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Loneliness is a pervasive experience with adverse impacts on health and well-being. Despite its significance, notable gaps impede a full understanding of how loneliness changes across the adult life span and what factors influence these changes. To address this, we conducted a coordinated data analysis of nine longitudinal studies encompassing 128,118 participants ages 13 to 103 from over 20 countries. Using harmonized variables and models, we examined loneliness trajectories and predictors. Analyses revealed that loneliness follows a U-shaped curve, decreasing from young adulthood to midlife and increasing in older adulthood. These patterns were consistent across studies. Several baseline factors (i.e., sex, marital status, physical function, education) were linked to loneliness levels, but few moderated the loneliness trajectories. These findings highlight the dynamic nature of loneliness and underscore the need for targeted interventions to reduce social disparities throughout adulthood.

Abstract This study aimed to examine whether psychological distress was cross-sectionally associated with meeting World Cancer Research Fund (WCRF) recommendations in people living with and beyond cancer. Participants were adults living with and beyond breast, prostate and colorectal cancer, participating in the baseline wave of the Advancing Survivorship after Cancer Outcomes Trial (ASCOT). Anxiety/depression was assessed using the EQ-5D-5L and dichotomised into any/no problems. WCRF recommendations were assessed via pedometers, 24-h dietary recalls, self-reported alcohol intake (AUDIT-C), and self-reported smoking status. Participants were categorised as meeting WCRF recommendations using the following cut-offs: average daily steps (≥ 10,000/day), average weekly aerobic steps (≥ 15,000/day), fruit and vegetables (≥ 400 g/day), fibre (≥ 30 g/day), red meat (

Abstract Studies examining lifestyle and cognitive decline often use healthy lifestyle indices, making it difficult to understand implications for interventions. We examined associations of 16 lifestyles with cognitive decline. Data from 32,033 cognitively-healthy adults aged 50-104 years participating in prospective cohort studies of aging from 14 European countries were used to examine associations of lifestyle with memory and fluency decline over 10 years. The reference lifestyle comprised not smoking, no-to-moderate alcohol consumption, weekly moderate-plus-vigorous physical activity, and weekly social contact. We found that memory and fluency decline was generally similar for non-smoking lifestyles. By contrast, memory scores declined up to 0.17 standard deviations (95% confidence interval= 0.08 – 0.27) and fluency scores up to 0.16 standard deviations (0.07 – 0.25) more over 10 years for those reporting smoking lifestyles compared with the reference lifestyle. We thus show that differences in cognitive decline between lifestyles were primarily dependent on smoking status.

Objectives We investigated the hypothetical impact of mandatory alcohol calorie labelling, comparing non-drinkers, low-risk and hazardous drinkers in terms of attitudes, knowledge about calorie content and hypothetical behaviour changes should labelling be introduced.Design Cross-sectional national telephone survey.Setting Community-dwelling adults in England between November 2022 and January 2023.Participants Data were collected from 4683 adults >18 years, of whom 24.7% were non-drinkers; 77.6% of alcohol drinkers were categorised as low-risk and 22.4% as hazardous drinkers according to the Alcohol Use Disorders Identification Test questionnaire.Primary outcome measures Attitudes to alcohol calorie labelling in shops and supermarkets and in hospitality venues, knowledge of the calorie content of alcoholic beverages (beer, wine, cider and spirits) and changes in drinking practices if calorie labelling was introduced.Results Comparisons were made between non-drinkers, low-risk drinkers and hazardous drinkers, with analyses adjusted for age, gender, ethnicity, socioeconomic status and education. Attitudes to calorie labelling were generally positive, but were less favourable among alcohol drinkers than non-drinkers. Hazardous drinkers were more accurate in their estimations of the calorie content of wine, cider and spirits than non-drinkers (p

Abstract Background Poorer health and well‐being are associated with diabetes risk. However, little is known about the trajectory of health and well‐being from before to after diabetes diagnosis. We compared depressive symptoms, quality of life, self‐rated health, and loneliness at three time points (prediagnosis, diagnosis, 2–4 years post diagnosis) in individuals who developed diabetes and a comparison group. Methods Health and well‐being measures were self‐reported by 3474 participants from the English Longitudinal Study of Ageing. Repeated measures analysis of variance and generalized estimating equations were used to investigate differences by group, time, and group‐by‐time interactions. Results A total of 473 (13.6%) participants developed diabetes. The diabetes group reported greater depressive symptoms (W2(1) = 20.67, p

Objectives Long-term sickness absence from employment has negative consequences for the economy and can lead to widened health inequalities. Sick notes (also called ‘fit notes’) are issued by general practitioners when a person cannot work for health reasons for more than 7 days. We quantified the sick note rate in people with evidence of COVID-19 in 2020, 2021 and 2022, as an indication of the burden for people recovering from COVID-19.Design Cohort study.Setting With National Health Service (NHS) England approval, we used routine clinical data (primary care, hospital and COVID-19 testing records) within the OpenSAFELY-TPP database.Participants People 18–64 years with a recorded positive test or diagnosis of COVID-19 in 2020 (n=365 421), 2021 (n=1 206 555) or 2022 (n=1 321 313); general population matched in age, sex and region in 2019 (n=3 140 326), 2020 (n=3 439 534), 2021 (n=4 571 469) and 2022 (n=4 818 870); people hospitalised with pneumonia in 2019 (n=29 673).Primary outcome measure Receipt of a sick note in primary care.Results Among people with a positive SARS-CoV-2 test or COVID-19 diagnosis, the sick note rate was 4.88 per 100 person-months (95% CI 4.83 to 4.93) in 2020, 2.66 (95% CI 2.64 to 2.67) in 2021 and 1.73 (95% CI 1.72 to 1.73) in 2022. Compared with the age, sex and region-matched general population, the adjusted HR for receipt of a sick note over the entire follow-up period (up to 10 months) was 4.07 (95% CI 4.02 to 4.12) in 2020 decreasing to 1.57 (95% CI 1.56 to 1.58) in 2022. The HR was highest in the first 30 days postdiagnosis in all years. Among people hospitalised with COVID-19, after adjustment, the sick note rate was lower than in people hospitalised with pneumonia.Conclusions Given the under-recording of postacute COVID-19-related symptoms, these findings contribute a valuable perspective on the long-term effects of COVID-19. Despite likely underestimation of the sick note rate, sick notes were issued more frequently to people with COVID-19 compared with those without, even in an era when most people are vaccinated. Most sick notes occurred in the first 30 days postdiagnosis, but the increased risk several months postdiagnosis may provide further evidence of the long-term impact.

Abstract Probabilistic projections from the UK Climate Projections 2018 are presented for four global warming levels (GWLs) at 1.5, 2, 3, and 4°C above the 1850–1900 baseline. Our results show how uncertainties associated with climate models and four representative concentration pathways (RCP) emission scenarios translate to UK regional scale changes in maximum temperature and precipitation, with data also available for minimum and mean temperatures, humidity and surface net downward shortwave radiation flux. We compare weighting the likelihood of RCPs based on (hypothetical) policy decisions, against our baseline assumption that each RCP is equally likely. Differences between weighted and unweighted GWL distributions are small, particularly in relation to the full breadth of uncertainties that are incorporated into the probabilistic projections. Finally we quantify the relative importance of scenario, model and internal variability on regional projected GWLs and show that uncertainty associated with an uncertain climate response to forcings dominates at all GWLs.

Abstract Background A cancer diagnosis and its treatment may be an especially isolating experience. Despite evidence that positive health behaviours can improve outcomes for people living with and beyond cancer (LWBC), no studies have examined associations between loneliness and different health behaviours in this population. This study aimed to describe the prevalence of loneliness in a large sample of UK adults LWBC and to explore whether loneliness was associated with multiple health behaviours. Methods Participants were adults (aged ≥ 18 years) diagnosed with breast, prostate or colorectal cancer who completed the Health and Lifestyle After Cancer Survey. Loneliness was reported using the UCLA loneliness score, dichotomised into higher (≥ 6) versus lower (

The currently available pharmacological anti-dementia treatments provide only temporary and limited benefits. Not surprisingly, patients and professionals increasingly explore non-pharmacological interventions that may alleviate dementia symptoms. Among these interventions is hyperbaric oxygen therapy (HBOT). A brief review is presented on HBOT use in medicine, with its mode of action in dementia, specifically Alzheimer’s disease, as well as a case report of self-initiated HBOT in a 62-year-old man with a clinical diagnosis of probable Alzheimer’s disease. He had over 400 HBOT sessions [2–3 times weekly, with a duration of 30–50 min, in a multi-place hyperbaric chamber at 2 atmospheres absolute (ATA)] over 7 years and use of donepezil (10 mg daily) for the last 3 years when formally diagnosed by the National Health Service (NHS) Memory Service. The patient’s longitudinal neurocognitive and neuroradiological evidence over 7 years of follow-up remained stable (with no major cognitive decline and no behavioral changes) when compared to his initial presentation when diagnosed by the private health provider. His driving remains unimpaired, and he continues to be independent. This highlights the potential HBOT benefits including those on visuospatial ability and activities of daily living in people with Alzheimer’s disease. This case report argues for more extensive research into the clinical effects of HBOT in Alzheimer’s disease. Discussion of HBOT use is along with the latest advances in anti-amyloid immunotherapy for Alzheimer’s disease, as well as HBOT augmentation of current and novel dementia drug delivery via nanotechnology.

Summary: Background: Physical abuse can lead to severe health consequences that extend beyond immediate harm. We explored the associations of physical abuse experienced during childhood and adulthood with a wide range of adult health conditions requiring hospital treatment. Methods: We utilised data from a sub-cohort of 157,366 UK Biobank participants (46.4% of the baseline population; age range 45–81; 89,101 women) and repeated analyses in an independent population of 85,929 adults from the Finnish Public Sector (FPS) study (age range 17–78; 68,544 women). Participants in both cohorts reported instances of physical and sexual abuse at study baseline. Follow-up included 77 common health conditions ascertained from linkage data to national hospital and mortality registries. Findings: Mean follow-up duration was 4.6 years (SD 0.14) in UK Biobank and 10.6 years (4.3) in FPS. Physical and sexual abuse was associated with 22 mental and physical health conditions. After multivariable adjustments, participants who experienced abuse during both early and later stages of life had a 2.12- (95% confidence interval 1.39–3.23) to 3.37-fold (1.52–7.45) increased risk of mental and behavioural disorders, a 1.46 (1.20–1.79) to 1.83 (1.05–3.20) times increased risk of metabolic, haematologic, and respiratory diseases, and a 1.24 (1.07–1.45) times higher risk of inflammatory diseases compared with non-exposed participants. The absolute risk difference between these groups was greatest for metabolic and haematologic conditions (rate 381 and risk difference 160 per 100,000 person-years). Frailty, comorbidities, and competing risk of death did not modify these associations, but the possibility of bias or residual confounding cannot be excluded. Interpretation: Repeated exposure to physical and sexual abuse amplifies the risk of hospitalisations from mental disorders and physical diseases spanning diverse organ systems. Addressing this issue may necessitate multifaceted strategies, including shifts in societal norms, legal measures, and increased healthcare provision for affected individuals and their families. Funding: Wellcome Trust, UK Medical Research Council, U.S. National Institute on Aging, Academy of Finland.

Abstract Background We test a novel ‘weight scarring’ hypothesis which suggests that past obesity is associated with impairments in current psychological well-being and this increases risk of negative physical health outcomes associated with obesity. Across two nationally representative studies, we tested whether past obesity is associated with current psychological outcomes and whether these psychological outcomes explain the association between past obesity and subsequent early mortality. Methods Data were from the National Health and Nutrition Examination Survey (NHANES) (n = 29,047) and the Health and Retirement Study (HRS) (n = 11,998). Past obesity was defined based on maximum lifetime weight in NHANES and the highest weight from past study waves in the HRS. Across both studies, current depressive symptoms were analysed. A set of 10 additional well-being measures were combined to produce an ‘index of impaired well-being’ in HRS. Subsequent all-cause mortality was examined using National Deaths Index records in NHANES and household interviews in HRS. Linear or logistic regression, Cox proportional hazard regression, and causal mediation models were used. Results We found that past obesity was associated with greater current depressive symptoms after controlling for current weight status and in analyses limited to those who were no longer classified as having obesity in NHANES (β = 0.17; 95% CI: 0.13, 0.22) and HRS (β = 0.20; 95% CI: 0.08, 0.31). In HRS, past obesity was also associated with a range of current negative psychological outcomes, including an index of impaired psychological well-being (β = 0.16; 95% CI: 0.05, 0.27). Past obesity was associated with a higher risk of early mortality in both NHANES and HRS (HR = 1.31; 95% CI: 1.16, 1.48 and HR = 1.34; 95% CI: 1.20, 1.50, respectively). Depressive symptoms explained 6% (95% CI: 0.01, 0.10) and 5% (95% CI: 0.01, 0.09) of the association between past obesity and premature mortality in NHANES and HRS, respectively. Impaired psychological well-being partly mediated the association between past obesity and premature mortality by 10% (95% CI: 0.04, 0.16) in HRS. Conclusions Our findings suggest that there may be a psychological legacy of past obesity that is associated with raised mortality risk. Ensuring people with obesity receive psychological support even after experiencing weight loss may be important.

Abstract Suboptimal sleep durations and depression frequently cooccur. Short-sleep and long-sleep are commonly thought of as symptoms of depression, but a growing literature suggests that they may be prodromal. While each represents a process of mutual influence, the directionality between them remains unclear. Using polygenic scores (PGS), we investigate the prospective direction involved in suboptimal sleep durations and depression. Male and female participants, aged ≥50, were recruited from the English Longitudinal Study of Ageing (ELSA). PGS for sleep duration, short-sleep, and long-sleep were calculated using summary statistics data from the UK Biobank cohort. Sleep duration, categorised into short-sleep (“≤5 h”), optimal-sleep (“>5 to

Polygenic indexes (PGIs) are DNA-based predictors. Their value for research in many scientific disciplines is growing rapidly. As a resource for researchers, we used a consistent methodology to construct PGIs for 47 phenotypes in 11 datasets. To maximize the PGIs' prediction accuracies, we constructed them using genome-wide association studies-some not previously published-from multiple data sources, including 23andMe and UK Biobank. We present a theoretical framework to help interpret analyses involving PGIs. A key insight is that a PGI can be understood as an unbiased but noisy measure of a latent variable we call the 'additive SNP factor'. Regressions in which the true regressor is this factor but the PGI is used as its proxy therefore suffer from errors-in-variables bias. We derive an estimator that corrects for the bias, illustrate the correction, and make a Python tool for implementing it publicly available.

Abstract Objective: To explore on-package formula messaging with reference to legislation and government-issued guidance in Great Britain (GB). Design: Formula products were identified, pictures of all sides of packs collated and on-package text and images were coded. Compliance with both GB legislation and guidance issued by the Department of Health and Social Care (DHSC) was assessed. Setting: All formula packs that were available for sale over the counter in GB between April and October 2020. Participants: Formula packs (n 71) including infant formula, follow-on formula, growing-up formula and specialist formula were identified, coded and analysed. Results: In total, 41 % of formula packs included nutrition claims, and 18 % included health claims that may be considered non-permitted, according to DHSC guidance. Additionally, 72 % of products showed images considered ‘non-permitted’. Breast Milk Substitute (BMS) legislation states infant and follow-on formula packs should be clearly distinguishable but does not provide criteria to assess similarity. Based on DHSC guidance, 72 % of infant and follow-on formula packs were categorised as showing a high degree of similarity. Marketing practices not covered by current legislation were widespread, such as 94 % of infant formula packs including advertisements for follow-on or growing-up formula. Conclusions: Text and images considered non-permitted according to DHSC guidance for implementing BMS legislation were widespread on formula products available in GB. As terms such as ‘similarity’ are not defined in BMS legislation, it was unclear if breaches had occurred. Findings support the WHO call for loopholes in domestic legislation to be closed as a matter of urgency.

Background and aimsDiabetes and/or hypertension are the most common conditions in older people, and also related to higher cardiovascular disease (CVD) incidence and mortality. This study aims to explore the risk of CVD incidence and mortality among older people with diabetes and/or hypertension over a 16 years follow-up period and investigates the role of depression and obesity in these relationships.Methods6,855 participants aged 50+ from the English Longitudinal Study of Ageing (ELSA). The main exposure is having diabetes and/or hypertension at baseline (2002/2003) compared to not having, but excluded those with coronary heart disease (CHD) and/or stroke (CVD). Survival models are used for CVD incidence and mortality up to 2018, adjusted for socio-demographic, health, health behaviours, cognitive function, and physical function characteristics.Results39.3% of people at baseline had diabetes and/or hypertension. The risk of CVD incidence was 1.7 (95%CI: 1.5; 1.9) higher among people with diabetes and/or hypertension compared to those without and was independent of covariates adjustment. People with diabetes and/or hypertension were also 1.3 (95%CI: 1.1; 1.8) times more likely to die from CVD than those without. We did not find evidence for an elevated risk of CVD incidence and mortality among people with obesity nor among those with depression.ConclusionsIn order to effectively reduce the risk of CVD incidence and mortality among older people, treatment as well as management of hypertension and diabetes should be routinely considered for older people with diabetes and/or hypertension.

Immunotherapies have emerged as promising strategies for cancer treatment. However, existing immunotherapies have poor activity in high-grade serous ovarian cancer (HGSC) due to the immunosuppressive tumor microenvironment and the associated low tumoral CD8+ T cell (CTL) infiltration. Through multiple lines of evidence, including integrative analyses of human HGSC tumors, we have identified miR-146a as a master regulator of CTL infiltration in HGSC. Tumoral miR-146a expression is positively correlated with anti-cancer immune signatures in human HGSC tumors, and delivery of miR-146a to tumors resulted in significant reduction in tumor growth in both ID8-p53−/− and IG10 murine HGSC models. Increasing miR-146a expression in tumors improved anti-tumor immune responses by decreasing immune suppressive neutrophils and increasing CTL infiltration. Mechanistically, miR-146a targets IL-1 receptor-associated kinase 1 and tumor necrosis factor receptor-associated factor 6 adaptor molecules of the transcription factor nuclear factor κB signaling pathway in ID8-p53−/− cells and decreases production of the downstream neutrophil chemoattractant, C-X-C motif chemokine ligand 1. In addition to HGSC, tumoral miR-146a expression also correlates strongly with CTL infiltration in other cancer types including thyroid, prostate, breast, and adrenocortical cancers. Altogether, our findings highlight the ability of miR-146a to overcome immune suppression and improve CTL infiltration in tumors.

Abstract Background Considering the co-morbidity of major psychiatric disorders and intelligence with smoking, to increase our understanding of why some people take up smoking or continue to smoke, while others stop smoking without progressing to nicotine dependence, we investigated the genetic propensities to psychiatric disorders and intelligence as determinants of smoking initiation, heaviness of smoking and smoking cessation in older adults from the general population. Results Having utilised data from the English Longitudinal Study of Ageing (ELSA), our results showed that one standard deviation increase in MDD-PGS was associated with increased odds of being a moderate-heavy smoker (odds ratio [OR] = 1.11, SE = 0.04, 95%CI = 1.00-1.24, p = 0.028). There were no other significant associations between SZ-PGS, BD-PGS, or IQ-PGS and smoking initiation, heaviness of smoking and smoking cessation in older adults from the general population in the UK. Conclusions Smoking is a behaviour that does not appear to share common genetic ground with schizophrenia, bipolar disorders, and intelligence in older adults, which may suggest that it is more likely to be modifiable by smoking cessation interventions. Once started to smoke, older adults with a higher polygenic predisposition to major depressive disorders are more likely to be moderate to heavy smokers, implying that these adults may require targeted smoking cessation services.

Abstract This research explored experiences across three cognitive function groups (no impairment, mild impairment, and dementia) with respect to shielding (either self-isolating or staying at home), COVID-19 infection, and access to health/care services during the COVID-19 pandemic. Analyses were conducted using data from the English Longitudinal Study of Ageing (ELSA) COVID-19 sub-study collected in 2020. We report bivariate estimates across our outcomes of interest by cognitive function group along with multivariate regression results adjusting for demographic, socioeconomic, geographic, and health characteristics. Rates of shielding were high across all cognitive function groups and three measured time points (April, June/July, and Nov/Dec 2020), ranging from 74.6% (95% confidence interval 72.9–76.2) for no impairment in Nov/Dec to 96.7% (92.0–98.7) for dementia in April (bivariate analysis). 44.1% (33.5–55.3) of those with dementia experienced disruption in access to community health services by June/July compared to 34.9% (33.2–36.7) for no impairment. A higher proportion of those with mild impairment reported hospital-based cancellations in June/July (23.1% (20.1–26.4)) and Nov/Dec (16.3% (13.4–19.7)) than those with no impairment (18.0% (16.6–19.4) and 11.7% (10.6–12.9)). Multivariate adjusted models found that those with dementia were 2.4 (1.1–5.0) times more likely than those with no impairment to be shielding in June/July. All other multivariate analyses found no statistically significant differences between cognitive function groups. People with dementia were more likely than people with no impairment to be shielding early in the pandemic, but importantly they were no more likely to experience disruption to services or hospital treatment.

Abstract The COVID-19 pandemic brought about an increased reliance on the Internet for various daily activities. Given the known digital divide, it is important to understand whether older adults changed their Internet use patterns, but current evidence is limited to cross-sectional studies. This study documents changes in frequency and types of Internet use among older adults from before to shortly after the outbreak of the COVID-19 pandemic (2018/2019 to June/July 2020), and the factors predicting regular use during these early days of the pandemic. Using data on 6,840 adults aged 50 + from the nationally representative English Longitudinal Study of Ageing, we apply longitudinal fixed-effects models to examine within-individual changes in Internet use behaviour. There was no change in the likelihood of daily Internet use between 2018/2019 and June/July 2020, despite the increased digitalisation of services over the pandemic. Daily use in June/July 2020 was negatively related to age, neighbourhood deprivation, and loneliness, and positively related to partnership status, education, employment, income, and organisation membership. Using the Internet for making calls and getting information about Government services increased, which was important given the social restrictions and overall uncertainty. However, Internet use for finding health-related information decreased. As the world moves towards digital alternatives post-pandemic, it is important to continually ensure older adults are not at risk of exclusion.