Sex-Specific Association Between Childhood Adversity and Accelerated Biological Aging.

Is childhood adversity associated with biological aging, and if so, does sex modify the association, and do lifestyle and mental health mediate the association? A lifespan analysis is conducted using data on 142 872 participants from the UK Biobank to address these questions. Childhood adversity is assessed through the online mental health questionnaire (2016), including physical neglect, physical abuse, emotional neglect, emotional abuse, sexual abuse, and a cumulative score. Biological aging is indicated by telomere length (TL) measured from leukocyte DNA using qPCR, and the shorter TL indicates accelerated biological aging; a lifestyle score is constructed using body mass index, physical activity, drinking, smoking, and diet; mental disorder is assessed using depression, anxiety, and insomnia at the baseline survey. The results reveal a sex-specific association such that childhood adversity is associated with shorter TL in women after adjusting for covariates including polygenic risk score for TL, but not in men. Unhealthy lifestyle and mental disorder partially mediate the association in women. The proportions of indirect effects are largest for sexual and physical abuse. These findings highlight the importance of behavioral and psychological interventions in promoting healthy aging among women who experienced childhood adversity, particularly sexual and physical abuse.

Impact of sarcopenic obesity on heart failure in people with type 2 diabetes and the role of metabolism and inflammation: A prospective cohort study.

AIMS: We aimed to prospectively evaluate the association of sarcopenic obesity (SO) with the incidence risk of heart failure (HF), and the mediating role of metabolomics and inflammation in people with type 2 diabetes (T2D). METHODS: 22,496 participants with T2D from the UK Biobank were included. SO was defined as the combination of obesity (body mass index ≥30 kg/m2) and sarcopenia (grip strength <27 kg in male or <16 kg in female). The incident HF was identified through linked hospital records. Cox proportional hazard regression models were used to estimate the associations. Mediation analysis was conducted to evaluate the mediating effect of the "metabolomic risk score" of HF, which was derived from 168 plasma metabolites through LASSO regression, and five inflammatory markers (e.g., C-reactive protein [CRP] level) on the aforementioned associations. RESULTS: 1946 (8.7 %) participants developed HF during a median follow-up of 12.0 years. Compared to participants with neither obesity nor sarcopenia, those with obesity & non-sarcopenia (hazard ratio [HR]: 1.80, 95 % confidence interval [CI]: 1.62, 2.00), sarcopenia & non-obesity (HR: 1.90, 95 % CI: 1.56, 2.31) and SO (HR: 2.29, 95 % CI: 1.92, 2.73) showed a higher risk of HF. The metabolomic risk score (20.0 %) and CRP (20.4 %) meditated this association. CONCLUSIONS: SO was associated with an increased risk of HF in people with T2D and metabolomics and inflammation partially mediated this association. Our findings suggest the importance of managing obesity and muscle strength simultaneously in preventing HF among people with T2D and shed light on the underlying mechanisms.

Associations of perceived stress with loneliness and depressive symptoms: the mediating role of sleep quality.

BACKGROUND: Whether perceived stress is associated with loneliness and depressive symptoms in general adults, and to what extent sleep quality mediates the associations, remains unknown. The aim of this study was to estimate the associations of perceived stress with loneliness and depressive symptoms, and the mediating role of sleep quality in these associations. METHODS: Cross-sectional data on 734 participants (aged 18-87 years) were analyzed. Perceived stress was assessed using the 10-item Perceived Stress Scale (PSS-10; range 0-40). Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI; range 0-21). Loneliness was assessed using the three-item short form of the Revised University of California, Los Angeles (UCLA) loneliness scale (range 3-9). Depressive symptoms were assessed using the 10-item Center for Epidemiologic Studies Depression (CESD-10) Scale (range 0-30). General linear regression models, multivariable logistic regression models, and formal mediation analysis were performed. RESULTS: After adjustment for age and sex, we found that with each 1-point increment in the perceived stress score, both the loneliness score (ß = 0.07; 95% confidence interval [CI]: 0.06, 0.08) and depression score (ß = 0.45; 95% CI: 0.40, 0.49) increased significantly. Robust results were observed when adjusting for more confounders. Furthermore, sleep quality mediated 5.3% (95% CI: 1.3%, 10.0%; P = 0.014) and 9.7% (95% CI: 6.2%, 14.0%; P < 0.001) of the associations of perceived stress score with loneliness score and depression score, respectively. CONCLUSIONS: In general Chinese adults, perceived stress was positively associated with loneliness and depressive symptoms, and sleep quality partially mediated these associations. The findings reveal a potential pathway from perceived stress to mental health through sleep behaviors, and highlight the importance of implementing sleep intervention programs for promoting mental health among those who feel highly stressed.

Influencing Factors of Healthy Aging Risk Assessed Using Biomarkers: A Life Course Perspective.

Assessing individual risks of healthy aging using biomarkers and identifying associated factors have become important areas of research. In this study, we conducted a literature review of relevant publications between 2018 and 2023 in both Chinese and English databases. Previous studies have predominantly used single biomarkers, such as C-reactive protein, or focused on specific life course stages and factors such as socioeconomic status, mental health, educational levels, and unhealthy lifestyles. By summarizing the progress in this field, our study provides valuable insights and future directions for promoting healthy aging from a life course perspective.

Trajectories of Body Mass Index and Waist Circumference in Relation to the Risk of Cardiac Arrhythmia: A Prospective Cohort Study.

BACKGROUND: The aim of the current study was to explore the trajectories, variabilities, and cumulative exposures of body mass index (BMI) and waist circumference (WC) with cardiac arrhythmia (CA) risks. METHODS: In total, 35,739 adults from the Kailuan study were included. BMI and WC were measured repeatedly during the 2006-2010 waves. CA was identified via electrocardiogram diagnosis. BMI and WC trajectories were fitted using a group-based trajectory model. The associations were estimated using Cox proportional hazards models. RESULTS: We identified four stable trajectories for BMI and WC, respectively. Neither the BMI trajectories nor the baseline BMI values were associated with the risk of CA. Compared to the low-stable WC group, participants in the high-stable WC group had a higher risk of CA (hazard ratio (HR) = 1.40, 95% confidence interval (CI): 1.06, 1.86). Interestingly, the cumulative exposures of BMI and WC instead of their variabilities were associated with the risk of CA. In the stratified analyses, the positive associations of the high-stable WC group with the risk of CA were found in females only (HR = 1.98, 95% CI: 1.02, 3.83). CONCLUSIONS: A high-stable WC trajectory is associated with a higher risk of CA among Chinese female adults, underscoring the potential of WC rather than BMI to identify adults who are at risk.

Accelerated aging mediates the associations of unhealthy lifestyles with cardiovascular disease, cancer, and mortality.

BACKGROUND: With two well-validated aging measures capturing mortality and morbidity risk, this study examined whether and to what extent aging mediates the associations of unhealthy lifestyles with adverse health outcomes. METHODS: Data were from 405,944 adults (40-69 years) from UK Biobank (UKB) and 9972 adults (20-84 years) from the US National Health and Nutrition Examination Survey (NHANES). An unhealthy lifestyles score (range: 0-5) was constructed based on five factors (smoking, drinking, physical inactivity, unhealthy body mass index, and unhealthy diet). Two aging measures, Phenotypic Age Acceleration (PhenoAgeAccel) and Biological Age Acceleration (BioAgeAccel) were calculated using nine and seven blood biomarkers, respectively, with a higher value indicating the acceleration of aging. The outcomes included incident cardiovascular disease (CVD), incident cancer, and all-cause mortality in UKB; CVD mortality, cancer mortality, and all-cause mortality in NHANES. A general linear regression model, Cox proportional hazards model, and formal mediation analysis were performed. RESULTS: The unhealthy lifestyles score was positively associated with PhenoAgeAccel (UKB: ß = 0.741; NHANES: ß = 0.874, all p < 0.001). We further confirmed the respective associations of PhenoAgeAccel and unhealthy lifestyles with the outcomes in UKB and NHANES. The mediation proportion of PhenoAgeAccel in associations of unhealthy lifestyles with incident CVD, incident cancer, and all-cause mortality were 20.0%, 17.8%, and 26.6% (all p < 0.001) in UKB, respectively. Similar results were found in NHANES. The findings were robust when using another aging measure-BioAgeAccel. CONCLUSIONS: Accelerated aging partially mediated the associations of lifestyles with CVD, cancer, and mortality in UK and US populations. The findings reveal a novel pathway and the potential of geroprotective programs in mitigating health inequality in late life beyond lifestyle interventions.

Association of Childhood Adversity With Frailty and the Mediating Role of Unhealthy Lifestyle: A Lifespan Analysis.

OBJECTIVES: Childhood adversity and lifestyle have been associated with frailty in later life, but not much is known about factors that may explain these associations. Therefore, this study aims to investigate the association of childhood adversity with frailty, and the mediating role of unhealthy lifestyle in the association. METHODS: This lifespan analysis included 152,914 adults aged 40-69 years old from the UK Biobank. We measured childhood adversity with five items: physical neglect, emotional neglect, sexual abuse, physical abuse, and emotional abuse through online mental health survey. Frailty was measured by the frailty index; an unhealthy lifestyle score (range: 0-5) was calculated based on unhealthy body mass index, smoking, alcohol consumption, physical inactivity, and unhealthy diet at the baseline survey. Multiple logistic regression and mediation analysis were performed. RESULTS: A total of 10,078 participants (6.6%) were defined as having frailty. Participants with any childhood adversity had higher odds of frailty. For example, in the fully adjusted model, with a one-point increase in cumulative score of childhood adversity, the odds of frailty increased by 38% (odds ratio: 1.38; 95% Confidence Interval: 1.36, 1.40). Unhealthy lifestyle partially mediated the associations of childhood adversity with frailty (mediation proportion: 4.4%-7.0%). The mediation proportions were largest for physical (8.2%) and sexual (8.1%) abuse. CONCLUSIONS: Childhood adversity was positively associated with frailty, and unhealthy lifestyle partially mediated the association. This newly identified pathway highlights the potential of lifestyle intervention strategies among those who experienced childhood adversity (in particular, physical, and sexual abuse) to promote healthy aging.

Sociodemographic Factors Predict Incident Mild Cognitive Impairment: A Brief Review and Empirical Study.

OBJECTIVES: Mild cognitive impairment (MCI) is a transitional stage between normal cognitive aging and dementia that increases the risk of progressive cognitive decline. Early prediction of MCI could be beneficial for identifying vulnerable individuals in the community and planning primary and secondary prevention to reduce the incidence of MCI. DESIGN: A narrative review and cohort study. SETTING AND PARTICIPANTS: We review the MCI prediction based on the assessment of sociodemographic factors. We included participants from 3 surveys: 8915 from wave 2011/2012 of the China Health and Retirement Longitudinal Study (CHARLS), 9765 from the 2011 Chinese Longitudinal Healthy Longevity Survey (CLHLS), and 1823 from the 2014 Rugao Longevity and Ageing Study (RuLAS). METHODS: We searched in PubMed, Embase, and Web of Science Core Collection between January 1, 2019, and December 30, 2022. To construct the composite risk score, a multivariate Cox proportional hazards regression model was used. The performance of the score was assessed using receiver operating characteristic (ROC) curves. Furthermore, the composite risk score was validated in 2 longitudinal cohorts, CLHLS and RuLAS. RESULTS: We concluded on 20 articles from 892 available. The results suggested that the previous models suffered from several defects, including overreliance on cross-sectional data, low predictive utility, inconvenient measurement, and inapplicability to developing countries. Our empirical work suggested that the area under the curve for a 5-year MCI prediction was 0.861 in CHARLS, 0.797 in CLHLS, and 0.823 in RuLAS. We designed a publicly available online tool for this composite risk score. CONCLUSIONS AND IMPLICATIONS: Attention to these sociodemographic factors related to the incidence of MCI can be beneficially incorporated into the current work, which will set the stage for better early prediction of MCI before its incidence and for reducing the burden of the disease.

Visit-to-visit HbA1c variability, dementia, and hippocampal atrophy among adults without diabetes.

OBJECTIVES: Adults without diabetes are not completely healthy; they are probably heterogeneous with several potential health problems. The management of hemoglobin A1c (HbA1c) is crucial among patients with diabetes; but whether similar management strategy is needed for adults without diabetes is unclear. Thus, this study aimed to investigate the associations of visit-to-visit HbA1c variability with incident dementia and hippocampal volume among middle-aged and older adults without diabetes, providing potential insights into this question. METHODS: We conducted a prospective analysis for incident dementia in 10,792 participants (mean age 58.9 years, 47.8 % men) from the UK Biobank. A subgroup of 3793 participants (mean age 57.8 years, 48.6 % men) was included in the analysis for hippocampal volume. We defined HbA1c variability as the difference in HbA1c divided by the mean HbA1c over the 2 sequential visits ([latter - former]/mean). Dementia was identified using hospital inpatient records with ICD-9 codes. T1-structural brain magnetic resonance imaging was conducted to derive hippocampal volume (normalized for head size). The nonlinear and linear associations were examined using restricted cubic spline (RCS) models, Cox regression models, and multiple linear regression models. RESULTS: During a mean follow-up (since the second round) of 8.4 years, 90 (0.8 %) participants developed dementia. The RCS models suggested no significant nonlinear associations of HbA1c variability with incident dementia and hippocampal volume, respectively (All P > 0.05). Above an optimal cutoff of HbA1c variability at 0.08, high HbA1c variability (increment in HbA1c) was associated with an increased risk of dementia (Hazard Ratio, 1.88; 95 % Confidence Interval, 1.13 to 3.14, P = 0.015), and lower hippocampal volume (coefficient, -96.84 mm3, P = 0.037), respectively, in models with adjustment of covariates including age, sex, etc. Similar results were found for a different cut-off of 0. A series of sensitivity analyses verified the robustness of the findings. CONCLUSIONS: Among middle-aged and older adults without diabetes, increasing visit-to-visit HbA1c variability was associated with an increased dementia risk and lower hippocampal volume. The findings highlight the importance of monitoring and controlling HbA1c fluctuation in apparently healthy adults without diabetes.

Associations of Midlife Dietary Patterns with Incident Dementia and Brain Structure: Findings from the UK Biobank Study.

BACKGROUND: At present, the results on the associations between dietary patterns and risk of dementia are inconsistent, and studies on the associations between dietary patterns and brain structures are limited. OBJECTIVES: We aimed to investigate the associations of midlife dietary patterns with incident dementia and brain structures. METHODS: On the basis of the UK Biobank Study, we investigated the 1) prospective associations of 4 healthy dietary pattern indices [healthy plant-based diet index (hPDI), Mediterranean diet score (MDS), recommended food score (RFS), and Mediterranean-DASH Intervention for Neurodegenerative Delay Diet (MIND)] with incident dementia (identified using linked hospital data; N = 114,684; mean age, 56.8 y; 55.5% females) using Cox proportional-hazards regressions and the 2) cross-sectional associations of these dietary pattern indices with brain structures (estimated using magnetic resonance imaging; N = 18,214; mean age, 55.9 y; 53.1% females) using linear regressions. A series of covariates were adjusted, and several sensitivity analyses were conducted. RESULTS: A total of 481 (0.42%) participants developed dementia during the average 9.4-y follow-up. Although the associations were not statistically significant, all dietary patterns exerted protective effects against incident dementia (all HRs < 1). Furthermore, higher dietary pattern indices were significantly associated with larger regional brain volumes, including volumes of gray matter in the parietal and temporal cortices and volumes of the hippocampus and thalamus. The main results were confirmed via sensitivity analyses. CONCLUSIONS: Greater adherence to hPDI, MDS, RFS, and MIND was individually associated with larger brain volumes in specific regions. This study shows a comprehensive picture of the consistent associations of midlife dietary patterns with risk of dementia and brain health, underscoring the potential benefits of a healthy diet in the prevention of dementia.

Associations Between Frailty and the Increased Risk of Adverse Outcomes Among 38,950 UK Biobank Participants With Prediabetes: Prospective Cohort Study.

BACKGROUND: Compared with adults with normal glucose metabolism, those with prediabetes tend to be frail. However, it remains poorly understood whether frailty could identify adults who are most at risk of adverse outcomes related to prediabetes. OBJECTIVE: We aimed to systematically evaluate the associations between frailty, a simple health indicator, and risks of multiple adverse outcomes including incident type 2 diabetes mellitus (T2DM), diabetes-related microvascular disease, cardiovascular disease (CVD), chronic kidney disease (CKD), eye disease, dementia, depression, and all-cause mortality in late life among middle-aged adults with prediabetes. METHODS: We evaluated 38,950 adults aged 40 years to 64 years with prediabetes using the baseline survey from the UK Biobank. Frailty was assessed using the frailty phenotype (FP; range 0-5), and participants were grouped into nonfrail (FP=0), prefrail (1≤FP≤2), and frail (FP≥3). Multiple adverse outcomes (ie, T2DM, diabetes-related microvascular disease, CVD, CKD, eye disease, dementia, depression, and all-cause mortality) were ascertained during a median follow-up of 12 years. Cox proportional hazards regression models were used to estimate the associations. Several sensitivity analyses were performed to test the robustness of the results. RESULTS: At baseline, 49.1% (19,122/38,950) and 5.9% (2289/38,950) of adults with prediabetes were identified as prefrail and frail, respectively. Both prefrailty and frailty were associated with higher risks of multiple adverse outcomes in adults with prediabetes (P for trend <.001). For instance, compared with their nonfrail counterparts, frail participants with prediabetes had a significantly higher risk (P<.001) of T2DM (hazard ratio [HR]=1.73, 95% CI 1.55-1.92), diabetes-related microvascular disease (HR=1.89, 95% CI 1.64-2.18), CVD (HR=1.66, 95% CI 1.44-1.91), CKD (HR=1.76, 95% CI 1.45-2.13), eye disease (HR=1.31, 95% CI 1.14-1.51), dementia (HR=2.03, 95% CI 1.33-3.09), depression (HR=3.01, 95% CI 2.47-3.67), and all-cause mortality (HR=1.81, 95% CI 1.51-2.16) in the multivariable-adjusted models. Furthermore, with each 1-point increase in FP score, the risk of these adverse outcomes increased by 10% to 42%. Robust results were generally observed in sensitivity analyses. CONCLUSIONS: In UK Biobank participants with prediabetes, both prefrailty and frailty are significantly associated with higher risks of multiple adverse outcomes, including T2DM, diabetes-related diseases, and all-cause mortality. Our findings suggest that frailty assessment should be incorporated into routine care for middle-aged adults with prediabetes, to improve the allocation of health care resources and reduce diabetes-related burden.

Comparison of healthspan-related indicators between adults with and without HIV infection aged 18-59 in the United States: a secondary analysis of NAHNES 1999-March 2020.

BACKGROUND: As persons with HIV (PWH) live longer they may experience a heightened burden of poor health. However, few studies have characterized the multi-dimentional health of PWH. Thus, we aimed to identify the extent and pattern of health disparities, both within HIV infection status and across age (or sex) specific groups. METHODS: We used cross-sectional data from the US National Health and Nutrition Examination Survey, 1999-March 2020. The adjusted prevalence of six healthspan-related indicators-physical frailty, activities of daily living (ADL) disability, mobility disability, depression, multimorbidity, and all-cause death-was evaluated. Logistic regression and Cox proportional hazards analyses were used to investigate associations between HIV status and healthspan-related indicators, with adjustment for individual-level demographic characteristics and risk behaviors. RESULTS: The analytic sample consisted of 33 200 adults (170 (0.51%) were PWH) aged 18-59 years in the United States. The mean (interquartile range) age was 35.1 (25.0-44.0) years, and 49.4% were male. PWH had higher adjusted prevalences for all of the 6 healthspan-related indicators, as compared to those without HIV, ranged from 17.4% (95% CI: 17.4%, 17.5%) vs. 2.7% (95%CI: 2.7%, 2.7%) for all-cause mortality, to 84.3% (95% CI: 84.0%, 84.5%) vs. 69.8% (95%CI: 69.7%, 69.8%) for mobility disability. While the prevalence difference was largest in ADL disability (23.4% (95% CI: 23.2%, 23.7%); P < 0.001), and least in multimorbidity (6.9% (95% CI: 6.8%, 7.0%); P < 0.001). Generally, the differences in prevalence by HIV status were greater in 50-59 years group than those in 18-29 group. Males with HIV suffered higher prevalence of depression and multimorbidity, while females with HIV were more vulnerable to functional limitation and disabilities. HIV infection was associated with higher odds for 3 of the 6 healthspan-related indicators after fully adjusted, such as physical frailty and depression. Sensitivity analyses did not change the health differences between adults with and without HIV infection. CONCLUSIONS: In a large sample of U.S. community-dwelling adults, by identifying the extent and pattern of health disparities, we characterized the multi-dimentional health of PWHs, providing important public health implications for public policy that aims to improve health of persons with HIV and further reduce these disparities.

Weight change across adulthood and accelerated biological aging in middle-aged and older adults.

BACKGROUND: Little is known regarding the association between weight change and accelerated aging. OBJECTIVES: This study aimed to estimate the influence of weight change across adulthood on biological aging acceleration in middle-aged and older adults in the United States. METHODS: We used data of 5553 adults (40-84 y) from the National Health and Nutrition Examination Survey 1999-2010. Weight change patterns (i.e., stable normal, maximal overweight, obese to nonobese, nonobese to obese, and stable obese) and absolute weight change groups across adulthood (i.e., from young to middle adulthood, young to late adulthood, and middle to late adulthood) were defined. A biological aging measure (i.e., phenotypic age acceleration [PhenoAgeAccel]) at late adulthood was calculated. Survey analysis procedures with the survey weights were performed. RESULTS: Across adulthood, maximal overweight, nonobese to obese, and stable obesity were consistently associated with higher PhenoAgeAccel. For instance, from young to middle adulthood, compared with participants who had stable normal weight, participants experiencing maximal overweight, moving from the nonobese to obese, and maintaining obesity had 1.71 (standard error [SE], 0.21; P < 0.001), 3.62 (SE, 0.28; P < 0.001), and 6.61 (SE, 0.58; P < 0.001) higher PhenoAgeAccel values, respectively. From young to middle adulthood, relative to absolute weight loss or gain of <2.5 kg, weight loss of ≥2.5 kg was marginally associated with lower PhenoAgeAccel (P = 0.054), whereas an obese to nonobese pattern from middle to late adulthood was associated with higher PhenoAgeAccel (P < 0.001). CONCLUSIONS: Maximal overweight, nonobese to obese, and stable obesity across adulthood, as well as an obese to nonobese pattern from middle to late adulthood, were associated with accelerated biological aging. In contrast, weight loss from young to middle adulthood was associated with decelerated biological aging. The findings highlight the potential role of weight management across adulthood for aging. Monitoring weight fluctuation may help identify the population at high risk of accelerated aging.

Association of Sarcopenia with Cognitive Function and Dementia Risk Score: A National Prospective Cohort Study.

The relationship between skeletal muscle and cognitive disorders has drawn increasing attention. This study aims to examine the associations of sarcopenia with cognitive function and dementia risk score. Data on 1978 participants (aged 65 years and older) from the 2011 wave of the China Health and Retirement Longitudinal Study, with four follow-up waves to 2018, were used. Cognitive function was assessed by four dimensions, with a lower score indicating lower cognitive function. Dementia risk was assessed by a risk score using the Rotterdam Study Basic Dementia Risk Model (BDRM), with a higher score indicating a greater risk. Sarcopenia was defined when low muscle mass plus low muscle strength or low physical performance were met. We used generalized estimating equations to examine the associations of sarcopenia. In the fully adjusted models, sarcopenia was significantly associated with lower cognitive function (standardized, ß = -0.15; 95% CIs: -0.26, -0.04) and a higher BDRM score (standardized, ß = 0.42; 95% CIs: 0.29, 0.55). Our findings may provide a new avenue for alleviating the burden of cognitive disorders by preventing sarcopenia.

Association of childhood adversity with frailty and the mediating role of unhealthy lifestyle: Findings from the UK biobank.

Background: Childhood adversity and lifestyle have been associated with frailty in later life, but not much is known about factors that may explain these associations. An unhealthy lifestyle may play an important role in the pathway from childhood adversity to frailty. Therefore, this study aims to investigate the association of childhood adversity with frailty, and the mediating role of unhealthy lifestyle in the association. Methods: This lifespan analysis included 152914 adults aged 40-69 years old from the UK Biobank. We measured childhood adversity with five items: physical neglect, emotional neglect, sexual abuse, physical abuse, and emotional abuse through online mental health survey. Frailty was measured by the frailty index; an unhealthy lifestyle score (range: 0-5) was calculated based on unhealthy body mass index, smoking, drinking, physical inactivity, and unhealthy diet at the baseline survey. Multiple logistic regression and mediation analysis were performed. Results: A total of 10078 participants (6.6%) were defined as having frailty. Participants with any childhood adversity had higher odds of frailty. For example, in the fully adjusted model, with a one-point increase in cumulative score of childhood adversity, the odds of frailty increased by 41% (Odds Ratio: 1.41; 95% Confidence Interval: 1.39, 1.44). Unhealthy lifestyle partially mediated the associations of childhood adversity with frailty (mediation proportion: 4.4%-7.0%). The mediation proportions were largest for physical (8.2%) and sexual (8.1%) abuse. Conclusions: Among this large sample, childhood adversity was positively associated with frailty, and unhealthy lifestyle partially mediated the association. This newly identified pathway highlights the potential of lifestyle intervention strategies among those who experienced childhood adversity (in particular, physical and sexual abuse) to promote healthy aging.

Association of frailty with the incidence risk of cardiovascular disease and type 2 diabetes mellitus in long-term cancer survivors: a prospective cohort study.

BACKGROUND: Comorbidities among cancer survivors remain a serious healthcare burden and require appropriate management. Using two widely used frailty indicators, this study aimed to evaluate whether frailty was associated with the incidence risk of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) among long-term cancer survivors. METHODS: We included 13,388 long-term cancer survivors (diagnosed with cancer over 5 years before enrolment) free of CVD and 6101 long-term cancer survivors free of T2DM, at the time of recruitment (aged 40-69 years), from the UK Biobank. Frailty was assessed by the frailty phenotype (FP_Frailty, range: 0-5) and the frailty index (FI_Frailty, range: 0-1) at baseline. The incident CVD and T2DM were ascertained through linked hospital data and primary care data, respectively. The associations were examined using Cox proportional hazards regression models. RESULTS: Compared with non-frail participants, those with pre-frailty (FP_Frailty [met 1-2 of the components]: hazard ratio [HR]=1.18, 95% confidence interval [CI]: 1.05, 1.32; FI_Frailty [0.10< FI ≤0.21]: HR=1.51, 95% CI: 1.32, 1.74) and frailty (FP_Frailty [met ≥3 of the components]: HR=2.12, 95% CI: 1.73, 2.60; FI_Frailty [FI >0.21]: HR=2.19, 95% CI: 1.85, 2.59) had a significantly higher risk of CVD in the multivariable-adjusted model. A similar association of FI_Frailty with the risk of incident T2DM was observed. We failed to find such an association for FP_Frailty. Notably, the very early stage of frailty (1 for FP_Frailty and 0.1-0.2 for FI_Frailty) was also positively associated with the risk of CVD and T2DM (FI_Frailty only). A series of sensitivity analyses confirmed the robustness of the findings. CONCLUSIONS: Frailty, even in the very early stage, was positively associated with the incidence risk of CVD and T2DM among long-term cancer survivors, although discrepancies existed between frailty indicators. While the validation of these findings is required, they suggest that routine monitoring, prevention, and interventive programs of frailty among cancer survivors may help to prevent late comorbidities and, eventually, improve their quality of life. Especially, interventions are recommended to target those at an early stage of frailty when healthcare resources are limited.

Association of spouse's health status with the onset of depressive symptoms in partner: Evidence from the China Health and Retirement Longitudinal Study.

BACKGROUND: This study aimed to evaluate the associations between the multidimensional health status of one spouse and the onset of depressive symptoms in partner, and whether the associations differed by gender and residence. METHODS: We analyzed data from 2401 females and their husbands (scenario 1), and 2830 males and their wives (scenario 2) who participated in the 2011/2012 and 2015 waves of China Health and Retirement Longitudinal Study. Depressive symptoms were assessed using the 10-item Centre for Epidemiological Studies Depression Scale. Multidimensional health indicators included mobility disability, activities of daily living disability, frailty, global cognition, depressive symptoms, comorbidity, and self-reported health. Principal component analysis was used to construct a composite health indicator reflecting overall health status that was then categorized into three groups (poor, moderate, and excellent). Logistic regression models were performed. RESULTS: We observed strong associations of spouse's health status with the onset of depressive symptoms in partner. For instance, females whose husbands had poor overall health status reported more depressive symptoms than those having husbands with excellent overall health after four years (OR: 1.75; 95 % CI: 1.35, 2.26). These associations were statistically significant in rural females and urban males, but surprisingly disappeared in rural males and urban females. LIMITATIONS: No exact timing of depressive symptoms onset. CONCLUSIONS: In Chinese middle-aged and older adults, spouse's health status is associated with depressive symptoms in partner and the associations vary by gender and residence. The findings underscore the importance of considering partner's health status to manage one spouse's mental health.

Transition of cooking fuel types and mortality risk in China, 1991-2015.

BACKGROUND: The decision for household cooking fuel choice is a complex and multi-dimensional process. This study aims to: 1) examine the trend of cooking fuel types during past decades; and 2) examine the association between switching from polluting to clean fuels for cooking and mortality risk. METHODS: This analysis included data on 39,359 participants from 9 waves of the China Health and Nutrition Survey (CHNS) (1991-2015). Participants with consistent polluting fuel use and with the polluting-to-clean transition were identified. Generalized estimating equations were used to examine the trend of clean fuel use from 1991 to 2015. Propensity score matching was used to address the data imbalance and confounding factors and Cox proportional hazards models were used to estimate the association. RESULTS: We found an increasing trend of clean fuel use after adjusting for potential confounders in the full sample (OR = 56.89, 95 % CI: 48.17, 67.19), which appeared to be more pronounced for those in rural areas and with low socioeconomic status. Switching from polluting to clean fuels was associated with a 75 % lower risk of mortality (HR = 0.25, 95 % CI: 0.11, 0.54). These associations became more pronounced during the lag period from 9 to 15 years. CONCLUSIONS: The transition from polluting to clean cooking fuels reduced excess deaths in China, particularly over a long period. Our findings support the increasing implementation of clean fuels and call for more efforts to improve its universal service, especially in rural and low socioeconomic status areas, to minimize health inequality.

Association of solid fuel use with a risk score capturing dementia risk among middle-aged and older adults: A prospective cohort study.

OBJECTIVES: Whether household air pollution is associated with dementia risk remains unknown. This study examined the associations between solid fuel use for cooking and heating (the main source of household air pollution) and dementia risk. METHODS: This analysis included data on 11,352 participants (aged 45+ years) from the 2011 wave of China Health and Retirement Longitudinal Study, with follow-up to 2018. Dementia risk was assessed by a risk score using the Rotterdam Study Basic Dementia Risk Model (BDRM), which was subsequently standardized for analysis. Household fuel types of cooking and heating were categorized as solid (e.g., coal and crop residue) and clean (e.g., central heating and solar). Multivariable analyses were performed using generalized estimating equations. Moreover, we examined the joint associations of solid fuel use for cooking and heating with the BDRM score. RESULTS: After adjusting for potential confounders, we found an independent and significant association of solid (vs. clean) fuel use for cooking and heating with a higher BDRM score (e.g., ß = 0.17 for solid fuel for cooking; 95% confidence interval [CI]: 0.15-0.19). Participants who used solid (vs. clean) fuel for both cooking and heating had the highest BDRM score (ß = 0.32; 95% CI: 0.29-0.36). Subgroup analysis suggested stronger associations in participants living in rural areas. CONCLUSIONS: Solid fuel use for cooking and heating was independently associated with increased dementia risk in Chinese middle-aged and older adults, particularly among those living in rural areas. Our findings call for more efforts to facilitate universal access to clean energy for dementia prevention.