The longitudinal associations between ambient air pollution exposure and dementia in the UK: results from the cognitive function and ageing study II and Wales.

BACKGROUND: Air pollution has been recognised as a potential risk factor for dementia. Yet recent epidemiological research shows mixed evidence. The aim of this study is to investigate the longitudinal associations between ambient air pollution exposure and dementia in older people across five urban and rural areas in the UK. METHODS: This study was based on two population-based cohort studies of 11329 people aged ≥ 65 in the Cognitive Function and Ageing Study II (2008-2011) and Wales (2011-2013). An algorithmic diagnosis method was used to identify dementia cases. Annual concentrations of four air pollutants (NO2, O3, PM10, PM2.5) were modelled for the year 2012 and linked via the participants' postcodes. Multistate modelling was used to examine the effects of exposure to air pollutants on incident dementia incorporating death and adjusting for sociodemographic factors and area deprivation. A random-effect meta-analysis was carried out to summarise results from the current and nine existing cohort studies. RESULTS: Higher exposure levels of NO2 (HR: 1.04; 95% CI: 0.94, 1.14), O3 (HR: 0.90; 95% CI: 0.70, 1.15), PM10 (HR: 1.17; 95% CI: 0.86, 1.58), PM2.5 (HR: 1.41; 95% CI: 0.71, 2.79) were not strongly associated with dementia in the two UK-based cohorts. Inconsistent directions and strengths of the associations were observed across the two cohorts, five areas, and nine existing studies. CONCLUSIONS: In contrast to the literature, this study did not find clear associations between air pollution and dementia. Future research needs to investigate how methodological and contextual factors can affect evidence in this field and clarity the influence of air pollution exposure on cognitive health over the lifecourse.

The Microglial Transcriptome of Age-Associated Deep Subcortical White Matter Lesions Suggests a Neuroprotective Response to Blood-Brain Barrier Dysfunction.

Age-associated deep-subcortical white matter lesions (DSCLs) are an independent risk factor for dementia, displaying high levels of CD68+ microglia. This study aimed to characterize the transcriptomic profile of microglia in DSCLs and surrounding radiologically normal-appearing white matter (NAWM) compared to non-lesional control white matter. CD68+ microglia were isolated from white matter groups (n = 4 cases per group) from the Cognitive Function and Ageing Study neuropathology cohort using immuno-laser capture microdissection. Microarray gene expression profiling, but not RNA-sequencing, was found to be compatible with immuno-LCM-ed post-mortem material in the CFAS cohort and identified significantly differentially expressed genes (DEGs). Functional grouping and pathway analysis were assessed using the Database for Annotation Visualization and Integrated Discovery (DAVID) software, and immunohistochemistry was performed to validate gene expression changes at the protein level. Transcriptomic profiling of microglia in DSCLs compared to non-lesional control white matter identified 181 significant DEGs (93 upregulated and 88 downregulated). Functional clustering analysis in DAVID revealed dysregulation of haptoglobin-haemoglobin binding (Enrichment score 2.5, p = 0.017), confirmed using CD163 immunostaining, suggesting a neuroprotective microglial response to blood-brain barrier dysfunction in DSCLs. In NAWM versus control white matter, microglia exhibited 347 DEGs (209 upregulated, 138 downregulated), with significant dysregulation of protein de-ubiquitination (Enrichment score 5.14, p < 0.001), implying an inability to maintain protein homeostasis in NAWM that may contribute to lesion spread. These findings enhance understanding of microglial transcriptomic changes in ageing white matter pathology, highlighting a neuroprotective adaptation in DSCLs microglia and a potentially lesion-promoting phenotype in NAWM microglia.

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.

Delirium is more common and associated with worse outcomes in Parkinson's disease compared to older adult controls: results of two prospective longitudinal cohort studies.

BACKGROUND: Inpatient prevalence of Parkinson's disease (PD) delirium varies widely across the literature. Delirium in general older populations is associated with adverse outcomes, such as increased mortality, dementia, and institutionalisation. However, to date there are no comprehensive prospective studies in PD delirium. This study aimed to determine delirium prevalence in hospitalised PD participants and the association with adverse outcomes, compared to a control group of older adults without PD. METHODS: Participants were hospitalised inpatients from the 'Defining Delirium and its Impact in Parkinson's Disease' and the 'Delirium and Cognitive Impact in Dementia' studies comprising 121 PD participants and 199 older adult controls. Delirium was diagnosed prospectively using the Diagnostic and Statistical Manual of Mental Disorders 5th Edition criteria. Outcomes were determined by medical note reviews and/or home visits 12 months post hospital discharge. RESULTS: Delirium was identified in 66.9% of PD participants compared to 38.7% of controls (p < 0.001). In PD participants only, delirium was associated with a significantly higher risk of mortality (HR = 3.3 (95% confidence interval [CI] = 1.3-8.6), p = 0.014) and institutionalisation (OR = 10.7 (95% CI = 2.1-54.6), p = 0.004) 12 months post-discharge, compared to older adult controls. However, delirium was associated with an increased risk of developing dementia 12 months post-discharge in both PD participants (OR = 6.1 (95% CI = 1.3-29.5), p = 0.024) and in controls (OR = 13.4 (95% CI = 2.5-72.6), p = 0.003). CONCLUSION: Delirium is common in hospitalised PD patients, affecting two thirds of patients, and is associated with increased mortality, institutionalisation, and dementia. Further research is essential to understand how to accurately identify, prevent and manage delirium in people with PD who are in hospital.

Associations between social networks, cognitive function, and quality of life among older adults in long-term care.

BACKGROUND: Having rich social networks is associated with better physical and cognitive health, however older adults entering long-term care may experience an increased risk of social isolation and consequent negative impacts on cognitive function. Our study aimed to identify if there is an association between accessing specific types of services or activities within long-term care on social networks and cognition. METHODS: A cross-sectional study of 96 residents from 2 aged care providers in New South Wales, Australia. Residents were given a battery of assessments measuring social network structure (Lubben Social Network Scale, LSNS-12), quality of life (EuroQol 5D, Eq. 5D5L) and cognitive function (Montreal Cognitive Assessment, MoCA). Demographic factors and service use factors were also collected from aged care providers' electronic records. Independent sample t-test, ANOVA and linear regression analyses were used to explore associated factors for cognition. RESULTS: Residents had a mean age of 82.7 ± 9.4 years (median = 81) and 64.6% were women. Most residents had cognitive impairment (70.8%) and reported moderate sized social networks (26.7/60) (Lubben Social Network Scale, LSNS-12). Residents who had larger social networks of both family and friends had significantly better cognitive performance. Service type and frequency of attendance were not associated with cognitive function. CONCLUSIONS: Among individuals most at risk of social isolation, having supportive and fulfilling social networks was associated with preserved cognitive function. The relationship between service provision and social interactions that offer psychosocial support within long-term facilities and its impact over time on cognitive function requires further exploration.

A Delphi consensus to identify the key screening tests/questions for a digital neurological examination for epidemiological research.

BACKGROUND: Most neurological diseases have no curative treatment; therefore, focusing on prevention is key. Continuous research to uncover the protective and risk factors associated with different neurological diseases is crucial to successfully inform prevention strategies. eHealth has been showing promising advantages in healthcare and public health and may therefore be relevant to facilitate epidemiological studies. OBJECTIVE: In this study, we performed a Delphi consensus exercise to identify the key screening tests to inform the development of a digital neurological examination tool for epidemiological research. METHODS: Twelve panellists (six experts in neurological examination, five experts in data collection-two were also experts in the neurological examination, and three experts in participant experience) of different nationalities joined the Delphi exercise. Experts in the neurological examination provided a selection of items that allow ruling out neurological impairment and can be performed by trained health workers. The items were then rated by them and other experts in terms of their feasibility and acceptability. RESULTS: Ten tests and seven anamnestic questions were included in the final set of screening items for the digital neurological examination. Three tests and five anamnestic questions were excluded from the final selection due to their low ratings on feasibility. CONCLUSION: This work identifies the key feasible and acceptable screening tests and anamnestic questions to build an electronic tool for performing the neurological examination, in the absence of a neurologist.

Visual processing speed and its association with future dementia development in a population-based prospective cohort: EPIC-Norfolk.

Visual processing deficits have frequently been reported when studied in individuals with dementia, which suggests their potential utility in supporting dementia screening. The study uses EPIC-Norfolk Prospective Population Cohort Study data (n = 8623) to investigate the role of visual processing speed assessed by the Visual Sensitivity Test (VST) in identifying the risk of future dementia using Cox regression analyses. Individuals with lower scores on the simple and complex VST had a higher probability of a future dementia diagnosis HR1.39 (95% CI 1.12, 1.67, P < 0.01) and HR 1.56 (95% CI 1.27, 1.90, P < 0.01), respectively. Although other more commonly used cognitive dementia screening tests were better predictors of future dementia risk (HR 3.45 for HVLT and HR 2.66, for SF-EMSE), the complex VST showed greater sensitivity to variables frequently associated with dementia risk. Reduced complex visual processing speed is significantly associated with a high likelihood of a future dementia diagnosis and risk/protective factors in this cohort. Combining visual processing tests with other neuropsychological tests could improve the identification of future dementia risk.

Relationships of brain cholesterol and cholesterol biosynthetic enzymes to Alzheimer's pathology and dementia in the CFAS population-derived neuropathology cohort.

Altered cholesterol metabolism is implicated in brain ageing and Alzheimer's disease. We examined whether key genes regulating cholesterol metabolism and levels of brain cholesterol are altered in dementia and Alzheimer's disease neuropathological change (ADNC). Temporal cortex (n = 99) was obtained from the Cognitive Function and Ageing Study. Expression of the cholesterol biosynthesis rate-limiting enzyme HMG-CoA reductase (HMGCR) and its regulator, SREBP2, were detected using immunohistochemistry. Expression of HMGCR, SREBP2, CYP46A1 and ABCA1 were quantified by qPCR in samples enriched for astrocyte and neuronal RNA following laser-capture microdissection. Total cortical cholesterol was measured using the Amplex Red assay. HMGCR and SREBP2 proteins were predominantly expressed in pyramidal neurones, and in glia. Neuronal HMGCR did not vary with ADNC, oxidative stress, neuroinflammation or dementia status. Expression of HMGCR neuronal mRNA decreased with ADNC (p = 0.022) and increased with neuronal DNA damage (p = 0.049), whilst SREBP2 increased with ADNC (p = 0.005). High or moderate tertiles for cholesterol levels were associated with increased dementia risk (OR 1.44, 1.58). APOE ε4 allele was not associated with cortical cholesterol levels. ADNC is associated with gene expression changes that may impair cholesterol biosynthesis in neurones but not astrocytes, whilst levels of cortical cholesterol show a weak relationship to dementia status.

Incident dementia risk among patients with type 2 diabetes receiving metformin versus alternative oral glucose-lowering therapy: an observational cohort study using UK primary healthcare records.

INTRODUCTION: 4.2 million individuals in the UK have type 2 diabetes, a known risk factor for dementia and mild cognitive impairment (MCI). Diabetes treatment may modify this association, but existing evidence is conflicting. We therefore aimed to assess the association between metformin therapy and risk of incident all-cause dementia or MCI compared with other oral glucose-lowering therapies (GLTs). RESEARCH DESIGN AND METHODS: We conducted an observational cohort study using the Clinical Practice Research Datalink among UK adults diagnosed with diabetes at ≥40 years between 1990 and 2019. We used an active comparator new user design to compare risks of dementia and MCI among individuals initially prescribed metformin versus an alternative oral GLT using Cox proportional hazards regression controlling for sociodemographic, lifestyle and clinical confounders. We assessed for interaction by age and sex. Sensitivity analyses included an as-treated analysis to mitigate potential exposure misclassification. RESULTS: We included 211 396 individuals (median age 63 years; 42.8% female), of whom 179 333 (84.8%) initiated on metformin therapy. Over median follow-up of 5.4 years, metformin use was associated with a lower risk of dementia (adjusted HR (aHR) 0.86 (95% CI 0.79 to 0.94)) and MCI (aHR 0.92 (95% CI 0.86 to 0.99)). Metformin users aged under 80 years had a lower dementia risk (aHR 0.77 (95% CI 0.68 to 0.85)), which was not observed for those aged ≥80 years (aHR 0.95 (95% CI 0.87 to 1.05)). There was no interaction with sex. The as-treated analysis showed a reduced effect size compared with the main analysis (aHR 0.90 (95% CI 0.83 to 0.98)). CONCLUSIONS: Metformin use was associated with lower risks of incident dementia and MCI compared with alternative GLT among UK adults with diabetes. While our findings are consistent with a neuroprotective effect of metformin against dementia, further research is needed to reduce risks of confounding by indication and assess causality.

Long-term impact of the COVID-19 pandemic on the quality of life of people with dementia and their family carers.

INTRODUCTION: Few studies have longitudinally mapped quality of life (QoL) trajectories of newly diagnosed people with dementia and their carers, particularly during coronavirus disease-2019 (COVID-19). METHODS: In a UK cohort study, 261 newly diagnosed people with dementia and 206 family carers were assessed prior to the pandemic (July 2019-March 2020), followed up after the first lockdown (July-October 2020) and then again a year and 2 years later. Latent growth curve modelling examined the level and change of QoL over the four time-points using dementia-specific QoL measures (DEMQOL and C-DEMQOL). RESULTS: Despite variations in individual change scores, our results suggest that generally people with dementia maintained their QoL during the pandemic and experienced some increase towards the end of the period. This contrasted with carers who reported a general deterioration in their QoL over the same period. 'Confidence in future' and 'Feeling supported' were the only carer QoL subscales to show some recovery post-pandemic. DISCUSSION: It is positive that even during a period of global disruption, decline in QoL is not inevitable following the onset of dementia. However, it is of concern that carer QoL declined during this same period even after COVID-19 restrictions had been lifted. Carers play an invaluable role in the lives of people with dementia and wider society, and our findings suggest that, post-pandemic, they may require greater support to maintain their QoL.

Lower mental health related quality of life precedes dementia diagnosis: findings from the EPIC-Norfolk prospective population-based study.

Lower Health Related Quality of Life (HRQoL) precedes dementia in older adults in the USA. We explore prospective associations between HRQoL and dementia in British adults in mid and late-life, when interventions to optimise cognitive ageing may provide benefit. 7,452 community-dwelling participants (57% women; mean age 69.3 ± 8.3 years) attended the European Prospective Investigation of Cancer-Norfolk study's third health check (3HC) and reported their HRQoL using Short-Form 36 (SF-36). Cox Proportional Hazard regression models explored associations between standard deviation differences in baseline Physical Component (PCS) and Mental Component Summary (MCS) scores, as well as eight SF-36 sub-scales (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, mental health), and incident dementia over ten years. Logistic regression models explored cross-sectional relationships at the 3HC between HRQoL and objective global cognitive function (n = 4435; poor cognition = lowest performance decile). The cohort was examined as a whole and by age-group (50-69, ≥ 70), considering socio-demographics and co-morbidity. Higher MCS scores were associated with lower chance of incident dementia (Hazard Ratio [HR] = 0.74, 95% CI 0.68-0.81) and lower odds of poor cognition (Odds Ratio [OR] = 0.82, 0.76-0.89), with findings similar by age-group. Higher PCS scores were not associated with dementia in the whole cohort (HR = 0.93, 0.84-1.04) or considering age-groups; and were only associated with poor cognition in younger participants (OR = 0.81, 0.72-0.92). Similarly, associations between higher scores on subscales pertaining to mental, but not physical, HRQoL and lower dementia incidence were observed. Lower mental HRQoL precedes dementia diagnosis in middle-aged and older British adults.

Factors That Influence Meeting the Recommended Weekly Physical Activity Target Among Older People With Physical Multimorbidity: Evidence From 6 Low- and Middle-Income Countries.

BACKGROUND: There is a scarcity of studies on the association between physical multimorbidity and lower levels of physical activity among older adults from low- and middle-income countries, while the potential mediating variables in this association are largely unknown. METHODS: Cross-sectional, community-based, nationally representative data from the World Health Organization Study on global AGEing and adult health were analyzed. Data on 11 chronic physical conditions were collected. Scoring <150 minutes of moderate- to high-intensity physical activity per week was considered low physical activity. Multivariable logistic regression and mediation analysis were done to assess associations and quality of life measures which might influence these associations. RESULTS: Data on 14,585 people aged ≥65 years were analyzed (mean [SD] age 72.6 (11.5) y, maximum age 114 y; 55.0% women). After adjustment for potential confounders, compared with no chronic conditions, ≥3 conditions were associated with a significant 1.59 to 2.42 times higher odds for low physical activity. Finally, mobility mediated the largest proportion of the association between ≥3 chronic physical conditions and low physical activity (mediated percentage 50.7%), followed by activities of daily living disability (30.7%), cognition (24.0%), affect (23.6%), and pain/discomfort (22.0%). CONCLUSIONS: Physical multimorbidity was associated with higher odds for low physical activity among older adults residing in low- and middle-income countries. Mobility, disability, cognition, affect, and pain/discomfort explained the largest proportion of this association. Given the universal benefits of regular and sustained participation in physical activity, it would be prudent to implement interventions among older people with physical multimorbidity to increase levels of physical activity. Future studies should assess the impact of addressing the identified potential mediators among people with multimorbidity on physical activity levels.

Umbrella review and Delphi study on modifiable factors for dementia risk reduction.

A 2013 systematic review and Delphi consensus study identified 12 modifiable risk and protective factors for dementia, which were subsequently merged into the "LIfestyle for BRAin health" (LIBRA) score. We systematically evaluated whether LIBRA requires revision based on new evidence. To identify modifiable risk and protective factors suitable for dementia risk reduction, we combined an umbrella review of systematic reviews and meta-analyses with a two-round Delphi consensus study. The review of 608 unique primary studies and opinions of 18 experts prioritized six modifiable factors: hearing impairment, social contact, sleep, life course inequalities, atrial fibrillation, and psychological stress. Based on expert ranking, hearing impairment, social contact, and sleep were considered the most suitable candidates for inclusion in updated dementia risk scores. As such, the current study shows that dementia risk scores need systematic updates based on emerging evidence. Future studies will validate the updated LIBRA score in different cohorts. HIGHLIGHTS: An umbrella review was combined with opinions of 18 dementia experts. Various candidate targets for dementia risk reduction were identified. Experts prioritized hearing impairment, social contact, and sleep. Re-assessment of dementia risk scores is encouraged. Future work should evaluate the predictive validity of updated risk scores.

Cognitive performance following stroke, transient ischaemic attack, myocardial infarction, and hospitalisation: an individual participant data meta-analysis of six randomised controlled trials.

BACKGROUND: Survivors of stroke are often concerned about cognitive problems, and information on the risk of cognitive problems often comes from small studies. We aimed to estimate years of cognitive ageing associated with stroke compared with transient ischaemic attack, myocardial infarction, and other hospitalisations in a large population. METHODS: Using data from six randomised controlled trials (ORIGIN, ONTARGET, TRANSCEND, COMPASS, HOPE-3, and NAVIGATE ESUS), we completed an individual participant data meta-analysis using data requested from the Public Health Research Institute to estimate the association of stroke (by type and severity), transient ischaemic attack, myocardial infarction, and other hospitalisations with cognitive performance measured at the end of each trial. We included participants in any of these randomised controlled trials with a cognitive assessment at baseline and at least one other timepoint. Cognitive performance was measured with the Mini-Mental State Examination or the Montreal Cognitive Assessment, transformed into Z scores. We estimated Z score differences in end of trial cognitive performance between people with and without events and calculated corresponding years of cognitive ageing in these trials, and additionally calculated using a population representative cohort-the Cognitive Function and Ageing Study. FINDINGS: In 64 106 participants from 55 countries, compared with no event, stroke was associated with 18 years of cognitive ageing (1487 strokes included in the model, 95% CI 10 to 28; p<0·0001) and transient ischaemic attack with 3 years (660 transient ischaemic attacks included in the model, 0 to 6; p=0·021). Myocardial infarction (p=0·60) and other hospitalisations (p=0·26) were not associated with cognitive ageing. The mean difference in SD compared with people without an event was -0·84 (95% CI -0·91 to -0·76; p<0·0001) for disabling stroke, and -0·12 (-0·19 to -0·05; p=0·0012) for non-disabling stroke. Haemorrhagic stroke was associated with worse cognition (-0·75, -0·95 to -0·55; p<0·0001) than ischaemic stroke (-0·42, -0·48 to -0·36; p <0·0001). INTERPRETATION: Stroke has a substantial effect on cognition. The effects of transient ischaemic attack were small, whereas myocardial infarction and hospitalisation had a neutral effect. Prevention of stroke could lead to a reduction in cognitive ageing in those at greatest risk. FUNDING: Population Health Research Institute and Chief Scientist Office of Scotland.

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.

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.

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.

Relationship between severe mental illness and physical multimorbidity: a meta-analysis and call for action.

BACKGROUND: People with severe mental illness (SMI) have a higher prevalence of several chronic physical health conditions, and the prevalence of physical multimorbidity is expected to rise. The aim of this study was to assess the strength of the association between SMI and physical multimorbidity. STUDY SELECTION AND ANALYSIS: We systematically searched PubMed/Medline, Scopus, Embase, Web of Science, PsycINFO and the behavioural sciences collection databases, from inception to 31 January 2023, for studies that investigated the association between SMI and physical multimorbidity. Humans of any age either clinically diagnosed and/or currently receiving treatment for SMI, specified as schizophrenia (and related psychotic disorders), bipolar disorder and psychotic depression, were eligible. Data from studies selected for inclusion were converted into ORs, with a subsequent meta-analysis conducted. FINDINGS: We included 19 studies with a total of 194 123 patients with SMI with different diagnoses and drawn from the general population. The pooled OR for physical multimorbidity in people with versus without SMI was 1.84 (95% CI 1.33 to 2.54), with the analysis indicating a high level of heterogeneity (98.38%). The other 15 studies included in the systematic review for which it was not possible to conduct a meta-analysis showed strong associations between SMI and physical multimorbidity. CONCLUSIONS: The current evidence highlights the link between SMI and physical multimorbidity. A multidisciplinary approach is now urgent to develop the best models of services tailored to patients with SMI with physical multimorbidities to improve physical, mental and social outcomes. PROSPERO registration number CRD42023395165.