Search

High blood pressure (BP) is a significant contributor to the disease burden globally and is emerging as an important cause of morbidity and mortality in the young as well as the old. The well-established impact of high BP on neurodegeneration, cognitive impairment, and dementia is widely acknowledged. However, the influence of BP across its full range remains unclear. This review aims to explore in more detail the effects of BP levels on neurodegeneration, cognitive function, and dementia. Moreover, given the pressing need to identify strategies to reduce BP levels, particular attention is placed on reviewing the role of magnesium (Mg) in ageing and its capacity to lower BP levels, and therefore potentially promote brain health. Overall, the review aims to provide a comprehensive synthesis of the evidence linking BP, Mg and brain health. It is hoped that these insights will inform the development of cost-effective and scalable interventions to protect brain health in the ageing population.

Several modifiable risk factors for neurodegeneration and dementia have been identified, although individuals vary in their vulnerability despite a similar risk of exposure. This difference in vulnerability could be explained at least in part by the variability in DNA repair mechanisms' efficiency between individuals. Therefore, the aim of this study was to test associations between documented, prevalent genetic variation (single nucleotide polymorphism, SNP) in DNA repair genes, cognitive function, and brain structure. Community-living participants ( n = 488,159; 56.54 years (8.09); 54.2% female) taking part in the UK Biobank study and for whom cognitive and genetic measures were available were included. SNPs in base excision repair (BER) genes of the bifunctional DNA glycosylases OGG1 (rs1052133, rs104893751), NEIL1 (rs7402844, rs5745906), NEIL2 (rs6601606), NEIL3 (rs10013040, rs13112390, rs13112358, rs1395479), MUTYH (rs34612342, rs200165598), NTHL1 (rs150766139, rs2516739) were considered. Cognitive measures included fluid intelligence, the symbol-digit matching task, visual matching, and trail-making. Hierarchical regression and latent class analyses were used to test the associations between SNPs and cognitive measures. Associations between SNPs and brain measures were also tested in a subset of 39,060 participants. Statistically significant associations with cognition were detected for 12 out of the 13 SNPs analyzed. The strongest effects amounted to a 1-6% difference in cognitive function detected for NEIL1 (rs7402844), NEIL2 (rs6601606), and NTHL1 (rs2516739). Associations varied by age and sex, with stronger effects detected in middle-aged women. Weaker associations with brain measures were also detected. Variability in some BER genes is associated with cognitive function and brain structure and may explain variability in the risk for neurodegeneration and dementia.

Background: Screening men for prostate cancer using prostate-specific antigen (PSA) testing remains controversial. We aimed to estimate the likely budgetary impact on secondary care in England and Wales to inform screening decision makers., Methods: The Cluster randomised triAl of PSA testing for Prostate cancer study (CAP) compared a single invitation to men aged 50-69 for a PSA test with usual care (no screening). Routinely collected hospital care data were obtained for all men in CAP, and NHS reference costs were mapped to each event via Healthcare Resource Group (HRG) codes. Secondary-care costs per man per year were calculated, and cost differences (and population-level estimates) between arms were derived annually for the first five years following randomisation., Results: In the first year post-randomisation, secondary-care costs averaged across all men (irrespective of a prostate cancer diagnosis) in the intervention arm (n = 189279) were £44.80 (95% confidence interval: £18.30-£71.30) higher than for men in the control arm (n = 219357). Extrapolated to a population level, the introduction of a single PSA screening invitation could lead to additional secondary care costs of £314 million., Conclusions: Introducing a single PSA screening test for men aged 50-69 across England and Wales could lead to very high initial secondary-care costs., (© 2023. The Author(s).)

Multiple sclerosis (MS) is a chronic neurological disease of the central nervous system that is currently incurable. Diet may influence the onset and progression of MS. A variety of literature reviews have been conducted in the field of diet and MS. However, conventional reviews mostly focus on specific topics rather than delivering a holistic view of the literature landscape. Using a data-driven approach, we aimed to provide an overview of the literature on diet and MS, revealing gaps in knowledge. We conducted citation network analysis to identify clusters of all available publications about diet and MS over the past 50 years. We also conducted topic analysis of each cluster and illustrated them in word clouds. Four main clusters were identified from 1626 publications: MS risk and symptom management; mouse models of MS; gluten sensitivity; and dysphagia. Citation network analysis revealed that in this emerging field, articles published after 1991 were more likely to be highly cited. Relatively few studies focused on MS disease progression compared to risk factors, and limited evidence was available for many foods and nutrients in relation to MS. Future studies could focus on filling these identified knowledge gaps., Competing Interests: The authors declare no conflicts of interest.

The "Black Summer" bushfires of 2019/2020 in Australia generated smoke that persisted for over three months, mainly affecting Eastern Australia. Most communication strategies focused on the fire itself, revealing a knowledge gap in effective communication of the impact of bushfire smoke on health, especially for children and those living in non-English speaking minority groups. To address this, semi-structured qualitative interviews were undertaken with sixteen adults with caring ( n = 11) or educational ( n = 5) responsibilities for primary-school aged children (5-12 years, with some also having children up to 16 years) who had direct experience of the "Black Summer" bushfires. Overall, 43% ( n = 7) of the sample spoke English as a first language, 25% ( n = 4) spoke Turkish, with the remainder speaking Persian, Arabic, and Spanish. Thematic inductive qualitative content analysis revealed predominant themes of the role of parents and caregivers as conduits and curators of information. Air quality apps were the most common source of information. Language barriers and the lack of child-friendly methods of communication were highlighted as particular challenges. This qualitative study provides evidence for future development of communication strategies to better serve culturally and linguistically diverse individuals and the children in their care.

The objectives of this study were to investigate the long-term associations between changes in physical activity levels and hippocampal volumes over time, while considering the influence of age, sex, and APOE-ε4 genotype. We investigated the effects of change in physical activity on hippocampal volumes in 411 middle age (mean age = 47.2 years) and 375 older age (mean age = 63.1 years) adults followed up to 12 years. An annual volume decrease was observed in the left (middle age: 0.46%; older age: 0.51%) but not in the right hippocampus. Each additional 10 metabolic equivalents (METs, ~2 h of moderate exercise) increase in weekly physical activity was associated with 0.33% larger hippocampal volume in middle age (equivalent to ~1 year of typical aging). In older age, each additional MET was associated with 0.05% larger hippocampal volume; however, the effects declined with time by 0.005% per year. For older age APOE-ε4 carriers, each additional MET was associated with a 0.10% increase in hippocampal volume. No sex effects of physical activity change were found. Increasing physical activity has long-term positive effects on hippocampal volumes and appears especially beneficial for older APOE-ε4 carriers. To optimize healthy brain aging, physical activity programs should focus on creating long-term exercise habits., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: To quantify the association between blood pressure (BP) across its full range, brain volumes and white matter lesions (WMLs) while investigating the effects of age, sex, body mass index (BMI), and antihypertensive medication., Methods: UK Biobank participants ( n = 36,260) aged (40-70) years were included and stratified by sex and four age groups (age ≤ 45, 46-55, 56-65 and > 65 years). Multi-level regression analyses were used to assess the association between mean arterial pressure (MAP), systolic BP (SBP), diastolic BP (DBP), and brain volumes segmented using the FreeSufer software (gray matter volume [GMV], white matter volume [WMV], left [LHCV] and right hippocampal volume [RHCV]) and WMLs. Interaction effects between body mass index (BMI), antihypertensive medication and BP in predicting brain volumes and WMLs were also investigated., Results: Every 10 mmHg higher DBP was associated with lower brain volumes (GMV: -0.19%--0.40%) [SE = 47.7-62.4]; WMV: -0.20--0.23% [SE = 34.66-53.03]; LHCV: -0.40--0.59% [SE = 0.44-0.57]; RHCV: -0.17--0.57% [SE = 0.32-0.95]) across all age groups. A similar pattern was detected in both sexes, although it was weaker in men. Every 10 mmHg higher MAP was associated with larger WMLs across all age groups but peaked >65 years (1.19-1.23% [SE = 0.002]). Both lower BMI and anti-hypertensive medication appeared to afford a protective effect., Conclusion: Higher BP is associated with worse cerebral health across the full BP range from middle adulthood and into old age.

Neuroinflammation and oxidative stress (OS) are implicated in the pathophysiology of Alzheimer's disease (AD). However, it is unclear at what stage of the disease process inflammation first becomes manifest. The aim of this study was to investigate the associations between specific plasma markers of inflammation and OS, tau, and Amyloid-β 38, 40, and 42 levels in cognitively unimpaired middle-age and older individuals. Associations between inflammatory states identified through principal component analysis and AD biomarkers were investigated in middle-age (52-56 years, n = 335, 52% female) and older-age (72-76 years, n = 351, 46% female) participants without dementia. In middle-age, a component reflecting variation in OS was most strongly associated with tau and to a lesser extent amyloid-β levels. In older-age, a similar component to that observed in middle-age was only associated with tau, while another component reflecting heightened inflammation independent of OS, was associated with all AD biomarkers. In middle and older-age, inflammation and OS states are associated with plasma AD biomarkers.

The 2019-20 bushfires that raged in eastern Australia were an overwhelming natural disaster leading to lives lost or upended, and communities destroyed. For almost a month, Canberra, Australia's capital city in the Australian Capital Territory (ACT), was obscured by smoke from fires which threatened the outer suburbs. While smoke itself is experientially different from many natural disasters, it nevertheless poses a significant public health threat. As the impact of extended bushfire smoke in an urban setting is relatively unexplored we aimed to capture the individual and community-level experiences of the event and their importance for community and social functioning. We responded rapidly by conducting semi-structured interviews with a range of Canberra residents who, due to their personal or social circumstances, were potentially vulnerable to the effects of the smoke. Three major themes emerging from the narratives depicted disruption to daily life, physical and psychological effects, and shifting social connectedness. This study highlighted the ambiguous yet impactful nature of a bushfire smoke event, and identified four simple key messages that may be critically relevant to policy making in preparation for similar smoke events in the future., 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., (Copyright © 2022 Williamson, Banwell, Calear, LaBond, Leach, Olsen, Walsh, Zulfiqar, Sutherland and Phillips.)

Background : Elevated blood pressure (BP) is a major health risk factor and the leading global cause of premature death. Hypertension is also a risk factor for cognitive decline and dementia. However, when elevated blood pressure starts impacting cerebral health is less clear. We addressed this gap by estimating how a validated measure of brain health relates to changes in BP over a period of 12 years. Methods : Middle-age (44-46 years at baseline, n = 335, 52% female) and older-age (60-64 years, n = 351, 46% female) cognitively intact individuals underwent up to four brain scans. Brain health was assessed using a machine learning approach to produce an estimate of "observed" age (BrainAGE), which can be contrasted with chronological age. Longitudinal associations between blood pressures and BrainAGE were assessed with linear mixed-effects models. Results : A progressive increase in BP was observed over the follow up (MAP = 0.8 mmHg/year, SD = 0.92; SBP = 1.41 mmHg/year, SD = 1.49; DBP = 0.61 mmHg/year, SD = 0.78). In fully adjusted models, every additional 10 mmHg increase in blood pressure (above 90 for mean, 114 for systolic, and 74 for diastolic blood pressure) was associated with a higher BrainAGE by 65.7 days for mean, and 51.1 days for systolic/diastolic blood pressure. These effects occurred across the blood pressure range and were not exclusively driven by hypertension. Conclusion : Increasing blood pressure is associated with poorer brain health. Compared to a person becoming hypertensive, somebody with an ideal BP is predicted to have a brain that appears more than 6 months younger at midlife., 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., (Copyright © 2021 Cherbuin, Walsh, Shaw, Luders, Anstey, Sachdev, Abhayaratna and Gaser.)

Background: To summarise and quantify the evidence on the association between Blood pressure (BP), white matter lesions (WMLs), and brain volumes., Method: Electronic databases PubMed, Scopus, and Clarivate were searched in February 2020 using an established methodology and pre-determined search terms. Studies were eligible for inclusion if they reported on the association between BP and WMLs or brain volume in cognitively healthy individuals, while adjusting for age and intra-cranial volume., Results: Searches yielded 7509 articles, of which 52 (26 longitudinal and 33 cross-sectional), were eligible and had a combined sample size of 343,794 individuals. Analyses found that 93.7% of studies reported that higher BP was associated with poorer cerebral health (higher WMLs and lower brain volumes). Meta-analysis of compatible results indicated a dose-dependent relationship with every one standard deviation increase in systolic BP (SBP) above 120 mmHg being associated with a 11.2% (95% CI 2.3, 19.9, p = 0.0128) increase in WMLs and -0.13% (95% CI -0.25, -0.023, p = 0.0183) smaller hippocampal volume., Conclusion: The association between BP and brain volumes appears across the full range of BP measurements and is not limited to hypertensive individuals. Higher BP in community-residing individuals is associated with poorer cerebral health.

Background: There is limited evidence relating to the cost-effectiveness of treatments for localised prostate cancer., Methods: The cost-effectiveness of active monitoring, surgery, and radiotherapy was evaluated within the Prostate Testing for Cancer and Treatment (ProtecT) randomised controlled trial from a UK NHS perspective at 10 years' median follow-up. Prostate cancer resource-use collected from hospital records and trial participants was valued using UK reference-costs. QALYs (quality-adjusted-life-years) were calculated from patient-reported EQ-5D-3L measurements. Adjusted mean costs, QALYs, and incremental cost-effectiveness ratios were calculated; cost-effectiveness acceptability curves and sensitivity analyses addressed uncertainty; subgroup analyses considered age and disease-risk., Results: Adjusted mean QALYs were similar between groups: 6.89 (active monitoring), 7.09 (radiotherapy), and 6.91 (surgery). Active monitoring had lower adjusted mean costs (£5913) than radiotherapy (£7361) and surgery (£7519). Radiotherapy was the most likely (58% probability) cost-effective option at the UK NICE willingness-to-pay threshold (£20,000 per QALY). Subgroup analyses confirmed radiotherapy was cost-effective for older men and intermediate/high-risk disease groups; active monitoring was more likely to be the cost-effective option for younger men and low-risk groups., Conclusions: Longer follow-up and modelling are required to determine the most cost-effective treatment for localised prostate cancer over a man's lifetime., Trial Registration: Current Controlled Trials number, ISRCTN20141297: http://isrctn.org (14/10/2002); ClinicalTrials.gov number, NCT02044172: http://www.clinicaltrials.gov (23/01/2014).

Background: A polygenic hazard score (PHS), the weighted sum of 54 SNP genotypes, was previously validated for association with clinically significant prostate cancer and for improved prostate cancer screening accuracy. Here, we assess the potential impact of PHS-informed screening., Methods: United Kingdom population incidence data (Cancer Research United Kingdom) and data from the Cluster Randomized Trial of PSA Testing for Prostate Cancer were combined to estimate age-specific clinically significant prostate cancer incidence (Gleason score ≥7, stage T3-T4, PSA ≥10, or nodal/distant metastases). Using HRs estimated from the ProtecT prostate cancer trial, age-specific incidence rates were calculated for various PHS risk percentiles. Risk-equivalent age, when someone with a given PHS percentile has prostate cancer risk equivalent to an average 50-year-old man (50-year-standard risk), was derived from PHS and incidence data. Positive predictive value (PPV) of PSA testing for clinically significant prostate cancer was calculated using PHS-adjusted age groups., Results: The expected age at diagnosis of clinically significant prostate cancer differs by 19 years between the 1st and 99th PHS percentiles: men with PHS in the 1st and 99th percentiles reach the 50-year-standard risk level at ages 60 and 41, respectively. PPV of PSA was higher for men with higher PHS-adjusted age., Conclusions: PHS provides individualized estimates of risk-equivalent age for clinically significant prostate cancer. Screening initiation could be adjusted by a man's PHS., Impact: Personalized genetic risk assessments could inform prostate cancer screening decisions., (©2020 American Association for Cancer Research.)

Background: Health experts including planners and policy-makers face complex decisions in diverse and constantly changing healthcare systems. Visual analytics may play a critical role in supporting analysis of complex healthcare data and decision-making. The purpose of this study was to examine the real-world experience that experts in mental healthcare planning have with visual analytics tools, investigate how well current visualisation techniques meet their needs, and suggest priorities for the future development of visual analytics tools of practical benefit to mental healthcare policy and decision-making., Methods: Health expert experience was assessed by an online exploratory survey consisting of a mix of multiple choice and open-ended questions. Health experts were sampled from an international pool of policy-makers, health agency directors, and researchers with extensive and direct experience of using visual analytics tools for complex mental healthcare systems planning. We invited them to the survey, and the experts' responses were analysed using statistical and text mining approaches., Results: The forty respondents who took part in the study recognised the complexity of healthcare systems data, but had most experience with and preference for relatively simple and familiar visualisations such as bar charts, scatter plots, and geographical maps. Sixty-five percent rated visual analytics as important to their field for evidence-informed decision-making processes. Fifty-five percent indicated that more advanced visual analytics tools were needed for their data analysis, and 67.5% stated their willingness to learn new tools. This was reflected in text mining and qualitative synthesis of open-ended responses., Conclusions: This exploratory research provides readers with the first self-report insight into expert experience with visual analytics in mental healthcare systems research and policy. In spite of the awareness of their importance for complex healthcare planning, the majority of experts use simple, readily available visualisation tools. We conclude that co-creation and co-development strategies will be required to support advanced visual analytics tools and skills, which will become essential in the future of healthcare.

Manual review of the extensive literature covering nutrition-based lifestyle interventions to promote healthy cognitive ageing has proved educational, however, data-driven techniques can better account for the large size of the literature (tens of thousands of potentially relevant publications to date) and interdisciplinary nature, where relevant publications may be found. In this study, we present a new way to map the literature landscape, focusing on nutrition-based lifestyle interventions to promote healthy cognitive ageing. We applied a combination of citation network analysis and text mining to map out the existing literature on nutritional interventions and cognitive health. Results indicated five overarching clusters of publications, which could be further deconstructed into a total of 35 clusters. These could be broadly distinguished by the focus on lifespan stages (e.g., infancy versus older age), and specificity regarding nutrition (e.g., a narrow focus on iodine deficiency versus a broad focus on weight gain). Rather than concentrating into a single cluster, interventions were present throughout the majority of the research. We conclude that a data-driven map of the nutritional intervention literature can benefit the design of future interventions, by highlighting topics and themes that could be synthesized across currently disconnected clusters of publications.

Background: There is a growing research focus on temporal cognition, due to its importance in memory and planning, and links with psychological wellbeing. Researchers are increasingly using diary studies, experience sampling and social media data to study temporal thought. However, it remains unclear whether such reports can be accurately interpreted for temporal orientation. In this study, temporal orientation judgements about text reports of thoughts were compared across human coding, automatic text mining, and participant self-report. Methods: 214 participants responded to randomly timed text message prompts, categorically reporting the temporal direction of their thoughts and describing the content of their thoughts, producing a corpus of 2505 brief (1-358, M = 43 characters) descriptions. Two researchers independently, blindly coded temporal orientation of the descriptions. Four approaches to automated coding used tense to establish temporal category for each description. Concordance between temporal orientation assessments by self-report, human coding, and automatic text mining was evaluated. Results: Human coding more closely matched self-reported coding than automated methods. Accuracy for human (79.93% correct) and automated (57.44% correct) coding was diminished when multiple guesses at ambiguous temporal categories (ties) were allowed in coding (reduction to 74.95% correct for human, 49.05% automated). Conclusion: Ambiguous tense poses a challenge for both human and automated coding protocols that attempt to infer temporal orientation from text describing momentary thought. While methods can be applied to minimize bias, this study demonstrates that researchers need to be wary about attributing temporal orientation to text-reported thought processes, and emphasize the importance of eliciting self-reported judgements.

Objectives: Cross-sectional studies suggest that around 6% of men undergo prostate-specific antigen (PSA) testing each year in UK general practice (GP). This longitudinal study aims to determine the cumulative testing pattern of men over a 10-year period and whether this testing can be considered equivalent to screening for prostate cancer (PCa)., Setting, Participants and Outcome Measures: Patient-level data on PSA tests, biopsies and PCa diagnoses were obtained from the UK Clinical Practice Research Datalink (CPRD) for the years 2002 to 2011. The cumulative risks of PSA testing and of being diagnosed with PCa were estimated for the 10-year study period. Associations of a man's age, region and index of multiple deprivation with the cumulative risk of PSA testing and PCa diagnosis were investigated. Rates of biopsy and diagnosis, following a high test result, were compared with those from the programme of PSA testing in the Prostate Testing for Cancer and Treatment (ProtecT) study., Results: The 10-year risk of exposure to at least one PSA test in men aged 45 to 69 years in UK GP was 39.2% (95% CI 39.0 to 39.4%). The age-specific risks ranged from 25.2% for men aged 45-49 years to 53.0% for men aged 65-69 years (p for trend <0.001). For those with a PSA level ≥3, a test in UK GP was less likely to result in a biopsy (6%) and/or diagnosis of PCa (15%) compared with ProtecT study participants (85% and 34%, respectively)., Conclusion: A high proportion of men aged 45-69 years undergo PSA tests in UK GP: 39% over a 10-year period. A high proportion of these tests appear to be for the investigation of lower urinary tract symptoms and not screening for PCa., Trial Registration Number: ISRCTN20141297,NCT02044172., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

High blood glucose and type 2 diabetes are associated with a range of adverse health and cognitive outcomes. One factor that contributes to high blood glucose and type 2 diabetes is dietary intake. This study investigated the relationship between dietary patterns, fasting blood glucose and diabetes status in a sample of 209 participants aged 60-65. Blood plasma glucose was measured from venous blood samples. Individual Prudent and Western dietary patterns were estimated from a self-completed food frequency questionnaire. The relationship between dietary patterns, diabetes, and blood glucose was assessed via general linear model analyses controlling for age, sex, height, and total caloric intake. Results indicated that there was no association between Prudent diet and fasting blood glucose levels, or type 2 diabetes. In contrast, an individual in the upper tertile for Western dietary score had a significantly higher risk of having diabetes than an individual in the lower tertile for Western dietary score. However, there was no significant association between Western diet and fasting blood glucose. Western diet may be associated with type 2 diabetes through mechanisms beyond impacting blood plasma glucose directly. The fact that the association between Western diet and type 2 diabetes remained even when total caloric intake was controlled for highlights the need for policy and population health interventions targeting the reduction of unhealthy food consumption.

Background: Sociodemographic characteristics are associated with participating in cancer screening and trials. We compared the characteristics of those responding with those not responding to a single invitation for prostate-specific antigen (PSA) testing for prostate cancer as part of the Cluster randomised triAl of PSA testing for Prostate cancer (CAP)., Methods: Age, rurality and deprivation among 197,763 men from 271 cluster-randomised primary care centres in the UK were compared between those responding (n = 90,300) and those not responding (n = 100,953) to a prostate cancer testing invitation., Results: There was little difference in age between responders and nonresponders. Responders were slightly more likely to come from urban rather than rural areas and were slightly less deprived than those who did not respond., Conclusion: These data indicate similarities in age and only minor differences in deprivation and urban location between responders and nonresponders. These differences were smaller, but in the same direction as those observed in other screening trials., Trial Registration: ISRCTN92187251 . Registered on 29 November 2004.