Benefits of population-level interventions for dementia risk factors: an economic modelling study for England.

BACKGROUND: Individual-level interventions for dementia risk factors could reduce costs associated with dementia and some are cost-effective. We aimed to estimate the cost-effectiveness of population-level interventions for tackling dementia risk factors. METHODS: In this economic modelling study, we included recommended population-based interventions from a previously published review article for which there was consistent and robust evidence of effectiveness in tackling a dementia risk factor (tobacco smoking, excess alcohol use, hypertension, obesity, air pollution, and head injury). We only included interventions if they had not been introduced in England or were in place but could be extended. The interventions studied were increases in tobacco pricing, minimum pricing for alcohol, raising alcohol price, salt reduction policies, sugar reduction policies, low emission zones, and compulsory helmet use for cycling by children (aged 5-18 years). We used published intervention effect sizes and relative risks for each risk factor and a Markov model to estimate progression to dementia in populations with and without the intervention, looking at lifetime risk, in the population of England. FINDINGS: We estimated that reductions in excess alcohol use through minimum unit pricing would lead to cost-savings of £280 million and 4767 quality-adjusted life-years (QALYs) gained over an indefinite succession of age cohorts. Reformulation of food products to reduce salt would lead to cost-savings of £2·4 billion and 39 433 QALYs gained and reformulation to reduce sugar would lead to cost-savings of £1·046 billion and 17 985 QALYs gained. Reducing dementia risk from air pollution by introducing low emission zones in English cities with a population of 100 000 or more (that do not already impose restrictions) would lead to £260 million cost-savings and 5119 QALYs gained. Raising cigarette prices by 10% to reduce dementia risk from smoking would lead to 2277 QALYs gained and cost-savings of £157 million. Making bicycle helmets compulsory for children (aged 5-18 years) to reduce dementia risk from head injury would lead to cost-savings of £91 million and 1554 QALYs gained. INTERPRETATION: Population-level interventions could help tackle life course dementia risk and save costs. FUNDING: UK National Institute for Health and Care Research Three Schools dementia research programme.

Considering challenges for the new Alzheimer's drugs: Clinical, population, and health system perspectives.

Recent approvals of amyloid immunotherapy drugs for early Alzheimer's disease (AD) have been highly controversial. In this piece, we consider challenges from the clinical, population health, and health systems perspectives to the role that the new AD drugs might be expected to play, now and in the future, in alleviating the morbidity caused by AD in the population. Clinically, short-term effects are small, adverse events are frequent, treatment regimens are burdensome, and, crucially, long-term effects are unknown. At a population level, there is always likely to be a trade-off between breadth of access and magnitude of benefit for any given individual. At a health system level, roll out of treatment even for only narrowly-defined patient groups will involve considerable resources to identify and treat eligible patients, with profound opportunity costs. Our considered view on current evidence is that there are challenges from each perspective to imagining a foreseeable future in which amyloid immunotherapy significantly alleviates AD morbidity at scale. HIGHLIGHTS: Recent approvals of Alzheimer's drugs have met with excitement but also controversy. Trial effects are small, adverse effects concerning, and long-term effects unknown. Results from trial cohorts may not generalize to broader, more complex patients. Significant resource requirements of eligibility assessment and drug administration. Use in "presymptomatic" populations is not supported by current evidence.

How many future dementia cases would be missed by a high-risk screening program? A retrospective cohort study in a population-based cohort.

INTRODUCTION: Risk prediction models aim to identify those at high risk to receive targeted interventions. We aimed to identify the proportion of future dementia cases that would be missed by a high-risk screening program. METHODS: We identified validated dementia risk prediction models from systematic reviews. We applied these to European Prospective Investigation of Cancer Norfolk, a large population-based cohort of 30,387 individuals with 29 years of linked healthcare data. RESULTS: A maximum of 16.0% (14.7,17.2) and 31.9% (30.2,33.5) of cases arose from the highest risk decile and quintiles, respectively. For every 1000 people considered to be at high risk, a maximum of 235 (215, 255) developed dementia. DISCUSSION: Seven in every 10 cases of dementia arose from people at normal risk, and eight in every 10 people at high risk did not develop dementia. Individual-level prevention approaches targeted at high-risk groups are unlikely to produce large reductions in disease incidence at the population level. HIGHLIGHTS: Dementia, a significant public health challenge, is not an inevitability of aging; risk reduction is possible. Several dementia risk prediction models have been validated in the general population, and these aim to identify people at high risk of the disease who can then be targeted with primary prevention interventions. An alternative prevention approach is to focus on interventions that reduce risk across the population, irrespective of risk status. In our study, seven out of every ten people who developed dementia during 29 year follow-up were classed as 'normal-risk' (rather than 'high risk') at baseline. Eight out of every ten people who were at high risk at baseline did not go on to develop dementia. Even if effective, dementia risk reduction efforts based upon targeted high-risk approaches are unlikely to reduce incidence of disease at the population level.

Changes in prevalence and incidence of dementia and risk factors for dementia: an analysis from cohort studies.

BACKGROUND: Some cohort studies have reported a decline in dementia prevalence and incidence over time, although these findings have not been consistent across studies. We reviewed evidence on changes in dementia prevalence and incidence over time using published population-based cohort studies that had used consistent methods with each wave and aimed to quantify associated changes in risk factors over time using population attributable fractions (PAFs). METHODS: We searched for systematic reviews of cohort studies examining changes in dementia prevalence or incidence over time. We searched PubMed for publications from database inception up to Jan 12, 2023, using the search terms "systematic review" AND "dementia" AND ("prevalence" OR "incidence"), with no language restrictions. We repeated this search on March 28, 2024. From eligible systematic reviews, we searched the references and selected peer-reviewed publications about cohort studies where dementia prevalence or incidence was measured in the same geographical location, at a minimum of two timepoints, and that reported age-standardised prevalence or incidence of dementia. Additionally, data had to be from population-based samples, in which participants' cognitive status was assessed and where validated criteria were used to diagnose dementia. We extracted summary-level data from each paper about dementia risk factors, contacting authors when such data were not available in the published paper, and calculated PAFs for each risk factor at all available timepoints. Where possible, we linked changes in dementia prevalence or incidence with changes in the prevalence of risk factors. FINDINGS: We identified 1925 records in our initial search, of which five eligible systematic reviews were identified. Within these systematic reviews, we identified 71 potentially eligible primary papers, of which 27 were included in our analysis. 13 (48%) of 27 primary papers reported change in prevalence of dementia, ten (37%) reported change in incidence of dementia, and four (15%) reported change in both incidence and prevalence of dementia. Studies reporting change in dementia incidence over time in Europe (n=5) and the USA (n=5) consistently reported a declining incidence in dementia. One study from Japan reported an increase in dementia prevalence and incidence and a stable incidence was reported in one study from Nigeria. Overall, across studies, the PAFs for less education or smoking, or both, generally declined over time, whereas PAFs for obesity, hypertension, and diabetes generally increased. The decrease in PAFs for less education and smoking was associated with a decline in the incidence of dementia in the Framingham study (Framingham, MA, USA, 1997-2013), the only study with sufficient data to allow analysis. INTERPRETATION: Our findings suggest that lifestyle interventions such as compulsory education and reducing rates of smoking through country-level policy changes could be associated with an observed reduction, and therefore future reduction, in the incidence of dementia. More studies are needed in low-income and middle-income countries, where the burden of dementia is highest, and continues to increase. FUNDING: National Institute for Health and Care Research Three Schools' Dementia Research Programme.

Population-level interventions for the primary prevention of dementia: a complex evidence review.

Dementia risk reduction is a global public health priority. Existing primary prevention approaches have favored individual-level interventions, with a research and policy gap for population-level interventions. We conducted a complex, multi-stage, evidence review to identify empirical evidence on population-level interventions for each of the modifiable risk factors identified by the Lancet Commission on dementia (2020). Through a comprehensive series of targeted searches, we identified 4604 articles, of which 135 met our inclusion criteria. We synthesized evidence from multiple sources, including existing non-communicable disease prevention frameworks, and graded the consistency and comprehensiveness of evidence. We derived a population-level intervention framework for dementia risk reduction, containing 26 high- and moderate-confidence policy recommendations, supported by relevant information on effect sizes, sources of evidence, contextual information, and implementation guidance. This review provides policymakers with the evidence they need, in a useable format, to address this critical public health policy gap. Funding: SW is funded by a National Institute for Health and Care Research (NIHR) Doctoral Fellowship. WW and LF are part funded by the NIHR Applied Research Collaboration East of England. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.

Evaluation of clinical benefits of treatments for Alzheimer's disease.

The need for regulatory approval of new therapies for the treatment of Alzheimer's disease-a progressive neurodegenerative condition-has made the assessment of treatment efficacy an urgent priority for discussion and investigation in the field. In the first part of this Personal View, we summarise current views on what constitutes a clinically meaningful benefit from treatment for Alzheimer's disease, including the concept of a minimum treatment effect against which to compare trial outcomes and its limitations. Considering existing and divergent definitions of clinically meaningful change, we define this concept in the second part of the Personal View by proposing a new approach that consecutively considers whether a treatment benefit for Alzheimer's disease is noticeable, valuable, and worthwhile in the context of costs and risks. This approach could be a useful foundation from which the field can move forwards on this issue and address existing gaps in understanding.

Population-level interventions for the primary prevention of dementia: a complex evidence review.

BACKGROUND: Dementia is a leading, global public health challenge. Recent evidence supporting a decrease in age-specific incidence of dementia in high-income countries (HICs) suggests that risk reduction is possible through improved life-course public health. Despite this, efforts to date have been heavily focused on individual-level approaches, which are unlikely to significantly reduce dementia prevalence or inequalities in dementia. In order to inform policy, we identified the population-level interventions for dementia risk reduction with the strongest evidence base. METHODS: We did this complex, multistage, evidence review to summarise the empirical, interventional evidence for population-level interventions to reduce or control each of the 12 modifiable life-course risk factors for dementia identified by the Lancet commission. We conducted a series of structured searches of peer-reviewed and grey literature databases (eg, Medline, Trip database, Cochrane library, Campbell Collaboration, the WHO, and Google Scholar), in January, March, and June, 2023. Search terms related to risk factors, prevention, and population-level interventions, without language restrictions. We extracted evidence of effectiveness and key contextual information to aid consideration and implementation of interventions by policymakers. We performed a narrative synthesis and evidence grading, and we derived a population-level dementia risk reduction intervention framework, structured by intervention type. This study is registered with PROSPERO, ID:CRD42023396193. FINDINGS: We identified clear and consistent evidence for the effectiveness of 26 population-level interventions to reduce the prevalence of nine of the risk factors, of which 23 have been empirically evaluated in HICs, and 16 in low-income and middle-income countries. We identified interventions that acted through fiscal levers (n=5; eg, removing primary school fees), marketing or advertising levers (n=5; eg, plain packaging of tobacco products), availability levers (n=8; eg, cleaner fuel replacement programmes for cooking stoves), and legislative levers (n=8; eg, mandated provision of hearing protective equipment at noisy workplaces). We were not able to recommend any interventions for diabetes (other than indirectly through action on obesity and physical inactivity), depression, or social isolation. INTERPRETATION: This complex evidence review provides policymakers and public health professionals with an evidence-based framework to help develop and implement population-level approaches for dementia risk reduction that could significantly reduce the population's risk of dementia and reduce health inequalities. FUNDING: None.

Exploring English policymakers' attitudes towards dementia risk reduction: A qualitative study.

AIM: A growing evidence-base indicates that dementia occurrence can be changed. This has been linked to potentially modifiable risk factors. Risk reduction and primary prevention strategies are increasingly recognized as needing to include population-level policies to tackle the social and commercial determinants of health. How this knowledge can influence policymaking on dementia prevention is unknown. Understanding attitudes of policymakers is an important step in translating evidence into practice, helping to gauge system readiness for implementation, and potential barriers and enablers for influencing policy. The aim of this qualitative study is to explore the understanding of, and attitudes to, dementia risk reduction and population-level prevention strategies amongst English policymakers at national, regional, and local level. METHODS: Semi-structured interviews were undertaken with a range of dementia and prevention policymakers, with purposive sampling of national and local policymakers, including politicians, government officials, health system leaders, academics, and dementia charity directors. Analysis of interview transcripts was undertaken by thematic analysis. RESULTS: 14 policymakers were interviewed between November 2021 and February 2022. Three main themes were identified (1) Preventability of dementia, (2) Prevention approach, (3) Barriers and facilitators to improving the approach. DISCUSSION: Policymakers generally held dementia to be partially preventable. Policymakers recognised that both individual- and population-level approaches to primary prevention of dementia are required - with some policymakers perceiving that population-level approaches are under-utilised. Key barriers to implementing more population-level approaches were identified as the complexity and co-ordination required to effectively tackle upstream determinants of health.

What would a population-level approach to dementia risk reduction look like, and how would it work?

Dementia is a leading global public health challenge. Prevention approaches have traditionally focused on individual-level strategies. However, such approaches have limited potential, particularly for resource-constrained populations in which exposure to risk factors is greatest, and exposure to protective factors is lowest. A population-level approach to dementia risk reduction is therefore essential to meet the scale of the challenge and to tackle global inequalities in risk and incidence of disease. Such approaches can be highly cost effective. In this viewpoint article, we describe what such an approach should look like, barriers and facilitators to success, and how we should go about achieving it. We include 10 strategic goals to achieve population-level dementia risk reduction and protection enhancement, targeted at researchers, professionals, funders, science communicators, governments, businesses, and policy makers. If we are to significantly reduce the prevalence of dementia there must be increased emphasis on population-level approaches. HIGHLIGHTS: Dementia risk reduction is a global public health priority Population-level approaches change societal conditions to make them less conducive to dementia's modifiable risk factors, and increase exposure to protective factors. Urgent development of population-level approaches is required to reduce the prevalence of, and inequalities in, dementia Action is required from researchers, governments and business, funders, public health professionals, and science communicators.

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.

Systematic review of post-COVID-19 syndrome rehabilitation guidelines.

Introduction: Post-COVID-19 syndrome is associated with significant health and potential socioeconomic burden. Due to its novel nature, there is a lack of clarity over best practice for the rehabilitation of patients with ongoing or new symptoms following acute COVID-19 infection. We conducted a systematic review of clinical and service guidelines for post-COVID-19 syndrome rehabilitation. Methods: This review was registered on PROSPERO and is reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We included guidelines formally published or endorsed by a recognised professional body, covering rehabilitation of people with symptoms following resolution of acute COVID-19 infection. We searched Medline, Embase, PsycINFO, CINAHL, Web of Science, NHS Evidence, MedRxiv, PsyArXiv and Google for terms related to COVID-19, rehabilitation and guideline. Two reviewers independently screened articles for inclusion, data extracted and quality assessed using the AGREE II and AGREE-REX tools for clinical guidelines and the AGREE-HS tool for service guidelines. We included guidelines of sufficient quality in a narrative synthesis. Results: We identified 12 790 articles, of which 37 guidelines (19 clinical only, 7 service only and 11 combined clinical and service) were included. Guidelines covered a range of countries, rehabilitation types, populations and rehabilitation settings. Synthesis of clinical guidelines (n=4) was structured following the patient pathway, from identification, to assessment, treatment and discharge, with consideration of specific patient groups. Synthesis of service guidelines (n=8) was structured according to the Donabedian framework. Discussion: Though the available post-COVID-19 syndrome rehabilitation guidelines were generally of poor quality, there was a high degree of consensus regarding the breadth of symptoms, the need for holistic assessment by a broad multidisciplinary team and person-centred care. There was less clarity on management options, measuring outcomes and discharge criteria. PROSPERO registration number: CRD42021236049.