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.

Assessing Sodium Intake in Middle-Aged and Older Adults with Elevated Blood Pressure: Validation of Spot Urine Excretion and Dietary Survey-Derived Estimates.

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.

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.

Associations between Aging and Vitamin D Status with Whole-Body Nitric Oxide Production and Markers of Endothelial Function.

BACKGROUND: Aging and vitamin D deficiency have been associated with reduced nitric oxide (NO) synthesis and impaired endothelial function (EF) but the evidence in humans remains weak. OBJECTIVES: Two independent cross-sectional studies were designed to evaluate the association between age, sex, and plasma vitamin D concentrations with physiological and biochemical biomarkers of NO synthesis and EF in young and older healthy participants (Study 1) and in overweight and obese postmenopausal females (Study 2). METHODS: In Study 1, 40 young (20-49 y) and older (50-75 y) males and females (10 participants per age and sex group) were included. Resting blood pressure and ear-to-finger peripheral pulse wave velocity (PWV) were measured. A stable-isotopic method was used to determine whole-body NO production. Plasma 25-hydroxyvitamin D (25(OH)D), nitrate, nitrite, and asymmetric dimethylarginine (ADMA) concentrations were determined. In Study 2, 80 older overweight and obese females (age 61.2 ± 6.2 y, body mass index 29.5 ± 4.4 kg/m2) were recruited. Postocclusion reactive hyperemia (PORH) and peripheral PWV were measured. Plasma concentrations of 25(OH)D, nitrate, cyclic guanosine monophosphate, 3-nitrotyrosine (3-NT), endothelin-1, vascular endothelial growth factor, and ADMA were determined. RESULTS: In Study 1, whole-body NO production was significantly greater in young compared with older participants (0.61 ± 0.30 µmol·h-1·kg-1 compared with 0.39 ± 0.10 µmol·h-1·kg-1, P = 0.01) but there was no evidence of a sex difference (P = 0.81). Plasma 25(OH)D concentration was not associated with PWV (r = 0.18, P = 0.28) or whole-body NO production (r = -0.20, P = 0.22). Plasma ADMA concentration was associated positively with age (r = 0.35, P = 0.03) and negatively with whole-body NO production (r = -0.33, P = 0.04). In Study 2, age was associated with lower PORH (r = -0.28, P = 0.02) and greater ADMA concentrations (r = 0.22, P = 0.04). Plasma 25(OH)D concentration was inversely associated with 3-NT concentrations (r = -0.31, P = 0.004). CONCLUSIONS: Older age was associated with lower whole-body NO production. Plasma vitamin D concentrations were not associated with NO production or markers of EF but showed a weak, significant correlation with oxidative stress in postmenopausal overweight females.

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.

Does dietary nitrate boost the effects of caloric restriction on brain health? Potential physiological mechanisms and implications for future research.

Dementia is a highly prevalent and costly disease characterised by deterioration of cognitive and physical capacity due to changes in brain function and structure. Given the absence of effective treatment options for dementia, dietary and other lifestyle approaches have been advocated as potential strategies to reduce the burden of this condition. Maintaining an optimal nutritional status is vital for the preservation of brain function and structure. Several studies have recognised the significant role of nutritional factors to protect and enhance metabolic, cerebrovascular, and neurocognitive functions. Caloric restriction (CR) positively impacts on brain function via a modulation of mitochondrial efficiency, endothelial function, neuro-inflammatory, antioxidant and autophagy responses. Dietary nitrate, which serves as a substrate for the ubiquitous gasotransmitter nitric oxide (NO), has been identified as a promising nutritional intervention that could have an important role in improving vascular and metabolic brain regulation by affecting oxidative metabolism, ROS production, and endothelial and neuronal integrity. Only one study has recently tested the combined effects of both interventions and showed preliminary, positive outcomes cognitive function. This paper explores the potential synergistic effects of a nutritional strategy based on the co-administration of CR and a high-nitrate diet as a potential and more effective (than either intervention alone) strategy to protect brain health and reduce dementia risk.

Vitamin C supplementation showed greater effects on systolic blood pressure in hypertensive and diabetic patients: an updated systematic review and meta-analysis of randomised clinical trials.

Results from randomised controlled trials (RCTs) testing the effect of vitamin C supplementation on blood pressure (BP) have been inconsistent. This systematic review evaluated the effects of vitamin C supplementation on BP and included RCTs testing the effects of vitamin C supplementation alone, on systolic and diastolic BP in adult participants (≥18 years). Random-effect models were conducted to estimate the pooled effects of vitamin C supplementation on BP. A total of 20 studies with 890 participants were included. The median dose of vitamin C was 757.5 mg/d, the median duration was 6 weeks. Vitamin C supplementation was found to reduce systolic BP by -3.0 mmHg (95%CI: -4.7, -1.3 mmHg; p = 0.001). Subgroup analysis showed a more pronounced effect on systolic BP in patients with hypertension (-3.2 mmHg, 95%CI -5.2, -1.2 mmHg, p = 0.002) and diabetes (-4.6 mmHg, 95%CI -8.9, -0.3 mmHg, p = 0.03). Further research needs to evaluate the long-term effect of vitamin C on BP in populations with impaired cardio-metabolic health.

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.

Caloric Restriction (CR) Plus High-Nitrate Beetroot Juice Does Not Amplify CR-Induced Metabolic Adaptation and Improves Vascular and Cognitive Functions in Overweight Adults: A 14-Day Pilot Randomised Trial.

Caloric restriction (CR) and dietary nitrate supplementation are nutritional interventions with pleiotropic physiological functions. This pilot study investigates the combined effects of CR and nitrate-rich beetroot juice (BRJ) on metabolic, vascular, and cognitive functions in overweight and obese middle-aged and older adults. This was a two-arm, parallel randomized clinical trial including 29 participants allocated to CR + BRJ (n = 15) or CR alone (n = 14) for 14 days. Body composition, resting energy expenditure (REE), and hand-grip strength were measured. Resting blood pressure (BP) and microvascular endothelial function were measured, and Trail-Making Test A and B were used to assess cognitive function. Salivary nitrate and nitrite, and urinary nitrate and 8-isoprostane concentrations were measured. Changes in body composition, REE, and systolic and diastolic BP were similar between the two interventions (p > 0.05). The CR + BRJ intervention produced greater changes in average microvascular flux (p = 0.03), NO-dependent endothelial activity (p = 0.02), and TMT-B cognitive scores (p = 0.012) compared to CR alone. Changes in urinary 8-isoprostane were greater in the CR + BRJ group (p = 0.02), and they were inversely associated with changes in average microvascular flux (r = -0.53, p = 0.003). These preliminary findings suggest that greater effects on vascular and cognitive functions could be achieved by combining CR with dietary nitrate supplementation.

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.

Cognition, function, and prevalent dementia in centenarians and near-centenarians: An individual participant data (IPD) meta-analysis of 18 studies.

INTRODUCTION: There are limited data on prevalence of dementia in centenarians and near-centenarians (C/NC), its determinants, and whether the risk of dementia continues to rise beyond 100. METHODS: Participant-level data were obtained from 18 community-based studies (N = 4427) in 11 countries that included individuals ≥95 years. A harmonization protocol was applied to cognitive and functional impairments, and a meta-analysis was performed. RESULTS: The mean age was 98.3 years (SD = 2.67); 79% were women. After adjusting for age, sex, and education, dementia prevalence was 53.2% in women and 45.5% in men, with risk continuing to increase with age. Education (OR 0.95;0.92-0.98) was protective, as was hypertension (odds ratio [OR] 0.51;0.35-0.74) in five studies. Dementia was not associated with diabetes, vision and hearing impairments, smoking, and body mass index (BMI). DISCUSSION: Among the exceptional old, dementia prevalence remains higher in the older participants. Education was protective against dementia, but other factors for dementia-free survival in C/NC remain to be understood.

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.