Population attributable fractions of modifiable risk factors for dementia: a systematic review and meta-analysis.

BACKGROUND: More than 57 million people have dementia worldwide. Evidence indicates a change in dementia prevalence and incidence in high-income countries, which is likely to be due to improved life-course population health. Identifying key modifiable risk factors for dementia is essential for informing risk reduction and prevention strategies. We therefore aimed to estimate the population attributable fraction (PAF) for dementia associated with modifiable risk factors. METHODS: In this systematic review and meta-analysis, we searched Embase, MEDLINE, and PsycINFO, via Ovid, from database inception up to June 29, 2023, for population-derived or community-based studies and reviews reporting a PAF value for one or more modifiable risk factor for later-life dementia (prevalent or incident dementia in people aged ≥60 years), with no restrictions on dementia subtype, the sex or baseline age of participants, or the period of study. Articles were independently screened for inclusion by four authors, with disagreements resolved through consensus. Data including unweighted and weighted PAF values (weighted to account for communality or overlap in risk) were independently extracted into a predefined template by two authors and checked by two other authors. When five or more unique studies investigated a given risk factor or combination of the same factors, random-effects meta-analyses were used to calculate a pooled PAF percentage estimate for the factor or combination of factors. The review protocol was registered on PROSPERO, CRD42022323429. FINDINGS: 4024 articles were identified, and 74 were included in our narrative synthesis. Overall, PAFs were reported for 61 modifiable risk factors, with sufficient data available for meta-analysis of 12 factors (n=48 studies). In meta-analyses, the highest pooled unweighted PAF values were estimated for low education (17·2% [95% CI 14·4-20·0], p<0·0001), hypertension (15·8% [14·7-17·1], p<0·0001), hearing loss (15·6% [10·3-20·9], p<0·0001), physical inactivity (15·2% [12·8-17·7], p<0·0001), and obesity (9·4% [7·3-11·7], p<0·0001). According to weighted PAF values, low education (9·3% [6·9-11·7], p<0·0001), physical inactivity (7·3% [3·9-11·2], p=0·0021), hearing loss (7·2% [5·2-9·7], p<0·0001), hypertension (7·1% [5·4-8·8], p<0·0001), and obesity (5·3% [3·2-7·4], p=0·0001) had the highest pooled estimates. When low education, midlife hypertension, midlife obesity, smoking, physical inactivity, depression, and diabetes were combined (Barnes and Yaffe seven-factor model; n=9 studies), the pooled unweighted and weighted PAF values were 55·0% (46·5-63·5; p<0·0001) and 32·0% (26·6-37·5; p<0·0001), respectively. The pooled PAF values for most individual risk factors were higher in low-income and middle-income countries (LMICs) versus high-income countries. INTERPRETATION: Governments need to invest in a life-course approach to dementia prevention, including policies that enable quality education, health-promoting environments, and improved health. This investment is particularly important in LMICs, where the potential for prevention is high, but resources, infrastructure, budgets, and research focused on ageing and dementia are limited. FUNDING: UK Research and Innovation (Medical Research Council).

Cardiovascular disease, associated risk factors, and risk of dementia: An umbrella review of meta-analyses.

Introduction: Cardiovascular diseases (CVDs) have been associated with an increased risk of dementia; yet the evidence is mixed. This review critically appraises and synthesises current evidence exploring associations between dementia risk and CVD and their risk factors, including coronary heart disease, heart failure, atrial fibrillation, hypertension, hyperlipidaemia, and arterial stiffness. Methods: MEDLINE, Embase, PsycINFO, and the Cochrane Database of Systematic Reviews were searched to identify systematic reviews with meta-analyses investigating the association between at least one of the CVDs of interest and dementia risk. The Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Systematic Reviews was used to assess methodological quality. Results: Twenty-five meta-analyses published between 2007 and 2021 were included. Studies largely consisted of cohorts from North America and Europe. Findings were variable, with coronary heart disease, heart failure, and atrial fibrillation consistently associated with increased risk for all-cause dementia, but results were inconsistent for Alzheimer's disease. Hypertension was more frequently associated with dementia during mid-life compared to late life. Findings concerning cholesterol were complex, and while results were inconsistent for low-density lipoprotein cholesterol and total cholesterol, there appeared to be no associations between triglycerides and high-density lipoprotein cholesterol. All meta-analyses investigating hypercholesterolaemia showed significant increases in dementia risk. There was a paucity of research on the association between arterial stiffness and dementia risk. Conclusion: Targeted CVD dementia prevention strategies could reduce dementia prevalence. Future research should determine the underpinning mechanisms linking heart and brain health to determine the most effective strategies for dementia risk reduction in CVD populations.

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.

Risk factors for dementia in the context of cardiovascular disease: A protocol of an overview of reviews.

BACKGROUND: Dementia is a major public health priority. Although there is abundant evidence of an association between dementia and poor cardiovascular health, findings have been inconsistent and uncertain in identifying which factors increase dementia risk in those with cardiovascular disease. Indeed, multiple variables including sociodemographic, economic, health, lifestyle and education may indicate who is at higher vs. lower dementia risk and could be used in prediction modelling. Therefore, the aim of this review is to synthesise evidence on the key risk factors for dementia in those with a history of cardiovascular disease. METHODS: This is an overview of reviews protocol, registered on PROSPERO (CRD42021265363). Four electronic databases including MEDLINE, EMBASE, PsycINFO, and the Cochrane Database of Systematic Reviews will be searched. Studies will be included if they are systematic reviews and/or meta-analyses that have investigated the risk of incident dementia (all-cause and subtypes including Alzheimer's disease and vascular dementia) in people with a history of coronary heart disease, heart failure, atrial fibrillation, hypertension, hyperlipidaemia, and vascular stiffness. Study selection will be completed by two independent researchers according to the eligibility criteria, and conflicts resolved by a third reviewer. References will be exported into Covidence for title and abstract sifting, full-text review, and data extraction. Methodological quality will be assessed using the AMSTAR-2 criteria and confidence of evidence will be assessed using the GRADE classification. This overview of reviews will follow PRISMA guidelines. If there is sufficient homogeneity in the data, the results will be pooled, and a meta-analysis conducted to determine the strength of association between each risk factor and incident all-cause dementia and its subtypes for each cardiovascular diagnoses separately. DISCUSSION: We will create a comprehensive summary of the key risk factors linking cardiovascular diseases to risk of incident dementia. This knowledge is essential for informing risk predictive model development as well as the development of risk reduction and prevention strategies.