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).

Apolipoprotein ɛ4 is associated with increased risk of fall- and fracture-related hospitalisation: the Perth Longitudinal Study of Ageing Women.

Apolipoprotein ɛ4 (APOE ɛ4) may be a genetic risk factor for reduced bone mineral density (BMD) and muscle function, which could have implications for fall and fracture risk. We examined the association between APOE ɛ4 status and long-term fall- and fracture-related hospitalisation risk in older women. 1276 community-dwelling women from the Perth Longitudinal Study of Ageing Women (mean age ± SD = 75.2 ± 2.7 years) were included. At baseline, women underwent APOE genotyping and detailed phenotyping for covariates including prevalent falls and fractures, as well as health and lifestyle factors. The association between APOE ɛ4 with fall-, any fracture-, and hip fracture-related hospitalisations, obtained over 14.5 years from linked health records, were examined using multivariable-adjusted Cox-proportional hazard models. Over 14.5 years, 507 (39.7%) women experienced a fall-related hospitalisation, 360 (28.2%) women experienced a fracture-related hospitalisation, including 143 (11.2%) attributed to a hip fracture. In multivariable-adjusted models, compared to non-carriers, APOE ɛ4 carriers (n=297, 23.3%) had greater risk for a fall- (HR 1.48 95%CI 1.22-1.81), fracture- (HR 1.28, 95%CI 1.01-1.63) or hip fracture-related hospitalisation (HR 1.83 95%CI 1.29-2.61). The estimates remained similar when specific fall and fracture risk factors (fear of falling, plasma 25-hydroxyvitamin D, grip strength, timed-up-and-go, hip BMD, vitamin K status, prevalent diabetes, HbA1c, cholesterol, abbreviated mental test score) were added to the multivariable model. In conclusion, APOE ɛ4 is a potential risk factor for fall- and fracture-related hospitalisation in community-dwelling older women. Screening for APOE ɛ4 could provide clinicians an opportunity to direct higher risk individuals to appropriate intervention strategies.

Body Composition, Sarcopenic Obesity, and Cognitive Function in Older Adults: Findings From the National Health and Nutrition Examination Survey (NHANES) 1999-2002 and 2011-2014.

OBJECTIVE: Sarcopenic-obesity (SO) is characterized by the concomitant presence of low muscle mass and high adiposity. This study explores the association of body composition and SO phenotypes with cognitive function in older adults. METHODS: Cross-sectional data in older adults (≥60 years) from NHANES 1999-2002 and 2011-2014 were used. In the 1999-2002 cohort, phenotypes were derived from body mass index (BMI) and dual-X-ray-absorptiometry, and cognition was assessed the by Digit-Symbol-Substitution-Test (DSST). In the 2011-2014 cohort, phenotypes were derived from BMI, waist-circumference (WC), and hand-grip-strength (HGS). Cognition was assessed using four tests: DSST, Animal Fluency, the Consortium-to-Establish-a-Registry-for-Alzheimer's-Disease-Delayed-Recall, and Word Learning. Mediation analysis was conducted to evaluate the contribution of inflammation (C-reactive-protein, CRP) and insulin resistance (Homeostatic-Model-Assessment-for-Insulin-Resistance, HOMA-IR) to the association between body composition and cognitive outcomes. RESULTS: The SO phenotype had the lowest DSST mean scores (p < 0.05) and was associated with a significant risk of cognitive impairment [Odds Ratio (OR) = 1.9; 95%CI 1.0-3.7, p = 0.027] in the 1999-2002 cohort. A higher ratio of fat mass and fat free mass (FM/FFM) also showed a greater risk of cognitive impairment (OR = 2.0; 95%CI 1.3-3.1, p = 0.004). In the 2011-2014 cohort, the high WC-Low HGS group showed significantly lower scores on all four cognitive tests (p < 0.05) and a higher risk of cognitive impairment. CRP and HOMA-IR were significant partial mediators of the association between FM/FFM and DSST in the 1999-2002 cohort. CONCLUSIONS: The SO phenotype was associated with a higher risk of cognitive impairment in older adults. Insulin resistance and inflammation may represent key mechanisms linking SO to the development of cognitive impairment.

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.

Cognitive trajectories: exploring the predictive role of subjective cognitive decline and awareness of age-related changes for cognitive functioning.

Background: We investigated whether aspects of subjective cognitive aging, including awareness of age-related gains and losses in cognition (AARC-gains, AARC-losses) and subjective cognitive decline (SCD), predict change in objective cognitive function as measured by verbal reasoning (VR) and working memory (WM). Methods: We used longitudinal data for 3,299 cognitively healthy UK residents aged 65+. We used data on AARC and SCD assessed in 2019, and cognitive tasks assessed in 2019, 2020, and 2021. We used latent growth curve modeling, latent class growth analysis, and growth mixture modeling. Results: For VR, multiple growth trajectories were not evident. Mean VR at baseline was 37.45; this remained stable over time. Higher AARC-gains in cognition (mean intercept = -0.23; 95%CI: -0.31; -0.16), higher AARC-losses in cognition (mean intercept = -0.37; 95%CI: -0.46; -0.28), and lower SCD (mean intercept = 2.92; 95%CI: 2.58; 3.58) were associated with poorer VR at baseline. A three-class growth mixture model-class varying best represented trajectories of WM. In Class 1 (N = 182) mean WM at baseline was 31.20; this decreased by 2.48 points each year. In Class 2 (N = 119) mean WM at baseline was 23.12; this increased by 3.28 points each year. In Class 3 (N = 2,998) mean WM at baseline was 30.11; and it remained stable. Higher AARC-gains (Odds Ratio = 1.08; 95%CI: 1.03; 1.14) and AARC-losses (Odds Ratio = 1.10; 95%CI: 1.04; 1.16) in cognition predicted greater likelihood of being in Class 2 than Class 3. Conclusion: Although both higher AARC-gains and AARC-losses indicate poorer concurrent cognition, higher AARC-gains may be a resource that facilitates future cognitive improvement.

Testing Bidirectionality in Associations of Awareness of Age-Related Gains and Losses With Physical, Mental, and Cognitive Functioning Across 1 Year: The Role of Age.

OBJECTIVES: The bidirectionality between self-perceptions of aging and health-related outcomes may depend on age group. Therefore, we tested such bidirectionality among individuals in late midlife (50-64 years), young-old age (65-74 years), and old-old age (75+ years), taking advantage of the construct of Awareness of Age-Related Change (AARC) and its 2-dimensionality in terms of AARC-gains and AARC-losses. Various conceptualizations of physical, mental, and cognitive functioning were used as outcomes. METHODS: Data from 2 measurement occasions (2019 and 2020) from the UK PROTECT study for individuals in late midlife (N = 2,385), young-old age (N = 2,430), and old-old age (N = 539) were used. Data on self-reported functional difficulties, depression, anxiety, and performance on four computerized cognitive tasks (i.e., verbal reasoning, paired associate learning, self-ordered search, and digit span) providing a score for verbal reasoning and a score for working memory were analyzed using cross-lagged panel models. RESULTS: Across all 3 age groups, the bidirectional associations of AARC-gains with indicators of functioning were not significant, whereas higher AARC-losses significantly predicted slightly greater functional difficulties and higher depression and anxiety levels. Higher AARC-losses predicted slightly poorer Verbal Reasoning only in old-old age and poorer Working Memory predicted slightly higher AARC-losses only in young-old age. The remaining associations of AARC-losses with cognitive tasks were not statistically significant. DISCUSSION: In accordance with previous research targeting other indicators of self-perceptions of aging, this study supported a stronger impact of AARC-losses on indicators of physical functioning and mental health than vice versa from midlife to old-old age.

Prevalence of dementia among older age people and variation across different sociodemographic characteristics: a cross-sectional study in Bangladesh.

Background: Dementia is a significant global health issue, particularly for low-income and middle-income countries which majorly contribute to the dementia cases reported globally (67%). We estimated the prevalence of dementia among older people in Bangladesh and compared the estimate across different sociodemographic characteristics and divisions. Methods: A cross-sectional study was conducted in 2019 among individuals aged 60 years or older in seven administrative divisions in Bangladesh. Equal numbers of male and female participants were recruited from each division through a multi-stage random sampling technique. Recruitment was proportionally distributed in urban and rural areas in each division. Following consent, the Mini Mental State Examination (MMSE) was performed on all participants. Dementia was defined as an MMSE score of <24 out of 30. Data on age, sex, education, marital status, occupation, socioeconomic status, and type of community (urban or rural) were obtained using a structured questionnaire to compare the prevalence of dementia across different sociodemographic characteristics. Findings: Between January and December 2019, 2795 individuals were recruited including ∼400 from each of the seven administrative divisions. The mean age was 67 years (SD: 7), 68% were from rural areas and 51% were female. The prevalence of dementia was 8.0% (95% CI: 7.0-8.9%) with variations across age, sex, education, marital status, occupation, and division. No variations in prevalence were observed across urban/rural locations or socioeconomic status. After adjusting for age, sex, education, occupation and marital status, the odds of dementia was two times higher in females than males (OR: 2.15, 95% CI: 1.43-3.28); nine times higher in people aged ≥90 years than people aged 60-69 years (OR: 9.62, 95% CI: 4.79-19.13), and three times higher in people with no education compared to those who had completed primary school (OR: 3.10, 95% CI: 1.95-5.17). Interpretations: The prevalence of dementia is high in Bangladesh and varies across sociodemographic characteristics with a higher prevalence among females, older people, and people with no education. There is an urgent need to identify the key risk factors for dementia in developing countries, such as Bangladesh, to inform the development of context-relevant risk reduction and prevention strategies. Funding: None.

How are hearing loss and physical activity related? Analysis from the English longitudinal study of ageing.

Although cross-sectional studies suggest that hearing loss in middle- and older-aged adults is associated with lower physical activity, longitudinal evidence is limited. This study aimed to investigate the potential bi-directional association between hearing loss and physical activity over time. Participants were from the English Longitudinal Study of Ageing (N = 11,292) who were 50-years or older at baseline assessment (1998-2000). Individuals were followed-up biannually for up to 20-years (2018-2019) and were classified as ever reporting hearing loss (n = 4946) or not reporting hearing loss (n = 6346). Data were analysed with Cox-proportional hazard ratios and multilevel logistic regression. The results showed that baseline physical activity was not associated with hearing loss over the follow-up. Time (i.e., wave of assessment) by hearing loss interactions showed that physical activity declined more rapidly over time in those with hearing loss, compared to those without (Odds Ratios = 0.94, 95% Confidence Intervals; 0.92-0.96, p < .001). These findings highlight the importance of addressing physical activity in middle- and older-aged adults with hearing loss. As physical activity is a modifiable behaviour that can reduce the risk of developing chronic health conditions, individuals with hearing loss may need additional, tailored support to be more physically active. Mitigating the decline in physical activity could be essential to support healthy ageing for adults with hearing loss.

Effects of dietary-based weight loss interventions on biomarkers of endothelial function: a systematic review and meta-analysis.

Endothelial dysfunction is closely linked to the development of atherosclerosis. This systematic review and meta-analysis reviewed the evidence on the effect of weight loss, achieved by dietary-based interventions, on biomarkers of endothelial function (EF). Two databases (Medline, Embase) were searched from inception until November 2022 for studies that met the following criteria: 1) adult subjects (≥ 18 years) without exclusion for health status, 2) dietary interventions for weight loss, and 3) measurements of changes in EF biomarkers. Random-effect meta-analysis and meta-regression were performed. Thirty-seven articles including 1449 participants were included in the systematic review. Study duration ranged from 3-52 weeks. Overall, weight loss significantly improved biomarkers of EF [standardised mean difference (SMD):0.65; 95%CI:0.49,0.81; P < 0.001;I2 = 91.9%]. Subgroup analyses showed weight loss significantly improved levels of E-selectin (P < 0.001), intercellular adhesion molecule-1 (ICAM-1) (P < 0.001), vascular cell adhesion molecule-1 (VCAM-1) (P < 0.001), nitrite/nitrate (NOx) (P < 0.001) and vascular endothelial growth factor (VEGF) (P < 0.001). Conversely, there was no significant improvement for von Willebrand Factor (vWF). Meta-regression analysis revealed that changes in EF biomarkers were not affected by age, BMI, quality of the studies or the amount of weight lost. A significant heterogeneity was observed for the effects of weight loss on changes in EF biomarkers. Dietary-induced weight loss may be associated with biomarkers changes indicating an improvement of EF, and it may represent a potential strategy to reduce atherosclerotic risk.

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

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

Mid- and later-life risk factors for predicting neuropathological brain changes associated with Alzheimer's and vascular dementia: The Honolulu Asia Aging Study and the Age, Gene/Environment Susceptibility-Reykjavik Study.

INTRODUCTION: Dementia prediction models are necessary to inform the development of dementia risk reduction strategies. Here, we examine the utility of neuropathological-based risk scores to predict clinical dementia. METHODS: Models were developed for predicting Alzheimer's disease (AD) and non-AD neuropathologies using the Honolulu Asia Aging neuropathological sub-study (HAAS; n = 852). Model accuracy for predicting clinical dementia, over 30 years, was tested in the non-autopsied HAAS sample (n = 2960) and the Age, Gene/Environment Susceptibility-Reykjavik Study (n = 4614). RESULTS: Different models were identified for predicting neurodegenerative and vascular neuropathology (c-statistic range: 0.62 to 0.72). These typically included age, APOE, and a blood pressure-related measure. The neurofibrillary tangle and micro-vascular lesion models showed good accuracy for predicting clinical vascular dementia. DISCUSSION: There may be shared risk factors across dementia-related lesions, suggesting common pathways. Strategies targeting these models may reduce risk or postpone clinical symptoms of dementia as well as reduce neuropathological burden associated with AD and vascular lesions.

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.

Dementia and hearing-aid use: a two-way street.

OBJECTIVES: Hearing-aid use may reduce risk of dementia, but cognitive impairment makes use more challenging. An observed association between reduced hearing-aid use and incident dementia could reflect either or both of these causal paths. The objective was to examine the effects of each path while minimising contamination between paths. METHODS: Health records data from 380,794 Veterans who obtained hearing aids from the US Veterans Affairs healthcare system were analysed. Analysis 1 (n = 72,180) used multivariable logistic regression to model the likelihood of incident dementia 3.5-5 years post hearing-aid fitting for patients free of dementia and mild cognitive impairment (MCI). Analysis 2 (n = 272,748) modelled the likelihood of being a persistent hearing-aid user at 3 years 2 months after fitting, contrasting subgroups by level of cognitive function at the time of fitting. Analysis time windows were optimized relative to dataset constraints. Models were controlled for available relevant predictors. RESULTS: The adjusted OR for incident dementia was 0.73 (95% CI 0.66-0.81) for persistent (versus non-persistent) hearing-aid users. The adjusted OR for hearing-aid use persistence was 0.46 (95% CI 0.43-0.48) in those with pre-existing dementia (versus those remaining free of MCI and dementia). CONCLUSION: Substantial independent associations are observed in both directions, suggesting that hearing-aid use decreases risk of dementia and that better cognitive function predisposes towards persistent use. Research studying protective effects of hearing-aid use against dementia needs to account for cognitive status. Clinically, hearing devices and hearing care processes must be accessible and usable for all, regardless of their cognitive status.

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.

Secular Trends in Dementia Free Cognitive Function in Older Adults: A Systematic Review.

BACKGROUND: Although numerous studies have reported a decrease in dementia risk in the last two decades, it is unclear whether dementia-free cognitive function is also changing across generations. OBJECTIVE: The objective was to systematically evaluate the published data on generational differences in cognitive function in the older population. METHODS: Searches were performed on PubMed, Embase, and PsychInfo for articles published in English before 28 June 2021. Included studies were from population-based samples that reported generational differences in cognition in individuals without dementia, aged ≥60 years. RESULTS: 28,101 studies were identified and 15 selected covering the period from 1971 to 2015: including studies from China, Europe, and the USA. The results show generally consistent findings of improvements or stability in dementia free cognitive function in later versus earlier born generations, but not for all cognitive domains. Prevalence of mild cognitive impairment and cognitive impairment no dementia has remained stable in the USA, UK, and China over the last two decades. RESULTS: Prevalence of vascular related mild cognitive impairment has increased in China. Improvements in cognition may only partially be explained by increased educational attainment across generations. CONCLUSION: This review provides evidence for generational effects in dementia-free cognitive function, predominately stability or improvements in performance, in later compared to earlier born individuals across different world regions. There is an urgent need to determine the factors driving such changes and whether they are being experienced in all world regions, particularly low- and middle-income countries where the burden of cognitive impairment is greatest and rising.

Delirium and Delirium Severity Predict the Trajectory of the Hierarchical Assessment of Balance and Mobility in Hospitalized Older People: Findings From the DECIDE Study.

BACKGROUND: Delirium is common, distressing, and associated with poor outcomes. Despite this, delirium remains poorly recognized, resulting in worse outcomes. There is an urgent need for methods to objectively assess for delirium. Physical function has been proposed as a potential surrogate marker, but few studies have monitored physical function in the context of delirium. We examined if trajectories of physical function are affected by the presence and severity of delirium in a representative sample of hospitalized participants older than 65 years. METHOD: During hospital admissions in 2016, we assessed participants from the Delirium and Cognitive Impact in Dementia study daily for delirium and physical function, using the Hierarchical Assessment of Balance and Mobility (HABAM). We used linear mixed models to assess the effect of delirium and delirium severity during admission on HABAM trajectory. RESULTS: Of 178 participants, 58 experienced delirium during admission. Median HABAM scores in those with delirium were significantly higher (indicating worse mobility) than those without delirium. Modeling HABAM trajectories, HABAM scores at first assessment were worse in those with delirium than those without, by 0.76 (95% CI: 0.49-1.04) points. Participants with severe delirium experienced a much greater perturbance in their physical function, with an even lower value at first assessment and slower subsequent improvement. CONCLUSIONS: Physical function was worse in those with delirium compared to without. This supports the assertion that motor disturbances are a core feature of delirium and monitoring physical function, using a tool such as the HABAM, may have clinical utility as a surrogate marker for delirium and its resolution.

Risk of conversion from mild cognitive impairment to dementia in low- and middle-income countries: A systematic review and meta-analysis.

Introduction: With no treatment for dementia, there is a need to identify high risk cases to focus preventive strategies, particularly in low- and middle-income countries (LMICs) where the burden of dementia is greatest. We evaluated the risk of conversion from mild cognitive ompairment (MCI) to dementia in LMICs. Methods: Medline, Embase, PsycINFO, and Scopus were searched from inception until June 30, 2020. The search was restricted to observational studies, conducted in population-based samples, with at least 1 year follow-up. There was no restriction on the definition of MCI used as long as it was clearly defined. PROSPERO registration: CRD42019130958. Results: Ten thousand six hundred forty-seven articles were screened; n = 11 retained. Of the 11 studies, most were conducted in China (n = 7 studies), with only two studies from countries classified as low income. A qualitative analysis of n = 11 studies showed that similar to high-income countries the conversion rate to dementia from MCI was variable (range 6 . 0%-44 . 8%; average follow-up 3 . 7 years [standard deviation = 1 . 2]). A meta-analysis of studies using Petersen criteria (n = 6 studies), found a pooled conversion rate to Alzheimer's disease (AD) of 23 . 8% (95% confidence interval = 15 . 4%-33.4%); approximately one in four people with MCI were at risk of AD in LMICs (over 3 . 0-5 . 8 years follow-up). Risk factors for conversion from MCI to dementia included demographic (e.g., age) and health (e.g., cardio-metabolic disease) variables. Conclusions: MCI is associated with high, but variable, conversion to dementia in LMICs and may be influenced by demographic and health factors. There is a notable absence of data from low-income settings and countries outside of China. This highlights the urgent need for research investment into aging and dementia in LMIC settings. Being able to identify those individuals with cognitive impairment who are at highest risk of dementia in LMICs is necessary for the development of risk reduction strategies that are contextualized to these unique settings.

Sarcopenic obesity is associated with telomere shortening: findings from the NHANES 1999-2002.

Sarcopenic obesity (SO) is characterised by the concurrent presence of sarcopenia and excess adiposity. Telomere shortening has been associated with sarcopenia and obesity alone but the association between SO and telomere length (TL) has not been investigated. This study aimed to investigate SO and TL in an adult population. Data were from 5397 individuals (mean age = 44.7 years, 51.3% male) enrolled in the National Health and Nutrition Examination Survey. Body composition (BC) was assessed by Dual Energy X-Ray Absorptiometry. Two models were used to assess SO: a BC model including four phenotypes derived from the combination of high or low adiposity and muscle mass; and, a truncal fat mass to appendicular skeletal mass ratio (TrFM/ASM). TL was assessed using quantitative polymerase chain reaction and expressed as base pairs. The mean TL, relative to the reference DNA, was calculated and expressed as the mean T/S ratio. A General Linear Model was applied to determine associations between TL for SO. In adjusted analysis, only individuals with SO, defined as the presence of high adiposity-low muscle mass (four-phenotype model), had significantly shorter telomeres (p = 0.05) than the reference group (i.e. low adiposity-high muscle mass), with a mean T/S ratio of 1.02 (95%CI: 0.98-1.05) compared to 1.05 (95%CI: 1.01-1.09), respectively. TrFM/ASM was not associated with TL. Preliminary findings suggest that sarcopenia and obesity may act synergistically to shorten telomeres.

Independent and interactive associations of dietary nitrate and salt intake with blood pressure and cognitive function: a cross-sectional analysis in the InCHIANTI study.

Blood pressure (BP) control is a key target for interventions to reduce cognitive decline. This cross-sectional study explored associations between objective (24-hour urine excretion) and subjective (food frequency questionnaire [FFQ]) measures of dietary sodium and nitrate intakes with cognitive function and resting BP in the InCHIANTI cohort. Baseline data from 989 participants aged >50 years were included. In fully adjusted models, participants with concurrent high nitrate and low sodium (Odds Ratio (OR)=0.49, 95%CI 0.32-0.76, p = 0.001) and high nitrate and high sodium (OR = 0.49, 95%CI 0.32-0.77, p = 0.002) 24-hour urinary concentrations had lower odds of high BP than participants with low nitrate and high sodium concentrations. We found no significant associations between sodium and nitrate intakes (24-hour urinary concentrations and FFQ) and poor cognitive performance. Urinary nitrate excretion was associated with lower BP and results appeared to be independent of sodium intake. Further analyses in longitudinal studies are required to substantiate these findings.