. Many drew on qualitative accounts of impact on health, well-being and broader community outcomes. Although many studies lacked methodological rigour, there was consistent evidence of positive impacts on key indicators of health and social capital, and the data have potential to inform theory. CONCLUSIONS: Methodologies for capturing impacts are often insufficiently robust to inform policy requirements and economic assessment, and there remains a need for objective, systematic evaluation of Community Exchange and Time Currency systems. There is also a strong argument for deeper investigation of 'programme theories' underpinning these activities, to better understand what needs to be in place to trigger their potential for generating positive health and well-being outcomes.

Frailty: an in-depth qualitative study exploring the views of community care staff.

BACKGROUND: Frailty is seen across various health and social care settings. However, little is known about how healthcare professionals, particularly those who provide care for older adults living in the community view frailty. There is also a dearth of information about the extent to which a shared understanding of frailty exists across the various disciplines of care. Such an understanding is crucial across care professionals as it ensures consistent assessment of frailty and facilitates interdisciplinary working/collaboration which is a key component in the management of frailty. This study aimed to explore: (i) how community care staff from various specialties viewed frailty; (ii) whether they had a shared understanding; and (iii) how they assessed frailty in everyday practice. METHODS: Semi-structured interviews were conducted with a purposive sample of 22 community care staff from seven specialties, namely: healthcare assistants, therapy assistants, psychiatric nurses, general nurses, occupational therapists, physiotherapists and social workers, recruited from four neighbourhood teams across Cambridgeshire, England. Interviews were analysed thematically. RESULTS: There was a shared narrative among participants that frailty is an umbrella term that encompasses interacting physical, mental health and psychological, social, environmental, and economic factors. However, various specialities emphasised the role of specific facets of the frailty umbrella. The assessment and management of frailty was said to require a holistic approach facilitated by interdisciplinary working. Participants voiced a need for interdisciplinary training on frailty, and frailty tools that facilitate peer-learning, a shared understanding of frailty, and consistent assessment of frailty within and across specialities. CONCLUSIONS: These findings underscore the need to: (i) move beyond biomedical descriptions of frailty; (ii) further explore the interacting nature of the various components of the frailty umbrella, particularly the role of modifiable factors such as psychological and socioeconomic resilience; (iii) care for frail older adults using holistic, interdisciplinary approaches; and (iv) promote interdisciplinary training around frailty and frailty tools to facilitate a shared understanding and consistent assessment of frailty within and across specialities.

Screening for dementia--is it a no brainer?

As people are living longer, dementia is becoming a significant issue for society. Dementia is now recognised as a major concern in society, and the numbers of people estimated to have dementia in the UK population appear to have stabilised at around 700,000 . Globally, 35.6 million people are estimated to meet criteria for dementia, a number predicted to double every 20 years . Given the absence of treatments that significantly alter the natural history of the clinical syndrome of dementia, there has been increased emphasis on early diagnosis, with research exploring assessment tools and biomarkers that might predict with certainty a particular clinical outcome. At the same time, there has been pressure to focus on biomedical profiles, which assume a very close link between the pathobiology and the manifest clinical syndrome.

Immunohistochemical evidence for the involvement of protein convertases 5A and 2 in the processing of pro-neurotensin in rat brain.

The neuropeptides/neurotransmitters neurotensin (NT) and neuromedin (NN) are synthesized by endoproteolytic cleavage of a common inactive precursor, pro-NT/NN. In vitro studies have suggested that the prohormone convertases PC5A and PC2 might both be involved in this process. In the present study, we used dual immunohistochemical techniques to determine whether either one or both of these two convertases were co-localized with pro-NT/NN maturation products and could therefore be involved in the physiological processing of this propeptide in rat brain. PC2-immunoreactive neurons were present in all regions immunopositive for NT. All but three regions expressing NT were also immunopositive for PC5A. Dual localization of NT with either convertase revealed that NT was extensively co-localized with both PC5A and PC2, albeit with regional differences. These results strongly suggest that PC5A and PC2 may play a key role in the maturation of pro-NT/NN in mammalian brain. The regional variability in NT/PC co-localization patterns may account for the region-specific maturation profiles previously reported for pro-NT/NN. The high degree of overlap between PC5A and PC2 in most NT-rich areas further suggests that these two convertases may act jointly to process pro-NT/NN. At the subcellular level, PC5A was largely co-localized with the mid-cisternae Golgi marker MG-160. By contrast, PC2 was almost completely excluded from MG-160-immunoreactive compartments. These results suggest that PC5A, which is particularly efficient at cleaving the two C-terminal-most dibasics of pro-NT/NN, may be acting as early as in the Golgi apparatus to release NT, whereas PC2, which is considerably more active than PC5A in cleaving the third C-terminal doublet, may be predominantly involved further distally along the secretory pathway to release NN.

Cost and health related quality of life consequences of multiple sclerosis.

OBJECTIVES: To (i) quantify the cost of multiple sclerosis (MS) to the Canadian health care system and society; (ii) measure health utility in MS patients, and (iii) examine the influence of disability on patient utility and health care costs. MATERIALS AND METHODS: A comprehensive patient survey and chart review of relapsing MS patients in remission, relapse and recalling a relapse. RESULTS: Annual remission costs increased with EDSS level ($7596 at EDSS 1, $33 206 at EDSS 6). At all EDSS levels the largest costs were due to inability to work, which increased with EDSS. The average relapse cost for all EDSS levels was $1367. An inverse correlation was found between EDSS level and patient utility for patients in remission and relapse. The decrease in remission health utility from EDSS 1 to 6 was 0.24, which is 25% greater than the difference in health status between an average 25 and 85 year-old. CONCLUSIONS: This study demonstrates that MS produces substantial health care costs and reductions in patient quality of life and ability to work, losses that can be avoided or delayed if disease progression is slowed. These data provide health-care decision-makers with the opportunity to consider the full impact of MS when faced with budget allocation decisions.

Expression of tumor necrosis factor alpha (TNF alpha) and interleukin 6 (IL-6) mRNA in adult human astrocytes: comparison with adult microglia and fetal astrocytes.

Astrocytes and microglia are cell populations which are implicated as being capable of regulating and effecting immune responses within the central nervous system (CNS). These functions are postulated to be mediated at least in part by production of soluble protein molecules termed cytokines. In this study, we utilized dissociated cultures of glial cells prepared from adult and fetal CNS tissue and a combined in situ hybridization-immunocytochemical technique in order to compare expression of TNF alpha and IL-6 mRNA between adult and fetal astrocytes and between adult astrocytes and microglia. Our results, using digoxygenin-labeled riboprobes, indicate that in contrast to fetal astrocytes only rare adult astrocytes express TNF alpha and IL-6 transcripts under our serum-supplemented basal culture conditions. Activation with LPS and IFN gamma increased the proportion of adult astrocytes expressing detectable TNF alpha and IL-6 mRNA signals; however, the proportion was significantly less than for microglia contained in the same cultures. These results suggest that microglia rather than astrocytes are more likely to be sources of these cytokines within the adult human CNS. Further studies of cytokine expression by glial cells will need to consider both the age and species of the glial cells used.

Post-translational processing of the neurotensin/neuromedin N precursor in the central nervous system of the rat--II. Immunohistochemical localization of maturation products.

The neurotensin/neuromedin N precursor molecule possesses four lysine-arginine dibasic residues which represent potential sites of cleavage by proteolytic maturation enzymes. As shown in the preceding paper, all of these dibasic residues are cleaved to a variable extent in rat brain. The aim of the present study was to localize immunohistochemically the resulting maturation products using site-specific antibodies directed against neurotensin, as well as against the exposed KLPLVL (K6L) and EKEEVI (E6I) sequences of the precursor. In a first set of experiments, each antigen was singly labelled in serial adjacent sections through the rat brain using a peroxidase-antiperoxidase technique. In a second series of experiments, neurotensin and either E61 or K6L antigens were double labelled in pairs using indirect immunofluorescence and visualized by confocal microscopy. In both types of preparations, immunoreactivity for all three antigens was detected in nerve cell bodies and axon terminals. In the absence of colchicine pretreatment, labelled nerve cell bodies were sparse in both neurotensin- and E6I-immunostained material and virtually undetectable in K6L-immunoreacted sections. By contrast, terminal immunostaining was intense and comparable in distribution for both neurotensin and E6I in most regions examined. K6L axonal labelling showed the same topographic pattern as that of E6I and neurotensin but was consistently weaker, except in the globus pallidus, where both E6I- and K6L-immunoreactive arbors were more widespread than those of neurotensin. These results suggest that the cleavage of the dibasic sites adjacent to the E6I and K6L sequences is more extensive in certain brain regions than in others. Colchicine pretreatment markedly increased the number of neurotensin- and, to a lesser extent. E6I-immunoreactive perikarya throughout the rat brain. However, it only marginally augmented the number of K6L-immunoreactive cell bodies, which remained sparse throughout. These results suggest that the maturation cleavages exposing the E6I and K6L sequences occur further distal to the cell body than the one giving rise to neurotensin. Both E6I- and K6L-immunoreactive perikarya were essentially confined to areas displaying neurotensin immunoreactivity. Furthermore, E6I and K6L antigens were shown in double labeling experiments to be present in the same cells as neurotensin, indicating that even if it is quantitatively different among brain regions, the basic pattern of neurotensin/neuromedin N precursor processing remains qualitatively similar throughout the brain.