Exposure to ambient air pollution and cognitive function: an analysis of the English Longitudinal Study of Ageing cohort.

BACKGROUND: An increasing number of studies suggest adverse effects of exposure to ambient air pollution on cognitive function, but the evidence is still limited. We investigated the associations between long-term exposure to air pollutants and cognitive function in the English Longitudinal Study of Ageing (ELSA) cohort of older adults. METHODS: Our sample included 8,883 individuals from ELSA, based on a nationally representative study of people aged ≥ 50 years, followed-up from 2002 until 2017. Exposure to air pollutants was modelled by the CMAQ-urban dispersion model and assigned to the participants' residential postcodes. Cognitive test scores of memory and executive function were collected biennially. The associations between these cognitive measures and exposure to ambient concentrations of NO2, PM10, PM2.5 and ozone were investigated using mixed-effects models adjusted for time-varying age, physical activity and smoking status, as well as baseline gender and level of education. RESULTS: Increasing long-term exposure per interquartile range (IQR) of NO2 (IQR: 13.05 µg/m3), PM10 (IQR: 3.35 µg/m3) and PM2.5 (IQR: 2.7 µg/m3) were associated with decreases in test scores of composite memory by -0.10 (95% confidence interval [CI]: -0.14, -0.07), -0.02 [-0.04, -0.01] and -0.08 [-0.11, -0.05], respectively. The same increases in NO2, PM10 and PM2.5 were associated with decreases in executive function score of -0.31 [-0.38, -0.23], -0.05 [-0.08, -0.02] and -0.16 [-0.22, -0.10], respectively. The association with ozone was inverse across both tests. Similar results were reported for the London-dwelling sub-sample of participants. CONCLUSIONS: The present study was based on a long follow-up with several repeated measurements per cohort participant and long-term air pollution exposure assessment at a fine spatial scale. Increasing long-term exposure to NO2, PM10 and PM2.5 was associated with a decrease in cognitive function in older adults in England. This evidence can inform policies related to modifiable environmental exposures linked to cognitive decline.

Adverse childhood experiences and trajectories of multimorbidity in individuals aged over 50: Evidence from the English Longitudinal Study of Ageing.

BACKGROUND: Adverse childhood experiences (ACE) are important for chronic diseases yet their association with multimorbidity remains understudied. Few studies consider the complexity of multimorbidity or observe multimorbidity development over time. OBJECTIVE: We investigated whether ACE were associated with multimorbidity at baseline and over a 12-year follow-up period. PARTICIPANTS AND SETTING: 5326 participants aged over 50 were obtained from the English Longitudinal Study of Ageing (ELSA). METHODS: An ACE summary score was derived using eight ACE items measuring abuse, social care, and household dysfunction. From repeated measurements of 29 chronic conditions over a 12-year period (2008-2019) we derived two multimorbidity measures: number of chronic diseases and number of chronic disease categories. We used multinomial logistic regression to assess associations between ACE and both measures. Mixed effects models were estimated to examine trajectories of multimorbidity by ACE over time. RESULTS: Graded associations between ACE and multimorbidity were observed. Compared to those without ACE, participants with ≥3 ACE had three times the risk of having ≥3 chronic diseases (RRR 3.06, 95 % CI 1.85-5.05) and falling into ≥3 chronic disease categories (RRR 2·93 95 % CI 1·74-4·95). Graded associations persisted during 12-year follow-up, though differences in multimorbidity between those with ≥3 ACE and those without ACE remained constant (B 0.02, 95 % CI 0·01-0·03, and B -0·01, 95 % CI -0·02-0·00, number of chronic conditions and chronic condition categories respectively). CONCLUSION: ACE are associated with multimorbidity risk and complexity, associations arising before the age of 50. Early intervention amongst those with ACE could attenuate this association.

Ethnic Differences in the Association Between Age at Natural Menopause and Risk of Type 2 Diabetes Among Postmenopausal Women: A Pooled Analysis of Individual Data From 13 Cohort Studies.

OBJECTIVE: To investigate associations between age at natural menopause, particularly premature ovarian insufficiency (POI) (natural menopause before age 40 years), and incident type 2 diabetes (T2D) and identify any variations by ethnicity. RESEARCH DESIGN AND METHODS: We pooled individual-level data of 338,059 women from 13 cohort studies without T2D before menopause from six ethnic groups: White (n = 177,674), Chinese (n = 146,008), Japanese (n = 9,061), South/Southeast Asian (n = 2,228), Black (n = 1,838), and mixed/other (n = 1,250). Hazard ratios (HRs) of T2D associated with age at menopause were estimated in the overall sample and by ethnicity, with study as a random effect. For each ethnic group, we further stratified the association by birth year, education level, and BMI. RESULTS: Over 9 years of follow-up, 20,064 (5.9%) women developed T2D. Overall, POI (vs. menopause at age 50-51 years) was associated with an increased risk of T2D (HR 1.31; 95% CI 1.20-1.44), and there was an interaction between age at menopause and ethnicity (P < 0.0001). T2D risk associated with POI was higher in White (1.53; 1.36-1.73), Japanese (4.04; 1.97-8.27), and Chinese women born in 1950 or later (2.79; 2.11-3.70); although less precise, the risk estimates were consistent in women of South/Southeast Asian (1.46; 0.89-2.40), Black (1.72; 0.95-3.12), and mixed/other (2.16; 0.83-5.57) ethnic groups. A similar pattern, but with a smaller increased risk of T2D, was observed with early menopause overall (1.16; 1.10-1.23) and for White, Japanese, and Chinese women born in 1950 or later. CONCLUSIONS: POI and early menopause are risk factors for T2D in postmenopausal women, with considerable variation across ethnic groups, and may need to be considered in risk assessments of T2D among women.

Adverse childhood experiences and diurnal cortisol patterns in older people in England.

Adverse childhood experiences (ACE) are associated with HPA axis dysregulation at younger ages, but there is scarcity of evidence for this association at older ages. To add to our knowledge of the lifetime impact of ACE on HPA axis function, we examined whether ACE were associated with diurnal cortisol patterns in a national sample of 587 participants (356 women) aged 55-79 years from the English Longitudinal Study of Ageing (ELSA). We conducted descriptive analyses and estimated sex-specific robust regression models of the associations between the 8-item summary ACE score and four measurements of salivary cortisol over a 24-h cycle (upon waking, 30 min later, at 7 pm, and at bedtime) as well as the cortisol awakening response (CAR) and the diurnal cortisol slope. Our models were adjusted for age, then for childhood socioeconomic position and finally for adult socioeconomic position. In men, we found significant differences that were independent of covariates, with more ACE being associated with lower salivary cortisol levels on waking, a greater CAR, and a flatter diurnal cortisol slope. In women, we observed a graded association between ACE and increased 7 pm salivary cortisol levels. Our findings indicate that childhood adversity is related to HPA axis in older people, especially men. The chronological distance (on average >50 years) between ACE and salivary cortisol levels suggests the existence of a lifelong association between childhood adversity and HPA axis and neuroendocrine function. Notwithstanding sex differences, based on our findings we suggest that HPA axis dysregulation could be a pathway that mediates the association between ACE and chronic disease later in life.

Using multiple imputation and intervention-based scenarios to project the mobility of older adults.

BACKGROUND: Projections of the development of mobility limitations of older adults are needed for evidence-based policy making. The aim of this study was to generate projections of mobility limitations among older people in the United States, England, and Finland. METHODS: We applied multiple imputation modelling with bootstrapping to generate projections of stair climbing and walking limitations until 2026. A physical activity intervention producing a beneficial effect on self-reported activities of daily living measures was identified in a comprehensive literature search and incorporated in the scenarios used in the projections. We utilised the harmonised longitudinal survey data from the Ageing Trajectories of Health - Longitudinal Opportunities and Synergies (ATHLOS) project (N = 24,982). RESULTS: Based on the scenarios from 2012 to 2026, the prevalence of walking limitations will decrease from 9.4 to 6.4%. A physical activity intervention would decrease the prevalence of stair climbing limitations compared with no intervention from 28.9 to 18.9% between 2012 and 2026. CONCLUSIONS: A physical activity intervention implemented on older population seems to have a positive effect on maintaining mobility in the future. Our method provides an interesting option for generating projections by incorporating intervention-based scenarios.

Could COVID-19's Aftermath on Children's Health Be Felt into the 22nd Century?

The COVID-19 pandemic has massively affected people's health, societies, and the global economy. Our lives are no longer as they were before COVID-19, and, most likely, will never be the same again. We hypothesize that the effect of the COVID-19 pandemic on population health and the economy will last for a very long time and will still be felt in the 22nd century. Our hypothesis is based on evidence from the 1918-1919 influenza pandemic, the Dutch famine during the Second World War, and the 2007-2008 economic crisis, as well as from the rationally predicted impact of COVID-19 on human development. We expect that the COVID-19 pandemic, including the mitigation measures taken against it, will affect children's development in multiple ways, including obesity, both while in utero and during critical and sensitive windows of development, including the early childhood years and those of puberty and adolescence. The psychosocial and biological impact of this effect will be considerable and unequally distributed. The implications will last at least a lifetime, and, through inter-generational transmission, will likely take us to future generations, into the 22nd century. We argue for the urgent need of designing and initiating comprehensive longitudinal cohort studies to closely monitor the long-term effects of COVID-19 on children conceived, born, and raised during the pandemic. Such an approach requires a close and effective collaboration between scientists, healthcare providers, policymakers, and the younger generations, and it will hopefully uncover evidence necessary to understand and mitigate the impact of the pandemic on people's lives in the 21st and 22nd centuries.

Adverse childhood experiences are associated with increased risk of hysterectomy and bilateral oophorectomy: A national retrospective cohort study of women in England.

OBJECTIVE: To examine the associations between adverse childhood experiences (ACE) and the risk of hysterectomy and bilateral oophorectomy in a national sample of women in England. DESIGN: Retrospective cohort study. SETTING: A stratified random sample of households across England. POPULATION: 2648 women aged ≥55 years in 2007 from the English Longitudinal Study of Ageing (ELSA) were included in the bilateral oophorectomy analyses and 2622 in the hysterectomy analyses. METHODS: Logistic and multinomial logistic regression analyses of the associations between categories of the ACE summary score (0, 1, 2, ≥3 ACE), eight individual ACE, and hysterectomy and bilateral oophorectomy. RESULTS: 615 women had undergone hysterectomy and 259 women bilateral oophorectomy. We found graded associations between the summary ACE score and risk of hysterectomy and bilateral oophorectomy. In the fully adjusted model, compared with women with no ACE, those with ≥3 ACE had double the odds of hysterectomy (odds ratio [OR] 2.01, 95% confidence interval [CI] 1.30-3.11) and more than double the odds of bilateral oophorectomy (OR 2.61, 95% CI 1.54-4.42). The exclusion of women with cancer history made the associations stronger, especially in women who underwent hysterectomy at age <40 years or bilateral oophorectomy at age ≤44 years. Several individual ACE were positively associated with both outcomes. CONCLUSIONS: ACE are associated with increased risk of hysterectomy and bilateral oophorectomy. Individual-level covariates did not explain these associations. Our findings highlight the importance of a life course approach to understanding surgical menopause and add to our knowledge of the societal and public health impact of ACE. TWEETABLE ABSTRACT: Adverse childhood experiences are associated with increased risk of hysterectomy and bilateral oophorectomy in a national sample of women in England.

Immediate and Longer-Term Changes in the Mental Health and Well-being of Older Adults in England During the COVID-19 Pandemic.

Importance: Despite the emphasis placed on the psychological impact of the COVID-19 pandemic, evidence from representative studies of older adults including pre-COVID-19 data and repeated assessments during the pandemic is scarce. Objective: To examine changes in mental health and well-being before and during the initial and later phases of the COVID-19 pandemic and test whether patterns varied with sociodemographic characteristics in a representative sample of older adults living in England. Design, Setting, and Participants: This longitudinal cohort study analyzed data from 5146 older adults participating in the English Longitudinal Study of Ageing who provided data before the COVID-19 pandemic (2018 and 2019) and at 2 occasions in 2020 (June or July as well as November or December). Exposures: The COVID-19 pandemic and sociodemographic characteristics, including sex, age, partnership status, and socioeconomic position. Main Outcomes and Measures: Changes in depression (8-item Centre for Epidemiological Studies Depression scale), anxiety (7-item Generalized Anxiety Disorder scale), quality of life (12-item Control, Autonomy, Self-realization, and Pleasure scale), and loneliness (3-item Revised University of California, Los Angeles, loneliness scale) were tested before and during the COVID-19 pandemic using fixed-effects regression models. Results: Of 5146 included participants, 2723 (52.9%) were women, 4773 (92.8%) were White, and the mean (SD) age was 67.7 (10.6) years. The prevalence of clinically significant depressive symptoms increased from 12.5% (95% CI, 11.5-13.4) before the COVID-19 pandemic to 22.6% (95% CI, 21.6-23.6) in June and July 2020, with a further rise to 28.5% (95% CI, 27.6-29.5) in November and December 2020. This was accompanied by increased loneliness and deterioration in quality of life. The prevalence of anxiety rose from 9.4% (95% CI, 8.8-9.9) to 10.9% (95% CI, 10.3-11.5) from June and July 2020 to November and December 2020. Women and nonpartnered people experienced worse changes in mental health. Participants with less wealth had the lowest levels of mental health before and during the COVID-19 pandemic. Higher socioeconomic groups had better mental health overall but responded to the COVID-19 pandemic with more negative changes. Conclusions and Relevance: In this longitudinal cohort study of older adults living in England, mental health and well-being continued to worsen as the COVID-19 pandemic progressed, and socioeconomic inequalities persisted. Women and nonpartnered people experienced greater deterioration in mental health.

Educational level as a cause of type 2 diabetes mellitus: Caution from triangulation of observational and genetic evidence.

BACKGROUND AND OBJECTIVE: Education might be causal to type 2 diabetes mellitus (T2DM). We triangulated cohort and genetic evidence to consolidate the causality between education and T2DM. METHODS: We obtained observational evidence from the English Longitudinal Study of Ageing (ELSA). Self-reporting educational attainment was categorised as high (post-secondary and higher), middle (secondary), and low (below secondary or no academic qualifications) in 6,786 community-dwelling individuals aged ≥ 50 years without diabetes at ELSA wave 2, who were followed until wave 8 for the first diabetes diagnosis. Additionally, we performed two-sample Mendelian randomisation (MR) using an inverse-variance weighted (IVW), MR-Egger, weighted median (WM), and weighted mode-based estimate (WMBE) method. Steiger filtering was further applied to exclude single-nucleotide polymorphisms (SNPs) that were correlated with an outcome (T2DM) stronger than exposure (education attainment). RESULTS: We observed 598 new diabetes cases after 10.4 years of follow-up. The adjusted hazard ratios (95% CI) of T2DM were 1.20 (0.97-1.49) and 1.58 (1.28-1.96) in the middle- and low-education groups, respectively, compared to the high-education group. Low education was also associated with increased glycated haemoglobin levels. Psychosocial resources, occupation, and health behaviours fully explained these inverse associations. In the MR analysis of 210 SNPs (R2 = 0.0161), the odds ratio of having T2DM per standard deviation-decreasing years (4.2 years) of schooling was 1.33 (1.01-1.75; IVW), 1.23 (0.37-4.17; MR-Egger), 1.56 (1.09-2.27; WM), and 2.94 (0.98-9.09; WMBE). However, applying Steiger filtering attenuated most MR results towards the null. CONCLUSIONS: Our inconsistent findings between cohort and genetic evidence did not support the causality between education and T2DM.

Socioeconomic position and use of hospital-based care towards the end of life: a mediation analysis using the English Longitudinal Study of Ageing.

BACKGROUND: Many patients prefer to avoid hospital-based care towards the end of life, yet hospitalisation is common and more likely for people with low socioeconomic position. The reasons underlying this socioeconomic inequality are not well understood. This study investigated health, service access, and social support as potential mediating pathways between socioeconomic position and receipt of hospital-based care towards the end of life. METHODS: For this observational cohort study, we included deceased participants from the nationally representative English Longitudinal Study of Ageing of people aged 50 years or older in England. We used a multiple mediation model with age-adjusted and gender-adjusted probit regression to estimate the direct effect of socioeconomic position (measured by wealth and education) on death in hospital and three or more hospital admissions in the last 2 years of life, and the indirect effects of socioeconomic position via three mediators: health and function, access to health-care services, and social support. FINDINGS: 737 participants were included (314 [42·6%] female, 423 [57·4%] male), with a median age at death of 78 years (IQR 71-85). For death in hospital, higher wealth had a direct negative effect (probit coefficient -0·16, 95% CI -0·25 to -0·06), which was not mediated by any of the pathways tested. For frequent hospital admissions, health and function mediated the effect of wealth (-0·04, -0·08 to -0·01), accounting for 34·6% of the total negative effect of higher wealth (-0·13, -0·23 to -0·02). Higher wealth was associated with better health and function (0·25, 0·18 to 0·33). Education was associated with the outcomes only indirectly via wealth. INTERPRETATION: Our findings suggest that worse health and function could partly explain why people with lower wealth have more hospital admissions, highlighting the importance of socioeconomically driven health differences in explaining patterns of hospital use towards the end of life. The findings should raise awareness about the related risk factors of low wealth and worse health for patients approaching the end of life, and strengthen calls for resource allocation to be made on the basis of health need and socioeconomic profile. FUNDING: Dunhill Medical Trust Fellowship Grant (RTF74/0116).

Adverse Childhood Experiences and Rate of Memory Decline From Mid to Later Life: Evidence From the English Longitudinal Study of Ageing.

Evidence on the role of early-life adversity in later-life memory decline is conflicting. We investigated the relationships between adverse childhood experiences (ACEs) and memory performance and rate of decline over a 10-year follow-up among middle-aged and older adults in England. Data were from biennial interviews with 5,223 participants aged 54 years or older in the population-representative English Longitudinal Study of Ageing from 2006/2007 to 2016/2017. We examined self-reports of 9 ACEs prior to age 16 years that related to abuse, household dysfunction, and separation from family. Memory was assessed at each time point as immediate and delayed recall of 10 words. Using linear mixed-effects models with person-specific random intercepts and slopes and adjusted for baseline age, participants' baseline age squared, sex, ethnicity, and childhood socioeconomic factors, we observed that most individual and cumulative ACE exposures had null to weakly negative associations with memory function and rate of decline over the 10-year follow-up. Having lived in residential or foster care was associated with lower baseline memory (adjusted ß = -0.124 standard deviation units; 95% confidence interval: -0.273, -0.025) but not memory decline. Our findings suggest potential long-term impacts of residential or foster care on memory and highlight the need for accurate and detailed exposure measures when studying ACEs in relation to later-life cognitive outcomes.

Association Between Reproductive Life Span and Incident Nonfatal Cardiovascular Disease: A Pooled Analysis of Individual Patient Data From 12 Studies.

Importance: Early menarche and early menopause are associated with increased risk of cardiovascular disease (CVD) in midlife, but little is known about the association between reproductive life span and the risk of CVD. Objective: To investigate the association between the length of reproductive life span and risk of incident CVD events, while also considering the timing of menarche and menopause. Design, Setting, and Participants: Individual-level data were pooled from 12 studies participating in the International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events consortium. Women provided complete information on the timing of menarche and menopause, nonfatal CVD events, and covariates. Cox proportional hazards models were used to estimate hazard ratios and 95% CIs, adjusted for covariates. The association between reproductive life span and CVD was adjusted for age at menarche and age at menopause separately. Analysis began March 2018 and ended December 2019. Exposures: Reproductive life span was calculated by subtracting age at menarche from age at menopause and categorized as younger than 30, 30 to 32, 33 to 35, 36 to 38 (reference group), 39 to 41, 42 to 44, and 45 years or older. Main Outcomes and Measures: First nonfatal CVD event, including coronary heart disease and stroke events. Results: A total of 307 855 women were included. Overall, the mean (SD) ages at menarche, menopause, and reproductive life span were 13.0 (1.5) years, 50.2 (4.4) years, and 37.2 (4.6) years, respectively. Pooled analyses showed that women with a very short reproductive life span (<30 years) were at 1.71 (95% CI, 1.58-1.84) times higher risk of incident CVD events than women with a reproductive life span of 36 to 38 years after adjustment for covariates. This association remained unchanged when adjusted for age at menarche but was attenuated to 1.26 (95% CI, 1.09-1.46) when adjusted for age at menopause. There was a significant interaction between reproductive life span and age at menarche associated with CVD risk (P < .001). Women who had both short reproductive life span (<33 years) and early menarche (age ≤11 years) had the highest risk of CVD (hazard ratio, 2.06; 95% CI, 1.76-2.41) compared with those with a reproductive life span of 36 to 38 years and menarche at age 13 years. Conclusions and Relevance: Short reproductive life span was associated with an increased risk of nonfatal CVD events in midlife, and the risk was significantly higher for women with early age at menarche.

Adverse childhood experiences are associated with increased risk of miscarriage in a national population-based cohort study in England.

STUDY QUESTION: Is there an association between adverse childhood experiences (ACE) and the risk of miscarriage in the general population? SUMMARY ANSWER: Specific ACE as well as the summary ACE score were associated with an increased risk of single and recurrent miscarriages. WHAT IS KNOWN ALREADY: There is scarce evidence on the association between ACE and miscarriage risk. STUDY DESIGN, SIZE, DURATION: We conducted a retrospective national cohort study. The sample consisted of 2795 women aged 55-89 years from the English Longitudinal Study of Ageing (ELSA). PARTICIPANTS/MATERIALS, SETTING, METHODS: Our study was population-based and included women who participated in the ELSA Life History Interview in 2007. We estimated multinomial logistic regression models of the associations of the summary ACE score and eight individual ACE variables (pertaining to physical and sexual abuse, family dysfunction and experiences of living in residential care or with foster parents) with self-reported miscarriage (0, 1, ≥2 miscarriages). MAIN RESULTS AND THE ROLE OF CHANCE: Five hundred and fifty-three women (19.8% of our sample) had experienced at least one miscarriage in their lifetime. Compared with women with no ACE, women with ≥3 ACE were two times more likely to experience a single miscarriage in their lifetime (relative risk ratio 2.00, 95% CI 1.25-3.22) and more than three times more likely to experience recurrent miscarriages (≥2 miscarriages) (relative risk ratio 3.10, 95% CI 1.63, 5.89) after adjustment for birth cohort, age at menarche and childhood socioeconomic position. Childhood experiences of physical and sexual abuse were individually associated with increased risk of miscarriage. LIMITATIONS, REASONS FOR CAUTION: Given the magnitude of the observed associations, their biological plausibility, temporal order and consistency with evidence suggesting a positive association between ACE and adverse reproductive outcomes, it is unlikely that our findings are spurious. Nevertheless, the observed associations should not be interpreted as causal as our study was observational and potentially susceptible to bias arising from unaccounted confounders. Non-response and ensuing selection bias may have also biased our findings. Retrospectively measured ACE are known to be susceptible to underreporting. Our study may have misclassified cases of ACE and possibly underestimated the magnitude of the association between ACE and the risk of miscarriage. WIDER IMPLICATIONS OF THE FINDINGS: Our study highlights experiences of psychosocial adversity in childhood as a potential risk factor for single and recurrent miscarriages. Our findings contribute to a better understanding of the role of childhood trauma in miscarriage and add an important life course dimension to the study of miscarriage. STUDY FUNDING/COMPETING INTEREST(S): ELSA is currently funded by the National Institute on Aging in USA (R01AG017644) and a consortium of UK government departments coordinated by the National Institute for Health Research. The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the article. The authors have no actual or potential competing financial interests to disclose.

Type of menopause, age of menopause and variations in the risk of incident cardiovascular disease: pooled analysis of individual data from 10 international studies.

STUDY QUESTION: How does the risk of cardiovascular disease (CVD) vary with type and age of menopause? SUMMARY ANSWER: Earlier surgical menopause (e.g. <45 years) poses additional increased risk of incident CVD events, compared to women with natural menopause at the same age, and HRT use reduced the risk of CVD in women with early surgical menopause. WHAT IS KNOWN ALREADY: Earlier age at menopause has been linked to an increased risk of CVD mortality and all-cause mortality, but the extent that this risk of CVD varies by type of menopause and the role of postmenopausal HRT use in reducing this risk is unclear. STUDY DESIGN, SIZE, DURATION: Pooled individual-level data of 203 767 postmenopausal women from 10 observational studies that contribute to the International collaboration for a Life course Approach to reproductive health and Chronic disease Events (InterLACE) consortium were included in the analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Postmenopausal women who had reported menopause (type and age of menopause) and information on non-fatal CVD events were included. Type of menopause (natural menopause and surgical menopause) and age at menopause (categorised as <35, 35-39, 40-44, 45-49, 50-54 and ≥55 years) were exposures of interest. Natural menopause was defined as absence of menstruation over a period of 12 months (no hysterectomy and/or oophorectomy) and surgical menopause as removal of both ovaries. The study outcome was the first non-fatal CVD (defined as either incident coronary heart disease (CHD) or stroke) event ascertained from hospital medical records or self-reported. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% CI for non-fatal CVD events associated with natural menopause and surgical menopause. MAIN RESULTS AND THE ROLE OF CHANCE: Compared with natural menopause, surgical menopause was associated with over 20% higher risk of CVD (HR 1.22, 95% CI 1.16-1.28). After the stratified analysis by age at menopause, a graded relationship for incident CVD was observed with lower age at menopause in both types of natural and surgical menopause. There was also a significant interaction between type of menopause and age at menopause (P < 0.001). Compared with natural menopause at 50-54 years, women with surgical menopause before 35 (2.55, 2.22-2.94) and 35-39 years (1.91, 1.71-2.14) had higher risk of CVD than those with natural menopause (1.59, 1.23-2.05 and 1.51, 1.33-1.72, respectively). Women who experienced surgical menopause at earlier age (<50 years) and took HRT had lower risk of incident CHD than those who were not users of HRT. LIMITATIONS, REASONS FOR CAUTION: Self-reported data on type and age of menopause, no information on indication for the surgery (e.g. endometriosis and fibroids) and the exclusion of fatal CVD events may bias our results. WIDER IMPLICATIONS OF THE FINDINGS: In clinical practice, women who experienced natural menopause or had surgical menopause at an earlier age need close monitoring and engagement for preventive health measures and early diagnosis of CVD. Our findings also suggested that timing of menopause should be considered as an important factor in risk assessment of CVD for women. The findings on CVD lend some support to the position that elective bilateral oophorectomy (surgical menopause) at hysterectomy for benign diseases should be discouraged based on an increased risk of CVD. STUDY FUNDING/COMPETING INTEREST(S): InterLACE project is funded by the Australian National Health and Medical Research Council project grant (APP1027196). GDM is supported by Australian National Health and Medical Research Council Principal Research Fellowship (APP1121844). There are no competing interests.

Type 2 diabetes and colorectal cancer screening: Findings from the English Longitudinal Study of Ageing.

Objectives: Type 2 diabetes has been identified as a risk factor for colorectal cancer, but little is known about whether it influences participation in colorectal cancer screening programmes. This study tested the extent to which Type 2 diabetes is negatively associated with colorectal cancer screening uptake. Methods: We analysed individual data of screening eligible men and women aged 60­75 without cancer diagnosis from wave 6 of the English Longitudinal Study of Ageing (collected 2012­2013), to investigate whether Type 2 Diabetes influences colorectal cancer screening behaviour independently of demographic characteristics, body mass index, socio-economic status and other chronic diseases. Results: Individuals who reported to have Type 2 diabetes or had glycated haemoglobin (HbA1c) levels of 48 mmol/mol or higher were less likely to have ever completed a screening test (faecal occult blood test; 62.8% vs. 75.8%, p < 0.01) or to be up-to-date with their biennial screening invitation (60.2% vs. 72.0%, p < 0.05). The negative associations of Type 2 diabetes on colorectal cancer screening were found both in unadjusted and adjusted regression models. Conclusions: Future qualitative and quantitative research should identify reasons for this discrepancy, to inform interventions to increase screening uptake in this high-risk population.

Cardiovascular risk factors and memory decline in middle-aged and older adults: the English Longitudinal Study of Ageing.

BACKGROUND: We investigated the association between trajectories of verbal episodic memory and burden of cardiovascular risk factors in middle-aged and older community-dwellers. METHODS: We analysed data from 4372 participants aged 50-64 and 3005 persons aged 65-79 years old from the English Longitudinal Study of Ageing who were repeatedly evaluated every 2 years and had six interviews of a 10-year follow-up. We measured the following baseline risk factors: diabetes, hypertension, smoking, physical inactivity and obesity to derive a cardiovascular risk factor score (CVRFs). Adjusted linear mixed effect regression models were estimated to determine the association between number of CVFRs and six repeated measurements of verbal memory scores, separately for middle-aged and older adults. RESULTS: CVRFs was not significantly associated with memory at baseline. CVFRs was significantly associated with memory decline in middle-aged (50-64y), but not in older (65-79y) participants. This association followed a dose-response pattern with increasing number of CVFRs being associated with greater cognitive decline. Comparisons between none versus some CVRFs yielded significant differences (p < 0.05). CONCLUSIONS: Our findings confirm that the effect of cumulative CVRFs on subsequent cognitive deterioration is age-dependent. CVRFs are associated with cognitive decline in people aged 50-64 years, but not in those aged ≥65 years. Although modest, the memory decline associated with accumulation of cardiovascular risk factors in midlife may increase the risk of late-life dementia.

Age at natural menopause and risk of incident cardiovascular disease: a pooled analysis of individual patient data.

BACKGROUND: Early menopause is linked to an increased risk of cardiovascular disease mortality; however, the association between early menopause and incidence and timing of cardiovascular disease is unclear. We aimed to assess the associations between age at natural menopause and incidence and timing of cardiovascular disease. METHODS: We harmonised and pooled individual-level data from 15 observational studies done across five countries and regions (Australia, Scandinavia, the USA, Japan, and the UK) between 1946 and 2013. Women who had reported their menopause status, age at natural menopause (if postmenopausal), and cardiovascular disease status (including coronary heart disease and stroke) were included. We excluded women who had hysterectomy or oophorectomy and women who did not report their age at menopause. The primary endpoint of this study was the occurrence of first non-fatal cardiovascular disease, defined as a composite outcome of incident coronary heart disease (including heart attack and angina) or stroke (including ischaemic stroke or haemorrhagic stroke). We used Cox proportional hazards models to estimate multivariate hazard ratios (HRs) and 95% CIs for the associations between age at menopause and incident cardiovascular disease event. We also adjusted the model to account for smoking status, menopausal hormone therapy status, body-mass index, and education levels. Age at natural menopause was categorised as premenopausal or perimenopausal, younger than 40 years (premature menopause), 40-44 years (early menopause), 45-49 years (relatively early), 50-51 years (reference category), 52-54 years (relatively late), and 55 years or older (late menopause). FINDINGS: Overall, 301 438 women were included in our analysis. Of these 301 438 women, 12 962 (4·3%) had a first non-fatal cardiovascular disease event after menopause, of whom 9369 (3·1%) had coronary heart disease and 4338 (1·4%) had strokes. Compared with women who had menopause at age 50-51 years, the risk of cardiovascular disease was higher in women who had premature menopause (age <40 years; HR 1·55, 95% CI 1·38-1·73; p<0·0001), early menopause (age 40-44 years; 1·30, 1·22-1·39; p<0·0001), and relatively early menopause (age 45-49 years; 1·12, 1·07-1·18; p<0·0001), with a significantly reduced risk of cardiovascular disease following menopause after age 51 years (p<0·0001 for trend). The associations persisted in never smokers, and were strongest before age 60 years for women with premature menopause (HR 1·88, 1·62-2·20; p<0·0001) and early menopause (1·40, 1·27-1·54; p<0·0001), but were attenuated at age 60-69 years, with no significant association observed at age 70 years and older. INTERPRETATION: Compared with women who had menopause at age 50-51 years, women with premature and early menopause had a substantially increased risk of a non-fatal cardiovascular disease event before the age of 60 years, but not after age 70 years. Women with earlier menopause need close monitoring in clinical practice, and age at menopause might also be considered as an important factor in risk stratification of cardiovascular disease for women. FUNDING: Australian National Health and Medical Research Council.

Premenopausal cardiovascular disease and age at natural menopause: a pooled analysis of over 170,000 women.

Early menopause is associated with an increased risk of subsequent cardiovascular disease (CVD). Few studies have investigated the converse. We examined whether premenopausal CVD events are associated with early age at menopause. We pooled the individual data of 177,131 women from nine studies. We used multinomial logistic regression models to estimate multivariable relative risk ratios (RRR) and 95% confidence intervals (CI) for the associations between age at onset of premenopausal CVD events-including coronary heart disease (CHD) and stroke-and age at natural menopause. Altogether 1561 (0.9%) premenopausal participants reported CVD events (including 1130 CHD and 469 stroke) at a mean age of 41.3 years. Compared with women without any premenopausal CVD events, women who experienced a first CVD event before age 35 years had a twofold risk of menopause before age 45 years (early menopause); adjusted RRR (95% CI) of 1.92 (1.17, 3.14) for any CVD, 1.86 (1.01, 3.43) for CHD and 2.17 (1.43, 3.30) for stroke. Women who experienced a first premenopausal CVD event after age 40 years underwent a natural menopause at the expected age (around 51 years). These associations were robust to adjustment for smoking status, BMI, educational level, race/ethnicity, age at menarche, parity, hypertension and family history of CVD. For premenopausal women, a first CVD event before age 35 years is associated with a doubling of the risk of an early menopause, while a first CVD event occurred after 35 years indicates a normal menopause at around 51 years. Shared genetic and environmental factors (such as smoking), as well as compromised vasculature following CVD events, may contribute to this outcome.

Childhood experiences of parenting and age at menarche, age at menopause and duration of reproductive lifespan: Evidence from the English Longitudinal Study of Ageing.

OBJECTIVES: The parent-child relationship is critical for human development, yet little is known about its association with offsprings' reproductive health outside the context of abuse and neglect. We investigated whether childhood experiences of poor-quality parenting (characterized as decreased parental care and increased parental overprotection) are associated with women's reproductive timing and lifespan. STUDY DESIGN: Observational study of 2383 women aged 55-89 years in 2007 from the English Longitudinal Study of Ageing (ELSA). Multinomial logistic regression models were estimated. MAIN OUTCOME MEASURES: Self-reported ages at menarche and menopause and duration of reproductive lifespan. RESULTS: Increasing maternal and paternal overprotection were associated with later menarche (≥16 years) after adjustment for age and childhood socioeconomic position (relative risk ratio (RRR) 1.11, 95% CI 1.02-1.21 and 1.11, 95% CI 1.01-1.21, respectively, per unit increase in the predictor). Increasing parental overprotection and decreasing paternal care were associated with earlier menarche (≤10 years). However, these associations were marginally non-significant. Maternal and paternal overprotection were also inversely associated with age at natural menopause after adjustment for age, childhood socioeconomic position and age at menarche (p value for linear trend = 0.041 and 0.004, respectively). Further, increasing paternal overprotection was associated with a shorter reproductive lifespan (≤33 years) (RRR 1.09 (1.01-1.18), per unit increase in the predictor) after adjustment for age and childhood socioeconomic position. Adjustment for additional childhood and adult factors did not explain these associations. CONCLUSIONS: Women who experienced poor-quality parenting in childhood, especially increased levels of parental overprotection, might be at increased risk of an unfavourable reproductive health profile that is characterized by late or early menarche, premature menopause and a shorter reproductive lifespan.