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.

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.

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.

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.

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.

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.

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

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

Nutritional interventions for the prevention of cognitive impairment and dementia in developing economies in East-Asia: a systematic review and meta-analysis.

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

Dietary nitrate and brain health. Too much ado about nothing or a solution for dementia prevention?

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

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.

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

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

Evaluating the performance of the PRISMA-7 frailty criteria for predicting disability and death after acute ischemic stroke.

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.

Recurrent delirium over 12 months predicts dementia: results of the Delirium and Cognitive Impact in Dementia (DECIDE) study.

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.

Hospitalisation without delirium is not associated with cognitive decline in a population-based sample of older people-results from a nested, longitudinal cohort study.

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 (ß = -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.

Relationship between urinary nitrate concentrations and cognitive function in older adults: findings from the NHANES survey.

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.

Feasibility and acceptability of a nutritional intervention testing the effects of nitrate-rich beetroot juice and folic acid on blood pressure in Tanzanian adults with elevated blood pressure.

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.

Assessing the Predictive Validity of Simple Dementia Risk Models in Harmonized Stroke Cohorts.

BACKGROUND AND PURPOSE: Stroke is associated with an increased risk of dementia. To assist in the early identification of individuals at high risk of future dementia, numerous prediction models have been developed for use in the general population. However, it is not known whether such models also provide accurate predictions among stroke patients. Therefore, the aim of this study was to determine whether existing dementia risk prediction models that were developed for use in the general population can also be applied to individuals with a history of stroke to predict poststroke dementia with equivalent predictive validity. METHODS: Data were harmonized from 4 stroke studies (follow-up range, ≈12-18 months poststroke) from Hong Kong, the United States, the Netherlands, and France. Regression analysis was used to test 3 risk prediction models: the Cardiovascular Risk Factors, Aging and Dementia score, the Australian National University Alzheimer Disease Risk Index, and the Brief Dementia Screening Indicator. Model performance or discrimination accuracy was assessed using the C statistic or area under the curve. Calibration was tested using the Grønnesby and Borgan and the goodness-of-fit tests. RESULTS: The predictive accuracy of the models varied but was generally low compared with the original development cohorts, with the Australian National University Alzheimer Disease Risk Index (C-statistic, 0.66) and the Brief Dementia Screening Indicator (C-statistic, 0.61) both performing better than the Cardiovascular Risk Factors, Aging and Dementia score (area under the curve, 0.53). CONCLUSIONS: Dementia risk prediction models developed for the general population do not perform well in individuals with stroke. Their poor performance could have been due to the need for additional or different predictors related to stroke and vascular risk factors or methodological differences across studies (eg, length of follow-up, age distribution). Future work is needed to develop simple and cost-effective risk prediction models specific to poststroke dementia.

Nitrate-Rich Beetroot Juice Reduces Blood Pressure in Tanzanian Adults with Elevated Blood Pressure: A Double-Blind Randomized Controlled Feasibility Trial.

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.

Dementia Research Fit for the Planet: Reflections on Population Studies of Dementia for Researchers and Policy Makers Alike.

In recent years, a rapidly increasing collection of investigative methods in addition to changes in diagnostic criteria for dementia have followed "high-tech" trends in medicine, with the aim to better define the dementia syndrome and its biological substrates, mainly in order to predict risk prior to clinical expression. These approaches are not without challenge. A set of guidelines have been developed by a group of European experts in population-based cohort research through a series of workshops, funded by the Joint Program for Neurodegenerative Disorders (JPND). The aims of the guidelines are to assist policy makers and researchers to understand (1) What population studies for ageing populations should encompass and (2) How to interpret the findings from population studies. Such studies are essential to provide evidence relevant to the understanding of healthy and frail brain ageing, including the dementia syndrome for contemporary and future societies by drawing on the past.