Search

Sarcopenic obesity (SO) is a body composition phenotype derived from the simultaneous presence in the same individual of an increase in fat mass and a decrease in skeletal muscle mass and/or function. Several protocols for the diagnosis of SO have been proposed in the last two decades making prevalence and disease risk estimates of SO heterogeneous and challenging to interpret. Dementia is a complex neurological disorder that significantly impacts patients, carers and healthcare systems. The identification of risk factors for early cognitive impairment and dementia is key to mitigating the forecasted trends of a 2-fold increase in dementia case numbers over the next two decades worldwide. Excess adiposity and sarcopenia have both been independently associated with risk of cognitive impairment and dementia. Whether SO is associated with a greater risk of cognitive impairment and dementia is currently uncertain. This review critically appraises the current evidence on the association between SO with cognitive outcomes and dementia risk. It also discusses some of the putative biological mechanisms that may link the SO phenotype with alteration of brain functions., (© 2024 British Nutrition Foundation.)

Objectives: This study investigated the associations between dementia caregivers' self-perceptions of aging (SPAs) and demographic, care related, and stress variables., Methods: Cross-sectional (2021) data collected online and from the German Aging Study comprising 190 dementia caregivers (Mean age= 65.69 years; SD= 10.11) were used. Predictive variables were age, sex, education, marital status, type of district of residence, caregiving hours per week, relationship to the person with dementia, care burden, and the Relative Stress Scale. Outcome variables were one item assessing felt age, the Lawton's Attitudes toward Own Aging Scale, and the age-related cognitions scales. Univariable, multivariable, and multivariate linear regression models were used., Results: Multivariable and multivariate linear regression models showed that those dementia caregivers who are older, have lower education, experience higher levels of caregiving-related burden and stress, and live in urban compared to rural districts, experience more negative SPAs compared to dementia caregivers without these characteristics. Associations were of moderate size for stress and of small size for the remaining variables., Conclusion: The results suggest that key characteristics in dementia caregivers are associated with more negative SPAs. Given that more negative SPAs are associated with poorer health outcomes, these individuals may benefit the most from interventions promoting positive SPAs.

Objectives: Approximately 55 million people are living with dementia globally. Global policies have suggested that screening for dementia in asymptomatic populations may support risk-reduction approaches to stem the rising numbers of people with the condition. A previous systematic review of literature up to 2012 indicated that healthcare professionals negatively view dementia screening; however, the research and clinical landscape has made significant advances in the last decade. Therefore, the aim of this systematic review is to re-examine the attitudes and preferences of healthcare professionals since 2012 regarding primary and community care-based dementia screening., Methods: This review was pre-registered on PROSPERO (CRD42024531455) and followed PRISMA guidelines. Key terms relevant to the aim were input into six databases, and articles between 2012 and 2024 were considered. Titles, abstracts and full texts were independently screened by two reviewers. Articles were eligible for inclusion if peer-reviewed, written in English, considered primary or community care-based dementia screening and included healthcare perspectives from either quantitative or qualitative methods., Results: From 18,732 identified titles, 19 articles were included in this review. Seventeen studies presented perspectives from primary care practitioners. Key findings suggest that healthcare professionals have mixed views regarding their willingness to conduct dementia screening, although limited studies suggest an interest in engaging in dementia risk reduction. Common influences on perspectives included knowledge, skills and training; resource provision; access to a dedicated screening service and referral pathways; and stigma., Conclusions: These findings suggest that healthcare professionals' perspectives and resource are not aligned with international policies promoting dementia screening. When considering implementing evidence-based dementia screening in the future, a dedicated screening service is recommended., (© 2025 The Author(s). International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.)

Background: Vascular dementia (VaD) is the second most common cause of dementia globally and is associated with a significant economic and social burden. Diet could represent an important tractable risk factor for VaD. We synthesised current evidence on associations between consumption of specific foods or dietary patterns and VaD risk., Methods: Five databases were searched from inception to January 2024 for prospective cohort studies exploring associations between individual foods or dietary patterns and incident VaD., Results: Sixteen studies were included. Compared with low intake reference groups, higher fruit and vegetable intake, moderate alcoholic drink intake (1-3 drinks/day), higher tea and coffee intake, and following a plant-based dietary pattern were associated with lower VaD risk. Conversely, moderate fried fish intake (0.25-2 servings/week), higher ultra-processed food intake (especially intake of sweetened beverages) and higher processed meat intake (≥ 2 servings/week) were associated with increased VaD risk. Inconsistent findings were observed for other dietary exposures., Discussion: A healthy diet could lower VaD risk. However, evidence is characterised by a limited number of studies for specific dietary exposures. Further research is needed to inform personalised and population-based approaches to lower VaD risk., Competing Interests: Declarations. Competing interests: ET’s salary is supported by an NIHR Clinical Lectureship. SG has received research funding to her institution from the Royal Society of Edinburgh, Scottish Neurological Research Fund and Alzheimer’s Association, alongside an ISTAART Travel Fellowship. SG has also received consulting fees from Scottish Brain Sciences and is a part time employee of Scottish Brain Sciences. SG is vice chair of an NHS research ethics committee, and her salary was funded during part of this project by a grant from the UK Medical Research Council. OMS has received research funding to his institution from the Fruit Juice Science Centre. All other authors declare no conflict of interest., (© 2024. The Author(s).)

Background: Appetite dysregulation in Parkinson's Disease (PD) appears to be linked to physical and cognitive deterioration. PD patients with and without cognitive impairment (CI) were compared to an age-matched control group to explore predictors of appetite control in fasting and post-prandial conditions., Methods: Fifty-five patients were recruited and divided into three groups: twenty controls (age: 74 y, BMI: 25.8 kg/m 2 ), nineteen PD patients without CI (72.5 y, 25.1 kg/m 2 ) and sixteen PD patients with CI (74.3 y, 24.0 kg/m 2 ). Self-reported appetite perception and circulating blood metabolic biomarkers were measured in fasting and over a 3-h post-prandial period. Biomarkers included glucose, insulin, tumour necrosis factor alpha (TNF-α), leptin, acyl-ghrelin, total ghrelin, peptide YY (PYY), glucagon like peptide 1 (GLP-1), insulin growth factor 1 (IGF-1), growth factor (GF) and triglycerides. Patients were then provided with a mixed meal to eat ad libitum with the aim to evaluate links between metabolic biomarkers and control of energy intake., Results: PD patients with CI had a significant lower protein intake (7.4 ± 2.5 g, p = 0.01) compared to controls (21.9 ± 3.1 g) and PD patients without CI (14.3 ± 3.0 g). Post-prandial plasma GLP-1 concentrations were associated with decreased hunger perception (B±SE, -5.3 ± 2.4  mm·h -1 , p = 0.04). PYY concentrations were significantly associated with GLP-1 in fasting (r = 0.40, p = 0.005) and post-prandial (r = 0.46, p < 0.001) conditions. In a multivariate model, post-prandial PYY concentrations were a significant predictor of ad libitum energy intake in all subjects (B±SE, -87.5 ± 34.9 kcal, p = 0.01) and in patients with PD (B±SE, -106.8 ± 44.9 kcal, p = 0.04)., Conclusions: PYY and GLP-1 appeared to influence appetite control in PD patients and their roles merit further investigation., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

It is estimated that more than one-tenth of adults aged ≥60 years are now classified as having sarcopenic obesity (SO), a clinical condition characterised by the concurrent presence of sarcopenia (low muscle mass and weakness) and obesity (excessive fat mass). Independently, sarcopenia and obesity are associated with a high risk of numerous adverse health outcomes including CVD and neurological conditions (e.g. dementia), but SO may confer a greater risk, exceeding either condition alone. This imposes a substantial burden on individuals, healthcare systems and society. In recent years, an increasing number of observational studies have explored the association between SO and the risk of CVD; however, results are mixed. Moreover, the pathophysiology of SO is governed by a complex interplay of multiple mechanisms including insulin resistance, inflammation, oxidative stress, hormonal shifts and alteration of energy balance, which may also play a role in the occurrence of various CVD. Yet, the exact mechanisms underlying the pathological connection between these two complex conditions remain largely unexplored. The aim of this review is to examine the association between SO and CVD. Specifically, we seek to: (1) discuss the definition, epidemiology and diagnosis of SO; (2) reconcile previously inconsistent findings by synthesising evidence from longitudinal studies on the epidemiological link between SO and CVD and (3) discuss critical mechanisms that may elucidate the complex and potentially bidirectional relationships between SO and CVD.

Dementia is a leading cause of disability and death globally. Individuals with diseases such as cardiovascular, cardiometabolic and cerebrovascular disease are often at increased dementia risk. However, while numerous models have been developed to predict dementia, they are often not tailored to disease-specific groups. Yet, different disease groups may have unique risk factor profiles and tailored models that account for these differences may have enhanced predictive accuracy. In this review, we synthesise findings from three previous systematic reviews on dementia risk model development and testing to present an overview of the literature on dementia risk prediction modelling in people with a history of disease. Nine studies met the inclusion criteria. Currently, disease-specific models have only been developed in people with a history of diabetes where demographic, disease-specific and comorbidity data were used. Some existing risk models, including CHA 2 DS 2 -VASc and CHADS 2 , have been externally validated for dementia outcomes in those with atrial fibrillation and heart failure. One study developed a dementia risk model for their whole population, which had similar predictive accuracy when applied in a sub-sample with stroke. This emphasises the importance of considering disease status in identifying key predictors for dementia and generating accurate prediction models for dementia.

Dementia is a leading cause of death and disability with over 60% of cases residing in low- and middle-income countries (LMICs). Therefore, new strategies to mitigate risk are urgently needed. However, despite the high burden of disease associated with dementia in LMICs, research into dementia risk profiling and risk prediction modelling is limited. Further, dementia risk prediction models developed in high income countries generally do not transport well to LMICs suggesting that context-specific models are instead needed. New prediction models have been developed, in China and Mexico only, with varying predictive accuracy. However, none has been externally validated or incorporated variables that may be important for predicting dementia risk in LMIC settings such as socio-economic status, literacy, healthcare access, nutrition, stress, pollutants, and occupational hazards. Since there is not yet any curative treatment for dementia, developing a context-specific dementia prediction model is urgently needed for planning early interventions for vulnerable groups, particularly for resource constrained LMIC settings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Alshahrani, Sabatini, Mohan, Brain, Pakpahan, Tang, Robinson, Siervo, Naheed and Stephan.)

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 hospitalization risk in older women. A total of 1 276 community-dwelling women from the Perth Longitudinal Study of Aging 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 and fall-, any fracture-, and hip fracture-related hospitalizations, obtained over 14.5 years from linked health records, was examined using multivariable-adjusted Cox-proportional hazard models. Over 14.5 years, 507 (39.7%) women experienced a fall-related hospitalization and 360 (28.2%) women experienced a fracture-related hospitalization, including 143 (11.2%) attributed to a hip fracture. In multivariable-adjusted models, compared to noncarriers, APOE ɛ4 carriers (n = 297, 23.3%) had greater risk for a fall- (hazard ratio [HR] 1.48, 95% CI: 1.22-1.81), fracture- (HR 1.28, 95% CI: 1.01-1.63), or hip fracture-related hospitalization (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, and abbreviated mental test score) were added to the multivariable model. In conclusion, APOE ɛ4 is a potential risk factor for fall- and fracture-related hospitalization in community-dwelling older women. Screening for APOE ɛ4 could provide clinicians an opportunity to direct higher-risk individuals to appropriate intervention strategies., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America.)

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.

Introduction: Identifying individuals at high risk of dementia is critical to optimized clinical care, formulating effective preventative strategies, and determining eligibility for clinical trials. Since our previous systematic reviews in 2010 and 2015, there has been a surge in dementia risk prediction modelling. The aim of this study was to update our previous reviews to explore, and critically review, new developments in dementia risk modelling., Methods: MEDLINE, Embase, Scopus, and Web of Science were searched from March 2014 to June 2022. Studies were included if they were population- or community-based cohorts (including electronic health record data), had developed a model for predicting late-life incident dementia, and included model performance indices such as discrimination, calibration, or external validation., Results: In total, 9,209 articles were identified from the electronic search, of which 74 met the inclusion criteria. We found a substantial increase in the number of new models published from 2014 (>50 new models), including an increase in the number of models developed using machine learning. Over 450 unique predictor (component) variables have been tested. Nineteen studies (26%) undertook external validation of newly developed or existing models, with mixed results. For the first time, models have also been developed in low- and middle-income countries (LMICs) and others validated in racial and ethnic minority groups., Conclusion: The literature on dementia risk prediction modelling is rapidly evolving with new analytical developments and testing in LMICs. However, it is still challenging to make recommendations about which one model is the most suitable for routine use in a clinical setting. There is an urgent need to develop a suitable, robust, validated risk prediction model in the general population that can be widely implemented in clinical practice to improve dementia prevention., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

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.)

This cross-sectional study evaluated the validity of three alternative methods compared to the gold standard 24-h urine collection for estimating dietary sodium intake, a modifiable risk factor for hypertension, among middle-aged and older adults with elevated blood pressure. These included spot urine collection (using Kawasaki, Tanaka, and INTERSALT equations), 24-h dietary recall, and food frequency questionnaire responses, compared to 24-h urine collection in a subset of 65 participants (aged 50-75 years, 58.5% women, 61.6% hypertensive) from the DePEC-Nutrition trial. The validity of the methods was assessed using bias, the Spearman correlation coefficient (SCC), the intraclass correlation coefficient (ICC), and Bland-Altman analysis. Among the alternative methods, spot urine collection using the Kawasaki equation showed the strongest correlation (SCC 0.238; ICC 0.119, 95% CI -0.079 to 0.323), but it exhibited a significant bias (1414 mg/day, p -value < 0.001) relative to 24-h urine collection. Conversely, dietary surveys had a smaller bias but wider limits of agreement. These findings underscore the complexities of accurately estimating dietary sodium intake using spot urine collection or dietary surveys in this specific population, suggesting that a combination or the refinement of existing methodologies might improve accuracy. Further research with larger samples is necessary to develop more reliable methods for assessing sodium intake in this high-risk group.

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., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Geriatrics Society.)

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., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America.)

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., Competing Interests: HB was employed by the Ecog Pro Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Sabatini, Cosentino, Chapman, Ballard, Brooker, Corbett and Stephan.)

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;I 2  = 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., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

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., Competing Interests: None., (© 2023 The Authors.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

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., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

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., (© 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Brain, Greene, Tang, Louise, Salter, Beach, Turnbull, Siervo, Stephan and Tully.)

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., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Geriatrics Society.)

Objectives: We aimed to evaluate the predictive performance of the PRISMA-7 frailty criteria regarding the composite outcome of disability or death in patients with an acute ischemic stroke, and to compare it with the Frailty Index and the National Institutes of Health Stroke Scale (NIHSS)., Materials and Methods: This prospective cohort study involved all patients aged ≥ 40 years admitted with an acute ischemic stroke between March 2019 and January 2020. We performed survival analyses, calculated risk ratios, sensitivity, specificity, and predictive values for the combined outcome of disability or death according to the presence of frailty as determined by the PRISMA-7 and the Frailty Index, and stroke severity based on the NIHSS., Results: In 174 patients with acute ischemic stroke, being frail in the week before the stroke according to the PRISMA-7 was associated with a Risk Ratio of 4·50 (95%CI 1·77-11·43, P <0·001) and a Positive Predictive Value of 89% (95%CI 77-99%) for being disabled or dead 90 days after the stroke, and a Hazard Ratio of 3·33 (95%CI 1·48-7·51, P = 0·004) for the survival outcome. The predictive performance of the PRISMA-7 was not significantly different from the Frailty Index or the NIHSS., Conclusions: We provide evidence that the PRISMA-7 frailty criteria may be a useful prognostication tool in acute ischemic stroke., Competing Interests: Declaration of Competing Interest The authors declare that they do not have any conflicts of interest to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of competing interest KA received a speaker honorarium from Nutricia in 2021. All other authors declare no interests., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

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., Competing Interests: The authors have declared that no competing interests exist.

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.

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., Competing Interests: Andrea M. McGrattan, Eduwin Pakpahan, Mario Siervo, Daniel D. Reidpath, Matthew Prina, Yueping Zhu, Chen Shulin, and Louise Robinson report no relevant disclosures. Authors who have received grants or contracts from any entity in the past 36 months: Devi Mohan—(1) Dementia toolkit for carers (DeToC): A comprehensive toolkit to support carers of people living with dementia in rural communities. Monash University Malaysia ASEAN grant; Role: Principal investigator. (2) Salivary lactoferrin for early identification of sleep related cognitive decline: A potential target for dementia prevention. Monash University Malaysia, School Strategic Grant; Role: Principal investigator. (3) Pathways of Acquired Epilepsy and their Comorbidities: A Translational Crosstalk between HMGB1 Mechanisms and Gut Microbiome. Monash University Malaysia, School Strategic Grant; Role: Co‐Investigator. (4) Global dementias: Examining structural vulnerability and dementia outcomes. Australian Research Council: Discovery Projects; Role: Partner investigator. (5) Investigating Multimorbidity Through capacity building (MUTUAL). MRC UK‐ GCRF Global Multimorbidity—Seed Funding; Role: Co‐Investigator. (6) Improving early detection and diagnosis of breast cancer among multi‐ethnic rural communities in Malaysia—the implementation of the community education and navigation programme (CENP). Newton Fund Impact Scheme Grant; Role: Co‐investigator. (7) Dementia Prevention and Enhanced Care (DePEC). National Institute of Health Research, UK: Global Health Group (Dementia)‐ (16/137/62); Role: Co‐investigator (all payments made to the institution). Jennifer Yates—NIHR RfPB Co‐investigator Enhance project (all payments made to the institution). Stella‐Maria Paddick—British council science South Asia grant; Broadening our horizons scheme; GCRF funding (Leicester university) for biomarker analysis; all small grants competitively awarded for research costs (all payments made to the institution). All authors who have received funding to travel to attend meetings in the past 36 months: Stella‐Maria Paddick—Cumbria, Northumberland, Tyne and wear NHS foundation trust—travel to Dhaka for a work related meeting; Newcastle University broadening our horizons scheme 2018—reciprocal visit between UK and Chile for one researcher at each site (all payments made to the institution). Blossom C. M. Stephan—NIHR Funded Global Health Research Group on Dementia Prevention and Enhanced care to attend ADI2020 conference (virtual due to COVID‐19; all payments made to the institution). All authors who have been members of external committees (within the past 36 months): Blossom C. M. Stephan—member of the Alzheimer's Society Research Strategy Council (chair the Dementia Prevention Subcommittee); an invited participant to the World Dementia Council, Prevention Workshop, 2021. Stella‐Maria Paddick—on the executive committee of the Royal College of Psychiatrists International Psychiatry and Volunteering Special interest group and attended a number of online meetings. Other financial or non‐financial interests in the past 36 months: Stella‐Maria Paddick—employed by the UK National Health Service., (© 2022 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America.)

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., (© 2021. The Author(s).)

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.

Background: Delirium is a serious acute neuropsychiatric condition associated with altered attention and arousal., Objective: To evaluate simple bedside tests for attention and arousal to detect delirium in those with and without Parkinson's disease (PD) and dementia., Methods: Participants from two prospective delirium studies were pooled comprising 30 with PD without cognitive impairment, 24 with Lewy body cognitive impairment (PD dementia or dementia with Lewy bodies), 16 with another dementia and 179 PD and dementia-free older adults. Participants completed standardised delirium assessments including tests of attention: digit span, Memorial Delirium Assessment Scale (MDAS) attention and months of the year backwards; and arousal: Glasgow Coma Scale (GSC), Observational Scale of Level of Arousal (OSLA), Modified Richmond Agitation Scale and MDAS consciousness. Delirium was diagnosed using the DSM-5 criteria., Results: On their first admission, 21.7%participants had prevalent delirium. Arousal measures accurately detected delirium in all participants (p < 0.01 for all), but only selected attention measures detected delirium in PD and dementia. In PD and dementia-free older adults, impaired digit span and OSLA were the optimal tests to detect delirium (area under the curve [AUC] = 0.838, p < 0.001) while in PD and dementia the optimal tests were MDAS attention and GCS (AUC=0.90 and 0.84, respectively, p < 0.001 for both)., Conclusion: Simple bedside tests of attention and arousal at a single visit could accurately detect delirium in PD, dementia and PD and dementia-free older adults; however, the optimal tests differed between groups. Combined attention and arousal scores increased accuracy, which could have clinical utility to aid the identification of delirium neurodegenerative disorders.

We envisage the development of new Brain Health Services to achieve primary and secondary dementia prevention. These services will complement existing memory clinics by targeting cognitively unimpaired individuals, where the focus is on risk profiling and personalized risk reduction interventions rather than diagnosing and treating late-stage disease. In this article, we review key potentially modifiable risk factors and genetic risk factors and discuss assessment of risk factors as well as additional fluid and imaging biomarkers that may enhance risk profiling. We then outline multidomain measures and risk profiling and provide practical guidelines for Brain Health Services, with consideration of outstanding uncertainties and challenges. Users of Brain Health Services should undergo risk profiling tailored to their age, level of risk, and availability of local resources. Initial risk assessment should incorporate a multidomain risk profiling measure. For users aged 39-64, we recommend the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) Dementia Risk Score, whereas for users aged 65 and older, we recommend the Brief Dementia Screening Indicator (BDSI) and the Australian National University Alzheimer's Disease Risk Index (ANU-ADRI). The initial assessment should also include potentially modifiable risk factors including sociodemographic, lifestyle, and health factors. If resources allow, apolipoprotein E ɛ4 status testing and structural magnetic resonance imaging should be conducted. If this initial assessment indicates a low dementia risk, then low intensity interventions can be implemented. If the user has a high dementia risk, additional investigations should be considered if local resources allow. Common variant polygenic risk of late-onset AD can be tested in middle-aged or older adults. Rare variants should only be investigated in users with a family history of early-onset dementia in a first degree relative. Advanced imaging with 18-fluorodeoxyglucose positron emission tomography (FDG-PET) or amyloid PET may be informative in high risk users to clarify the nature and burden of their underlying pathologies. Cerebrospinal fluid biomarkers are not recommended for this setting, and blood-based biomarkers need further validation before clinical use. As new technologies become available, advances in artificial intelligence are likely to improve our ability to combine diverse data to further enhance risk profiling. Ultimately, Brain Health Services have the potential to reduce the future burden of dementia through risk profiling, risk communication, personalized risk reduction, and cognitive enhancement interventions., (© 2021. The Author(s).)

Background: Acute hospitalisation and delirium have individually been shown to adversely affect trajectories of cognitive decline but have not previously been considered together. This work aimed to explore the impact on cognition of hospital admission with and without delirium, compared to a control group with no hospital admissions., Methods: The Delirium and Cognitive Impact in Dementia (DECIDE) study was nested within the Cognitive Function and Ageing Study II (CFAS II)-Newcastle cohort. CFAS II participants completed two baseline interviews, including the Mini-Mental State Examination (MMSE). During 2016, surviving participants from CFAS II-Newcastle were recruited to DECIDE on admission to hospital. Participants were reviewed daily to determine delirium status.During 2017, all DECIDE participants and age, sex and years of education matched controls without hospital admissions during 2016 were invited to repeat the CFAS II interview. Delirium was excluded in the control group using the Informant Assessment of Geriatric Delirium Scale (i-AGeD). Linear mixed effects modelling determined predictors of cognitive decline., Results: During 2016, 82 of 205 (40%) DECIDE participants had at least one episode of delirium. At 1 year, 135 of 205 hospitalised participants completed an interview along with 100 controls. No controls experienced delirium (i-AGeD>4). Delirium was associated with a faster rate of cognitive decline compared to those without delirium (β = -2.2, P < 0.001), but number of hospital admissions was not (P = 0.447)., Conclusions: These results suggest that delirium during hospitalisation rather than hospitalisation per se is a risk factor for future cognitive decline, emphasising the need for dementia prevention studies that focus on delirium intervention., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Geriatrics Society.)

This study evaluated the association of urinary nitrate concentrations with cognition in older subjects enrolled in the NHANES study. We also explored whether associations between urinary nitrate and cognition were modified by cardiovascular risk, vitamin D status and vitamin C intake. Two NHANES cycles were merged (2011-2012 and 2013-2014) and a total of 1,015 adults aged 60-80 (69.4 ± 0.3) years were included. Cognition was assessed using the Word List Learning, Word List Recall, Animal Fluency and the Digit Symbol Substitution tests. Urinary nitrate was analysed using electrospray tandem mass spectrometry. Urinary nitrate concentrations were not associated with cognitive performance on any of the cognitive tests. Associations were also not significant in subjects at greater risk for cognitive impairment (i.e. high cardiovascular risk and non-optimal vitamin D status). Longitudinal analyses are needed to explore the associations of urinary nitrate concentrations with dietary nitrate intake and cognitive function.

Ageing is a multifactorial process associated with reduced function and increased risk of morbidity and mortality. Recently, nine cellular and molecular hallmarks of ageing have been identified, which characterise the ageing process, and collectively, may be key determinants of the ageing trajectory. These include genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion and altered intercellular communication. Healthier dietary patterns reduce the risk of age-related diseases and increase longevity and may influence positively one or more of these hallmarks. The Mediterranean dietary pattern (MedDiet) is a plant-based eating pattern that was typical of countries such as Greece, Spain, and Italy pre-globalisation of the food system and which is associated with better health during ageing. Here we review the potential effects of a MedDiet on each of the nine hallmarks of ageing, and provide evidence that the MedDiet as a whole, or individual elements of this dietary pattern, may influence each hallmark positively-effects which may contribute to the beneficial effects of this dietary pattern on age-related disease risk and longevity. We also highlight potential avenues for future research., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited part of Springer Nature.)

Background: Delirium is common, distressing and associated with poor outcomes. Previous studies investigating the impact of delirium on cognitive outcomes have been limited by incomplete ascertainment of baseline cognition or lack of prospective delirium assessments. This study quantified the association between delirium and cognitive function over time by prospectively ascertaining delirium in a cohort aged ≥ 65 years in whom baseline cognition had previously been established., Methods: For 12 months, we assessed participants from the Cognitive Function and Ageing Study II-Newcastle for delirium daily during hospital admissions. At 1-year, we assessed cognitive decline and dementia in those with and without delirium. We evaluated the effect of delirium (including its duration and number of episodes) on cognitive function over time, independently of baseline cognition and illness severity., Results: Eighty two of 205 participants recruited developed delirium in hospital (40%). One-year outcome data were available for 173 participants: 18 had a new dementia diagnosis, 38 had died. Delirium was associated with cognitive decline (-1.8 Mini-Mental State Examination points [95% CI -3.5 to -0.2]) and an increased risk of new dementia diagnosis at follow up (OR 8.8 [95% CI 1.9-41.4]). More than one episode and more days with delirium (>5 days) were associated with worse cognitive outcomes., Conclusions: Delirium increases risk of future cognitive decline and dementia, independent of illness severity and baseline cognition, with more episodes associated with worse cognitive outcomes. Given that delirium has been shown to be preventable in some cases, we propose that delirium is a potentially modifiable risk factor for dementia., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Geriatrics Society.)

Sub-Saharan African countries are experiencing an alarming increase in hypertension prevalence. This study evaluated the feasibility and acceptability of nitrate-rich beetroot and folate supplementation, alone or combined, for the reduction of blood pressure (BP) in Tanzanian adults with elevated BP. This was a three-arm double-blind, placebo-controlled, parallel randomised clinical trial. Forty-eight participants were randomised to one of three groups to follow a specific 60-day intervention which included a: (1) combined intervention (beetroot juice + folate), (2) single intervention (beetroot juice + placebo), and (3) control group (nitrate-depleted beetroot juice + placebo). Forty-seven participants (age: 50-70 years) completed the study. The acceptability of the interventions was high. Self-reported compliance to the interventions was more than 90% which was confirmed by the significant increase in nitrate and folate concentrations in plasma and saliva samples in the treatment arms. This study provides important information for the design of high-nitrate interventions to reduce BP in Sub-Saharan African countries.

Background: Mild cognitive impairment (MCI) is a cognitive state associated with increased risk of dementia. Little research on MCI exists from low-and middle-income countries (LMICs), despite high prevalence of dementia in these settings., Objective: This systematic review aimed to review epidemiological reports to determine the prevalence of MCI and its associated risk factors in LMICs., Methods: Medline, Embase, and PsycINFO were searched from inception until November 2019. Eligible articles reported on MCI in population or community-based studies from LMICs and were included as long as MCI was clearly defined., Results: 5,568 articles were screened, and 78 retained. In total, n = 23 different LMICs were represented; mostly from China (n = 55 studies). Few studies were from countries defined as lower-middle income (n = 14), low income (n = 4), or from population representative samples (n = 4). There was large heterogeneity in how MCI was diagnosed; with Petersen criteria the most commonly applied (n = 26). Prevalence of amnesic MCI (aMCI) (Petersen criteria) ranged from 0.6%to 22.3%. Similar variability existed across studies using the International Working Group Criteria for aMCI (range 4.5%to 18.3%) and all-MCI (range 6.1%to 30.4%). Risk of MCI was associated with demographic (e.g., age), health (e.g., cardio-metabolic disease), and lifestyle (e.g., social isolation, smoking, diet and physical activity) factors., Conclusion: Outside of China, few MCI studies have been conducted in LMIC settings. There is an urgent need for population representative epidemiological studies to determine MCI prevalence in LMICs. MCI diagnostic methodology also needs to be standardized. This will allow for cross-study comparison and future resource planning.

Background: Subjective cognitive decline (SCD) is recognized as a risk stage for Alzheimer's disease (AD) and other dementias, but its prevalence is not well known. We aimed to use uniform criteria to better estimate SCD prevalence across international cohorts., Methods: We combined individual participant data for 16 cohorts from 15 countries (members of the COSMIC consortium) and used qualitative and quantitative (Item Response Theory/IRT) harmonization techniques to estimate SCD prevalence., Results: The sample comprised 39,387 cognitively unimpaired individuals above age 60. The prevalence of SCD across studies was around one quarter with both qualitative harmonization/QH (23.8%, 95%CI = 23.3-24.4%) and IRT (25.6%, 95%CI = 25.1-26.1%); however, prevalence estimates varied largely between studies (QH 6.1%, 95%CI = 5.1-7.0%, to 52.7%, 95%CI = 47.4-58.0%; IRT: 7.8%, 95%CI = 6.8-8.9%, to 52.7%, 95%CI = 47.4-58.0%). Across studies, SCD prevalence was higher in men than women, in lower levels of education, in Asian and Black African people compared to White people, in lower- and middle-income countries compared to high-income countries, and in studies conducted in later decades., Conclusions: SCD is frequent in old age. Having a quarter of older individuals with SCD warrants further investigation of its significance, as a risk stage for AD and other dementias, and of ways to help individuals with SCD who seek medical advice. Moreover, a standardized instrument to measure SCD is needed to overcome the measurement variability currently dominant in the field.

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.)

Malnutrition is common in older adults and is associated with functional impairment, reduced quality of life, and increased morbidity and mortality. The aim of this study was to explore the association between health (including depression), physical functioning, disability and cognitive decline, and risk of malnutrition. Participants were recruited from nursing homes in Italy and completed a detailed multidimensional geriatric evaluation. All the data analyses were completed using Stata Version 15.1. The study included 246 participants with an age range of 50 to 102 (80.4 ± 10.5). The sample was characterised by a high degree of cognitive and functional impairment, disability, and poor health and nutritional status (according to Mini Nutritional Assessment (MNA), 38.2% were at risk for malnutrition and 19.5% were malnourished). Using a stepwise linear regression model, age (B = -0.043, SE = 0.016, p = 0.010), depression (B = -0.133, SE = 0.052, p = 0.011), disability (B = 0.517, SE = 0.068, p < 0.001), and physical performance (B = -0.191, SE = 0.095, p = 0.045) remained significantly associated with the malnutrition risk in the final model (adjusted R-squared = 0.298). The logistic regression model incorporating age, depression, disability, and physical performance was found to have high discriminative accuracy (AUC = 0.747; 95%CI: 0.686 to 0.808) for predicting the risk of malnutrition. The results of the study confirm the need to assess nutritional status and to investigate the presence of risk factors associated with malnutrition in order to achieve effective prevention and plan a better intervention strategy.

Background: In Sub-Saharan Africa, current strategies are struggling to control the burgeoning hypertension epidemic. Dietary interventions such as inorganic nitrate or folic acid supplementation could represent promising strategies for reducing blood pressure (BP) in this setting., Objectives: This feasibility study explores the effects of dietary inorganic nitrate supplementation, alone or in combination with folic acid, on BP in Tanzanian adults with elevated BP in Tanzania., Methods: A placebo-controlled, double-blind, randomized controlled feasibility trial was conducted. Forty-seven middle-aged and older participants (age: 50-70 y, BMI: 26.3-29.1 kg/m2) were randomly assigned to 3 conditions for a period of 60 d: 1) high-nitrate beetroot juice (∼400 mg nitrate) and folic acid (∼5 mg folic acid) (N + F), 2) high-nitrate beetroot juice and placebo (N + P), or 3) nitrate-depleted beetroot juice and placebo (P + P). Clinic and 24-h ambulatory BP and measurements of compliance in plasma (nitrate and folate concentrations) and saliva (nitrate and nitrite) were obtained at baseline, 30 d, and 60 d., Results: Baseline resting systolic and diastolic BP (mean ± SD) was 151.0 ± 19.4 mm Hg and 91.8 ± 11.7 mm Hg, respectively. Compliance to the interventions was high (>90%) in all groups which was confirmed by the significant increase in nitrate and folic acid concentrations in plasma and saliva samples in the treatment arms. After 60 d, 24-h systolic BP dropped by -10.8 ± 9.8 mm Hg (P < 0.001), -6.1 ± 13.2 mm Hg (P = 0.03), and -0.3 ± 9.7 mm Hg (P = 0.83) in the N + P, N + F, and P + P groups, respectively. There was a significant decrease in 24-h diastolic BP in the N + P group (-5.4 ± 5.0 mm Hg, P = 0.004), whereas changes were not significant in the N + F (-1.8 ± 8.1 mm Hg, P = 0.32) and P + P (1.6 ± 8.3 mm Hg, P = 0.43) groups., Conclusions: Dietary inorganic nitrate represents a potential nutritional strategy to lessen the hypertension epidemic in Sub-Saharan Africa. These findings support the rationale for future long-term investigations exploring the efficacy of dietary nitrate for lowering BP and attenuating cardiovascular disease risk in this setting.This trial was registered at isrctn.com as ISRCTN67978523., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)