BACKGROUND:Incidental findings are often found in imaging research, especially in older people (aged ≥75 years). Understanding their prevalence is essential to inform consent and disclosure protocols as well as anticipate onward investigation balanced against minimising unnecessary anxiety and health-care burden. The aim of this study was to determine the prevalence of incidental findings in a population-based sample of individuals aged 75-77 years using cardiovascular magnetic resonance (CMR) imaging and to inform duty-of-care frameworks for their reporting. METHODS:MyoFit46 was a prospective imaging cohort substudy of the National Survey of Health and Development (NSHD) study. Participants were prospectively recruited from the NSHD study, between May 18, 2020, and March 15, 2024, and underwent 3-Tesla contrast-enhanced CMR. An incidental finding was defined as a previously unknown abnormality that had not been identified by the participant or the research team before the study date. Incidental findings were classified into cardiac, non-cardiac, and clinical, and predefined according to the required urgency of follow-up as routine (reported to participants and their general practitioners within 28 days) or or immediate (reported within 48 hours). This study is registered with ClinicalTrials.gov, NCT05455125. FINDINGS:Of 505 participants prospectively recruited, 484 (96%) completed a full CMR scan. Of these, 432 (89%) had at least one incidental finding, including 58 (12%) immediate and 429 (89%) routine findings. Incidental findings were more common in male participants than in female participants (routine: 250 [92%] of 271 men vs 182 [85%] of 213 women, p=0·018; immediate: 39 [14%] of 271 men vs 19 [9%] of 213 women, p=0·069). The commonest routine cardiac incidental finding was late gadolinium enhancement (145 [43%] of 334 participants) and the commonest immediate cardiac finding was a left ventricular ejection fraction lower than 40% (seven [2%] of 334 participants). Non-cardiac incidental findings were predominantly routine (203 [42%] of 484) whereas immediate non-cardiac incidental findings were very uncommon (four [1%] of 484). Clinical findings were found in 201 (42%) of 484 participants, of which 28 (6%) were classified as immediate and 187 (39%) classified as routine. INTERPRETATION:CMR and baseline assessments revealed that incidental findings are common in imaging research in adults aged 75 years and older, underscoring the need for robust duty-of-care frameworks to ensure timely, ethical, and appropriate management of these findings in older age. These findings provide a population benchmark that can inform the design, governance, and resource planning of future large-scale imaging studies in ageing cohorts. FUNDING:British Heart Foundation and Medical Research Council.

OBJECTIVES:This study examines the employment trajectories of women experiencing early and surgical menopause over a 10-year period bracketing their final menstruation or surgery, representing for most women the menopause transition. It also investigates the potential mediating role of hormone therapy in early postmenopause in these relationships. METHODS:We used data from 1,386 women in the English Longitudinal Study of Aging (ELSA) who had undergone natural menopause, premenopausal bilateral oophorectomy or hysterectomy. We used sequence analysis of employment histories to define 3 different 10-year employment trajectories. We then carried out regression analysis to assess associations between timing and type of menopause on employment, followed by mediation analysis. Sensitivity analysis was conducted by excluding cases with hysterectomy with preserved ovaries. RESULTS:Women with early menopause, compared with those who undergo menopause at 45 or older, are less likely to have flexible working arrangements (part-time work or self-employment) compared with full-time work during this sensitive period (relative risk ratio [RRR], 0.70; 95% CI: 0.51-0.97). However, the likelihood of leaving the labor market compared with working full-time is similar in women with early and later menopause (RRR, 0.95; 95% CI: 0.62-1.41). Surgical menopause, compared with natural menopause, is associated with an increased risk of labor market exit (RRR, 1.45; 95% CI: 1.01-2.32), particularly for women aged 45 or older at the time of surgery (RRR, 1.50; 95% CI: 0.94-2.38). Hormone therapy use may help reduce the risk of labor market exit for women with both early (RRR NATURAL INDIRECT EFFECT [NIE] , 0.79; 95% CI BIAS-CORRECTED [BC] , 0.58-1.04) and surgical menopause (RRR NIE , 0.73; 95% CI BC , 0.53-1.01). Sensitivity analysis suggests that the potential reduction in labor market exit risk via hormone therapy for early menopausal women holds true only when women with hysterectomy with preserved ovaries are included. CONCLUSIONS:Our study highlights that early menopause and surgical menopause, including hysterectomy with preserved ovaries, impact women's labor market trajectories and suggests that hormone therapy within the early years of the final menstruation may help women remain employed. We advocate for further research on the impact of the timing and type of menopause on women's labor market circumstances and for workplace policies that consider their diverse experiences.

BACKGROUND:People exist at a combination of different individual and neighbourhood deprivations. Each of these combinations may have a unique impact on health. However, little is known about the intersectional inequality of these combinations on general and central obesity, including when considering their demographics. This study aims to answer these questions. METHODS:The sample comprised 452,339 participants from the UK Biobank study. Individuals were grouped into 320 intersectional strata according to their household income, neighbourhood deprivation, sex, ethnicity and age. Linear and logistic multilevel analysis of individual heterogeneity and discriminatory accuracy was used to establish the total, additive and interactive inequality of body mass index (BMI), fat mass index (FMI), and waist to height ratio (WHtR), as well as the associated obesity classifications. RESULTS:6.5%, 25.2% and 9.1% of the total variation in BMI, FMI and WHtR, respectively, was due to inequality between the strata. Of this, 26.5%, 3.5% and 22.0% is interactive. 79, 58 and 93 strata for BMI, FMI and WHtR demonstrate a significant interactive effect. We found some patterns; for example, affluent white women have an advantaged interactive effect, whilst deprived black women have a disadvantaged effect. Meanwhile men experience the inverse relationship. The relationship between individual and neighbourhood deprivation is not universally experienced by all strata. For example, black men living in areas of high deprivation have higher BMIs as their household income increases. CONCLUSIONS:A large proportion of variation in general and central obesity is due to intersectional inequality, with up to 26.5% being interactive. It is important that these intersectional effects are considered when designing policy interventions to avoid policy failure, such as by focussing on groups with high total and interactive risk.

Abstract Background Menopause is a transitional life stage marked by the end of menstruation, during which approximately 80–90% of women experience persistent symptoms such as vasomotor symptoms, musculoskeletal pain, fatigue, and sleep disturbance. While menopausal hormone therapy is effective for some symptoms, non-pharmacological psychosocial interventions are increasingly recommended as alternatives or adjuncts. This review evaluates the efficacy of psychosocial interventions for managing physiological menopausal symptoms. Methods Six databases were systematically searched from inception to October 2024 for randomised controlled trials evaluating psychosocial interventions for menopausal women with physiological symptoms. Outcomes were grouped into nine categories, including sleep quality, insomnia, pain, fatigue, urogenital symptoms, sexual functioning, and vasomotor symptoms (classified as frequency, bothersomeness, and severity). Primary analyses used post-intervention data, with sensitivity analyses based on change scores. Effect sizes were expressed as Hedges’ g. The protocol was preregistered on PROSPERO, CRD42024572869. Results 28 randomised controlled trials involving 2,887 women were included, of which 24 were included in the meta-analysis and four synthesised narratively. Psychosocial interventions produced medium-to-large reductions in the bothersomeness of hot flushes and night sweats at short-term follow-up (Hedges’ g = − 0.60 to − 0.87) and medium-term follow-up (g = − 0.50 to − 0.77), while effects on symptom frequency and severity were smaller. Significant improvements were observed in sleep quality (short-term: g = − 0.77 to − 1.04; medium-term: g = − 0.46) and insomnia (short-term: g = − 1.77 to − 2.48; medium-term: g = − 1.56 to − 1.79). Psychosocial interventions did not demonstrate improvements on sexual functioning or urogenital symptoms. Intervention dose varied across studies, and retention rates were high (mean = 86.7%), indicating good feasibility. Conclusion Psychosocial interventions, particularly cognitive behavioural therapy, were associated with improvements in menopausal symptoms, with the strongest and most consistent effects observed for vasomotor symptom bothersomeness and sleep outcomes. These findings support psychosocial approaches as valuable non-pharmacological options, either alone or alongside pharmacological treatments. Future research should focus on tailoring interventions to individual needs, assessing whether benefits are maintained long-term, and examining whether effectiveness varies across different stages of menopause.

Objective: To examine the association between race/ethnicity and type 2 diabetes risk in women and assess the interaction between race/ethnicity and body mass index (BMI). Research design and methods: We analysed individual-level data from 730,408 women across 15 cohort studies. Six racial/ethnic groups were identified: White, Chinese, Japanese, South/Southeast Asian, Black, and Mixed/Other. Cox proportional hazards models with study as a random effect were used to estimate hazard ratios (HRs) for type 2 diabetes associated with race/ethnicity. The joint association of race/ethnicity and BMI was assessed using BMI categories incorporating Asian-specific cutoffs (<18.5, 18.5-22.9, 23.0-24.9, 25.0-27.4, 27.5-29.9, and ≥30 kg/m2), with White women having a BMI of 18.5-22.9 kg/m2 as the reference. Results: Overall, 37,329 (5.1%) women were diagnosed with type 2 diabetes. By age 70, the cumulative incidence was highest among South/Southeast Asian (24.6%) and Black women (23.6%), with baseline obesity rates of 40.0% (BMI ≥27.5 kg/m²) and 45.6% (BMI ≥30 kg/m²), respectively. After adjusting for BMI, South/Southeast Asian women had the highest diabetes risk compared with White women (HR:4.13, 95%CI 3.78-4.51), while other racial/ethnic groups had about twice the risk. Joint effect analysis showed South/Southeast Asian women with a BMI ≥23 kg/m2 had a substantially greater diabetes risk than other racial/ethnic groups with the same BMI, especially those with BMI 27.5-29.9 kg/m2 (HR:23.17, 19.21-27.95) and ≥30 kg/m2 (HR:35.52, 30.57-41.28). Conclusions: South/Southeast Asian women have a markedly elevated risk of type 2 diabetes, further amplified by modestly higher BMI, highlighting the need for ethnicity-specific diabetes prevention strategies for women.

Background: High blood pressure (BP) leads to coronary artery disease. Aim: We explored the impact of life-course BP, especially the steepness of BP increase and cumulative BP burden, on later-life stress myocardial blood flow (sMBF) and perfusion reserve (MPR) by cardiovascular magnetic resonance (CMR). Methods: MyoFit46 prospectively undertook stress perfusion and late gadolinium enhancement (LGE) CMR at age 76 in age-matched participants of the National Survey of Health and Development 1946 birth cohort. Myocardial perfusion was quantified as global sMBF normalized (sMBF N ) to contemporaneous rate pressure product (heart rate x central aortic BP) and MPR. Systolic (SBPs) and diastolic BPs (DBPs) were recorded at 36, 43, 53, 62, 69, and 76 years. For each participant, annual rates of BP change (steepness) and the area under the BP trajectory curve (AUC BP ; cumulative burden) were calculated using mixed-effect models. Participants were clustered by BP trajectory using latent class mixed models. Associations between BP and CMR metrics were tested using generalized models, adjusted for antihypertensive use, demographics, lifestyle, and comorbidities. Mediation analyses explored mechanistic pathways. Results: Among 459 participants (53% male), each 10mmHg SBP increase at 36, 43, 53, 62, and 69 years associated with a 3-6% lower sMBF N at 76. For midlife BPs (43-62 years), associations were independent of SBP at 76 and the decrease in sMBF N was steepest as SBPs rose from 120 to 140mmHg ( Figure 1 ). Having a sustained higher SBP by 10mmHg from 36 to 76 years associated with an 11% (95% CI: 8-14) lower sMBF N . Exemplar CMR perfusion maps based on AUC SBP are shown in Figure 2 . Each 1 mmHg/year steeper SBP rise during age intervals 36–43, 43–53, 53–62, and 62–69 was associated with a 2–5% lower sMBF N at age 76, independent of baseline or final BPs in each interval. sMBF N mediated 20-40% of the life-course SBPs and myocardial fibrosis by LGE associations. Results were similar for DBP, MPR, or unnormalized sMBF. Participants with the steepest BP rises from 36 to 53 years had the lowest myocardial perfusion at 76 ( Figure 3 ). Conclusion: Higher life-course BPs (even from age 36), steeper increases (regardless of final BP), and more years spent at higher BP levels associate with lower myocardial perfusion in older age. This underscores the importance of early-life BP screening, guiding treatment based on BP trajectories and cumulative burden, and rigorous midlife BP control.

Abstract Background Prenatal maternal smoking, lower birthweight, and shorter breastfeeding duration have all been associated with an earlier age at menopause in daughters. We estimated the extent to which birthweight-for-gestational-age z-score and breastfeeding duration mediate the effect of prenatal maternal smoking on time to natural menopause in daughters. Methods Using pooled data from two prospective birth cohort studies – the 1970 British Cohort Study (n = 3,878) followed-up to age 46 years and the 1958 National Child Development Study (n = 4,822) followed-up to age 50 years – we perform mediation analysis with inverse odds weighting implemented in Cox proportional-hazards models. Results Prenatal maternal smoking was associated with lower birthweight z-scores [β: -0.29; 95% CI -0.34, -0.24] and reduced breastfeeding duration [RRR< 1month: 0.90; 95% CI 0.79, 1.02; RRR≥ 1 month: 0.66; 95% CI 0.59, 0.73 relative to women who were never breastfed]. Greater z-score for birthweight [HR: 0.96; 95% CI 0.91, 1.01] and longer breastfeeding duration [HR≥ 1 month: 0.84; 95% CI 0.74, 0.96] were associated with lower hazards for earlier age at natural menopause. The total effect of prenatal maternal smoking on the time to natural menopause in daughters was estimated as a HR of 1.13 [95% CI 1.02, 1.24]. Birthweight z-score and breastfeeding duration jointly explained an estimated 14% of the total effect [HRNIE: 1.02; 95% CI 0.99, 1.05]. Conclusions The consequences of smoking during pregnancy on the earlier experience of natural menopause in daughters may partly be offset by intrauterine growth and longer breastfeeding duration to the extent that they mediate the risk of earlier menopause. However, since the extent of mediation by birthweight z-score and breastfeeding duration is small, other factors, including the direct effect of maternal smoking in utero, may play a more important role.

STUDY QUESTION:What is the association between endometriosis and the type and age of menopause? SUMMARY ANSWER:Women with endometriosis had a 7-fold increased risk of undergoing surgical menopause rather than natural menopause and were more likely to experience premature or early menopause, both surgically and naturally. WHAT IS KNOWN ALREADY:Endometriosis is associated with reduced ovarian reserve, but evidence on its relationship with the type of menopause (surgical vs natural) and timing (especially premature and early menopause) is limited. Women with endometriosis are more likely to undergo hysterectomy and/or oophorectomy (either unilateral or bilateral), but the average age of these surgeries remains unclear. STUDY DESIGN, SIZE, DURATION:The study analysed individual-level data from 279 948 women in five cohort studies conducted in the UK, Australia, Sweden, and Japan between 1996 and 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS:Women whose menopause type and age could not be determined due to premenopausal hysterectomy with ovarian preservation or use of menopausal hormone therapy were excluded. Endometriosis was identified through self-reports and administrative data. Surgical menopause was defined as premenopausal bilateral oophorectomy. Fine-Gray subdistribution hazard models estimated hazard ratios (HRs) for surgical and natural menopause. Age at menopause was determined by the ages at the final menstrual period or bilateral oophorectomy. Linear regression assessed mean differences in menopause age, while multinomial logistic regression estimated odds ratios (ORs) for categorical menopause age: <40 (premature), 40-44 (early), 45-49, 50-51 (reference), 52-54, and ≥55 years. Spontaneous premature ovarian insufficiency (POI) was defined as natural menopause before age 40 years. MAIN RESULTS AND THE ROLE OF CHANCE:Endometriosis was identified in 3.7% of women. By the end of follow-up, 7.9% had surgical menopause and 58.2% experienced natural menopause. Using a competing risk model, women with endometriosis had a 7-fold increased risk of surgical menopause (HR: 7.54, 95% CI 6.84, 8.32) and were less likely to experience natural menopause (HR: 0.40, 95% CI 0.33, 0.49). On average, surgical menopause occurred 1.6 years (19 months) earlier (β: -1.59, 95% CI -1.77, -1.42) in women with endometriosis. Among women who experienced natural menopause, it was 0.4 years (5 months) earlier (β: -0.37, 95% CI -0.46, -0.28) for those with endometriosis. Women with endometriosis were twice as likely to experience premature surgical menopause (<40 years) (OR: 2.11, 95% CI 2.02, 2.20) or 1.4 times more likely to develop spontaneous POI (OR: 1.36, 95% CI 1.17, 1.59). They were also at increased odds of early surgical and natural menopause (40-44 years). LIMITATIONS, REASONS FOR CAUTION:This study could not differentiate between subtypes and stages of endometriosis or assess treatments for ovarian endometrioma, which may impact ovarian reserve. Self-reported menopause type and age could introduce recall bias. WIDER IMPLICATIONS OF THE FINDINGS:Given the consistent findings across individual studies, our results are likely to be generalizable to different populations, highlighting the need for tailored management of endometriosis to prevent medically induced or premature menopause. Long-term monitoring of women with endometriosis is recommended, given their elevated risk of surgical menopause and premature or early menopause, which are associated with adverse health outcomes in later life. STUDY FUNDING/COMPETING INTEREST(S):The InterLACE Consortium is funded by the Australian National Health and Medical Research Council project grant (APP1027196) and Centres of Research Excellence (APP1153420). G.D.M. is funded by the Australian National Health and Medical Research Council Leadership Fellowship (APP2009577). This research is funded in part by the Japan Society for the Promotion of Science (JSPS KAKENHI: 19KK0235, 23KK0167). The authors have no conflict of interest. Where authors are identified as personnel of the International Agency for Research on Cancer or WHO, the authors alone are responsible for the views expressed in this article, and they do not necessarily represent the decisions, policy, or views of the International Agency for Research on Cancer or WHO. TRIAL REGISTRATION NUMBER:N/A.

BACKGROUND:Cross-sectional studies have demonstrated an association between menopausal symptoms and chronic pain, but the direction of the association remains unknown. We assessed whether chronic pain is associated with subsequent clusters of menopausal symptoms. METHODS:We used data from the National Child Development Study, a birth cohort of people born in 1958 in England, Scotland and Wales, which has included a biomedical sweep at age 44 when chronic pain was assessed and a 20-item menopause symptom questionnaire at age 50. Chronic pain was defined as lasting longer than 3 months, and chronic widespread pain was defined as chronic contralateral upper and lower quadrant pain and spinal pain. Latent class analysis was used to define menopause symptom classes (n = 4897) and structural equation models (n = 3308) to relate chronic pain and chronic widespread pain to these classes, adjusting for confounding variables. RESULTS:We found four latent classes of menopause symptom experience at 50 years. These were a low symptom burden class, one defined by vasomotor symptoms, one by psychological symptoms and one with high symptom burden. Chronic pain and chronic widespread pain at 44 years were related to greater odds of being in the higher symptom burden classes compared with the low burden group. For example, the odds ratio (95 % confidence interval) for the high symptom burden class was 2.90 (2.21, 3.81) for chronic pain and 3.50 (2.23, 5.49) for chronic widespread pain, and for the vasomotor symptom class 1.50 (1.16, 1.94) for chronic pain and 1.93 (1.19, 3.13) for chronic widespread pain. CONCLUSION:Women with chronic pain and chronic widespread pain earlier in life may experience greater burden of menopausal symptoms and this should be considered in their clinical management.

BACKGROUND:Elevated blood pressure (BP) is a major contributor to coronary artery disease. We explored the impact of life-course BP on later-life normalized stress myocardial blood flow (sMBFN) and myocardial perfusion reserve by cardiovascular magnetic resonance (CMR). METHODS:MyoFit46 prospectively recruited ≈500 National Survey of Health and Development 1946 birth cohort participants, aged ≈77 years, to undergo stress perfusion and late gadolinium enhancement CMR. Systolic (SBPs) and diastolic BPs were recorded at 36, 43, 53, 63, 69, and 77 years. For each participant, the annual rates of BP change (steepness of BP increase) and area under the BP trajectory curve (cumulative life-course BP burden) were derived using mixed-effects models. The associations between BP measures and CMR metrics were tested using generalized linear and additive models, adjusted for antihypertensive use, demographics, lifestyle choices, and comorbidities. Cross-sectional associations between CMR metrics and major adverse cardiovascular events (myocardial infarction, stroke, and heart failure) were also tested. Mediation analyses explored the mechanistic pathways linking life-course BPs, myocardial perfusion, and myocardial fibrosis. RESULTS:Among 459 included MyoFit46 participants, each 10 mm Hg higher SBP at 36 to 69 years was associated with 3% to 6% lower sMBFN by CMR at 77 years. At 43 to 63 years, as SBPs rose from 120 to 140 mm Hg, sMBFN was 18% to 24% lower. Having a sustained higher SBP by 10 mm Hg from 36 to 77 years was associated with 11% (95% CI, 8-14) lower sMBFN at 77 years. Each 1 mm Hg/y steeper SBP rise during age intervals 36 to 43, 43 to 53, 53 to 63, and 63 to 69 years was associated with 2% to 6% lower sMBFN at 77 years, associations not conditional on baseline or final BPs in each age interval. Associations may be clinically relevant as each 1% lower sMBFN was associated with 3% higher odds of major adverse cardiovascular events. sMBFN mediated ≈20% to ≈40% of the associations between life-course SBPs and late gadolinium enhancement at 77 years. Results were similar for diastolic BP, myocardial perfusion reserve, or sMBF (not normalized). CONCLUSIONS:Higher life-course BPs, steeper increases, and greater cumulative BP burden associate with lower myocardial perfusion by CMR at 77 years, which can be linked with higher odds of major adverse cardiovascular events and greater myocardial fibrosis burden. This underscores the importance of early life BP screening and guiding hyperetension treatment based on longitudinal BP trajectories (rather than relying solely on cross-sectional BPs). REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT05455125.

BACKGROUND:Existing evidence on associations between exposure to air pollution and psychological distress from middle to older age is limited by consideration of short exposure periods, poor historical covariates, exposures and outcomes, and cross-sectional study designs. We aimed to examine this association over a 26-year period between ages 43 and 69. METHODS:We utilised data from the Medical Research Council National Survey of Health and Development Study (the 1946 British birth cohort). Land-use regression models estimated exposure to specific air pollutants using household addresses for 1991 (NO2), 2001 (PM10, NO2), and 2010 (NO2, NOx, PM10, PM2.5, PMcoarse, PM2.5abs). These were linked to the closest data collection wave at ages 43, 53 and 60-64, respectively. Psychological distress was assessed through the 28-item version of the General Health Questionnaire (GHQ-28), at ages 53, 60-64 and 69. Associations between each of the pollutants with psychological distress were analysed using generalised linear mixed models, adjusted for pollution exposure before age 43, assigned sex, social class, smoking status, neighbourhood deprivation, and previous mental health problems. We also examined effect modification by social class. RESULTS:At age 69, 2125 participants completed the GHQ-28. In fully adjusted models, higher NO2 exposure was associated with higher GHQ-28 scores across a 26-year period (β=0.023, 95%CI:0.005, 0.040 per interquartile range increase in exposure), whereas higher exposure to PM10 was associated with lower GHQ-28 scores across a 16-year period (β=-0.021, 95%CI:-0.037, -0.006). There was no evidence of associations between exposure to other pollutants at age 60-64 and GHQ-28 at age 69. We found no effect modification by social class. CONCLUSIONS:In this cohort there was some evidence of an association between higher cumulative exposure to NO2 and higher psychological distress, but mixed associations with other exposures. Policies to reduce pollutant exposure may help improve psychological symptoms in middle to late adulthood.

Dysregulation of hypothalamic-pituitary-adrenal axis (HPA axis) and of the autonomic nervous system may link stress throughout the life course with poorer health. This study aims to investigate whether multiple adverse childhood experiences have a long-term impact on markers of these systems - cortisol secretion and heart rate variability - in adulthood. Data were from the Whitehall II cohort study. Fourteen adversities, collected retrospectively in midlife, were considered. Outcomes were total amount of cortisol secretion during the day (area under the curve [AUC]), cortisol awakening response (CAR), and diurnal slope, estimated from six saliva samples taken on a weekday; and resting heart rate (rHR) and heart rate variability (HRV) measured for five minutes at three time points over 10 years with the last measures taken at the same time as the salivary measurement. Regression models were used to examine the association of adversities with AUC, CAR, rHR and HRV and multilevel modelling was applied to analyses of cortisol diurnal slope and the 10-year follow-up of rHR and HRV. At least one early life adversity was reported by 68 % of participants. There was little evidence that increasing number of adversities was associated with any measures of cortisol, rHR or HRV or 10-year change in rHR or HRV. Of the individual adversities, only parental death was associated with increased AUC and CAR. In conclusion, although the HPA axis and autonomic nervous system have been hypothesized as mechanisms relating to adverse childhood experiences with health, our study finds no evidence to support this.

BACKGROUND:Previous research has linked higher exposure to air pollution to increased cognitive impairment at older ages. We aimed to extend the existing evidence in this area by incorporating exposures across the life course in addition to measures of cognition and brain structural imaging in participants at midlife to older age. METHODS:For this population-based study, we used data from the Medical Research Council National Survey of Health and Development (NSHD; also known as the 1946 British Birth Cohort) and a neuroimaging substudy of the NSHD known as Insight 46. Participants were recruited after birth in a single week during March, 1946. Our objectives were to assess whether exposure to air pollutants in midlife (age 45-64 years) was associated with poorer processing speed and poorer verbal memory between the ages of 43 years and 69 years, and whether exposures were associated with poorer cognitive state and brain structure outcomes at age 69-71 years. Air pollution exposure data were available for nitrogen dioxide (NO2; ages 45-64 years); particulate matter with diameter less than 10 μm (PM10; ages 55-64 years); and nitrogen oxides (NOx) and particulate matter with diameters less than 2·5 μm (PM2·5) and between 2·5 μm and less than 10 μm (PMcoarse) and particulate matter absorbance (PM2·5abs) as a measure of black carbon absorption (ages 60-64 years), with adjustments for early-life exposures to black smoke and sulphur dioxide. Verbal memory was tested with a 15-item recall task and processing speed with a visual search task at ages 43, 53, 60-64, and 69 years. The Addenbrooke's Cognitive Examination III (ACE-III), a measure of cognitive state, was conducted at age 69 years. Whole-brain, ventricular, hippocampal, and white matter hyperintensity volumes were assessed by MRI at age 69-71 years. Generalised linear models and generalised mixed linear models were used to explore associations between pollution exposure, cognitive measures, and brain structural outcomes, adjusted for sociodemographic factors including smoking status and neighbourhood deprivation. FINDINGS:Between the ages of 43 years and 69 years, we included 1534 NSHD participants in the verbal memory and processing speed analysis. Of 2148 participants who underwent testing during the wave of follow-up in 2015-16, at age 69 years, 1761 were included in the ACE-III analysis. Of the 502 NSHD participants recruited into the Insight 46 substudy, 453 were included in the analysis. Higher exposure to NO2 and PM10 was associated with slower processing speed between the ages of 43 years and 69 years (NO2 β -8·121 [95% CI -10·338 to -5·905 per IQR increase in exposure]; PM10 β -4·518 [-6·680 to -2·357]). Higher exposure to all tested pollutants was associated with lower ACE-III score at age 69 years (eg, NO2 β -0·589 [-0·921 to -0·257]). Higher exposure to NOx was associated with smaller hippocampal volume (β -0·088 [-0·172 to -0·004]) and higher exposure to NO2 and PM10 was associated with larger ventricular volume (NO2 β 2·259 [0·457 to 4·061]; PM10 β 1·841 [0·013 to 3·669]) at age 69-71 years. INTERPRETATION:Acknowledging the probable effects of exposure early in life, higher exposure to nitrogen dioxide, nitrogen oxides, and coarse particulate matter in midlife to older age was associated with poorer cognition, processing speed, and brain structural outcomes, strengthening evidence for the adverse effects of air pollution on brain function in older age. FUNDING:The National Institute for Health and Care Research, the Medical Research Council (MRC), Alzheimer's Research UK, the Alzheimer's Association, MRC Dementias Platform UK, and Brain Research UK.

Background/Objectives: Chronic pain (CP) affects more females than males, but it is unclear how differences present at mid-life, a period characterized by distinct changes which may exacerbate inequality. Methods: Using a search strategy combining MeSH terms and Boolean operators, we searched MEDLINE, EMBASE, AMED, and PSYCHinfo for population-representative cohort or cross-sectional studies of CP prevalence. We conducted a systematic review of CP prevalence by sex and the difference in prevalence of CP between sexes at mid-life through narrative synthesis and random-effects meta-analysis. A sensitivity analysis assessed how sex differences varied by pain type, pain definition, and geographic region. Results: Eighteen eligible articles provided information on CP prevalence by sex and demonstrated variation according to pain type. All but three studies found a higher prevalence of CP in females than males. Based on a random-effects meta-analysis of eight studies, the overall relative risk (RR) was 1.16 (95% CI: 1.11–1.21) for females compared with males, with no evidence of heterogeneity. However, in subgroup analyses, the RR was lower for generic CP (RR = 1.16, 95% CI: 1.11–1.21) than for fibromyalgia (RR = 3.13, 95% CI: 1.22–8.04). Conclusions: Our review found that females are more likely to experience CP at mid-life, although the RR was small. Larger sex differences may be observed for fibromyalgia, but the small sample sizes highlight the need for larger studies to provide more precise estimates of different types of pain.

Background: We investigated associations of childhood socioeconomic position and health with trajectories of grip strength from middle to older ages in two distinct populations. Methods: We used data from the China Health and Retirement Longitudinal Study (CHARLS, n = 16,701) and English Longitudinal Study of Ageing (ELSA, n = 12,695). Hand grip strength was measured at three timepoints in CHARLS (2011-2015) and four in ELSA (2001-2020). Random-effects growth models were applied to assess associations between each childhood factor and age trajectories of grip strength. Findings: Lower parental education was associated with weaker grip strength, by 0.36 kg(95 % CI:0.17,0.56) for participants of illiterate (vs literate) parents in CHARLS and 1.88 kg(0.43,3.33) for participants of parents without education (vs >= high school) in ELSA, after adjusting for parental occupation and own adult socioeconomic position. Low parental occupation was associated with weaker grip strength, although the difference diminished after adjustment for adult socioeconomic position. Financial hardship was associated with weaker grip strength only in CHARLS, by 0.19 kg(0.01,0.38) after adjustment. Self-rated poor childhood health and school absenteeism were associated with weaker grip strength (both studies). Being confined to bed and hospitalised for more than a month due to health were associated with weaker grip strength only in CHARLS. Each additional childhood illness (only reported in ELSA) was associated with 0.52 kg(0.28,0.81) lower mean grip strength. Reported poor childhood health (CHARLS), low parental education and school absenteeism (ELSA) were associated with grip strength decline. Interpretation: Lower socioeconomic position and poor health in childhood were associated with weaker grip strength in later life in both Chinese and English populations. Addressing socioeconomic disparities and promoting health of children may enhance life-course physical capacity, promote healthy ageing and reduce agerelated adversities.

Adults living with overweight or obesity do not represent a single homogenous group in terms of mortality and disease risks. The aim of our study was to evaluate how the associations of adulthood overweight and obesity with mortality and incident disease are modified by (i.e., differ according to) self-reported childhood body weight categories. The sample comprised 191,181 men and 242,806 women aged 40–69 years (in 2006–2010) in the UK Biobank. The outcomes were all-cause mortality, incident cardiovascular disease (CVD), and incident obesity-related cancer. Cox proportional hazards regression models were used to estimate how the associations with the outcomes of adulthood weight status (normal weight, overweight, obesity) differed according to perceived body weight at age 10 years (about average, thinner, plumper). To triangulate results using an approach that better accounts for confounding, analyses were repeated using previously developed and validated polygenic risk scores (PRSs) for childhood body weight and adulthood BMI, categorised into three-tier variables using the same proportions as in the observational variables. In both sexes, adulthood obesity was associated with higher hazards of all outcomes. However, the associations of obesity with all-cause mortality and incident CVD were stronger in adults who reported being thinner at 10 years. For example, obesity was associated with a 1.28 (1.21, 1.35) times higher hazard of all-cause mortality in men who reported being an average weight child, but among men who reported being a thinner child this estimate was 1.63 (1.53, 1.75). The ratio between these two estimates was 1.28 (1.17, 1.40). There was also some evidence that the associations of obesity with all-cause mortality and incident CVD were stronger in adults who reported being plumper at 10 years. In genetic analyses, however, there was no evidence that the association of obesity (according to the adult PRS) with mortality or incident CVD differed according to childhood body size (according to the child PRS). For incident obesity-related cancer, the evidence for effect modification was limited and inconsistent between the observational and genetic analyses. Greater risks for all-cause mortality and incident CVD in adults with obesity who perceive themselves to have been a thinner or plumper than average child may be due to confounding and/or recall bias.

Cardiovascular disease remains an important health challenge with high prevalence across the globe. This chapter acknowledges the importance of key adult risk factors including the classic cardiovascular risk factors and, for women, reproductive characteristics, but focusses on the pre-adult period. It details the relevance of understanding early-life trajectories of the classic risk factors, providing examples for blood pressure and lipids, and discussing the methodological challenges. The evidence relating early-life factors, such as physical growth, and social and environmental exposures, to cardiovascular disease is reviewed and highlights how new approaches in epidemiology have added to the evidence from observational studies to further understanding of causal processes. The chapter finishes by considering new risks, such as COVID-19 and climate change, that will need to be integrated within a life course approach and the policy considerations for early-life intervention.

In this Open Letter we bring together researchers from the Biosocial Birth Cohort Research (BBCR) network to reflect on interdisciplinary research and methods within birth cohorts and to draw attention to social science approaches to this field, which we argue are underutilized. A more comprehensive and consistent integration of social science approaches would expand the scope and value of research with birth cohorts. We critically engage three specific areas of birth cohort research that provide significant opportunities for exchange across disciplines; how exposure is defined and measured in birth cohorts, the harmonisation of data within and between birth cohorts and the broader experience of interdisciplinary collaboration in birth cohorts and birth cohort research. By reflecting on these three areas, we highlight the need for more in-depth dialogue between life and social sciences in the design of birth cohorts, the measures that are used, and the research made possible. We argue that improving the methodological tools for measuring social and biological exposures, incorporating the complexity of participant experience, and ensuring that longitudinal studies are recognised by a wider range of disciplines are essential for collaborative biosocial research with the goal of mitigating health disparities in global and public health.