Positive affect during adolescence and health and well-being in adulthood: An outcome-wide longitudinal approach.

BACKGROUND: Several intergovernmental organizations, including the World Health Organization and United Nations, are urging countries to use well-being indicators for policymaking. This trend, coupled with increasing recognition that positive affect is beneficial for health/well-being, opens new avenues for intervening on positive affect to improve outcomes. However, it remains unclear if positive affect in adolescence shapes health/well-being in adulthood. We examined if increases in positive affect during adolescence were associated with better health/well-being in adulthood across 41 outcomes. METHODS AND FINDINGS: We conducted a longitudinal cohort study using data from Add Health-a prospective and nationally representative cohort of community-dwelling U.S. adolescents. Using regression models, we evaluated if increases in positive affect over 1 year (between Wave I; 1994 to 1995 and Wave II; 1995 to 1996) were associated with better health/well-being 11.37 years later (in Wave IV; 2008; N = 11,040) or 20.64 years later (in Wave V; 2016 to 2018; N = 9,003). Participants were aged 15.28 years at study onset, and aged 28.17 or 37.20 years-during the final assessment. Participants with the highest (versus lowest) positive affect had better outcomes on 3 (of 13) physical health outcomes (e.g., higher cognition (ß = 0·12, 95% CI = 0·05, 0·19, p = 0.002)), 3 (of 9) health behavior outcomes (e.g., lower physical inactivity (RR = 0·80, CI = 0·66, 0·98, p = 0.029)), 6 (of 7) mental health outcomes (e.g., lower anxiety (RR = 0·81, CI = 0·71, 0·93, p = 0.003)), 2 (of 3) psychological well-being (e.g., higher optimism (ß = 0·20, 95% CI = 0·12, 0·28, p < 0.001)), 4 (of 7) social outcomes (e.g., lower loneliness (ß = -0·09, 95% CI = -0·16, -0·02, p = 0.015)), and 1 (of 2) civic/prosocial outcomes (e.g., more voting (RR = 1·25, 95% CI = 1·16, 1·36, p < 0.001)). Study limitations include potential unmeasured confounding and reverse causality. CONCLUSIONS: Enhanced positive affect during adolescence is linked with a range of improved health/well-being outcomes in adulthood. These findings suggest the promise of testing scalable positive affect interventions and policies to more definitively assess their impact on outcomes.

Childhood maltreatment and health in the UK Biobank: triangulation of outcome-wide and polygenic risk score analyses.

BACKGROUND: Childhood maltreatment is common globally and impacts morbidity, mortality, and well-being. Our understanding of its impact is constrained by key substantive and methodological limitations of extant research, including understudied physical health outcomes and bias due to unmeasured confounding. We address these limitations through a large-scale outcome-wide triangulation study. METHODS: We performed two outcome-wide analyses (OWAs) in the UK Biobank. First, we examined the relationship between self-reported maltreatment exposure (number of maltreatment types, via Childhood Trauma Screener) and 414 outcomes in a sub-sample of 157,316 individuals using generalized linear models ("observational OWA"). Outcomes covered a broad range of health themes including health behaviors, cardiovascular disease, digestive health, socioeconomic status, and pain. Second, we examined the relationship between a polygenic risk score for maltreatment and 298 outcomes in a non-overlapping sample of 243,006 individuals ("genetic OWA"). We triangulated results across OWAs based on differing sources of bias. RESULTS: Overall, 23.8% of the analytic sample for the observational OWA reported at least one maltreatment type. Of 298 outcomes examined in both OWAs, 25% were significant in both OWAs and concordant in the direction of association. Most of these were considered robust in the observational OWA according to sensitivity analyses and included outcomes such as marital separation (OR from observational OWA, ORo = 1.25 (95% CI: 1.21, 1.29); OR from genetic OWA, ORg = 1.06 (1.03, 1.08)), major diet changes due to illness (ORo = 1.27 (1.24, 1.29); ORg = 1.01 (1.00, 1.03)), certain intestinal diseases (ORo = 1.14 (1.10, 1.18); ORg = 1.03 (1.01, 1.06)), hearing difficulty with background noise (ORo = 1.11 (1.11, 1.12); ORg = 1.01 (1.00, 1.01)), knee arthrosis (ORo = 1.13 (1.09, 1.18); ORg = 1.03 (1.01, 1.05)), frequent sleeplessness (ORo = 1.21 (1.20, 1.23); ORg = 1.02 (1.01, 1.03)), and low household income (ORo = 1.28 (1.26, 1.31); ORg = 1.02 (1.01, 1.03)). Approximately 62% of results were significant in the observational OWA but not the genetic OWA, including numerous cardiovascular outcomes. Only 6 outcomes were significant in the genetic OWA and null in the observational OWA; these included diastolic blood pressure and glaucoma. No outcomes were statistically significant in opposite directions in the two analyses, and 11% were not significant in either OWA. CONCLUSIONS: Our findings underscore the far-reaching negative effects of childhood maltreatment in later life and the utility of an outcome-wide triangulation design with sensitivity analyses for improving causal inference.

The silent epidemic of loneliness: identifying the antecedents of loneliness using a lagged exposure-wide approach.

BACKGROUND: A large and accumulating body of evidence shows that loneliness is detrimental for various health and well-being outcomes. However, less is known about potentially modifiable factors that lead to decreased loneliness. METHODS: We used data from the Health and Retirement Study to prospectively evaluate a wide array of candidate predictors of subsequent loneliness. Importantly, we examined if changes in 69 physical-, behavioral-, and psychosocial-health factors (from t0;2006/2008 to t1;2010/2012) were associated with subsequent loneliness 4 years later (t2;2014/2016). RESULTS: Adjusting for a large range of covariates, changes in certain health behaviors (e.g. increased physical activity), physical health factors (e.g. fewer functioning limitations), psychological factors (e.g. increased purpose in life, decreased depression), and social factors (e.g. greater number of close friends) were associated with less subsequent loneliness. CONCLUSIONS: Our findings suggest that subjective ratings of physical and psychological health and perceived social environment (e.g. chronic pain, self-rated health, purpose in life, anxiety, neighborhood cohesion) are more strongly associated with subsequent loneliness. Yet, objective ratings (e.g. specific chronic health conditions, living status) show less evidence of associations with subsequent loneliness. The current study identified potentially modifiable predictors of subsequent loneliness that may be important targets for interventions aimed at reducing loneliness.

Effects of Screen-Based Leisure Time on 24 Subsequent Health and Wellbeing Outcomes: A Longitudinal Outcome-Wide Analysis.

BACKGROUND: Previous research has shown that screen-based leisure time is related to physical and mental health, relationships, and prosocial behaviors. However, it remains unclear whether screen-based leisure time causally affects wellbeing, as previous studies have relied on cross-sectional data, focused on one type of media use (e.g., social media, video games, or internet), or assessed a narrow set of outcomes. METHOD: We used three waves (2016, 2017, 2019) of national longitudinal data from the New Zealand Attitudes and Values Study to investigate the effects of screen-based leisure time on 24 parameters of wellbeing (n = 11,085). We operationalized screen-based leisure as the sum of time spent browsing the internet, using social media, watching/reading the news, watching videos, and playing video games. We followed the outcome-wide analytic design for observational data by performing a series of multivariable regression models estimating the effect of screen-based leisure time on 24 wellbeing outcomes and assessed potential unmeasured confounding using sensitivity analyses. RESULTS: In our primary analysis with the total sample, total screen-based leisure time was associated with a very modest decrease in body satisfaction and a very modest increase in body mass index. Possible evidence of associations was found with increases in number of hours spent exercising and volunteering each week, as well as decreases in number of average daily hours of sleep, self-control, and subjective health. CONCLUSION: Screen-based leisure time has the potential to affect health and wellbeing. Results are discussed in light of the high prevalence of screen-based leisure time.

Longitudinal associations of spousal support and strain with health and well-being: An outcome-wide study of married older U.S. Adults.

In the present study, we examined the prospective associations of both spousal support and spousal strain with a wide range of health and well-being outcomes in married older adults. Applying the analytic template for outcome-wide designs, three waves of longitudinal data from the Health and Retirement Study (n = 7788, Mage = 64.2 years) were analyzed using linear regression, logistic regression, and generalized linear models. A set of models was performed for spousal support and another set of models for spousal strain (2010/2012, t1). Outcomes included 35 different aspects of physical health, health behaviors, psychological well-being, psychological distress, and social factors (2014/2016, t2). All models adjusted for pre-baseline levels of sociodemographic covariates and all outcomes (2006/2008, t0). Spousal support evidenced positive associations with five psychological well-being outcomes, as well as negative associations with five psychological distress outcomes and loneliness. Conversely, spousal strain evidenced negative associations with three psychological well-being outcomes, in addition to positive associations with three psychological distress outcomes and loneliness. The magnitude of these associations was generally small, although some effect estimates were somewhat larger. Associations of both spousal support and strain with other social and health-related outcomes were more negligible. Both support and strain within a marital relationship have the potential to impact various aspects of psychological well-being, psychological distress, and loneliness in the aging population.

Connected communities: Perceived neighborhood social cohesion during adolescence and subsequent health and well-being in young adulthood-An outcome-wide longitudinal approach.

Does higher perceived neighborhood social cohesion in adolescence lead to better health and well-being 10-12 years later? We evaluated this question using data from a large, prospective, and nationally representative sample of US adolescents (Add Health; N = 10,963), and an outcome-wide approach. Across 38 outcomes, perceived neighborhood social cohesion was associated with some: mental health outcomes (i.e., depressive symptoms, suicidal ideation, perceived stress), psychological well-being outcomes (i.e., happiness, optimism), social outcomes (i.e., loneliness, romantic relationship quality, satisfaction with parenting), and civic/prosocial outcomes (i.e., volunteering). However, it was not associated with health behaviors nor physical health outcomes. These results were maintained after robust control for a wide range of potential confounders.

Associations of online religious participation during COVID-19 lockdown with subsequent health and well-being among UK adults.

BACKGROUND: In-person religious service attendance has been linked to favorable health and well-being outcomes. However, little research has examined whether online religious participation improves these outcomes, especially when in-person attendance is suspended. METHODS: Using longitudinal data of 8951 UK adults, this study prospectively examined the association between frequency of online religious participation during the stringent lockdown in the UK (23 March -13 May 2020) and 21 indicators of psychological well-being, social well-being, pro-social/altruistic behaviors, psychological distress, and health behaviors. All analyses adjusted for baseline socio-demographic characteristics, pre-pandemic in-person religious service attendance, and prior values of the outcome variables whenever data were available. Bonferroni correction was used to correct for multiple testing. RESULTS: Individuals with online religious participation of ≥1/week (v. those with no participation at all) during the lockdown had a lower prevalence of thoughts of self-harm in week 20 (odds ratio 0.24; 95% CI 0.09-0.62). Online religious participation of <1/week (v. no participation) was associated with higher life satisfaction (standardized ß = 0.25; 0.11-0.39) and happiness (standardized ß = 0.25; 0.08-0.42). However, there was little evidence for the associations between online religious participation and all other outcomes (e.g. depressive symptoms and anxiety). CONCLUSIONS: There was evidence that online religious participation during the lockdown was associated with some subsequent health and well-being outcomes. Future studies should examine mechanisms underlying the inconsistent results for online v. in-person religious service attendance and also use data from non-pandemic situations.

Who Benefits From Helping? Moderators of the Association Between Informal Helping and Mortality.

BACKGROUND: While informal helping has been linked to a reduced risk of mortality, it remains unclear if this association persists across different levels of key social structural moderators. PURPOSE: To examine whether the longitudinal association between informal helping and all-cause mortality differs by specific social structural moderators (including age, gender, race/ethnicity, wealth, income, and education) in a large, prospective, national, and diverse sample of older U.S. adults. METHODS: We analyzed data from the Health and Retirement Study, a national sample of U.S. adults aged >50 (N = 9,662). Using multivariable Poisson regression, we assessed effect modification by six social structural moderators (age, gender, race/ethnicity, wealth, income, and education) for the informal helping (2006/2008) to mortality (2010-2016/2012-2018) association on the additive and multiplicative scales. RESULTS: Participants who reported ≥100 hr/year of informal helping (vs. 0 hr/year), had a lower mortality risk. Those who engaged in 1-49 hr/year most consistently displayed lower mortality risk across moderators, while those who engaged in 50-99 and ≥100 hr/year only showed decreased mortality risk across some moderators. When formally testing effect modification, there was evidence that the informal helping-mortality associations were stronger among women and the wealthiest. CONCLUSIONS: Informal helping is associated with decreased mortality. Yet, there appear to be key differences in who benefits from higher amounts of informal helping across social structural moderators. Further research is needed to evaluate how the associations between informal helping and health and well-being are patterned across key social structural moderators.

Informal helping has been associated with a decreased mortality risk, but it remains unclear if this association persists across different levels of key social structural moderators. We examined whether the longitudinal association between informal helping and all-cause mortality differs across age, gender, race/ethnicity, wealth, income, and education, in a large sample of older U.S. adults from the Health and Retirement Study (N = 9,662). Participants who reported ≥100 hr/year of informal helping (vs. 0 hr/year), had a lower mortality risk. Those who engaged in 1­49 hr/year most consistently displayed lower mortality risk across moderators, while those who engaged in 50­99 and ≥100 hr/year only showed decreased mortality risk across some moderators. There was evidence that the informal helping­mortality associations were stronger among women and the wealthiest when testing effect modification. While informal helping was associated with decreased mortality, there appear to be key differences in who benefits from higher amounts of informal helping across social structural moderators. Further research is needed to evaluate how the associations between informal helping and health and well-being differ across important social structural factors.

Effect of religious service attendance on mortality and hospitalisations among Danish men and women: longitudinal findings from REGLINK-SHAREDK.

Research suggests a protective effect of religious service attendance on various health outcomes. However, most research has been done in religious societies, raising the question of whether these associations are also prominent in secular cultures. Here we examine mortality and hospitalisations by religious service attendance among men and women in a secular society. We performed a cohort study including 2987 Danes aged 40+ interviewed in SHARE from 2004 to 2007 and followed up in the Danish registries until 2018. We used Cox regressions and negative binomial regressions to examine associations, including interactions with sex and adjusting for age, wave, socioeconomic factors, lifestyle factors, body mass index, and history of diseases. Overall, 5.0% of men and 6.6% of women reported that they had taken part in a religious organisation within the last month. Among 848 deaths, we found lower mortality for people who attended religious services (hazard ratio (HR) 0.70; 95% CI 0.50-0.99). There was evidence for an association among women (HR 0.56; 95% CI 0.35-0.89), but not among men (HR 0.95; 95% CI 0.59-1.53). In contrast, regarding hospital admissions (n = 12,010), we found lower hospitalisation rates among men who attended religious services (incidence rate ratio (IRR) 0.67; 95% CI 0.45-0.98), whereas no association was found among women (IRR 0.95; 95% CI 0.70-1.29). Sensitivity analyses with E-values were moderately robust. Our results contribute to the limited literature on possible health benefits of religious service attendance in secular societies, demonstrating lower mortality among women and fewer hospitalisations among men.

Prospective associations between strengths of moral character and health: longitudinal evidence from survey and insurance claims data.

PURPOSE: Excellent character, reflected in adherence to high standards of moral behavior, has been argued to contribute to well-being. The study goes beyond this claim and provides insights into the role of strengths of moral character (SMC) for physical and mental health. METHODS: This study used longitudinal observational data merged with medical insurance claims data collected from 1209 working adults of a large services organization in the US. Self-reported physical and mental health as well as diagnostic information on depression, anxiety, and cardiovascular disease were used as outcomes. The prospective associations between SMC (7 indicators and a composite measure) and physical and mental health outcomes were examined using lagged linear and logistic regression models. A series of sensitivity analyses provided evidence for the robustness of results. RESULTS: The results suggest that persons who live their life according to high moral standards have substantially lower odds of depression (by 21-51%). The results were also indicative of positive associations between SMC and self-reports of mental health (ß = 0.048-0.118) and physical health (ß = 0.048-0.096). Weaker indications were found for a protective role of SMC in mitigating anxiety (OR = 0.797 for the indicator of delayed gratification) and cardiovascular disease (OR = 0.389 for the indicator of use of SMC for helping others). CONCLUSIONS: SMC may be considered relevant for population mental health and physical health. Public health policies promoting SMC are likely to receive positive reception from the general public because character is both malleable and aligned with the nearly universal human desire to become a better person.

Informal Helping and Subsequent Health and Well-Being in Older U.S. Adults.

BACKGROUND: Growing evidence suggests that informal helping (unpaid volunteering not coordinated by an organization or institution) is associated with improved health and well-being outcomes. However, studies have not investigated whether changes in informal helping are associated with subsequent health and well-being. METHODS: This study evaluated if changes in informal helping (between t0;2006/2008 and t1;2010/2012) were associated with 35 indicators of physical, behavioral, and psychosocial health and well-being (at t2;2014/2016) using data from 12,998 participants in the Health and Retirement study - a national cohort of US adults aged > 50. RESULTS: Over the four-year follow-up period, informal helping ≥ 100 (versus 0) hours/year was associated with a 32% lower mortality risk (95% CI [0.54, 0.86]), and improved physical health (e.g., 20% reduced risk of stroke (95% CI [0.65, 0.98])), health behaviors (e.g., 11% increased likelihood of frequent physical activity (95% CI [1.04, 1.20])), and psychosocial outcomes (e.g., higher purpose in life (ß = 0.15, 95% CI [0.07, 0.22])). However, there was little evidence of associations with various other outcomes. In secondary analyses, this study adjusted for formal volunteering and a variety of social factors (e.g., social network factors, receiving social support, and social participation) and results were largely unchanged. CONCLUSIONS: Encouraging informal helping may improve various aspects of individuals' health and well-being and also promote societal well-being.

The Mental Illness-Health Matrix and the Mental State Space Matrix: Complementary meta-conceptual frameworks for evaluating psychological states.

OBJECTIVE: It is increasingly appreciated that mental health may not just involve a relative absence of mental illness, but the active presence of positive psychological desiderata. However, research attention on mental illness and health has tended to remain siloed and disconnected-proceeding along parallel tracks-with their potential relationship underexplored and undertheorized. As such, we sought to develop theoretical models to help us better understand the interaction of these two domains of experience. METHODS: Through extensive engagement with relevant literature, we created two complementary meta-conceptual frameworks to represent and evaluate states of mental illness and health. RESULTS: The Mental Illness-Health Matrix allows different forms of mental illness and health to be situated and assessed within a common framework. The Mental State Space Matrix further enables these various forms to be conceptualized and appraised in terms of numerous common parameters (e.g., valence and arousal). CONCLUSION: It is hoped that these frameworks will stimulate and support further research on the inter-relational dynamics of illness and health. Indeed, the matrices themselves are provisional works-in-progress, with their articulation here intended as a foundation for their further development as understanding of these topics evolves and improves.

Invited Commentary: Religious Service Attendance and Implications for Clinical Care, Community Participation, and Public Health.

In this commentary, we review the evidence concerning associations between religious service attendance and subsequent health and wellbeing outcomes. The evidence base for a link between religious service attendance and health has increased substantially over the past 2 decades. The interpretation and implications of this research require careful consideration (Am J Epidemiol. 2022;191(1):20-30). It would be inappropriate to universally promote service attendance solely on the grounds of the associations with health. Nevertheless, a more nuanced approach, within both clinical care and public health, may be possible-one that encouraged participation in religious community for those who already positively self-identified with a religious or spiritual tradition and encouraged other forms of community participation for those who did not. Discussion is given to potential future research directions and the challenges and opportunities for promotion efforts by the public health community.

Methods to Address Confounding and Other Biases in Meta-Analyses: Review and Recommendations.

Meta-analyses contribute critically to cumulative science, but they can produce misleading conclusions if their constituent primary studies are biased, for example by unmeasured confounding in nonrandomized studies. We provide practical guidance on how meta-analysts can address confounding and other biases that affect studies' internal validity, focusing primarily on sensitivity analyses that help quantify how biased the meta-analysis estimates might be. We review a number of sensitivity analysis methods to do so, especially recent developments that are straightforward to implement and interpret and that use somewhat less stringent statistical assumptions than do earlier methods. We give recommendations for how these newer methods could be applied in practice and illustrate using a previously published meta-analysis. Sensitivity analyses can provide informative quantitative summaries of evidence strength, and we suggest reporting them routinely in meta-analyses of potentially biased studies. This recommendation in no way diminishes the importance of defining study eligibility criteria that reduce bias and of characterizing studies' risks of bias qualitatively.

Constructed Measures and Causal Inference: Towards a New Model of Measurement for Psychosocial Constructs.

Psychosocial constructs can only be assessed indirectly, and measures are typically formed by a combination of indicators that are thought to relate to the construct. Reflective and formative measurement models offer different conceptualizations of the relation between the indicators and what is sometimes conceived of as a univariate latent variable supposed to correspond in some way to the construct. I argue that the empirical implications of reflective and formative models will often be violated by data since the causally relevant constituents will generally be multivariate, not univariate. These empirical implications can be formally tested but factor analysis is not adequate to do so. I argue that formative models misconstrue the relation between the constructed measures and the underlying reality by which causal processes operate, but that reflective models misconstrue the nature of the underlying reality itself by typically presuming that the constituents of it that are causally efficacious are unidimensional. I discuss the ensuing problems arising from these misconstruals. I propose a causal interpretation of associations between constructed measures and various outcomes that is applicable to both reflective and formative models and is applicable even if the usual assumptions of these models are violated. I put forward an outline for a new model of the process of measure construction and discuss the practical implications of these observations and proposals for the provision of definitions, the selection of items, item-by-item analyses, the construction of measures, and the interpretation of the associations of these measures with subsequent outcomes.

Purpose in life and 8-year mortality by gender and race/ethnicity among older adults in the U.S.

We examined the associations between a sense of purpose and all-cause mortality by gender and race/ethnicity groups. Data were from the Health and Retirement Study, a nationally representative cohort study of U.S. adults aged >50 (n = 13,159). Sense of purpose was self-reported at baseline (2006/2008), and risk of all-cause mortality was assessed over an 8-year follow-up period. We also formally tested for potential effect modification by gender and race/ethnicity. We observed the associations between higher purpose and lower all-cause mortality risk across all gender and race/ethnicity groups. There was modest evidence that the highest level of purpose (versus lowest quartile) was associated with even lower risk of all-cause mortality among women (risk ratio = 0.66, 95% confidence interval: 0.56, 0.77) compared to men (risk ratio = 0.80, 95% confidence interval: 0.69, 0.93; p-value for multiplicative effect modification =0.07). However, we observed no evidence of effect modification by race/ethnicity. Having a higher sense of purpose appears protective against all-cause mortality regardless of gender and race/ethnicity. Purpose, a potentially modifiable factor, might be a health asset across diverse populations.

A statistical test to reject the structural interpretation of a latent factor model.

Factor analysis is often used to assess whether a single univariate latent variable is sufficient to explain most of the covariance among a set of indicators for some underlying construct. When evidence suggests that a single factor is adequate, research often proceeds by using a univariate summary of the indicators in subsequent research. Implicit in such practices is the assumption that it is the underlying latent, rather than the indicators, that is causally efficacious. The assumption that the indicators do not have effects on anything subsequent, and that they are themselves only affected by antecedents through the underlying latent is a strong assumption, effectively imposing a structural interpretation on the latent factor model. In this paper, we show that this structural assumption has empirically testable implications, even though the latent variable itself is unobserved. We develop a statistical test to potentially reject the structural interpretation of a latent factor model. We apply this test to data concerning associations between the Satisfaction-with-Life-Scale and subsequent all-cause mortality, which provides strong evidence against a structural interpretation for a univariate latent underlying the scale. Discussion is given to the implications of this result for the development, evaluation, and use of measures, and for the use of factor analysis itself.

APOE ε4 and late-life cognition: mediation by structural brain imaging markers.

The apolipoprotein E allele 4 (APOE-ε4) is established as a major genetic risk factor for cognitive decline and late-onset Alzheimer's disease. Accumulating evidence has linked ε4 carriership to abnormal structural brain changes across the adult lifespan. To better understand the underlying causal mechanisms, we investigated the extent to which the effect of the ε4 allele on cognition is mediated by structural brain imaging markers in the population-based Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-Reykjavik). This study included 4527 participants (aged 76.3 ± 5.4 at baseline) who underwent the brain magnetic resonance imaging assessment (of brain tissue volumes, white matter lesion volume, subcortical and cortical infarcts, and cerebral microbleeds) and a battery of neuropsychological tests at baseline. Causal mediation analysis was used to quantify the mediation of the ε4 effect on cognition by these MRI markers, both individually and jointly. We observed that about 9% of the total effect of ε4 carriership on cognition was mediated by white matter lesion volume. This proportion increased to 25% when total brain tissue volume was jointly considered with white matter lesion volume. In analyses separating ε4 homozygotes from ε4 heterozygotes, the effect on global cognition of specifically ε4 homozygosity appeared to be partially mediated by cerebral microbleeds, particularly lobar microbleeds. There was no evidence of mediation of the ε4 effect by cortical or subcortical infarcts. This study shows that the ε4 effect on cognition is partly mediated by white matter lesion volume and total brain tissue volume. These findings suggest the joint role of cerebral small vessel disease and neurodegeneration in the ε4-cognition relationship.

Are all domains of life satisfaction equal? Differential associations with health and well-being in older adults.

PURPOSE: Growing evidence documents strong associations between overall life satisfaction and favorable health and well-being outcomes. However, because most previous studies have assessed satisfaction with one's life as a whole, we know little about whether specific domains of life satisfaction (e.g., satisfaction with family life, income) might be responsible for longitudinally driving better health and well-being. METHODS: Data were from 13,752 participants in the Health and Retirement Study-a prospective and nationally representative cohort of US adults aged > 50. We evaluated if positive changes in seven individual domains of life satisfaction (between t0; 2008/2010 and t1; 2012/2014) were associated with 35 indicators of physical, behavioral, and psychosocial health and well-being (at t2; 2016/2018). RESULTS: Most domains of life satisfaction were associated with psychological outcomes: satisfaction with family and non-work activities showed the largest associations (sometimes double in magnitude) with subsequent psychological factors, followed by satisfaction with financial situation and income. Further, some domains showed associations with specific physical health outcomes (e.g., mortality, number of chronic conditions, physical functioning limitations), health behaviors (e.g., sleep problems), and social factors (e.g., loneliness). CONCLUSIONS: As countries seek innovative and cost-effective methods of enhancing the health and well-being of our rapidly aging populations, findings from our study suggest that some domains of life satisfaction have a substantially larger influence on health and well-being outcomes than others. Individual domains of life satisfaction might be novel targets for interventions and policies seeking to enhance specific facets of health and well-being.

Timing and severity of COVID-19 during pregnancy and risk of preterm birth in the International Registry of Coronavirus Exposure in Pregnancy.

BACKGROUND: Studies of preterm delivery after COVID-19 are often subject to selection bias and do not distinguish between early vs. late infection in pregnancy, nor between spontaneous vs. medically indicated preterm delivery. This study aimed to estimate the risk of preterm birth (overall, spontaneous, and indicated) after COVID-19 during pregnancy, while considering different levels of disease severity and timing. METHODS: Pregnant and recently pregnant people who were tested for or clinically diagnosed with COVID-19 during pregnancy enrolled in an international internet-based cohort study between June 2020 and July 2021. We used several analytic approaches to minimize confounding and immortal time bias, including multivariable regression, time-to-delivery models, and a case-time-control design. RESULTS: Among 14,264 eligible participants from 70 countries who did not report a pregnancy loss before 20 gestational weeks, 5893 had completed their pregnancies and reported delivery information; others were censored at time of their last follow-up. Participants with symptomatic COVID-19 before 20 weeks' gestation had no increased risk of preterm delivery compared to those testing negative, with adjusted risks of 10.0% (95% CI 7.8, 12.0) vs. 9.8% (9.1, 10.5). Mild COVID-19 later in pregnancy was not clearly associated with preterm delivery. In contrast, severe COVID-19 after 20 weeks' gestation led to an increase in preterm delivery compared to milder disease. For example, the risk ratio for preterm delivery comparing severe to mild/moderate COVID-19 at 35 weeks was 2.8 (2.0, 4.0); corresponding risk ratios for indicated and spontaneous preterm delivery were 3.7 (2.0, 7.0) and 2.3 (1.2, 3.9), respectively. CONCLUSIONS: Severe COVID-19 late in pregnancy sharply increased the risk of preterm delivery compared to no COVID-19. This elevated risk was primarily due to an increase in medically indicated preterm deliveries, included preterm cesarean sections, although an increase in spontaneous preterm delivery was also observed. In contrast, mild or moderate COVID-19 conferred minimal risk, as did severe disease early in pregnancy.