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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)., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: The identification of effective dementia prevention strategies is a major public health priority, due to the enormous and growing societal cost of this condition. Consumption of a Mediterranean diet (MedDiet) has been proposed to reduce dementia risk. However, current evidence is inconclusive and is typically derived from small cohorts with limited dementia cases. Additionally, few studies have explored the interaction between diet and genetic risk of dementia., Methods: We used Cox proportional hazard regression models to explore the associations between MedDiet adherence, defined using two different scores (Mediterranean Diet Adherence Screener [MEDAS] continuous and Mediterranean diet Pyramid [PYRAMID] scores), and incident all-cause dementia risk in 60,298 participants from UK Biobank, followed for an average 9.1 years. The interaction between diet and polygenic risk for dementia was also tested., Results: Higher MedDiet adherence was associated with lower dementia risk (MEDAS continuous: HR = 0.77, 95% CI = 0.65-0.91; PYRAMID: HR = 0.86, 95% CI = 0.73-1.02 for highest versus lowest tertiles). There was no significant interaction between MedDiet adherence defined by the MEDAS continuous and PYRAMID scores and polygenic risk for dementia., Conclusions: Higher adherence to a MedDiet was associated with lower dementia risk, independent of genetic risk, underlining the importance of diet in dementia prevention interventions., (© 2023. The Author(s).)

Dementia is a significant public health priority with approximately 55 million cases worldwide, and this number is predicted to quadruple by 2050. Adherence to a healthy diet and achieving optimal nutritional status are vital strategies to improve brain health. The importance of this area of research has been consolidated into the new term ‘nutritional psychiatry’. Dietary nitrate, closely associated with the intake of fruits and vegetables, is a compound that is increased in dietary patterns such as the Mediterranean and MIND diets and has protective effects on cognition and brain health. Nitrate is characterised by a complex metabolism and is the precursor of the nitrate–nitrite–nitric oxide (NO) pathway contributing to systemic NO generation. A higher intake of dietary nitrate has been linked to protective effects on vascular outcomes including blood pressure and endothelial function. However, the current evidence supporting the protective effects of dietary nitrate on brain health is less convincing. This article aims to provide a critical appraisal of the current evidence for dietary nitrate supplementation for improving brain health and provide suggestions for future research.

Introduction: More than two-thirds of people with dementia live in low- and middle-income countries (LMICs), resulting in a significant economic burden in these settings. In this systematic review, we consolidate the existing evidence on the cost of dementia in LMICs., Methods: Six databases were searched for original research reporting on the costs associated with all-cause dementia or its subtypes in LMICs. The national-level dementia costs inflated to 2019 were expressed as percentages of each country's gross domestic product (GDP) and summarised as the total mean percentage of GDP. The risk of bias of studies was assessed using the Larg and Moss method., Results: We identified 14 095 articles, of which 24 studies met the eligibility criteria. Most studies had a low risk of bias. Of the 138 LMICs, data were available from 122 countries. The total annual absolute per capita cost ranged from US$590.78 for mild dementia to US$25 510.66 for severe dementia. Costs increased with the severity of dementia and the number of comorbidities. The estimated annual total national costs of dementia ranged from US$1.04 million in Vanuatu to US$195 billion in China. The average total national expenditure on dementia estimated as a proportion of GDP in LMICs was 0.45%. Indirect costs, on average, accounted for 58% of the total cost of dementia, while direct costs contributed 42%. Lack of nationally representative samples, variation in cost components, and quantification of indirect cost were the major methodological challenges identified in the existing studies., Conclusion: The estimated costs of dementia in LMICs are lower than in high-income countries. Indirect costs contribute the most to the LMIC cost. Early detection of dementia and management of comorbidities is essential for reducing costs. The current costs are likely to be an underestimation due to limited dementia costing studies conducted in LMICs, especially in countries defined as low- income., Prospero Registration Number: The protocol was registered in the International Prospective Register of Systematic Reviews database with registration number CRD42020191321., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Dementia represents a key impending global health challenge. The aim of this systematic review was to evaluate the current evidence on nutritional interventions for the prevention of dementia in developing economies in East-Asia. Four comprehensive databases were searched from inception until January 2020: MEDLINE, Embase, PsycInfo, and Scopus. The search was restricted to randomized controlled trials [RCTs] in adult humans, assessing the effect of nutritional interventions on global and domain specific cognitive performance and dementia risk. Meta-analysis of data was conducted for each domain and sub-categorized according to the type of nutritional intervention. Twenty-four RCTs were included, of which, fifteen studies showed significant beneficial effects on cognition. Eighteen studies were included in the meta-analysis. Significant beneficial effects were found for essential fatty acids (EPA/DHA) and micronutrient supplementation on specific cognitive domains including attention and orientation, perception, verbal functions and language skills. The effect size of the interventions appeared to be greater in older subjects with cognitive impairment. Supplementation with B-vitamins and essential fatty acids may represent promising strategies to minimize age-related cognitive decline in Asian populations. Large, high-quality, long-term trials are needed to confirm these findings.

Introduction: Dementia prevalence continues to increase, and effective interventions are needed to prevent, delay or slow its progression. Higher adherence to the Mediterranean diet (MedDiet) and increased physical activity (PA) have been proposed as strategies to facilitate healthy brain ageing and reduce dementia risk. However, to date, there have been no dementia prevention trials in the UK focussed on combined dietary and PA interventions. This study aims to: (1) assess feasibility and acceptability of a theory-underpinned digital and group-based intervention for dementia risk reduction in an 'at risk' UK cohort; (2) evaluate behaviour change responses to the intervention; and, (3) provide information on cognitive, neurological, vascular and physiological outcomes to inform the design of a follow-on, full-scale efficacy trial., Methods: One hundred and eight participants aged 55 to 74 years with a QRISK2 score of ≥10% will be recruited to take part in this 24-week multi-site study. Participants will be randomised into three parallel arms: (1) Control; (2) MedDiet; and, (3) MedDiet+PA. The study will evaluate a personalised website, group session and food delivery intervention to increase MedDiet adherence and PA in older adults at risk of dementia. Diet and PA will be monitored prior to, during and following the intervention. Feasibility, acceptability and hypothesised mediators will be assessed in addition to measures of cognitive function, brain structure/perfusion (MRI), vascular function and metabolic markers (blood, urine and faecal) prior to, and following, the intervention., Discussion: This trial will provide insights into the feasibility, acceptability and mechanism of effect of a multi-domain intervention focussed on the MedDiet alone and PA for dementia risk reduction in an 'at risk' UK cohort., Ethics and Dissemination: The study has received NHS REC and HRA approval (18/NI/0191). Findings will be disseminated via conference presentations, public lectures, and peer-reviewed publications., Trial Registration Details: ClinicalTrials.gov NCT03673722., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

In the last two decades, there has been in-depth investigation into understanding the pathogenesis, epidemiological profiling, and clinical characterization of dementia. However, these investigations have not led to successful interventions to prevent, delay, or reverse the pathological processes underlying dementia. Recent findings of a decrease in dementia risk in high-income countries such as the UK, USA and the Netherlands highlight that dementia, at least in some cases, is preventable. This article includes a synthesis of current knowledge on dementia epidemiology, biological underpinnings, risk factors, and current prevention programs, with the aim to set the path for research, funding, and policy initiatives to address the global public health challenge of how to prevent dementia or reduce risk within the framework of population-based studies. We advocate for development of novel approaches for intelligent data synthesis that go well beyond single approaches to enable powerful risk stratification analyses. An integrated approach is needed where researchers, funders, policymakers, and stakeholders contribute to and work together to formulate effective strategies for the global monitoring and development of population-based risk reduction, treatment, and prevention programs for dementia., (© 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.)

Background: To date, dementia prediction models have been exclusively developed and tested in high-income countries (HICs). However, most people with dementia live in low-income and middle-income countries (LMICs), where dementia risk prediction research is almost non-existent and the ability of current models to predict dementia is unknown. This study investigated whether dementia prediction models developed in HICs are applicable to LMICs., Methods: Data were from the 10/66 Study. Individuals aged 65 years or older and without dementia at baseline were selected from China, Cuba, the Dominican Republic, Mexico, Peru, Puerto Rico, and Venezuela. Dementia incidence was assessed over 3-5 years, with diagnosis according to the 10/66 Study diagnostic algorithm. Discrimination and calibration were tested for five models: the Cardiovascular Risk Factors, Aging and Dementia risk score (CAIDE); the Study on Aging, Cognition and Dementia (AgeCoDe) model; the Australian National University Alzheimer's Disease Risk Index (ANU-ADRI); the Brief Dementia Screening Indicator (BDSI); and the Rotterdam Study Basic Dementia Risk Model (BDRM). Models were tested with use of Cox regression. The discriminative accuracy of each model was assessed using Harrell's concordance (c)-statistic, with a value of 0·70 or higher considered to indicate acceptable discriminative ability. Calibration (model fit) was assessed statistically using the Grønnesby and Borgan test., Findings: 11 143 individuals without baseline dementia and with available follow-up data were included in the analysis. During follow-up (mean 3·8 years [SD 1·3]), 1069 people progressed to dementia across all sites (incidence rate 24·9 cases per 1000 person-years). Performance of the models varied. Across countries, the discriminative ability of the CAIDE (0·52≤c≤0·63) and AgeCoDe (0·57≤c≤0·74) models was poor. By contrast, the ANU-ADRI (0·66≤c≤0·78), BDSI (0·62≤c≤0·78), and BDRM (0·66≤c≤0·78) models showed similar levels of discriminative ability to those of the development cohorts. All models showed good calibration, especially at low and intermediate levels of predicted risk. The models validated best in Peru and poorest in the Dominican Republic and China., Interpretation: Not all dementia prediction models developed in HICs can be simply extrapolated to LMICs. Further work defining what number and which combination of risk variables works best for predicting risk of dementia in LMICs is needed. However, models that transport well could be used immediately for dementia prevention research and targeted risk reduction in LMICs., Funding: National Institute for Health Research, Wellcome Trust, WHO, US Alzheimer's Association, and European Research Council., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: A key focus for dementia risk-reduction is the prevention of socio-demographic, lifestyle, and nutritional risk factors. High sodium intake is associated with hypertension and cardiovascular disease (both are linked to dementia), generating numerous recommendations for salt reduction to improve cardiovascular health., Objective: This systematic review aimed to assess, in middle- and older-aged people, the relationship between dietary sodium intake and cognitive outcomes including cognitive function, risk of cognitive decline, or dementia., Methods: Six databases (PubMed, EMBASE, CINAHL, Psych info, Web of Science, and Cochrane Library) were searched from inception to 1 March 2020. Data extraction included information on study design, population characteristics, sodium reduction strategy (trials) or assessment of dietary sodium intake (observational studies), measurement of cognitive function or dementia, and summary of main results. Risk-of-bias assessments were performed using the National Heart, Lung, and Blood Institute (NHLBI) assessment tool., Results: Fifteen studies met the inclusion criteria including one clinical trial, six cohorts, and eight cross-sectional studies. Studies reported mixed associations between sodium levels and cognition. Results from the only clinical trial showed that a lower sodium intake was associated with improved cognition over six months. In analysis restricted to only high-quality studies, three out of four studies found that higher sodium intake was associated with impaired cognitive function., Conclusion: There is some evidence that high salt intake is associated with poor cognition. However, findings are mixed, likely due to poor methodological quality, and heterogeneous dietary, analytical, and cognitive assessment methods and design of the studies. Reduced sodium intake may be a potential target for intervention. High quality prospective studies and clinical trials are needed.

Background: Time trends for dementia prevalence and incidence rates have been reported over the past seven decades in different countries and some have reported a decline., Objective: To undertake a systematic review to critically appraise and provide an evidence-based summary of the magnitude and direction of the global changes in dementia prevalence and incidence across time., Methods: Medline, EMBASE, and PsychINFO were searched for studies focused on secular trends in dementia prevalence and/or incidence until 18 December 2017. In total, 10,992 articles were identified and 43 retained., Results: Overall, prevalence rates are largely increasing (evidence primarily from record-based surveys and cohort studies in Japan, Canada, and France) or have remained stable (evidence primarily from cohort studies in Sweden, Spain and China). A significant decline in prevalence has however been reported in more recent studies (i.e., from 2010 onwards) from Europe (e.g., UK and Sweden) and the USA. Incidence rates have generally remained stable or decreased in China, Canada, France, Germany, Denmark, Sweden, the Netherlands, UK, and USA. An increase has only been reported in five countries: Italy, Japan, Wales, Germany, and the Netherlands. Only one study reported findings (stability in incidence) from a low and middle-income country using data from Nigeria., Conclusions: The evidence on secular trends in the prevalence and incidence of dementia is mixed including contradictory findings using different (and in some cases the same) datasets in some countries (e.g., the USA, UK, and Sweden). This making it difficult to draw concrete conclusions. However, declining trends recently observed in some high-income Western countries in the most recent two decades including the UK, USA, and Sweden are encouraging. Updated dementia prevalence and incidence estimates will inform public health and financial planning as well as development of prevention strategies.

Purpose of Review: In this review, we summarise the evidence on the association between cardiovascular disease (CVD) and cognitive impairment and explore the role of the nitric oxide (NO) pathway as a causal mechanism., Recent Findings: Evidence from epidemiological studies suggests that the presence of CVD and its risk factors in midlife is associated with an increased risk of later life cognitive impairment and dementia. It is unclear what is driving this association but risk may be conveyed via an increase in neurodegeneration (e.g. amyloid deposition), vascular changes (e.g. small vessel disease) and mechanistically due to increased levels of oxidative stress and inflammation as well as changes in NO bioavailability. CVDs and dementia are major challenges to global health worldwide. The NO pathway may be a promising biological candidate for future studies focused on reducing not only CVD but also risk of cognitive decline and dementia.

Background: Cardiovascular disease and its risk factors have consistently been associated with poor cognitive function and incident dementia. Whether cardiovascular disease prediction models, developed to predict an individual's risk of future cardiovascular disease or stroke, are also informative for predicting risk of cognitive decline and dementia is not known., Objective: The objective of this systematic review was to compare cohort studies examining the association between cardiovascular disease risk models and longitudinal changes in cognitive function or risk of incident cognitive impairment or dementia., Materials and Methods: Medline, PsychINFO, and Embase were searched from inception to March 28, 2014. From 3,413 records initially screened, 21 were included., Results: The association between numerous different cardiovascular disease risk models and cognitive outcomes has been tested, including Framingham and non-Framingham risk models. Five studies examined dementia as an outcome; fourteen studies examined cognitive decline or incident cognitive impairment as an outcome; and two studies examined both dementia and cognitive changes as outcomes. In all studies, higher cardiovascular disease risk scores were associated with cognitive changes or risk of dementia. Only four studies reported model prognostic performance indices, such as Area Under the Curve (AUC), for predicting incident dementia or cognitive impairment and these studies all examined non-Framingham Risk models (AUC range: 0.74 to 0.78)., Conclusions: Cardiovascular risk prediction models are associated with cognitive changes over time and risk of dementia. Such models are easily obtainable in clinical and research settings and may be useful for identifying individuals at high risk of future cognitive decline and dementia.

Background: We aimed to investigate the association between dementia severity and weight loss in countries with low and middle incomes, where most prevalent cases reside., Methods: Cross-sectional catchment area surveys were performed in Cuba, Mexico, Venezuela, Peru, Dominican Republic, Puerto Rico, China, and India. In 16,538 older adults (≥65 years of age), significant weight loss was self-reported and confirmed by an informant. We conducted neuropsychological testing and clinical and neurological assessments. Dementia severity was determined by applying a validated algorithm and was quantified by the Clinical Dementia Rating Scale., Results: The characteristics of those who reported weight loss varied across countries. In Poisson models, after controlling for relevant covariates and for waist and arm circumferences, dementia severity was associated with reported weight loss (pooled prevalence ratios [95% confidence intervals {CI}] 2.19 [1.98, 2.41]; 3.81 [3.35, 4.33]; and 5.18 [4.41, 6.10] for CDR 0.5, 1, and 2/3, respectively, compared with CDR 0). The association increased linearly through stages of dementia severity in all countries (P for trend < .001), and between-country heterogeneity was minimal., Conclusions: We found a strong gradient effect in the direct association between dementia severity and reported weight loss, homogeneous across sites from eight countries, consistent with mechanistic data on the role of neurodegenerative processes on energy balance and with dietary changes due to disease severity. Considering the well-recognized effect of weight loss on morbidity and mortality and the large number affected by dementia in less resourced countries, amelioration of weight loss in dementia patients should be considered with priority in these settings., (Published by Elsevier Inc.)

The transition in the world age demographic toward older age is associated with an increased risk of neurodegenerative diseases, such as Alzheimer's disease. Risk profiles for dementia may also be changing. Obesity and type 2 diabetes have increased in prevalence in the last half-century and have been associated with increased dementia risk. Specific changes in nutrition may also represent a direct risk. A diet transition in the United States has occurred in the intake of refined sugar, particularly high-fructose corn syrup (HFCS) from a yearly estimate of 8.1 kg/person at the beginning of the XIX century to a current estimate of 65 kg/person. This article considers the association between refined sugar intake, markers of cardiovascular disease risk, and the possible promotion of the development of dementia.

Summary High adiposity in middle age is associated with higher dementia risk. The association between weight loss and cognitive function in older adults is still controversial. A meta-analysis was undertaken to estimate the effectiveness of intentional weight loss on cognitive function in overweight and obese adults. A structured strategy was used to search randomized and non-randomized studies reporting the effect of intentional and significant weight loss on cognitive function in overweight and obese subjects. Information on study design, age, nutritional status, weight-loss strategy, weight lost and cognitive testing was extracted. A random-effect meta-analysis was conducted to obtain summary effect estimates for memory and attention-executive domains. Twelve studies met inclusion criteria. Seven were randomized trials and the remaining five included a control group. A low-order significant effect was found for an improvement in cognitive performance with weight loss in memory (effect size 0.13, 95% CI 0.00-0.26, P = 0.04) and attention/executive functioning (effect size 0.14, 95% CI 0.01-0.27, P < 0.001). Studies were heterogeneous in study design, sample selection, weight-loss intervention and assessment of cognitive function. Weight loss appears to be associated with low-order improvements in executive/attention functioning and memory in obese but not in overweight individuals. [ABSTRACT FROM AUTHOR]