BACKGROUND:Physical activity (PA) is a widely recognised modifiable risk factor for cognitive health. The role of diet and their combined associations on cognition in midlife remains unclear. We assessed the additive and interactive associations of moderate-to-vigorous PA (MVPA) and diet quality on cognition in midlife. METHODS:At age 46, participants from the 1970 British Cohort Study wore activPAL accelerometers for 1 week and completed the Oxford WebQ dietary questionnaire, from which the Pyramid-Based Mediterranean Diet Score (PyrMDS) was derived. Global cognitive z-scores were derived from standardised tests of processing speed, verbal memory and fluency at age 46 and 51. Multivariate linear regression examined independent and mutually adjusted associations between MVPA and PyrMDS at age 46 with cognitive z-scores at both timepoints. Combined MVPA-PyrMDS tertiles and interaction terms were also tested. RESULTS:In a sample of n=3028 (55% female), mean MVPA was 52±25 min/day and mean PyrMDS was 6.31±1.65. In mutually adjusted models at age 51, only PyrMDS was associated with global cognitive z-scores after covariate adjustment (per hour MVPA: β=0.228, 95% CI -0.026 to 0.481; per point PyrMDS: β=0.045, 95% CI 0.025 to 0.065). In combined analyses, PyrMDS was associated with better age 51 global cognitive z-scores irrespective of MVPA (high-PyrMDS:low-MVPA vs low-PyrMDS:low-MVPA: β=0.185, 95% CI 0.046 to 0.325). No interactions were observed. CONCLUSION:Diet quality demonstrated prospective associations with better cognition independently of MVPA, with associations remaining more consistent than for PA after adjustment of confounders. Diet quality may represent an under-recognised lifestyle target for cognitive health.

AIMS:The relationship between retirement and mental health remains unclear, with mixed evidence likely driven by methodological challenges and heterogeneity across population subgroups. This study explores the relationship between retirement, time since retirement and mental health, focusing on differences between those living alone and cohabiting. METHODS:We used data from 10,698 participants (48,815 observations) in the Survey of Health, Ageing and Retirement in Europe, waves 1-8, spanning 20 countries and 16 years. Participants were included if they were employed at baseline and retired during follow-up. We applied a triangulated approach using (1) multilevel linear spline models to examine trajectories and (2) fixed-effects instrumental variable analyses (IV) using statutory retirement age as an instrument to establish causal effects. The outcome was depressive symptoms measured using the EURO-D scale (higher scores indicate more depressive symptoms). RESULTS:Multilevel spline models showed minimal change in depressive symptoms before retirement. At retirement, a small decline in EURO-D scores was indicated (-0.07 points per year [95% CI: -0.13 to -0.0003]), followed by an increase starting two years post-retirement (0.09 per year, 95% CI: 0.02 to 0.16). IV analyses showed that retirement was associated with fewer depressive symptoms (-0.26, 95% CI: -0.45 to -0.07). Individuals living alone reported higher depressive symptoms, but cohabitation status did not moderate the relationship between retirement and mental health. CONCLUSIONS:Retirement is associated with a short-term reduction in depressive symptoms, but the effect diminishes over time. While individuals living alone consistently report higher depressive symptoms, cohabitation status does not moderate the retirement-mental health relationship.

Amid worsening mental health of adolescents, the proliferation of digital technologies over the last two decades has attracted particular attention as one potential contributing factor. However, there is a widely cited lack of causal evidence and most prior studies rely on correlational designs vulnerable to reverse causation, unmeasured confounding, and measurement error, while being limited in geographic scope. We estimate the effects of screen time and social media use on adolescent wellbeing using data from 615,133 fifteen-year-olds across 54 countries, applying instrumental variable methods that exploit cross-national and temporal variation in digital environments during the rapid technological diffusion of the mid-2010s. We use year-specific country-level Information and Communication Technology (ICT) usage index and social media penetration rate as instruments generating exogenous variation in adolescents' digital engagement. Instrumental Variables analyses indicate that higher screen time and more social media use caused lower wellbeing in the mid 2010s. The findings were robust to assumption testing and robustness checks. This study contributes multinational causally informed evidence to an empirically contested but policy-relevant debate on the impacts of digital technology on adolescent wellbeing.

Background:Carotid-intima media-thickness (cIMT) predicts cardiovascular events and informs mechanistic research on cardiovascular diseases. However, cardiovascular disease research remains Eurocentric despite etiological differences across ancestries. Incorporating Asian populations who face substantial cardiovascular disease burden with distinct etiological landscape can enhance our understanding of cIMT biology and subclinical processes linked to CVD. This study aims to elucidate methylation-based mechanisms of cIMT through DNA methylation profiling integrated with multi-omics data and clinically informative cIMT thresholds, leveraging an Asian cohort to enhance discovery. Methods:We conducted an epigenome-wide association study (EWAS) of cIMT using peripheral blood DNA methylation at ~850,000 CpG sites in the Asian Health for Life in Singapore (HELIOS) cohort (n=1,357), followed by targeted trans-ancestry meta-analysis with European cohorts (overall n=2,765). Causal inference analyses (summary data-based Mendelian Randomisation [SMR] and colocalisation) evaluated methylation-mediated effects on cIMT, cardiovascular disease and proximal gene expression. We derived a methylation risk score (MRS) and tested its association with cIMT thresholds indicative of elevated cardiovascular risk (≥75th percentile for age, sex and ethnicity). Results:Three novel CpG-cIMT associations were identified (P<9.35E-07). Causal analyses supported cg08227773 methylation-mediated effects on both coronary artery disease risk (PSMR=2.91E-05, coloc PP.H4 =0.91) and NBEAL2 (Neurobeachin-like 2) expression (PSMR=9.13E-08, coloc PP.H4=0.69), a gene implicated in immune dysregulation. MRS of cIMT aggregating the three sentinel CpGs was associated with clinically-informative cIMT elevation (Odds Ratio=2.75 for Q4 vs Q1, 95% CI: 1.47-5.13). Conclusions:Through Asian-led discovery, this study identifies three novel DNA methylation markers for cIMT that are linked to cIMT elevation above clinically meaningful risk thresholds. Causal inference analyses suggest methylation-mediated coronary artery disease risk via NBEAL2 regulation, nominating biologically relevant targets while underscoring the need for larger multi-omics resources to refine mechanisms.

OBJECTIVE:To assess the impact of cardiorespiratory fitness (CRF) and muscle strength on depression and individual depression symptoms. METHODS:Mendelian randomisation (MR) analysis was conducted in up to 341,326 participants of European ancestry from UK Biobank (aged 37-73 years). Genetic variants from previous genome-wide association studies (GWAS) of CRF and grip strength (to proxy overall muscle strength) were utilised to instrument exposures. A broad depression phenotype based on self-report and hospital records, as well as individual measures of depression symptoms from the Patient Health Questionnaire-9 (PHQ-9) were used as outcomes. Analysis was repeated stratifying by sex and using summary statistics from a major depressive disorder (MDD) GWAS. RESULTS:There was no clear evidence for association between CRF and any depression outcome. There was robust evidence suggesting greater grip was associated with lower odds of broad depression (OR per 0.1 kg increase in weight adjusted grip: 0.86, 95% CI:0.80,0.93), as well as the PHQ-9 items appetite changes (OR:0.56, 95% CI:0.49,0.65), and anhedonia (OR:0.79, 95% CI:0.69,0.90), a core symptom of depression. There was also some evidence for associations between greater grip and lower odds of depressed mood (OR:0.85, 95% CI:0.74,0.97), psychomotor changes (OR:0.79, 95% CI:0.64,0.97), fatigue (OR:0.83, 95% CI:0.74,0.93) and concentration problems (OR:0.85, 95% CI:0.74,0.98) in the MR-inverse variance weighted analysis. Effects were mostly driven by stronger associations in females and results replicated in the two-sample MR for MDD. CONCLUSION:Muscle strength may represent an important modifiable factor for preventing and treating depression and several specific symptoms, including core symptoms such as anhedonia.

INTRODUCTION:Psychological distress has been linked with cognitive impairment. However, whether the relationship is causal, reflects preclinical dementia neuropathology, or confounding by common causes remains unclear. METHODS:In five UK longitudinal studies, we examined associations of psychological distress with subsequent cognition using linear and mixed effects models, and dementia using logistic regression. We examined variation by age-at-assessment, severity, and distress persistence, combining study-specific estimates using two-stage individual participant data meta-analysis. RESULTS:Pooling across studies (N = 24,564), greater baseline psychological distress was associated with lower subsequent cognitive level (β = -0.03 [95% confidence interval [CI]: -0.06; -0.01]; I2 = 70%), and dementia (odd ratio [OR] = 1.1 [1.0; 1.2]; I2 = 0%), but not cognitive change. Associations were found for clinically significant, persistent and intermittent distress. Dementia was associated with distress assessed at ages 65-75, and 55-64, but not 45-54 years. DISCUSSION:Findings highlight the relevance of psychological distress in later cognitive outcomes, with potential future implications for dementia prevention and identifying high-risk groups.

BACKGROUND:Social health is increasingly recognised as an important factor influencing cognitive ageing and experiences of dementia. Yet definitions and measurements remain inconsistent, and evidence on how social health relates to cognitive outcomes remains limited. AIM AND METHODS:This narrative review presents the conceptual framework and synthesises the empirical findings from the Social Health and Reserve in the Dementia Patient Journey (SHARED) consortium, established to advance understanding of social health across the continuum from preclinical cognitive change to dementia, with a central aim to develop a comprehensive social health framework. SHARED combined conceptual framework development, global qualitative and quantitative studies, coordinated analyses across more than 40 cohorts (∼150,000 participants) and investigations of pathways underlying cognitive resilience. RESULTS:We refined the conceptualisation of social health by integrating individual capacities with features of the social environment. Qualitative interviews further identified novel and often unmeasured dimensions, informing refinement of the framework. Across multiple global cohorts, better social health was associated with higher cognitive performance, slower decline, and reduced risks of mild cognitive impairment and dementia, although associations varied across markers, domains, and contexts. Mechanistic analyses linked social health to markers of brain reserve, including total brain volume and white matter microstructure, and showed that depressive symptoms partially mediated social support-cognition associations. CONCLUSIONS:SHARED delivers a comprehensive, multidimensional framework for social health and provides strong multi-cohort evidence of its importance for cognitive ageing and dementia. Findings highlight the need for improved social health measurement and further work to disentangle its mechanisms and bidirectional links with cognitive ageing and dementia.

Background and Objectives:The long-term effect of persistent financial adversity on cognitive aging remains unclear. We examined how sustained financial hardship across adulthood associates with midlife cognition, cognitive decline, and later-life brain health and whether impacts vary by sex, childhood socioeconomic circumstances (SECs), and genetic risk. Research Design and Methods:Using data from the 1946 British birth cohort (N = 2,759) and its neuroimaging sub-study, Insight 46 (N = 356-468), we linked financial adversity (low household income, financial hardships between ages 26 and 53) with cognitive performance at age 53, cognitive decline from ages 53 to 69, and neuroimaging measures at ages 69-71. We tested moderating roles of sex, childhood SEC, and APOE-ɛ4. Results:Increased exposure to low household income and financial hardships was associated with lower processing speed (-0.07 [-0.13, -0.02] and -0.05 [-0.11, -0.00]) and verbal memory at age 53 (-0.16 [-0.21, -0.11] and -0.10 [-0.15, -0.05]). This was followed by slower verbal memory decline, attributable to lower baseline scores. Persistent low income was associated with greater ventricular volume (b = 4.67 ml [1.01, 8.32]). Stronger associations between financial adversity and brain atrophy were found for male participants, those with lower childhood SEC, and APOE-ɛ4 carriers who were consistently more vulnerable. Discussion and Implications:Persistent financial adversity impacts cognitive performance by midlife and later-life brain atrophy, with larger effects for men, those from disadvantaged childhoods, and individuals with greater genetic risk. Supporting financially vulnerable working-age adults could help prevent dementia in an aging population.

Accelerated epigenetic ageing has been associated with various age-related health outcomes, but its relevance for dementia risk prediction is unclear. We investigated whether accelerated midlife epigenetic age associates with poor later-life brain health. Participants were 230 individuals from Insight 46, drawn from the 1946 British Birth Cohort, a population-based study of individuals born in the first week of March 1946. DNA methylation was measured at 53 years using Infinium MethylationEPIC BeadChip and GrimAge and PhenoAge were calculated. ‘Age acceleration’ was derived for each clock (AgeAccelGrim and AgeAccelPheno), as previously. At 69-71 years, we measured MRI whole brain and white matter hyperintensity volume, amyloid-PET burden, plasma neurofilament light, and MRI Brain Age (with chronological age subtracted to produce the Brain-Predicted Age Difference/Brain-PAD). For n=176 with follow-up MRI aged 72-75 (n=176), whole brain atrophy was calculated using the boundary shift integral. CSF p-tau181 was measured in n=64. Despite participants’ highly similar chronological age (mean=53.4 years, SD=0.2), there was considerable variation in AgeAccelGrim (SD=4.8yr) and AgeAccelPheno (SD=5.6yr). Linear regression revealed that accelerated GrimAge was associated with smaller later-life whole brain volume, (b=-1.9ml, p=0.010), whilst accelerated PhenoAge was associated with greater whole brain atrophy (b=0.403, p=0.001). Neither GrimAge nor PhenoAge acceleration was associated with amyloid-PET burden. Accelerated PhenoAge was associated with higher white matter hyperintensity burden (b=0.03, p=0.04). Acceleration in both GrimAge (b=0.4pg/ml, p=0.001) and PhenoAge (b=0.4pg/ml, p=0.001) was linked to higher plasma neurofilament light, and both AgeAccelGrim (r=0.32, p=0.010) and AgeAccelPheno (r=0.35, p=0.005) were positively correlated with CSF p-Tau181. MRI brain age (Brain-PAD) was significantly correlated with AgeAccelGrim (r=0.15, p=0.02) but not AgeAccelPheno (r=0.08, p=0.2). Acceleration of midlife epigenetic age was associated with a wide range of features of poor brain health ∼20 years later, in a population-based sample. Epigenetic clocks may hold promise as tools for future brain health prediction.

Despite extensive research on self-rated health (SRH), the extent to which mental health is a component part of SRH assessments and whether this relationship varies by country remains underexplored. This study quantifies the contribution of depressive symptoms to self-rated health and assesses cross-national variation in this association. Using general population data from older adults (age 55 years+) in 18 countries in the Survey of Health, Ageing and Retirement in Europe (SHARE, 2011-2015), we employed four approaches: (1) country-specific pseudo R² models assessing the contribution of depressive symptoms (EURO-D) to SRH, adjusting for socio-demographics, physical health, and functional limitations; (2) partial correlation networks to visualize relationships between SRH, depressive symptoms, and physical health indicators; (3) Blinder-Oaxaca decompositions to quantify cross-country differences in SRH attributable to depressive symptoms and (4) stratification of the estimates by gender. Depressive symptoms explained nearly as much variance in SRH as physical health. Partial correlation networks revealed SRH as central to all health measures, and correlations with depressive symptoms ranging from 0.15 (Israel) to 0.35 (Hungary). Decomposition analyses identified three distinct patterns: Nordic countries (e.g., Denmark, Sweden) had lower depression prevalence but stronger depression-SRH associations; Eastern European countries (e.g., Estonia, Hungary) showed lower depression levels but weaker depression-SRH associations; and Mediterranean countries (e.g., Greece, Spain) exhibited higher depressive symptoms prevalence but weaker depression-SRH associations. Gender disparities in SRH were largely explained by differences in depressive symptom levels rather than differential weighting of depressive symptoms in self-assessments. Depressive symptoms contribute to self-rated health independently of physical health, confirming that mental health is integral to how individuals perceive their health. However, the extent to which this is the case varies cross-nationally highlighting that the meaning of ‘health’ is shaped by national and cultural contexts and this should be considered in any within-country or cross-national research using self-rated health measures. - Mental health is a component as important as physical health in self-rated health. - The contribution of depressive symptoms to SRH varies across countries - Depressive symptoms levels partly explain country differences in self-rated health. - Gender gaps in self-rated health are largely explained by differences in extent of depressive symptoms rather than differences in its weighting

BACKGROUND:Psychological distress has shown links with cognitive functioning in late-life, although the nature of the association remains unclear. Using a multi-cohort approach, we examined longitudinal associations of psychological distress with cognition and dementia, testing whether findings varied by severity, persistence and type of psychiatric symptom. The role of temporality, age-at-symptom-assessment, sex, and socio-economic position will also be examined. METHOD:We used five longitudinal studies: Caerphilly Prospective Study (CAPS), English Longitudinal Study of Ageing (ELSA), National Child Development Study (NCDS), National Survey of Health and Development (NSHD), and Whitehall II (WHII). Psychological distress and global cognition were standardised to facilitate cross-study and longitudinal comparisons. Associations with cognition were examined using linear regression and mixed effects models, with Cox and logistic regression models applied to examine links with dementia. Results were pooled using two-stage individual participant data meta-analysis. RESULTS:Pooled analyses (total N = 20,934; five studies) showed greater psychological distress was associated with poorer global cognitive score (β=-0.04 [95%CI: -0.07; -0.01]; I2=74.6%), including with cut-offs indicating clinically-significant distress (β=-0.08 [-0.15; -0.01]; I2=70.6%). Associations were present for both persistent (β=-0.16 [-0.27; -0.06]; I2=78.1%) and intermittent distress (β=-0.09 [-0.12; -0.05]; I2=79.1%), and were observed individually for depressive and anxiety subscales. Baseline distress was not associated with cognitive decline pooling across three studies. In ELSA, persistent (β=-0.008 [-0.016; -0.002]), but not intermittent distress was associated with cognitive decline. Psychological distress was associated with subsequent dementia in ELSA (hazard ratio (HR)=1.11 [1.00; 1.22]) and CAPS (odds ratio (OR)=1.29 [1.07; 1.57]), including for clinically-significant symptoms (ELSA HR=1.29 [1.02; 1.63]; CAPS OR=1.64 [1.05; 2.56]). In WHII, associations with subsequent dementia were not found with baseline psychological distress (1985-1988), but became apparent when distress was assessed later (2001 HR=1.27 [1.06; 1.52]). CONCLUSIONS:In this multi-cohort study, psychological distress was associated with subsequent dementia and poorer cognitive scores, although between-study heterogeneity was high. Associations were present for both depressive and anxiety symptoms, for clinically-significant symptoms, and were stronger for persistent distress. Findings highlight the potential relevance of psychological distress in informing prevention and early detection approaches in dementia, both of which are major global public health priority areas.

Psychological distress has shown links with cognitive functioning in late-life, although the nature of the association remains unclear. Using a multi-cohort approach, we examined longitudinal associations of psychological distress with cognition and dementia, testing whether findings varied by severity, persistence and type of psychiatric symptom. The role of temporality, age-at-symptom-assessment, sex, and socio-economic position will also be examined. We used five longitudinal studies: Caerphilly Prospective Study (CAPS), English Longitudinal Study of Ageing (ELSA), National Child Development Study (NCDS), National Survey of Health and Development (NSHD), and Whitehall II (WHII). Psychological distress and global cognition were standardised to facilitate cross-study and longitudinal comparisons. Associations with cognition were examined using linear regression and mixed effects models, with Cox and logistic regression models applied to examine links with dementia. Results were pooled using two-stage individual participant data meta-analysis. Pooled analyses (total N  = 20,934; five studies) showed greater psychological distress was associated with poorer global cognitive score (β=-0.04 [95%CI: -0.07; -0.01]; I2=74.6%), including with cut-offs indicating clinically-significant distress (β=-0.08 [-0.15; -0.01]; I2=70.6%). Associations were present for both persistent (β=-0.16 [-0.27; -0.06]; I2=78.1%) and intermittent distress (β=-0.09 [-0.12; -0.05]; I2=79.1%), and were observed individually for depressive and anxiety subscales. Baseline distress was not associated with cognitive decline pooling across three studies. In ELSA, persistent (β=-0.008 [-0.016; -0.002]), but not intermittent distress was associated with cognitive decline. Psychological distress was associated with subsequent dementia in ELSA (hazard ratio (HR)=1.11 [1.00; 1.22]) and CAPS (odds ratio (OR)=1.29 [1.07; 1.57]), including for clinically-significant symptoms (ELSA HR=1.29 [1.02; 1.63]; CAPS OR=1.64 [1.05; 2.56]). In WHII, associations with subsequent dementia were not found with baseline psychological distress (1985-1988), but became apparent when distress was assessed later (2001 HR=1.27 [1.06; 1.52]). In this multi-cohort study, psychological distress was associated with subsequent dementia and poorer cognitive scores, although between-study heterogeneity was high. Associations were present for both depressive and anxiety symptoms, for clinically-significant symptoms, and were stronger for persistent distress. Findings highlight the potential relevance of psychological distress in informing prevention and early detection approaches in dementia, both of which are major global public health priority areas.

Background: Little is known about the effect of persistent financial adversity across adulthood on cognitive ageing, and whether these impacts vary based on sex, childhood socioeconomic circumstances (SEC) and genetic risk. Methods: Using data from the 1946 Birth cohort study (N=2,759), with extensive data spanning over 70 years, as well as an embedded neuroimaging study (Insight46, N=356-468), we examined the prospective association between financial adversity (low household income, financial hardships; 26-53 years) and cognitive ageing (cognitive performance at 53 years; decline between 53-69 years, modelled using latent growth curve model; neuroimaging measures of brain health between 69-74 years), and the moderating role of sex, childhood SEC and APOE-ɛ4. Covariates included sex at birth, childhood SEC, childhood cognition (8 years), symptoms of depression and anxiety (13-15 years), and educational attainment (26 years). Findings: Increased exposure to low household income as well as financial hardships was associated with lower processing speed (SE: -0.07 [95% CI: -0.13, -0.02], -0.05 [-0.11, -0.00], respectively) and verbal memory at age 53 (-0.16 [-0.21, -0.11], -0.10 [-0.15, -0.05] respectively). Increased exposure to financial adversity was also associated with slower verbal memory decline from 53 to 69 years, due to already lower baseline scores at 53 years. Persistent financial adversity was associated with greater ventricular volume at 69-71 years, and stronger associations between financial adversity and brain atrophy were found for males, those with lower childhood SEC, and APOE-ɛ4 carriers. APOE-ɛ4 carriers in particular were consistently more vulnerable to the effect of persistent financial adversity on brain atrophy. Interpretation: Persistent exposure to financial adversity influences cognitive performance by midlife and later-life brain atrophy, with impacts being larger for males, disadvantaged childhood SEC and individuals with greater genetic risk. These highlight the potential role of poverty reduction efforts in working-age adults for preventing dementia and promoting cognitive health in an ageing population.

Background Diet is an important risk factor for cardiovascular disease and shows well-established socioeconomic patterning among adults. However, less clear is how socioeconomic inequalities in diet develop across the life course. This study assessed the associations of early adulthood socioeconomic trajectories (SETs) with adult diet quality, adjusting for childhood socioeconomic position (SEP) and testing for mediation by adulthood SEP. Methods Participants from the 1970 British Cohort Study with socioeconomic data in early adulthood were included (n=12 434). Diet quality at age 46 years, evaluated using the Mediterranean diet pyramid, was regressed on six previously identified classes of early adulthood SETs between ages 16 and 24 years including a continued education class, four occupation-defined classes and an economically inactive class. Causal mediation analyses tested the mediation of the association via household income and neighbourhood deprivation at age 46 years separately. Models were adjusted for sex, childhood SEP, adolescent diet quality and adolescent health. Results The continued education class showed the best diet quality at age 46 years while little difference in diet quality was found among the remaining SET classes. The association between the continued education class and adult diet quality was independent of parental SEP in childhood and was largely not mediated by household income or neighbourhood deprivation (0.7% and 3.7% of the total effect mediated, respectively) in mid-adulthood. Conclusions Early adulthood SETs independently contribute to adult diet quality with continuing education associated with better adherence to the Mediterranean diet. Early adulthood therefore represents a sensitive period for intervention to alleviate dietary inequalities in later life.

Abstract Background There is limited evidence on the relationship between dietary sodium intake (dNa) and brain health, and very little on sex differences in associations. Purpose To study the relationship between dNa and imaging measures of brain health in men and women from the INSIGHT 46 substudy of the MRC National Survey of Health and Development (British 1946 birth cohort). Methods Participants had measurements (dNa using 5-day food diary, anthropometrics, blood pressure (BP) body mass index (BMI)) at 60-64years. Whole-brain and hippocampal volumes, white matter hyperintensity volume (WMHV) and florbetapir amyloid-β positivity were measured using MRI-PET imaging at 69-71years. Associations (β (95% confidence intervals)) were estimated separately in men and women using generalized linear models with robust standard errors adjusted for potential confounders (age, diet quality, energy intake, socioeconomic status) or potential mediators (BMI, BP). Results Participants’ characteristics are shown in Table 1. In women but not men dNa was positively associated with higher WMHV (β[women]=32(1, 72) %/g; p=0.043; β[men]=-10(-27, 11)%/g; p=0.342); this relationship in women was independent of BMI (β = 32(1, 72)%/g; p = 0.043) or systolic BP (β = 31(1, 70)%/g; p=0.041). dNa was not associated with total brain volume, hippocampal volume or amyloid-β positivity in either sex. Conclusions Elevated sodium consumption in the diet is associated with cerebral small vessel disease in older age women but not men. This association was independent of BMI or BP.Table 1

Background and Objectives Unprecedented social restrictions during the COVID-19 pandemic have provided a new lens for considering the inter-relationship between social isolation and loneliness in later life. We present these inter-relationships before and during the COVID-19 restrictions and investigate to what extent demographic, socio-economic, and health factors associated with such experiences differed during the pandemic. Research Design and Method We used data from four British longitudinal population-based studies (1946 MRC NSHD, 1958 NCDS, 1970 BCS, and ELSA). Rates, co-occurrences, and correlates of social isolation and loneliness are presented prior to and during the early stage of the COVID-19 pandemic and the inter-relationships between these experiences are elucidated in both periods. Results Across the four studies, pre-pandemic proportions reporting social isolation ranged from 15 to 54%, with higher rates in older ages (e.g., 32% of 70-79 and 54% of those over 80). During the pandemic, the percentage of older people reporting both social isolation and loneliness and isolation only slightly increased. The inter-relationship between social isolation and loneliness did not change. Associations between socio-demographic and health characteristics and social isolation and loneliness also remained consistent, with greater burden among those with greater economic precarity (females, non-homeowners, unemployed, illness and greater financial stress). Discussion and Implications There were already large inequalities in experiences of social isolation and loneliness and the pandemic had a small impact on worsening these inequalities. The concepts of loneliness and social isolation are not transferable and clarity is needed in how they are conceptualised, operationalised, and interpreted.

BACKGROUND:Social health markers, including marital status, contact frequency, network size, and social support, have been shown to be associated with cognition. However, the mechanisms underlying these associations remain poorly understood. We investigated whether depressive symptoms and inflammation mediated associations between social health and subsequent cognition. METHODS:In the English Longitudinal Study of Ageing (ELSA), a nationally representative longitudinal study in England, UK, we sampled 7136 individuals aged 50 years or older living in private households without dementia at baseline or at the intermediate mediator assessment timepoint, who had recorded information on at least one social health marker and potential mediator. We used four-way decomposition to examine to what extent depressive symptoms, C-reactive protein, and fibrinogen mediated associations between social health and subsequent standardised cognition (verbal fluency and delayed and immediate recall), including cognitive change, with slopes derived from multilevel models (12-year slope). We examined whether findings were replicated in the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), a population-based longitudinal study in Sweden, in a sample of 2604 individuals aged 60 years or older living at home or in institutions in Kungsholmen (central Stockholm) without dementia at baseline or at the intermediate mediator assessment timepoint (6-year slope). Social health exposures were assessed at baseline, potential mediators were assessed at an intermediate timepoint (wave 2 in ELSA and 6-year follow-up in SNAC-K); cognitive outcomes were assessed at a single timepoint (wave 3 in ELSA and 12-year follow-up in SNAC-K), and cognitive change (between waves 3 and 9 in ELSA and between 6-year and 12-year follow-ups in SNAC-K). FINDINGS:The study sample included 7136 participants from ELSA, of whom 3962 (55·5%) were women and 6934 (97·2%) were White; the mean baseline age was 63·8 years (SD 9·4). Replication analyses included 2604 participants from SNAC-K, of whom 1604 (61·6%) were women (SNAC-K did not collect ethnicity data); the mean baseline age was 72·3 years (SD 10·1). In ELSA, we found indirect effects via depressive symptoms of network size, positive support, and less negative support on subsequent verbal fluency, and of positive support on subsequent immediate recall (pure indirect effect [PIE] 0·002 [95% CI 0·001-0·003]). Depressive symptoms also partially mediated associations between less negative support and slower decline in immediate recall (PIE 0·001 [0·000-0·002]) and in delayed recall (PIE 0·001 [0·000-0·002]), and between positive support and slower decline in immediate recall (PIE 0·001 [0·000-0·001]). We did not observe mediation by inflammatory biomarkers. Findings of mediation by depressive symptoms in the association between positive support and verbal fluency and between positive support and change in immediate recall were replicated in SNAC-K. INTERPRETATION:The findings of this study provide new insights into mechanisms linking social health with cognition, suggesting that associations between interactional aspects of social health, especially social support, and cognition are partly underpinned by depressive symptoms. FUNDING:EU Joint Programme-Neurodegenerative Disease Research (JPND) and Alzheimer's Society. TRANSLATION:For the Swedish translation of the abstract see Supplementary Materials section.

High streets have been shown to be central to socio-economic activity, given their diverse residential, leisure, and commercial activities. This study explores the link between adolescent social isolation and proximity to, and land use mix in, high streets. Hypothesising that greater distance from high streets might increase social isolation, measured via social activities, friend contact frequency, and social support, we used multilevel modelling with data from the Millennium Cohort Study. We did not observe a relationship between proximity to high streets and these social isolation indicators, suggesting that high streets may either not significantly influence adolescent social engagement or that young people are willing to travel greater distances.