National Survey Of Health And Development Research Articles

Associations between residential daytime indoor temperature and self-reported sleep disturbances in UK adults: A cross-sectional study

BackgroundIn the past few decades, research on the association between indoor temperature and sleep has primarily used laboratory rather than field data collected in epidemiological cohorts. MethodsSecondary data on 2493 individuals aged 43 years was obtained from the National Survey of Health and Development (NSHD). Logistic regression models were used to investigate the associations between temperatures (indoor at home, spot measurement when the nurses visited during the day; and outdoor, monthly average) and self-reported sleep disturbances, adjusting for socio-demographics, health variables, housing variables, and temperature-related variables. ResultsAssociations were found between daytime indoor temperature with difficulty initiating (OR: 0.95, 95%CI: 0.91–0.98) and maintaining sleep (OR: 0.96, 95%CI: 0.93–0.99). Compared with neutral indoor temperatures (17–28 °C), low indoor temperature (≤17 °C) was associated with difficulty initiating sleep (OR: 1.79, 95%CI: 1.21–2.65). Stratified analysis results across tertiles showed that associations with difficulty initiating (OR: 0.87, 95%CI: 0.77–0.99) and maintaining sleep (OR: 0.88, 95%CI: 0.79–0.98) were observed respectively in the lowest (≤20 °C) and highest tertile (≥23 °C) of indoor temperature. There was no association between outdoor temperature and self-reported sleep disturbances in this study. ConclusionIn this first UK-based epidemiology study investigating temperature and sleep, self-reported sleep disturbances were associated with residential daytime indoor temperatures. Low indoor temperature had significantly higher odds ratio for difficulty initiating sleep compared with the neutral indoor temperature. A warmer indoor environment might be more suitable for sleep maintenance than sleep initiation. Indoor temperature in this study was a superior indicator of sleep disturbances than outdoor temperature. Although these findings are based on a UK sample, they may be relevant to other high-income settings with similar housing stock and climatic conditions.

Skylark Wiki: Accessing research data of the MRC National Survey of Health and Development

Background & IntroductionThe Medical Research Council National Survey of Health and Development (NSHD) is the oldest and longest-running of the British birth cohort studies. In 2018 we launched the Skylark Wiki, a central metadata repository and the first port of call for any data sharing queries. In 2023 we utilised the HDRUK funding initiative to work with our advisory group and research community to improve the transparency of our data access process and make the content more accessible. MethodsWe conducted a focus group session with the NSHD Participant Advisory Panel to understand their views on the data sharing process and whether the information we provided them, sufficiently explained how their data are shared. We also sent out a questionnaire to all Skylark Users to identify areas of improvement. Lastly, we undertook an audit of the website’s content and used Google Analytics to see how Users navigated across the site. Combining all this information we identified areas requiring improvements, from the point of view of our stakeholders, and comparing these to the requirements indicated in the HDRUK Transparency Standards we mapped out updates to the Skylark Wiki. The work was carried out by an external agency (Aubergine262 Ltd). ResultsTo increase transparency and searchability, we improved the flow diagram of the data sharing process to include links to the relevant web pages. We also created guidance to explain why the information in the data request application form is being asked. As feedback from Skylark Users suggested difficulties in finding the required information, the navigation has been updated. We have also changed the layout of the front page to include navigation boxes that takes users straight to the content. The NSHD Advisory Panel reinforced the notion of trust that study participants place in the study and its approach to data sharing. They confirmed the information provided on data sharing was adequate and appreciated that this information was placed on the main study website (https://nshd.mrc.ac.uk/) for their benefit. Initial feedback from Users indicates that it is easier to find information on the website. We will keep monitoring access to the website, the number of queries, and data access requests to evaluate long-term benefits. We have changed the sitemap and added in large link boxes, to make it easier to find the different sections. We hope this will improve the searchability of the site so users can find information they required. We hope this will therefore lead to fewer emails and correspondence between the data sharing team and users. We have also updated the flow diagram of the data sharing process to include links to the web pages which are related to that section. We hope this will help the users find the information they require. ConclusionsThe new Skylark data-sharing website supports easier navigation providing a better User experience. In return, this should lead to fewer queries from Users. The website will be easier to maintain having changed the content management system from a Wiki to WordPress. WordPress requires less technical knowledge, allowing more staff to contribute to regular maintenance. References Skylark data-sharing website: https://skylark.ucl.ac.uk/NSHD/ Aubergine: https://www.aubergine262.com/

Investigating associations between blood metabolites, later life brain imaging measures, and genetic risk for Alzheimer’s disease

BackgroundIdentifying blood-based signatures of brain health and preclinical pathology may offer insights into early disease mechanisms and highlight avenues for intervention. Here, we systematically profiled associations between blood metabolites and whole-brain volume, hippocampal volume, and amyloid-β status among participants of Insight 46—the neuroscience sub-study of the National Survey of Health and Development (NSHD). We additionally explored whether key metabolites were associated with polygenic risk for Alzheimer’s disease (AD).MethodsFollowing quality control, levels of 1019 metabolites—detected with liquid chromatography-mass spectrometry—were available for 1740 participants at age 60–64. Metabolite data were subsequently clustered into modules of co-expressed metabolites using weighted coexpression network analysis. Accompanying MRI and amyloid-PET imaging data were present for 437 participants (age 69–71). Regression analyses tested relationships between metabolite measures—modules and hub metabolites—and imaging outcomes. Hub metabolites were defined as metabolites that were highly connected within significant (pFDR < 0.05) modules or were identified as a hub in a previous analysis on cognitive function in the same cohort. Regression models included adjustments for age, sex, APOE genotype, lipid medication use, childhood cognitive ability, and social factors. Finally, associations were tested between AD polygenic risk scores (PRS), including and excluding the APOE region, and metabolites and modules that significantly associated (pFDR < 0.05) with an imaging outcome (N = 1638).ResultsIn the fully adjusted model, three lipid modules were associated with a brain volume measure (pFDR < 0.05): one enriched in sphingolipids (hippocampal volume: ß = 0.14, 95% CI = [0.055,0.23]), one in several fatty acid pathways (whole-brain volume: ß = − 0.072, 95%CI = [− 0.12, − 0.026]), and another in diacylglycerols and phosphatidylethanolamines (whole-brain volume: ß = − 0.066, 95% CI = [− 0.11, − 0.020]). Twenty-two hub metabolites were associated (pFDR < 0.05) with an imaging outcome (whole-brain volume: 22; hippocampal volume: 4). Some nominal associations were reported for amyloid-β, and with an AD PRS in our genetic analysis, but none survived multiple testing correction.ConclusionsOur findings highlight key metabolites, with functions in membrane integrity and cell signalling, that associated with structural brain measures in later life. Future research should focus on replicating this work and interrogating causality.

Technical development and feasibility of a reusable vest to integrate cardiovascular magnetic resonance with electrocardiographic imaging

BackgroundElectrocardiographic imaging (ECGI) generates electrophysiological (EP) biomarkers while cardiovascular magnetic resonance (CMR) imaging provides data about myocardial structure, function and tissue substrate. Combining this information in one examination is desirable but requires an affordable, reusable, and high-throughput solution. We therefore developed the CMR-ECGI vest and carried out this technical development study to assess its feasibility and repeatability in vivo. MethodsCMR was prospectively performed at 3T on participants after collecting surface potentials using the locally designed and fabricated 256-lead ECGI vest. Epicardial maps were reconstructed to generate local EP parameters such as activation time (AT), repolarization time (RT) and activation recovery intervals (ARI). 20 intra- and inter-observer and 8 scan re-scan repeatability tests. Results77 participants were recruited: 27 young healthy volunteers (HV, 38.9 ± 8.5 years, 35% male) and 50 older persons (77.0 ± 0.1 years, 52% male). CMR-ECGI was achieved in all participants using the same reusable, washable vest without complications. Intra- and inter-observer variability was low (correlation coefficients [rs] across unipolar electrograms = 0.99 and 0.98 respectively) and scan re-scan repeatability was high (rs between 0.81 and 0.93). Compared to young HV, older persons had significantly longer RT (296.8 vs 289.3 ms, p = 0.002), ARI (249.8 vs 235.1 ms, p = 0.002) and local gradients of AT, RT and ARI (0.40 vs 0.34 ms/mm, p = 0,01; 0.92 vs 0.77 ms/mm, p = 0.03; and 1.12 vs 0.92 ms/mm, p = 0.01 respectively). ConclusionOur high-throughput CMR-ECGI solution is feasible and shows good reproducibility in younger and older participants. This new technology is now scalable for high throughput research to provide novel insights into arrhythmogenesis and potentially pave the way for more personalised risk stratification. Clinical trial registration: Title: Multimorbidity Life-Course Approach to Myocardial Health—A Cardiac Sub-Study of the MRC National Survey of Health and Development (NSHD) (MyoFit46). National Clinical Trials (NCT) number: NCT05455125. URL: https://clinicaltrials.gov/ct2/show/NCT05455125?term=MyoFit&draw=2&rank=1

Abstract 13367: APOE ε4 Carriage Associates With Improved Myocardial Performance in Older Age

Introduction: Although APOE ε 4 allele carriage confers a risk of coronary disease, its persistence in human populations might be explained by certain survival advantages (antagonistic pleiotropy) . Hypothesis: Combining data from two British cohorts– the 1946 National Survey of Health and Development (NSHD) and Southall and Brent Revised (SABRE)–we explored whether APOE ε 4 carriage associates with beneficial or unfavorable left ventricular (LV) structural and functional echocardiography parameters in older age. Methods: Based on the presence of APOE ε 4, genotypes were divided into: APOE ε 4 (ε2ε4, ε3ε4, ε 4 ε 4) and non- APOE ε 4 carriers. Echocardiographic data included: LV ejection fraction, E/e’, systolic and diastolic posterior wall and interventricular septal thickness (LVPWT s/d , IVS s/d ), LV mass and the ratio of the LV stroke volume to the LV myocardial volume called myocardial contraction fraction (MCF). Generalized linear models explored associations between APOE ε 4 genotypes as exposures and echocardiographic biomarkers as outcomes. As APOE genotype is a genetic instrumental variable (unconfounded), Model 1 was unadjusted. Model 2 was adjusted for factors associated with the outcome (sex and socio-economic position) to yield more precise estimates; subsequent models were individually adjusted for mediators (body mass index, cardiovascular disease [CVD], high cholesterol and hypertension) to explore mechanistic pathways. Random-effects meta-analyses were performed across the cohorts. Results: 2596 participants were included. Compared to non- APOE ε 4 carriers, APOE ε 4 carriers had similar cardiac phenotypes in terms of EF, E/e’, LVPWT s/d , IVS s/d and LV mass but had a 4% higher MCF (95% confidence interval [CI]: 1–7%, p =0.016) which persisted in Model 2 (95% CI 1–7%, p =0.008) but was attenuated to 3% after adjustment for CVD, diabetes and hypertension (all 95% CI 0–6% all p &lt;0.070). Conclusions: APOE ε 4 carriage associates with improved myocardial performance in older age resulting in greater LV stroke volume generation per 1 mL of myocardium. This potentially favorable cardiac phenotype adds to the growing number of reported survival advantages attributed to APOE ε4 carriage that might collectively explain its persistence in humans.

Heterozygous APOE ε4 carriage associates with improved myocardial efficiency in older age

Abstract Background Carriage of the ancestral APOE ε4 allele confers a risk of developing Alzheimer's and coronary artery disease, but its persistence in human populations also suggests some potential survival advantages. To date it remains unclear whether APOE ε4 carriage independently associates with a better or worse long-term cardiac phenotype. Purpose Using data from the 1946 National Survey of Health and Development (NSHD) birth cohort, we investigated whether APOE ε4 carriage associates with adverse or beneficial left ventricular (LV) size and function parameters by echocardiography in older age. Methods Based on the presence or absence of APOE ε4, genotypes were divided into: non-APOE ε4 (ε2ε2, ε2ε3, ε3ε3), heterozygous-APOE ε4 (ε2ε4 and ε3ε4) and homozygous-APOE ε4 (ε4ε4). Echocardiographic data at 60–64 years included: left ventricular ejection fraction (LV EF), E/e', systolic and diastolic LV posterior wall and interventricular septal thickness (LVPWTs/d, IVSs/d), and body-surface area indexed LV mass (LVmassi) and myocardial contraction fraction (MCFi). Generalized linear models explored associations between APOE ε4 genotypes as exposures and echocardiographic biomarkers as outcomes. As a combination of gene variants, APOE ε genotype is expected to be an instrumental variable and therefore unconfounded. Thus, Model 1 was unadjusted. To obtain more precise regression estimates, Model 2 was adjusted for factors associated with the outcome, namely sex and socio-economic position (SEP). To explore the mechanistic pathway downstream of APOE ε genotype but upstream of the echocardiographic outcomes, subsequent models were adjusted for mediators as follows: Model 3 for body mass index, Model 4 for the presence of cardiovascular disease (CVD), Model 5 for diabetes, Model 6 for high cholesterol and Model 7 for hypertension. Results 1464 participants were included. Compared to non-APOE ε4 and homozygous groups, heterozygous-APOE ε4 individuals had similar cardiac phenotypes in terms of EF, E/e', LVPWTs/d, IVSs/d and LVmassi but had a 7% higher MCFi 95% confidence interval [CI]: 1%-13%, p=0.017) which persisted even after adjustment for sex and SEP (95% CI 1%-12%, p=0.026) that was attenuated to 6% after adjustment for CVD (95% CI 0–13% p=0.050) and hypertension (95% CI 1–13% p=0.022). Conclusion The heterozygous-APOE ε4 state associates with improved myocardial shortening in older age resulting in greater LV stroke volume generation per 1 mL of myocardium. As we found no association between APOE ε4 carriage and LVPWTs/d, IVSs/d or LVmassi, MCFi enhancement may be mediated by improved myocardial energetics and contractility, with calcium and androgens potentially implicated, rather than through pathological ventricular thickening. Although a dose relationship is normally expected with ε4 carriage, any benefit from increased energetics and contractility is likely to be counterbalances by the higher risk of CVD and cardiovascular risk factors. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): UK Medical Research Council British Heart Foundation

Alzheimer's disease risk biomarkers: progress and challenges

Alzheimer's disease risk biomarkers: progress and challenges

Life course trajectories of affective symptoms and their early life predictors.

Life course trajectories of affective symptoms (depression and anxiety) are heterogenous. However, few studies have investigated the role of early life risk factors in the development of these trajectories. The present study aimed to: (1) derive latent trajectories of affective symptoms over a period of more than 50 years (ages 13-69), and (2) examine early life risk factors for associations with specific life course trajectories of affective symptoms. Participants are from the MRC National Survey of Health and Development (NSHD) (n = 5,362). Affective symptoms were measured prospectively at ages 13, 15, 36, 43, 53, 60-64 and 69. A latent variable modelling framework was implemented to model longitudinal profiles of affective symptoms. Twenty-four prospectively measured early life predictors were tested for associations with different symptom profiles using multinomial logistic regression. Four life course profiles of affective symptoms were identified: (1) absence of symptoms (66.6% of the sample); (2) adolescent symptoms with good adult outcome (15.2%); (3) adult symptoms only (with no symptoms in adolescence and late life) (12.9%); (4) symptoms in adolescence and mid adulthood (5.2%). Of the 24 early life predictors observed, only four were associated with life course trajectories, with small effect sizes observed. People differ in their life course trajectories of anxiety and depression symptoms and that these differences are not largely influenced by early life factors tested in this study.

Declining Levels and Bioavailability of IGF-I in Cardiovascular Aging Associate With QT Prolongation-Results From the 1946 British Birth Cohort.

BackgroundAs people age, circulating levels of insulin-like growth factors (IGFs) and IGF binding protein 3 (IGFBP-3) decline. In rat cardiomyocytes, IGF-I has been shown to regulate sarcolemmal potassium channel activity and late sodium current thus impacting cardiac repolarization and the heart rate-corrected QT (QTc). However, the relationship between IGFs and IGFBP-3 with the QTc interval in humans, is unknown.ObjectivesTo examine the association of IGFs and IGFBP-3 with QTc interval in an older age population-based cohort.MethodsParticipants were from the 1946 Medical Research Council (MRC) National Survey of Health and Development (NSHD) British birth cohort. Biomarkers from blood samples at age 53 and 60–64 years (y, exposures) included IGF-I/II, IGFBP-3, IGF-I/IGFBP-3 ratio and the change (Δ) in marker levels between the 60–64 and 53y sampled timepoints. QTc (outcome) was recorded from electrocardiograms at the 60–64y timepoint. Generalized linear multivariable models with adjustments for relevant demographic and clinical factors, were used for complete-cases and repeated after multiple imputation.ResultsOne thousand four hundred forty-eight participants were included (48.3% men; QTc mean 414 ms interquartile range 26 ms). Univariate analysis revealed an association between low IGF-I and IGF-I/IGFBP-3 ratio at 60–64y with QTc prolongation [respectively: β −0.30 ms/nmol/L, (95% confidence intervals −0.44, −0.17), p < 0.001; β−28.9 ms/unit (-41.93, −15.50), p < 0.001], but not with IGF-II or IGFBP-3. No association with QTc was found for IGF biomarkers sampled at 53y, however both ΔIGF-I and ΔIGF-I/IGFBP-3 ratio were negatively associated with QTc [β −0.04 ms/nmol/L (−0.08, −0.008), p = 0.019; β −2.44 ms/unit (-4.17, −0.67), p = 0.007] while ΔIGF-II and ΔIGFBP-3 showed no association. In fully adjusted complete case and imputed models (reporting latter) low IGF-I and IGF-I/IGFBP-3 ratio at 60–64y [β −0.21 ms/nmol/L (−0.39, −0.04), p = 0.017; β −20.14 ms/unit (−36.28, −3.99), p = 0.015], steeper decline in ΔIGF-I [β −0.05 ms/nmol/L/10 years (−0.10, −0.002), p = 0.042] and shallower rise in ΔIGF-I/IGFBP-3 ratio over a decade [β −2.16 ms/unit/10 years (−4.23, −0.09), p = 0.041], were all independently associated with QTc prolongation. Independent associations with QTc were also confirmed for other previously known covariates: female sex [β 9.65 ms (6.65, 12.65), p < 0.001], increased left ventricular mass [β 0.04 ms/g (0.02, 0.06), p < 0.001] and blood potassium levels [β −5.70 ms/mmol/L (−10.23, −1.18) p = 0.014].ConclusionOver a decade, in an older age population-based cohort, declining levels and bioavailability of IGF-I associate with prolongation of the QTc interval. As QTc prolongation associates with increased risk for sudden death even in apparently healthy people, further research into the antiarrhythmic effects of IGF-I on cardiomyocytes is warranted.

Study protocol: MyoFit46\u2014the cardiac sub-study of the MRC National Survey of Health and Development

BackgroundThe life course accumulation of overt and subclinical myocardial dysfunction contributes to older age mortality, frailty, disability and loss of independence. The Medical Research Council National Survey of Health and Development (NSHD) is the world’s longest running continued surveillance birth cohort providing a unique opportunity to understand life course determinants of myocardial dysfunction as part of MyoFit46–the cardiac sub-study of the NSHD.MethodsWe aim to recruit 550 NSHD participants of approximately 75 years+ to undertake high-density surface electrocardiographic imaging (ECGI) and stress perfusion cardiovascular magnetic resonance (CMR). Through comprehensive myocardial tissue characterization and 4-dimensional flow we hope to better understand the burden of clinical and subclinical cardiovascular disease. Supercomputers will be used to combine the multi-scale ECGI and CMR datasets per participant. Rarely available, prospectively collected whole-of-life data on exposures, traditional risk factors and multimorbidity will be studied to identify risk trajectories, critical change periods, mediators and cumulative impacts on the myocardium.DiscussionBy combining well curated, prospectively acquired longitudinal data of the NSHD with novel CMR–ECGI data and sharing these results and associated pipelines with the CMR community, MyoFit46 seeks to transform our understanding of how early, mid and later-life risk factor trajectories interact to determine the state of cardiovascular health in older age.Trial registration: Prospectively registered on ClinicalTrials.gov with trial ID: 19/LO/1774 Multimorbidity Life-Course Approach to Myocardial Health- A Cardiac Sub-Study of the MCRC National Survey of Health and Development (NSHD).

Menopause and later‐life cognition: Findings from the longest‐running population‐based birth cohort

AbstractBackgroundAlzheimer’s Disease is more common in women than men. Menopause timing and type have been linked with cognition post‐menopause, but associations with dementia risk are unclear. Within the MRC National Survey of Health and Development (NSHD), childhood cognition predicts later‐life cognition and has largely explained menopause‐cognition associations post‐menopause. We now explore to what extent childhood cognition explains menopause‐cognition associations in later‐life and whether residual associations emerge.MethodProspective questionnaires at ages 43‐54 provided menopause age (years since birth until period cessation) and type (surgical/natural). Addenbrooke’s Cognitive Examination (ACE‐III) gave a measure of cognitive state at age 69 (maximum n=913). Cognitive domains were investigated using ACE‐III sub‐domains and cognitive tasks in a neuroimaging sub‐study (age 69‐71; maximum n=246) assessing memory, executive function, attention, visuospatial function, processing speed and non‐verbal reasoning. All cognitive outcomes were standardised. Multivariable regression analyses adjusted for relevant affective, early cognitive, sociodemographic, hormonal, health and genetic covariables, with multiple imputation of missing values using chained equations.ResultsMenopause associated with the following cognitive outcomes: total ACE‐III, ACE‐III verbal fluency, ACE‐III memory, ACE‐III visuospatial function, pre‐clinical Alzheimer’s cognitive composite, response inhibition, and intra‐individual variability in reaction times. Later menopause associated with better performance, while surgical menopause associated with worse performance. After accounting for childhood cognition, associations remained between menopause age and total ACE‐III (β=.012; 95% CI .001, .023), ACE‐III visuospatial function (β=.012; 95% CI .000, .023) and response inhibition (β=.034; 95% CI .008, .061), and between menopause type and response inhibition (β=‐.368; 95% CI ‐.665, ‐.070). With full adjustments, associations persisted between menopause age and ACE‐III memory (β=.011; 95% CI .000, .023). Intra‐individual variability in reaction times also remained associated with menopause age (β=‐.049; 95% CI ‐.079, ‐.019) and type (β=.413; 95% CI .076, .750).ConclusionIn later‐life, associations emerge between menopause and cognitive domains implicated in dementia (memory, processing speed, attention). Later menopause associates with better performance and surgical menopause with worse. Associations are not fully explained by known predictors of later‐life cognition including childhood cognition and other lifetime covariables accounted for. Further exploration of the link between menopause and dementia risk in women is warranted.

Childhood bradycardia associates with atrioventricular conduction defects in older age: a longitudinal birth cohort study

Abstract Background A high resting heart rate (RHR) has been associated with cardiovascular morbidity and mortality. However, little is known about the long-term effects of childhood bradycardia. Purpose This study aimed to explore the association between childhood bradycardia and later-life cardiac phenotype using longitudinal data from the 1946 Medical Research Council National Survey of Health and Development (NSHD) birth cohort. Methods RHR was recorded at ages 6 and 7 to provide the bradycardia exposure defined as a childhood RHR&amp;lt;75. Three outcomes were studied: i) echocardiographic data at 60–64 consisting of ejection fraction (EF), left ventricular mass index (LVmassi), myocardial contraction fraction index (MCFi) and E/e'; ii) electrocardiographic (ECG) evidence of atrio-ventricular (AV) conduction defects (Minnesota categories: 6-1, 6-2-1, 6-2-2, 6-2-3, 6-3, 6-8, 8-5-1, 8-5-2, 8-6-1, 8-6-2, 8-6-3 and 8-6-4) or ventricular conduction defects (any Minnesota group 7) by age 60–64; and iii) all-cause and cardiovascular mortality. Generalized linear models (glm) with gamma distribution were used for echocardiographic analyses, glms with binomial distribution for ECG analyses and Cox proportional hazards models for mortality. Adjustment was made for relevant demographic and health-related covariates, and for multiple testing. In order to account for within-subject correlated repeated measures at 6 and 7 years of age, mixed glms (glmms) were used as a sensitivity analysis. To explore any nonlinear relationships, we modeled each outcome as a sum of best fitting fractional polynomials of RHR at 6 and 7 (as continuous variables) and covariates using a “closed test procedure” with backward elimination. Results The number of participants included was: 4381 for mortality, 1631 for ECG and 1617 for echocardiography analyses. Childhood bradycardia was associated with male sex (p&amp;lt;0.0001) and higher BMI (p=0.009). In fully adjusted models, childhood bradycardia was associated with 2.91 higher odds of AV conduction defects (95% confidence interval [CI] 1.59–5.31, p=0.0005), even at a false discovery rate of 0.05. Associations persisted in random coefficients glmm models (odds ratio 2.50, 95% CI 1.01–4.31). The fractional polynomials analyses revealed that the log odds of AV conduction defects at 60–64 years of age were linearly associated with RHR at 7 years. There was no association between bradycardia in childhood and ventricular conduction defects, echocardiographic parameters or mortality outcomes. Conclusions Longitudinal data indicate that childhood bradycardia trebles the odds of having AV conduction defects, but does not influence mortality or heart size and function in older age. As one in three older adults with AV conduction defects will have been bradycardic in childhood, future research should concentrate on identifying children at risk, the potential mechanisms involved and whether AV blocking drugs accelerate nodal dysfunction. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): British Heart Foundation (MyoFit46 Special Programme Grant SP/20/2/34841)

Childhood Bradycardia Associates With Atrioventricular Conduction Defects in Older Age: A Longitudinal Birth Cohort Study.

BackgroundThis study explored the association between childhood bradycardia and later‐life cardiac phenotype using longitudinal data from the 1946 National Survey of Health and Development (NSHD) birth cohort.Methods and ResultsResting heart rate was recorded at 6 and 7 years of age to provide the bradycardia exposure defined as a childhood resting heart rate <75 bpm. Three outcomes were studied: (1) echocardiographic data at 60 to 64 years of age, consisting of ejection fraction, left ventricular mass index, myocardial contraction fraction index, and E/e′; (2) electrocardiographic evidence of atrioventricular or ventricular conduction defects by 60 to 64 years of age; and (3) all‐cause and cardiovascular mortality. Generalized linear models or Cox regression models were used, and adjustment was made for relevant demographic and health‐related covariates, and for multiple testing. Mixed generalized linear models and fractional polynomials were used as sensitivity analyses. One in 3 older adults with atrioventricular conduction defects had been bradycardic in childhood, with defects being serious (Mobitz type II second‐degree atrioventricular block or higher) in 12%. In fully adjusted models, childhood bradycardia was associated with 2.91 higher odds of atrioventricular conduction defects (95% CI, 1.59–5.31; P=0.0005). Associations persisted in random coefficients mixed generalized linear models (odds ratio, 2.50; 95% CI, 1.01–4.31). Fractional polynomials confirmed a linear association between the log odds of atrioventricular conduction defects at 60 to 64 years of age and resting heart rate at 7 years of age. There was no association between bradycardia in childhood and mortality outcomes or with echocardiographic parameters and ventricular conduction defects in older age.ConclusionsLongitudinal birth cohort data indicate that childhood bradycardia trebles the odds of having atrioventricular conduction defects in older age, 88% of which are benign. In addition, it does not influence mortality or heart size and function. Future research should concentrate on identifying children at risk.

Socioeconomic inequalities in prevalence and development of multimorbidity across adulthood: A longitudinal analysis of the MRC 1946 National Survey of Health and Development in the UK.

BackgroundWe aimed to estimate multimorbidity trajectories and quantify socioeconomic inequalities based on childhood and adulthood socioeconomic position (SEP) in the risks and rates of multimorbidity accumulation across adulthood.Methods and findingsParticipants from the UK 1946 National Survey of Health and Development (NSHD) birth cohort study who attended the age 36 years assessment in 1982 and any one of the follow-up assessments at ages 43, 53, 63, and 69 years (N = 3,723, 51% males). Information on 18 health conditions was based on a combination of self-report, biomarkers, health records, and prescribed medications. We estimated multimorbidity trajectories and delineated socioeconomic inequalities (based on childhood and adulthood social class and highest education) in multimorbidity at each age and in longitudinal trajectories.Multimorbidity increased with age (0.7 conditions at 36 years to 3.7 at 69 years). Multimorbidity accumulation was nonlinear, accelerating with age at the rate of 0.08 conditions/year (95% CI 0.07 to 0.09, p < 0.001) at 36 to 43 years to 0.19 conditions/year (95% CI 0.18 to 0.20, p < 0.001) at 63 to 69 years. At all ages, the most socioeconomically disadvantaged had 1.2 to 1.4 times greater number of conditions on average compared to the most advantaged. The most disadvantaged by each socioeconomic indicator experienced an additional 0.39 conditions (childhood social class), 0.83 (adult social class), and 1.08 conditions (adult education) at age 69 years, independent of all other socioeconomic indicators. Adverse adulthood SEP was associated with more rapid accumulation of multimorbidity, resulting in 0.49 excess conditions in partly/unskilled compared to professional/intermediate individuals between 63 and 69 years. Disadvantaged childhood social class, independently of adulthood SEP, was associated with accelerated multimorbidity trajectories from age 53 years onwards.Study limitations include that the NSHD cohort is composed of individuals of white European heritage only, and findings may not be generalizable to the non-white British population of the same generation and did not account for other important dimensions of SEP such as income and wealth.ConclusionsIn this study, we found that socioeconomically disadvantaged individuals have earlier onset and more rapid accumulation of multimorbidity resulting in widening inequalities into old age, with independent contributions from both childhood and adulthood SEP.

Sex-related differences in whole brain volumes at age 70 in association with hyperglycemia during adult life

Longitudinal studies of the relationship between hyperglycemia and brain health are rare and there is limited information on sex differences in associations. We investigated whether glycosylated hemoglobin (HbA1c) measured at ages of 53, 60–64 and 69 years, and cumulative glycemic index (CGI), a measure of cumulative glycemic burden, were associated with metrics of brain health in later life.Participants were from Insight 46, a substudy of the Medical Research Council National Survey of Health and Development (NSHD) who undertook volumetric MRI, florbetapir amyloid-PET imaging and cognitive assessments at ages of 69–71. Analyses were performed using linear and logistic regression as appropriate, with adjustment for potential confounders. We observed a sex interaction between HbA1c and whole brain volume (WBV) at all 3 time points. Following stratification of our sample, we observed that HbA1c at all ages, and CGI were positively associated with lower WBV exclusively in females. HbA1c (or CGI) was not associated with amyloid status, white matter hyperintensities (WMHs), hippocampal volumes (HV) or cognitive outcomes in either sex.Higher HbA1c in adulthood is associated with smaller WBV at 69–71 years in females but not in males. This suggests that there may be preferential target organ damage in the brain for females with hyperglycemia.

Grip strength from midlife as an indicator of later-life brain health and cognition: evidence from a British birth cohort

BackgroundGrip strength is an indicator of physical function with potential predictive value for health in ageing populations. We assessed whether trends in grip strength from midlife predicted later-life brain health and cognition.Methods446 participants in an ongoing British birth cohort study, the National Survey of Health and Development (NSHD), had their maximum grip strength measured at ages 53, 60–64, and 69, and subsequently underwent neuroimaging as part of a neuroscience sub-study, referred to as “Insight 46”, at age 69–71. A group-based trajectory model identified latent groups of individuals in the whole NSHD cohort with below- or above-average grip strength over time, plus a reference group. Group assignment, plus standardised grip strength levels and change from midlife were each related to measures of whole-brain volume (WBV) and white matter hyperintensity volume (WMHV), plus several cognitive tests. Models were adjusted for sex, body size, head size (where appropriate), sociodemographics, and behavioural and vascular risk factors.ResultsLower grip strength from midlife was associated with smaller WBV and lower matrix reasoning scores at age 69–71, with findings consistent between analysis of individual time points and analysis of trajectory groups. There was little evidence of an association between grip strength and other cognitive test scores. Although greater declines in grip strength showed a weak association with higher WMHV at age 69–71, trends in the opposite direction were seen at individual time points with higher grip strength at ages 60–64, and 69 associated with higher WMHV.ConclusionsThis study provides preliminary evidence that maximum grip strength may have value in predicting brain health. Future work should assess to what extent age-related declines in grip strength from midlife reflect concurrent changes in brain structure.

Characterisation of growth plate dynamics in surgical and non-invasive loaded murine models of osteoarthritis

Purpose: Our recent work in the MRC National Survey of Health and Development (NSHD) found that increased height in childhood was associated, albeit modestly, with lower odds of knee OA at age 53 years. We build upon this previous work exploring the relationship between adolescent long bone growth and osteoarthritis predisposition, to examine growth plate dynamics in surgical and non-invasive (loaded) mouse models of osteoarthritis (OA).

The relationship of childhood adversity with diurnal cortisol patterns and C-reactive protein at 60–64 years of age in the 1946 National Survey of Health and Development

BackgroundEarly life adversity is increasingly prevalent and associated with greater morbidity and mortality. It is hypothesised that the link between psychosocial early life adversity and poor health in adulthood is due to abnormal hypothalamic-pituitary-adrenal (HPA) axis functioning (often measured as cortisol patterning) and inflammation (often measured via c-reactive protein (CRP)). This study aimed to investigate the relationship between early life psychosocial adversity and cortisol patterning and CRP at 60–64 years of age. MethodsThe MRC National Survey of Health and Development (NSHD) was used. The analytic “cortisol sample” included 843 individuals and the “CRP sample” included 1150 individuals. Data on adversity experienced between ages 0–15 years were utilised to compose a cumulative childhood psychosocial early life adversity (ELA) score (0, 1, 2, 3+). CRP and salivary cortisol (waking, 30 min after waking, and evening) were collected at 60–64 years. Associations between the psychosocial ELA score and cortisol outcomes (cortisol awakening response (CAR), diurnal slope (DS), and evening and morning cortisol) were assessed using general linear regression. Tobit regression was used to assess the association between psychosocial ELA score and CRP. Adjustments were made for age at follow-up, sex, childhood maternal education, childhood paternal social class, childhood housing tenure, and birth weight. After testing for sex by ELA score interactions, analyses were repeated stratified by sex for the CRP sample. ResultsIn fully adjusted models, individuals who experienced the highest level of childhood psychosocial adversity (3+) had a 24.63 (−41.49, −7.76) % lower waking cortisol and a 7.30 (1.49, 13.12) % lower decline in cortisol across the day compared to those with a psychosocial ELA score of zero. In females, the highest level of childhood psychosocial adversity, compared to the lowest, was associated with 32.61 (2.98, 62.25) % higher CRP at 60–64 years, which attenuated to 20.38% (−9.38, 50.14) upon adjustment for measures of early life socioeconomic position. Conversely, the association between childhood psychosocial adversity and CRP in males was null. ConclusionsOur results suggest that high-levels of psychosocial adversity in childhood might result in a lower morning cortisol and flatter DS in mid-to-late-adulthood. The finding that adversity was related to higher CRP in females but not males requires replication and further investigation.

488 GRIP STRENGTH FROM MIDLIFE AS AN INDICATOR OF LATER-LIFE COGNITION AND BRAIN HEALTH: EVIDENCE FROM A BRITISH BIRTH COHORT

Abstract Introduction Grip strength is an objective measure of physical function with potential predictive value for health in ageing populations. We aimed to assess whether levels and changes in grip strength from midlife predicted later-life brain health and cognition. Methods 446 participants in an ongoing British birth cohort study, the MRC National Survey of Health and Development (NSHD), had their maximum grip strength measured at ages 53, 60–64, and 69, and underwent neuroimaging as part of its neuroscience sub-study, Insight 46, at 69–71. A group-based trajectory model identified latent groups of individuals in the whole NSHD cohort with below- and above-average grip strength over time, plus a reference group. Trajectory group membership, plus standardised grip strength levels and change from age 53, were each related to MRI-derived measures of whole-brain volume (WBV) and white-matter hyperintensity volume (WMHV), plus several cognitive tests. Models were adjusted for sex, body size, head size (where appropriate), sociodemographics, and behavioural and vascular risk factors. Results Consistently below-average grip strength from midlife was associated with lower WBV and non-verbal reasoning ability at age 69–71 (e.g. low group WBV vs. reference group β = −13.38 cm^3; 95% CI = (−24.12 cm^3, −2.64 cm^3); p = 0.015). There was some accompanying evidence that above-average maximum grip strength showed a positive association with WBV, which was more pronounced in female participants (high group female WBV vs. reference group β = 18.30 cm^3; 95% CI = (1.34 cm^3, 35.29 cm^3); p = 0.034). Steeper than average declines in grip strength between 53 and 69 were additionally weakly associated with an estimated 10% higher WMHV at age 69–71 (β = 1.10, 95% CI = (1.00, 1.22); p = 0.053). Conclusion This study provides preliminary evidence that tests of maximum grip strength may have value in predicting brain health. Future work should assess how these observed differences relate to later-life negative health outcomes, and whether changes in grip strength reflect concurrent changes in brain structure and connectivity.

From cohort to community: The emotional work of birthday cards in the Medical Research Council National Survey of Health and Development, 1946-2018.

The Medical Research Council National Survey of Health and Development (NSHD) is Britain’s longest-running birth cohort study. From their birth in 1946 until the present day, its research participants, or study members, have filled out questionnaires and completed cognitive or physical examinations every few years. Among other outcomes, the findings of these studies have framed how we understand health inequalities. Throughout the decades and multiple follow-up studies, each year the study members have received a birthday card from the survey staff. Although the birthday cards were originally produced in 1962 as a method to record changes of address at a time when the adolescent study members were potentially leaving school and home, they have become more than that with time. The cards mark, and have helped create, an ongoing evolving relationship between the NSHD and the surveyed study members, eventually coming to represent a relationship between the study members themselves. This article uses the birthday cards alongside archival material from the NSHD and oral history interviews with survey staff to trace the history of the growing awareness of importance of emotion within British social science research communities over the course of the 20th and early 21st centuries. It documents changing attitudes to science’s dependence on research participants, their well-being, and the collaborative nature of scientific research. The article deploys an intertextual approach to reading these texts alongside an attention to emotional communities drawing on the work of Barbara Rosenwein.