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.

Association between adult education, brain volume and dementia risk: longitudinal cohort study of UK Biobank participants.

Less childhood education is a potentially modifiable risk factor for developing incident dementia but it is not known if education in later life is protective. We sought to add to previous work by testing the association between adult education and brain volume as well as exploring the impact of continuing adult education versus intermittent participation. We used data from participants of the UK Biobank cohort, with no prevalent dementia who were asked about adult education participation at baseline and at follow-up. Dementia status was ascertained from self-report or electronic health records. Cox proportional hazards models were built to estimate hazard ratios (HRs) between participation in adult education and dementia risk. In 499,337 participants aged between 40 and 69 at baseline with 13.2 years mean follow-up, in analyses adjusted for age, sex, education, deprivation, ethnicity, hypertension, diabetes, ethnicity, obesity, smoking, alcohol use, physical inactivity and social isolation, we replicated previous findings of a protective effect of adult education on dementia risk (HR 0.82, 95% CI 0.74-0.90, P < 0.001), and showed a trend towards protection against dementia if adult education was continued rather than intermittent. Additionally, adult education did not impact on total brain volume (coefficient - 657.4, 95% CI - 2795.1 to 1480.3, P = 0.547) but it was associated with increased hippocampal volume (coefficient 33.9, 95% CI 8.9 to 59.0, P = 0.008) indicating a potential mechanism for protection against dementia. We have added evidence indicating that continuing adult education participation may be beneficial, although numbers for this analysis were very small. Analysis of brain volume indicated that adult education may have a protective effect by preserving hippocampal size or slowing volume loss, in line with the cognitive reserve hypothesis.

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.

Interpreter-mediated neuropsychological assessment: Clinical considerations and recommendations from the European Consortium on Cross-Cultural Neuropsychology (ECCroN).

OBJECTIVE: With increasing international migration, societies have become increasingly diverse worldwide. Although neuropsychological assessment is influenced by several diversity characteristics, language barriers have repeatedly been identified as one of the main challenges to cross-cultural neuropsychological assessment in migrant populations. Importantly, neuropsychologists are often required to conduct interpreter-mediated neuropsychological assessments without any graduate training or continuing education on the topic. To address this gap, the objective of this paper is to provide guidelines for interpreter-mediated neuropsychological assessment. METHOD: A European Consortium on Cross-Cultural Neuropsychology (ECCroN) task force conducted a conceptual literature review and provided recommendations for good practice and working principles to inform the preparation and administration of interpreter-mediated assessments. RESULTS: ECCroN takes the position that it is the responsibility of neuropsychologists, as well as the institutions or organizations that employ them, to ensure effective communication between themselves and their patients. This may be accomplished by preparing for an interpreter-mediated assessment by engaging an appropriate interpreter, which in most circumstances will be a professional in-person interpreter speaking the same language(s) or dialect(s) as the patient, and considering practical, language, and cross-cultural issues. During the assessment, reasonable steps should be taken to proactively manage the proceedings and adopt a communication style that facilitates effective patient-directed communication, and when interpreting test data and determining formulations and diagnoses, the limitations of interpreter-mediated assessment should be carefully considered. CONCLUSION: Adhering to the provided recommendations and working principles may help neuropsychologists provide competent interpreter-mediated neuropsychological assessments to linguistically diverse patients.

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.

The Effects of Estrogen on the Risk of Developing Dementia: A Cohort Study Using the UK Biobank Data.

OBJECTIVES: The protective role of estrogen in the development of dementia remains uncertain. We investigated the role of lifetime cumulative exposure to estrogen in dementia in the UK Biobank. METHODS: Reproductive characteristics, including estrogen length and history of surgery (hysterectomy/oophorectomy), were used as exposure variables. Cox Proportional Hazard models were used to estimate hazard ratios (HR) for the development of dementia. RESULTS: A total of 273,260 female participants were included in this study. Compared to women with the shortest estrogen length, women with the longer estrogen length (38-42) had a 28% decreased risk of dementia (HR = 0.718, 95% confidence interval [CI] = 0.651-0.793). Women with later last age at estrogen exposure (50-52) had a 24% decreased risk for dementia (HR = 0.763, 95% CI = 0.695-0.839) compared to women with younger age at last estrogen exposure (≤45). Later age at menarche (≥15) was associated with a 12% increased risk for dementia (HR = 1.121, 95% CI = 1.018-1.234) compared to women with earlier age at menarche (≤12). Women with a history of surgery had an 8% increased risk of dementia (HR = 1.079, 95% CI = 1.002-1.164) compared to women without a history of surgery. CONCLUSION: This study found that more prolonged exposure to estrogen (longer estrogen length and later age at last estrogen exposure) had a decreased risk for dementia, and shorter exposure to estrogen (later age at menarche and history of reproductive surgery) had an increased risk for dementia. Based on the results of this study, estrogen might have a protective role in women in the development of dementia.

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.

Systematic Review and Meta-Analysis of Brief Cognitive Instruments to Evaluate Suspected Dementia in Chinese-Speaking Populations.

Background: Chinese is the most commonly spoken world language; however, most cognitive tests were developed and validated in the West. It is essential to find out which tests are valid and practical in Chinese speaking people with suspected dementia. Objective: We therefore conducted a systematic review and meta-analysis of brief cognitive tests adapted for Chinese-speaking populations in people presenting for assessment of suspected dementia. Methods: We searched electronic databases for studies reporting brief (≤20 minutes) cognitive test's sensitivity and specificity as part of dementia diagnosis for Chinese-speaking populations in clinical settings. We assessed quality using Centre for Evidence Based Medicine (CEBM) criteria and translation and cultural adaptation using the Manchester Translation Reporting Questionnaire (MTRQ), and Manchester Cultural Adaptation Reporting Questionnaire (MCAR). We assessed heterogeneity and combined sensitivity in meta-analyses. Results: 38 studies met inclusion criteria and 22 were included in meta-analyses. None met the highest CEBM criteria. Five studies met the highest criteria of MTRQ and MCAR. In meta-analyses of studies with acceptable heterogeneity (I2 <  75%), Addenbrooke's Cognitive Examination Revised &III (ACE-R & ACE-III) had the best sensitivity and specificity; specifically, for dementia (93.5% & 85.6%) and mild cognitive impairment (81.4% & 76.7%). Conclusions: Current evidence is that the ACE-R and ACE-III are the best brief cognitive assessments for dementia and mild cognitive impairment in Chinese-speaking populations. They may improve time taken to diagnosis, allowing people to access interventions and future planning.

South Asian, Black and White ethnicity and the effect of potentially modifiable risk factors for dementia: A study in English electronic health records.

INTRODUCTION: We aimed to investigate ethnic differences in the associations of potentially modifiable risk factors with dementia. METHODS: We used anonymised data from English electronic primary care records for adults aged 65 and older between 1997 and 2018. We used Cox regression to investigate main effects for each risk factor and interaction effects between each risk factor and ethnicity. RESULTS: We included 865,674 people with 8,479,973 person years of follow up. Hypertension, dyslipidaemia, obesity and diabetes were more common in people from minority ethnic groups than White people. The impact of hypertension, obesity, diabetes, low HDL and sleep disorders on dementia risk was increased in South Asian people compared to White people. The impact of hypertension was greater in Black compared to White people. DISCUSSION: Dementia prevention efforts should be targeted towards people from minority ethnic groups and tailored to risk factors of particular importance.

Traumatic life events and risk for dementia: a systematic review and meta-analysis.

OBJECTIVES: To systematically review the association between traumatic life events (TLE) and dementia risk. DESIGN: Systematic review and meta-analysis. DATA SOURCES: APA, PsychINFO, Embase and MEDLINE from their inception to 29.05.21 and updated on 20.04.22. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Original research articles published in peer reviewed journals examining the association between TLE and all cause dementia in individuals aged 60 and over. Two researchers independently assessed the risk of bias using the Newcastle-Ottawa Scale. We conducted a generic inverse variance random effects meta-analysis to provide an overall estimate of TLE impact on dementia risk. MAIN OUTCOME MEASURES: Risk, odds and hazards ratios relating to dementia risk. RESULTS: Initially, 3,487 studies were retrieved in the search and seven studies were included in the meta-analysis with data being used from 276,570 participants. TLE were associated with increased dementia risk. Trauma in general had a pooled HR of 1.21, (95% CI 1.03, 1.43, P = 0.0001). War/ Holocaust trauma and childhood trauma were also associated with increased dementia risk (HR = 1.28 (95% CI 1.01-1.63, P = 0.02) and HR = 1.76 (95% CI 1.17-2.64, P = 0.007) respectively). CONCLUSIONS: We have found an association between TLE and dementia risk. Future research exploring the dimensions of TLE and individual level factors are needed to better understand the relationship between TLE and dementia. TRIAL REGISTRATION: PROSPERO CRD42021253090.

Trans-ethnic genomic informed risk assessment for Alzheimer's disease: An International Hundred K+ Cohorts Consortium study.

BACKGROUND: As a collaboration model between the International HundredK+ Cohorts Consortium (IHCC) and the Davos Alzheimer's Collaborative (DAC), our aim was to develop a trans-ethnic genomic informed risk assessment (GIRA) algorithm for Alzheimer's disease (AD). METHODS: The GIRA model was created to include polygenic risk score calculated from the AD genome-wide association study loci, the apolipoprotein E haplotypes, and non-genetic covariates including age, sex, and the first three principal components of population substructure. RESULTS: We validated the performance of the GIRA model in different populations. The proteomic study in the participant sites identified proteins related to female infertility and autoimmune thyroiditis and associated with the risk scores of AD. CONCLUSIONS: As the initial effort by the IHCC to leverage existing large-scale datasets in a collaborative setting with DAC, we developed a trans-ethnic GIRA for AD with the potential of identifying individuals at high risk of developing AD for future clinical applications.

Dementia prevention in memory clinics: recommendations from the European task force for brain health services.

Observational population studies indicate that prevention of dementia and cognitive decline is being accomplished, possibly as an unintended result of better vascular prevention and healthier lifestyles. Population aging in the coming decades requires deliberate efforts to further decrease its prevalence and societal burden. Increasing evidence supports the efficacy of preventive interventions on persons with intact cognition and high dementia risk. We report recommendations for the deployment of second-generation memory clinics (Brain Health Services) whose mission is evidence-based and ethical dementia prevention in at-risk individuals. The cornerstone interventions consist of (i) assessment of genetic and potentially modifiable risk factors including brain pathology, and risk stratification, (ii) risk communication with ad-hoc protocols, (iii) risk reduction with multi-domain interventions, and (iv) cognitive enhancement with cognitive and physical training. A roadmap is proposed for concept validation and ensuing clinical deployment.

Equity in care and support provision for people affected by dementia: experiences of people from UK South Asian and White British backgrounds.

OBJECTIVES: To explore the care and support received and wanted by United Kingdom (UK) South Asian and White British people affected by dementia and whether access to it is equitable. DESIGN: Semi-structured interviews using a topic guide. SETTING: Eight memory clinics across four UK National Health Service Trusts; three in London and one in Leicester. PARTICIPANTS: We purposefully recruited a maximum variation sample of people living with dementia from South Asian or White British backgrounds, their family carers, and memory clinic clinicians. We interviewed 62 participants including 13 people living with dementia, 24 family carers, and 25 clinicians. MEASUREMENTS: We audio-recorded interviews, transcribed them, and analyzed them using reflexive thematic analysis. RESULTS: People from either background were willing to accept needed care and wanted competence and communication from carers. South Asian people frequently discussed needing care from someone with a shared language, but language differences could also be an issue for White British people. Some clinicians thought South Asian people had a stronger preference to provide care within the family. We found that preferences for who provides care varied across families regardless of ethnicity. Those with more financial resources and English language have more options for care that meets their needs. CONCLUSIONS: People of the same background make differing choices about care. Equitable access to care is impacted by people's personal resources, and people from South Asian backgrounds may experience the double disadvantage of having fewer options for care that meets their needs and fewer resources to seek care elsewhere.

Tailoring STrAtegies for RelaTives for Black and South Asian dementia family carers in the United Kingdom: A mixed methods study.

OBJECTIVES: We culturally adapted STrAtegies for RelaTives (START), a clinically and cost-effective intervention for dementia family carers, for Black and South Asian families. It had previously been delivered to family carers around the time of diagnosis, when most people with dementia had very mild, mild or moderate dementia. METHODS: We interviewed a maximum variation sample of family carers (phase one; n = 15 South Asian; n = 11 Black) about what aspect of START, required cultural adaptation, then analysed it thematically using the Cultural Treatment Adaptation Framework then adapted it in English and into Urdu. Facilitators then delivered START individually to carers (phase two; n = 13 South Asian; n = 8 Black). We assessed acceptability and feasibility through the number of sessions attended, score for fidelity to the intervention and interviewing family carers about their experiences. We used the Hospital Anxiety and Depression Scale. to examine whether immediate changes in family carers' mental health were in line with previous studies. RESULTS: In phase one we made adaptations to peripheral elements of START, clarifying language, increasing illustrative vignettes numbers, emphasising privacy and the facilitator's cultural competence and making images ethnically diverse. In phase two 21 family carers consented to receive the adapted intervention; 12 completed ≥5/8 sessions; four completed fewer sessions and five never started. Baseline HADS score (n = 21) was 14.4 (SD = 9.8) but for those who we were able to follow up was 12.3 (SD 8.1) and immediately post-intervention was 11.3 (n = 10; SD = 6.1). Family carers were positive about the adapted START and continued to use elements after the intervention. CONCLUSIONS: Culturally adapted START was acceptable and feasible in South Asian and Black UK-based family carers and changes in mental health were in line with those in the original clinical trial. Our study shows that culturally inclusive START was also acceptable. Changes made in adaptations were relevant to all populations. We now use the adapted version for all family carers irrespective of ethnicity.

Systematic review of arts and culture-based interventions for people living with dementia and their caregivers.

AIMS: To explore and summarize studies investigating the effect of arts and culture interventions for people living with dementia and their caregivers on the well-being and cognition of the person living with dementia and, caregiver strain. METHODS: We carried out a systematic search of five electronic databases (PubMed, PsychINFO, Embase, CINAHL, and Cochrane Library). We included original research published in peer-reviewed journals including both qualitative and quantitative studies. We assessed quality of included studies using the Cochrane Collaboration's Risk of Bias tools. A narrative synthesis was conducted of all included studies. RESULTS: Of the 4827 articles screened, 34 articles met inclusion criteria. A variety of interventions were identified, with more than half taking place in a museum or gallery. Five RCTs showed improvements in wellbeing outcomes but no cognitive improvements except in some subscales in a music intervention. Most non-randomised studies reported cognitive improvements and well-being improvements for people living with dementia and their caregivers. Studies primarily focused on individuals with mild to moderate dementia. CONCLUSIONS: The use of arts and culture interventions may provide benefits for people living with dementia and their caregivers. However, heterogeneity of the interventions and outcome measures prevented generalization of the results. Further research of arts and culture interventions for people living with dementia and their caregivers should utilize larger controlled trials, standardized outcome measures and include individuals with moderate to severe dementia.

Incidence, age at diagnosis and survival with dementia across ethnic groups in England: A longitudinal study using electronic health records.

INTRODUCTION: We investigated the incidence of diagnosed dementia and whether age at diagnosis and survival afterward differs among the United Kingdom's three largest ethnic groups. METHODS: We used primary care electronic health records, linked Hospital Episode Statistics and mortality data for adults aged ≥65 years. We compared recorded dementia incidence 1997-2018, age at diagnosis, survival time and age at death after diagnosis in White, South Asian, and Black people. RESULTS: Dementia incidence was higher in Black people (incidence rate ratios [IRR] 1.22, 95% CI 1.15-1.30). South Asian and Black people with dementia had a younger age of death than White participants (mean difference for South Asian participants -2.97 years, (95% CI -3.41 to -2.53); and Black participants -2.66 years, (95% CI -3.08 to -2.24). DISCUSSION: South Asian and Black peoples' younger age of diagnosis and death means targeted prevention and care strategies for these groups should be prioritized and tailored to facilitate take-up.

Risk factors for dementia in Brazil: Differences by region and race.

INTRODUCTION: Twelve risk factors (RFs) account for 40% of dementia cases worldwide. However, most data for population attributable fractions (PAFs) are from high-income countries (HIC). We estimated how much these RFs account for dementia cases in Brazil, stratifying estimates by race and socioeconomic level. METHODS: We calculated the prevalence and communalities of 12 RFs using 9412 Brazilian Longitudinal Study of Aging participants, then stratified according to self-reported race and country macro-regions. RESULTS: The overall weighted PAF was 48.2%. Less education had the largest PAF (7.7%), followed by hypertension (7.6%), and hearing loss (6.8%). PAF was 49.0% and 54.0% in the richest and poorest regions, respectively. PAFs were similar among White and Black individuals (47.8% and 47.2%, respectively) but the importance of the main RF varied by race. DISCUSSION: Brazil's potential for dementia prevention is higher than in HIC. Education, hypertension, and hearing loss should be priority targets.

Genetic risk scores and dementia risk across different ethnic groups in UK Biobank.

BACKGROUND: Genetic Risk Scores (GRS) for predicting dementia risk have mostly been used in people of European ancestry with limited testing in other ancestry groups. METHODS: We conducted a logistic regression with all-cause dementia as the outcome and z-standardised GRS as the exposure across diverse ethnic groups. FINDINGS: There was variation in frequency of APOE alleles across ethnic groups. Per standard deviation (SD) increase in z-GRS including APOE, the odds ratio (OR) for dementia was 1.73 (95%CI 1.69-1.77). Z-GRS excluding APOE also increased dementia risk (OR 1.21 per SD increase, 95% CI 1.18-1.24) and there was no evidence that ethnicity modified this association. Prediction of secondary outcomes was less robust in those not of European ancestry when APOE was excluded from the GRS. INTERPRETATION: z-GRS derived from studies in people of European ancestry can be used to quantify genetic risk in people from more diverse ancestry groups. Urgent work is needed to include people from diverse ancestries in future genetic risk studies to make this field more inclusive.

Risk factors, ethnicity and dementia: A UK Biobank prospective cohort study of White, South Asian and Black participants.

BACKGROUND: Our knowledge of the effect of potentially modifiable risks factors on people developing dementia is mostly from European origin populations. We aimed to explore if these risk factors had similar effects in United Kingdom (UK) White, South Asian and Black UK Biobank participants recruited from 2006-2010 and followed up until 2020. METHODS: We reviewed the literature to 25.09.2020 for meta-analyses identifying potentially modifiable risk factors preceding dementia diagnosis by ≥10 years. We calculated prevalence of each identified risk factor and association with dementia for participants aged ≥55 at registration in UK Biobank. We calculated hazard ratios using Cox regression for each risk factor, stratified by ethnic group, and tested for differences using interaction effects between each risk factor and ethnicity. FINDINGS: We included education, hearing loss, hypertension, obesity, excess alcohol consumption, physical inactivity, smoking, high total cholesterol, depression, diabetes, social isolation, and air pollution as risks. Out of 294,162 participants, there were 287,806 White, 3590 South Asian and 2766 Black people, followed up for up to 14.8 years, with a total follow-up time of 3,392,095 years. During follow-up, 5,972 people (2.03%) developed dementia. Risk of dementia was higher in Black participants than White participants (HR for dementia compared to White participants as reference 1.43, 95% CI 1.16-1.77, p = 0.001) but South Asians had a similar risk. Association between each risk factor and dementia was similar in each ethnic group with no evidence to support any differences. INTERPRETATION: We find that Black participants were more likely to develop dementia than White participants, but South Asians were not. Identified risk factors in White European origin participants had a similar effect in Black and South Asian origin participants. Volunteers in UK Biobank are not representative of the population and interaction effects were underpowered so further work is needed.