A Critique and Examination of the Polysocial Risk Score Approach: Predicting Cognition in the Health and Retirement Study.

Polysocial risk scores were recently proposed as a strategy to improve clinical relevance of knowledge about social determinants of health. The objective of this paper was to assess if the polysocial risk score model improves prediction of cognition and all-cause mortality in middle-aged and older adults beyond simpler models including a smaller set of key social determinants of health. We used a sample of 13,773 individuals aged 50+ at baseline from the 2006 to 2018 waves of the Health and Retirement Study, a US population-based longitudinal cohort. Four linear mixed models were compared: two simple models including a priori selected covariates and two polysocial risk score models which used LASSO regularization to select covariates among 9 or 21 candidate social predictors. All models included age. Predictive accuracy was assessed via R-squared and root mean-squared prediction error (RMSPE) using training/test split and cross-validation. For predicting cognition, the simple model including age, race, gender, and education had an R-squared of 0.31 and an RMSPE of 0.880. Compared with this, the most complex polysocial risk score selected 12 predictors (R-squared=0.35 and RMSPE=0.858; 2.2% improvement). For all-cause mortality, the simple model including age, race, gender, and education had an AUROC of 0.747, while the most complex polysocial risk score did not demonstrate improved performance (AUROC = 0.745). Models built on a smaller set of key social determinants performed comparably to models built on a more complex set of social "risk factors".

Overcoming Data Gaps in Life Course Epidemiology by Matching Across Cohorts.

Life course epidemiology is hampered by the absence of large studies with exposures and outcomes measured at different life stages in the same individuals. We describe when the effect of an exposure ( A ) on an outcome ( Y ) in a target population is identifiable in a combined ("synthetic") cohort created by pooling an early-life cohort including measures of A with a late-life cohort including measures of Y . We enumerate causal assumptions needed for unbiased effect estimation in the synthetic cohort and illustrate by simulating target populations under four causal models. From each target population, we randomly sampled early- and late-life cohorts and created a synthetic cohort by matching individuals from the two cohorts based on mediators and confounders. We estimated the effect of A on Y in the synthetic cohort, varying matching variables, the match ratio, and the strength of association between matching variables and A . Finally, we compared bias in the synthetic cohort estimates when matching variables did not d-separate A and Y to the bias expected in the original cohort. When the set of matching variables includes all variables d-connecting exposure and outcome (i.e., variables blocking all backdoor and front-door pathways), the synthetic cohort yields unbiased effect estimates. Even when matching variables did not fully account for confounders, the synthetic cohort estimate was sometimes less biased than comparable estimates in the original cohort. Methods based on merging cohorts may hasten the evaluation of early- and mid-life determinants of late-life health but rely on available measures of both confounders and mediators.

Practical Guide to Honest Causal Forests for Identifying Heterogeneous Treatment Effects.

"Heterogeneous treatment effects" is a term which refers to conditional average treatment effects (i.e., CATEs) that vary across population subgroups. Epidemiologists are often interested in estimating such effects because they can help detect populations that may particularly benefit from or be harmed by a treatment. However, standard regression approaches for estimating heterogeneous effects are limited by preexisting hypotheses, test a single effect modifier at a time, and are subject to the multiple-comparisons problem. In this article, we aim to offer a practical guide to honest causal forests, an ensemble tree-based learning method which can discover as well as estimate heterogeneous treatment effects using a data-driven approach. We discuss the fundamentals of tree-based methods, describe how honest causal forests can identify and estimate heterogeneous effects, and demonstrate an implementation of this method using simulated data. Our implementation highlights the steps required to simulate data sets, build honest causal forests, and assess model performance across a variety of simulation scenarios. Overall, this paper is intended for epidemiologists and other population health researchers who lack an extensive background in machine learning yet are interested in utilizing an emerging method for identifying and estimating heterogeneous treatment effects.

Propensity Scores in Health Disparities Research: The Example of Cognitive Aging and the Hispanic Paradox.

BACKGROUND: Individuals of Mexican ancestry in the United States experience substantial socioeconomic disadvantages compared with non-Hispanic white individuals; however, some studies show these groups have similar dementia risk. Evaluating whether migration selection factors (e.g., education) associated with risk of Alzheimer disease and related dementia (ADRD) explain this paradoxical finding presents statistical challenges. Intercorrelation of risk factors, common with social determinants, could make certain covariate patterns very likely or unlikely to occur for particular groups, which complicates their comparison. Propensity score (PS) methods could be leveraged here to diagnose nonoverlap and help balance exposure groups. METHODS: We compare conventional and PS-based methods to examine differences in cognitive trajectories between foreign-born Mexican American, US-born Mexican American, and US-born non-Hispanic white individuals in the Health and Retirement Study (1994-2018). We examined cognition using a global measure. We estimated trajectories of cognitive decline from linear mixed models adjusted for migration selection factors also associated with ADRD risk conventionally or with inverse probability weighting. We also employed PS trimming and match weighting. RESULTS: In the full sample, where PS overlap was poor, unadjusted analyses showed both Mexican ancestry groups had worse baseline cognitive scores but similar or slower rates of decline compared with non-Hispanic white adults; adjusted findings were similar, regardless of method. Focusing analyses on populations where PS overlap was improved (PS trimming and match weighting) did not alter conclusions. CONCLUSIONS: Attempting to equalize groups on migration selection and ADRD risk factors did not explain paradoxical findings for Mexican ancestry groups in our study.

History of Low Hourly Wage and All-Cause Mortality Among Middle-aged Workers.

Importance: Earning a low wage is an increasingly recognized public health concern, yet little research exists on the long-term health consequences of sustained low-wage earning. Objective: To examine the association of sustained low-wage earning and mortality in a sample of workers with hourly wage reported biennially during peak midlife earning years. Design, Setting, and Participants: This longitudinal study included 4002 US participants, aged 50 years or older, from 2 subcohorts of the Health and Retirement Study (1992-2018) who worked for pay and reported earning hourly wages at 3 or more time points during a 12-year period during their midlife (1992-2004 or 1998-2010). Outcome follow-up occurred from the end of the respective exposure periods until 2018. Exposures: Low-wage-less than the hourly wage for full-time, full-year work at the federal poverty line-earning history was categorized as never earning a low wage, intermittently earning a low wage, and sustained earning a low wage. Main Outcomes and Measures: Cox proportional hazards and additive hazards regression models sequentially adjusted for sociodemographics, and economic and health covariates were used to estimate associations between low-wage history and all-cause mortality. We examined interaction with sex or employment stability on multiplicative and additive scales. Results: Of the 4002 workers (aged 50-57 years at the beginning of exposure period and 61-69 years at the end), 1854 (46.3%) were female; 718 (17.9%) experienced employment instability; 366 (9.1%) had a history of sustained low-wage earning; 1288 (32.2%) had intermittent low-wage earning periods; and 2348 (58.7%) had never earned a low wage. In unadjusted analyses, those who had never earned low wages experienced 199 deaths per 10 000 person-years, those with intermittent low wages, 208 deaths per 10 000 person-years, and those with sustained low wages, 275 deaths per 10 000 person-years. In models adjusted for key sociodemographic variables, sustained low-wage earning was associated with mortality (hazard ratio [HR], 1.35; 95% CI, 1.07-1.71) and excess deaths (66; 95% CI, 6.6-125); these findings were attenuated with additional adjustments for economic and health covariates. Significant excess death and elevated mortality risk were observed for workers with sustained low-wage exposure and employment fluctuations (eg, for sustained low-wage × employment fluctuated, HR, 2.18; 95% CI, 1.35-3.53; for sustained low-wage × stable employment, HR, 1.17; 95% CI, 0.89,-1.54; P for interaction = .003). Conclusions and Relevance: Sustained low-wage earning may be associated with elevated mortality risk and excess deaths, especially when experienced alongside unstable employment. If causal, our findings suggest that social and economic policies that improve the financial standing of low-wage workers (eg, minimum wage laws) could improve mortality outcomes.

Association of Low Hourly Wages in Middle Age With Faster Memory Decline in Older Age: Evidence From the Health and Retirement Study.

Little research has investigated the long-term relationship between low wages and memory decline, despite the growing share of low-wage workers in the US labor market. Here, we examined whether cumulative exposure to low wages over 12 years in midlife is associated with memory decline in later life. Using 1992-2016 data from the Health and Retirement Study, we analyzed data from 2,879 individuals born in 1936-1941 using confounder-adjusted linear mixed-effects models. Low-wage work was defined as an hourly wage lower than two-thirds of the federal median wage for the corresponding year and was categorized into "never," "intermittent," and "sustained" based on wages earned from 1992 to 2004. Memory function was measured at each study visit from 2004 to 2016 via a memory composite score. The confounder-adjusted annual rate of memory decline among "never" low-wage earners was -0.12 standard units (95% confidence interval: -0.13, -0.10). Compared with this, memory decline among workers with sustained earning of low midlife wages was significantly faster (ßtime×sustained = -0.014, 95% confidence interval: -0.02, -0.01), corresponding to an annual rate of -0.13 standard units for this group. Sustained low-wage earning in midlife was significantly associated with a downward trajectory of memory performance in older age. Enhancing social policies to protect low-wage workers may be especially beneficial for their cognitive health.

Racial Residential Segregation in Young Adulthood and Brain Integrity in Middle Age: Can We Learn From Small Samples?

Racial residential segregation is associated with multiple adverse health outcomes in Black individuals. Yet, the influence of structural racism and racial residential segregation on brain aging is less understood. In this study, we investigated the association between cumulative exposure to racial residential segregation over 25 years (1985-2010) in young adulthood, as measured by the Getis-Ord Gi* statistic, and year 25 measures of brain volume (cerebral, gray matter, white matter, and hippocampal volumes) in midlife. We studied 290 Black participants with available brain imaging data who were enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) Study, a prospective cohort study. CARDIA investigators originally recruited 2,637 Black participants aged 18-30 years from 4 field centers across the United States. We conducted analyses using marginal structural models, incorporating inverse probability of treatment weighting and inverse probability of censoring weighting. We found that compared with low/medium segregation, greater cumulative exposure to a high level of racial residential segregation throughout young adulthood was associated with smaller brain volumes in general (e.g., for cerebral volume, ß = -0.08, 95% confidence interval: -0.15, -0.02) and with a more pronounced reduction in hippocampal volume, though results were not statistically significant. Our findings suggest that exposure to segregated neighborhoods may be associated with worse brain aging.

Is the Way Forward to Step Back? Documenting the Frequency With Which Study Goals Are Misaligned With Study Methods and Interpretations in the Epidemiologic Literature.

In any research study, there is an underlying process that should begin with a clear articulation of the study's goal. The study's goal drives this process; it determines many study features, including the estimand of interest, the analytic approaches that can be used to estimate it, and which coefficients, if any, should be interpreted. Misalignment can occur in this process when analytic approaches and/or interpretations do not match the study's goal; misalignment is potentially more likely to arise when study goals are ambiguously framed. In this study, misalignment in the observational epidemiologic literature was documented and how the framing of study goals contributes to misalignment was explored. The following 2 misalignments were examined: use of an inappropriate variable selection approach for the goal (a "goal-methods" misalignment) and interpretation of coefficients of variables for which causal considerations were not made (e.g., Table 2 Fallacy, a "goal-interpretation" misalignment). A random sample of 100 articles published 2014-2018 in the top 5 general epidemiology journals were reviewed. Most reviewed studies were causal, with either explicitly stated (n = 13; 13%) or associational-framed (n = 71; 69%) aims. Full alignment of goal-methods-interpretations was infrequent (n = 9; 9%), although clearly causal studies (n = 5 of 13; 38%) were more often fully aligned than were seemingly causal ones (n = 3 of 71; 4%). Goal-methods misalignments were common (n = 34 of 103; 33%), but most frequently, methods were insufficiently reported to draw conclusions (n = 47; 46%). Goal-interpretations misalignments occurred in 31% (n = 32) of the studies and occurred less often when the methods were aligned (n = 2; 2%) compared with when the methods were misaligned (n = 13; 13%).

Prepregnancy overweight and obesity are associated with impaired child neurodevelopment.

The authors examined the relationship of prepregnancy body mass index (BMI) and gestational weight gain (GWG) with child neurodevelopment. Mother-child dyads were a subgroup (n = 2,084) of the Child Health and Development Studies from the Oakland, California, area enrolled during pregnancy from 1959 to 1966 and followed at child age 9 years. Linear regression was used to examine associations between prepregnancy BMI, GWG, and standardized Peabody Picture Vocabulary Test and Raven Progressive Matrices scores and to evaluate effect modification of GWG by prepregnancy BMI. Before pregnancy, 77% of women were normal weight, 8% were underweight, 11% were overweight, and 3% were obese. Associations between GWG and child outcomes did not vary by prepregnancy BMI, suggesting no evidence for interaction. In multivariable models, compared to normal prepregnancy BMI, prepregnancy overweight and obesity were associated with lower Peabody scores (b: -1.29; 95% CI [-2.6, -0.04] and b: -2.7; 95% CI [-5.0, -0.32], respectively). GWG was not associated with child Peabody score [b: -0.03 (95% CI: -0.13, 0.07)]. Maternal BMI and GWG were not associated with child Raven score (all P >0.05). Maternal prepregnancy overweight and obesity were associated with lower scores for verbal recognition in mid-childhood. These results contribute to evidence linking maternal BMI with child neurodevelopment. Future research should examine the role of higher prepregnancy BMI values and the pattern of pregnancy weight gain in child cognitive outcomes.

Social Determinants of Health and Biological Age among Diverse U.S. Adults, NHANES 2011-2018.

We examined the sex-specific association between education and income with biological age (BA) and by race/ethnicity. The Klemera-Doubal method was used to calculate BA among 6,213 females and 5,938 males aged 30-75 years who were Hispanic, non-Hispanic (NH) White, NH Black (NHB), or NH Asian (NHA). Compared with a college education, less than a high school education was associated with greater BA by 3.06 years (95% CI: 1.58, 4.54) among females only; associations were strongest among NHB, Hispanic, and NHA females. Compared with an annual income of ≥$75,000, an income <$25,000 was associated with greater BA by 4.95 years (95% CI: 3.42, 6.48) among males and 2.76 years among females (95% CI: 1.51, 4.01); associations were strongest among NHW and NHA adults, and Hispanic males. Targeting upstream sources of structural disadvantage among racial/ethnic minority groups, in conjunction with improvements in income and education, may promote healthy aging in these populations.

Associations of childhood, adolescence, and midlife cognitive function with DNA methylation age acceleration in midlife.

Prior studies showed increased age acceleration (AgeAccel) is associated with worse cognitive function among old adults. We examine the associations of childhood, adolescence and midlife cognition with AgeAccel based on DNA methylation (DNAm) in midlife. Data are from 359 participants who had cognition measured in childhood and adolescence in the Child Health and Development study, and had cognition, blood based DNAm measured during midlife in the Disparities study. Childhood cognition was measured by Raven's Progressive Matrices and Peabody Picture Vocabulary Test (PPVT). Adolescent cognition was measured only by PPVT. Midlife cognition included Wechsler Test of Adult Reading (WTAR), Verbal Fluency (VF), Digit Symbol (DS). AgeAccel measures including Horvath, Hannum, PhenoAge, GrimAge and DunedinPACE were calculated from DNAm. Linear regressions adjusted for potential confounders were utilized to examine the association between each cognitive measure in relation to each AgeAccel. There are no significant associations between childhood cognition and midlife AgeAccel. A 1-unit increase in adolescent PPVT, which measures crystalized intelligence, is associated with 0.048-year decrease of aging measured by GrimAge and this association is attenuated after adjustment for adult socioeconomic status. Midlife crystalized intelligence measure WTAR is negatively associated with PhenoAge and DunedinPACE, and midlife fluid intelligence measure (DS) is negatively associated with GrimAge, PhenoAge and DunedinPACE. AgeAccel is not associated with VF in midlife. In conclusion, our study showed the potential role of cognitive functions at younger ages in the process of biological aging. We also showed a potential relationship of both crystalized and fluid intelligence with aging acceleration.

Sufficient component cause simulations: an underutilized epidemiologic teaching tool.

Simulation studies are a powerful and important tool in epidemiologic teaching, especially for understanding causal inference. Simulations using the sufficient component cause framework can provide students key insights about causal mechanisms and sources of bias, but are not commonly used. To make them more accessible, we aim to provide an introduction and tutorial on developing and using these simulations, including an overview of translation from directed acyclic graphs and potential outcomes to sufficient component causal models, and a summary of the simulation approach. Using the applied question of the impact of educational attainment on dementia, we offer simple simulation examples and accompanying code to illustrate sufficient component cause-based simulations for four common causal structures (causation, confounding, selection bias, and effect modification) often introduced early in epidemiologic training. We show how sufficient component cause-based simulations illuminate both the causal processes and the mechanisms through which bias occurs, which can help enhance student understanding of these causal structures and the distinctions between them. We conclude with a discussion of considerations for using sufficient component cause-based simulations as a teaching tool.

Racial Differences in Employment and Poverty Histories and Health in Older Age.

INTRODUCTION: Black Americans encounter more barriers in the job market and earn less than White Americans. However, the extent to which racial disparities in employment and poverty histories impact health is not fully understood. This study characterized employment‒poverty histories for Black and White middle-aged adults and examined their association with health. METHODS: Respondents born in 1948-1953 and enrolled in the 2004 Health and Retirement Study (NBlack=555, NWhite=2,209) were included. Sequence analysis grouped respondents with similar employment‒poverty trajectories from 2004 to 2016, and confounder-adjusted regression analyses estimated the associations between these trajectories and health in 2018. Analyses were conducted in 2021-2022. RESULTS: More than 23% of Black respondents experienced both employment and poverty fluctuations, including bouts of extreme poverty (<50% of the federal poverty threshold), whereas no trajectory for White respondents included extreme poverty. Adversities in employment‒poverty were associated with worse health. For example, among Black respondents, those who experienced both employment and poverty fluctuations had worse cognition than those employed and not poor (ß= -0.55 standardized units, 95% CI= -0.81, -0.30). Similarly, among White respondents, those who experienced employment fluctuations had worse cognition than those employed (ß= -0.35, 95% CI= -0.46, -0.24). Notably, the employed and not poor trajectory was associated with worse survival among Black respondents than among White respondents. CONCLUSIONS: Employment fluctuations were associated with worse health, especially cognitive function, where the association was stronger among Black Americans who experienced both employment fluctuations and poverty. Findings highlight the importance of enhancing employment stability and of antipoverty programs, especially for Black Americans.

Associations of Religious Service Attendance With Cognitive Function in Midlife: Findings From The CARDIA Study.

OBJECTIVES: Growing evidence suggests that religiosity is an important social determinant of health, including cognitive health. Yet most prior work focused on older adults or was conducted in racially and denominationally homogeneous regional samples. This study investigates the association of religious service attendance in midlife with cognitive function later in midlife. METHODS: Using data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a racially and geographically diverse prospective cohort study, we explored the association of religious service attendance in midlife with cognitive function 5 years later. Cognitive function was measured using four cognitive tests administered by CARDIA technicians. Multivariable linear regression was used for analyses. Primary analyses controlled for sociodemographics, physical health, depression, and prior religious involvement. Sensitivity analyses additionally controlled for baseline cognition and social support. RESULTS: Our study population included 2,716 participants (57.2% female, 44.9% Black, and mean age 50). In primary analyses, attending services more than weekly (compared to never) in midlife was associated with better global cognition (ß = 0.14 standard deviations, 95% [confidence interval] CI = 0.02, 0.26) and verbal memory (ß = 0.17 standard deviations, 95% CI = 0.04, 0.30), but not with processing speed (ß = 0.04 standard deviations, 95% CI = -0.08, 0.16). A reverse association was observed with executive function (ß = -0.16 standard deviations, 95% CI = -0.30, -0.02). Most findings persisted in analyses accounting for loss to follow-up via inverse probability weighting. DISCUSSION: Our findings suggest that frequent involvement in religious services at midlife is associated with better global cognition and verbal memory but worse executive function. There was no association with processing speed.

Association Between Supplemental Nutrition Assistance Program Use and Memory Decline: Findings From the Health and Retirement Study.

BACKGROUND AND OBJECTIVES: Studies on the effect of the Supplemental Nutrition Assistance Program (SNAP) on the cognitive health of older adults are scarce. We sought to examine the associations between SNAP use and memory decline among SNAP-eligible US older adults. METHODS: Participants aged 50+ years and SNAP-eligible in 1996 from the Health and Retirement Study were included. Participants' SNAP eligibility was constructed using federal criteria. Participants also self-reported whether they used SNAP. Memory function was assessed biennially from 1996 through 2016 using a composite score. To account for preexisting differences in characteristics between SNAP users and nonusers, we modeled the probability of SNAP use using demographic and health covariates. Using linear mixed-effects models, we then modeled trajectories of memory function for SNAP users and nonusers using inverse probability (IP) weighting and propensity score (PS) matching techniques. In all models, we accounted for study attrition. RESULTS: Of the 3,555 SNAP-eligible participants, a total of 15.7% were SNAP users. At baseline, SNAP users had lower socioeconomic status and a greater number of chronic conditions than nonusers and were more likely to be lost to follow-up. Our multivariable IP-weighted models suggested that SNAP users had worse memory scores at baseline but slower rates of memory decline compared with nonusers (the annual decline rate is -0.038 standardized units [95% CI = -0.044 to -0.032] for users and -0.046 [95% CI = -0.049 to -0.043] for nonusers). Results were slightly stronger from the PS-matched sample (N = 1,014) (the annual decline rate was -0.046 units [95% CI = -0.050 to -0.042] for users and -0.060 units [95% CI = -0.064 to -0.056] for nonusers). Put in other words, our findings suggested that SNAP users had approximately 2 fewer years of cognitive aging over a 10-year period compared with nonusers. DISCUSSION: After accounting for preexisting differences between eligible SNAP users and nonusers as well as differential attrition, we find SNAP use to be associated with slower memory function decline.

Associations of Food Insecurity and Memory Function Among Middle to Older-Aged Adults in the Health and Retirement Study.

Importance: Food insecurity is a leading public health issue in the US. Research on food insecurity and cognitive aging is scarce, and is mostly cross-sectional. Food insecurity status and cognition both can change over the life course, but their longitudinal relationship remains unexplored. Objective: To examine the longitudinal association between food insecurity and changes in memory function during a period of 18 years among middle to older-aged adults in the US. Design, Setting, and Participants: The Health and Retirement Study is an ongoing population-based cohort study of individuals aged 50 years or older. Participants with nonmissing information on their food insecurity in 1998 who contributed information on memory function at least once over the study period (1998-2016) were included. To account for time-varying confounding and censoring, marginal structural models were created, using inverse probability weighting. Data analyses were conducted between May 9 and November 30, 2022. Main outcomes and Measures: In each biennial interview, food insecurity status (yes/no) was assessed by asking respondents whether they had enough money to buy food or ate less than they felt they should. Memory function was a composite score based on self-completed immediate and delayed word recall task of a 10-word list and proxy-assessed validated instruments. Results: The analytic sample included 12 609 respondents (mean [SD] age, 67.7 [11.0] years, 8146 [64.60%] women, 10 277 [81.51%] non-Hispanic White), including 11 951 food-secure and 658 food-insecure individuals in 1998. Over time, the memory function of the food-secure respondents decreased by 0.045 SD units annually (ß for time, -0.045; 95% CI, -0.046 to -0.045 SD units). The memory decline rate was faster among food-insecure respondents than food-secure respondents, although the magnitude of the coefficient was small (ß for food insecurity × time, -0.0030; 95% CI, -0.0062 to -0.00018 SD units), which translates to an estimated 0.67 additional (ie, excess) years of memory aging over a 10-year period for food-insecure respondents compared with food-secure respondents. Conclusions and Relevance: In this cohort study of middle to older-aged individuals, food insecurity was associated with slightly faster memory decline, suggesting possible long-term negative cognitive function outcomes associated with exposure to food insecurity in older age.

Depressive symptoms mediate the relationship between sustained food insecurity and cognition: a causal mediation analysis.

PURPOSE: This study aimed to investigate the association of change in food insecurity over time with cognitive function in midlife, and whether depressive symptoms mediated that relationship. METHODS: We used longitudinal data from the Coronary Artery Risk Development in Young Adults study. Change in food insecurity in 2000-2005 was coded as "persistently food-secure," "persistently food-insecure," "became food-insecure," and "became food-secure." Depressive symptoms were measured in 2010, and cognitive function was measured in 2015. Multivariable linear regression controlled for sociodemographic and cardiovascular health factors was used. We also conducted causal mediation analysis. RESULTS: Our study population included 2448 participants (57.23% female and 43.18% Black, mean age = 40.31 in 2000). Compared with persistent food security, persistently and became food-insecure were associated with worse cognition, particularly with processing speed (ßpersistent = -0.20 standard unit, 95% CI = -0.36, -0.04; ßbecame = -0.17, 95% CI = -0.31, -0.03), and these associations appeared mediated by depressive symptoms (proportion-mediated = 14% for persistently food-insecure and 18% for became food-insecure). CONCLUSIONS: Persistent and transition to food insecurity were associated with worse cognition, both directly and indirectly through increasing depressive symptoms. Targeting food insecurity or depressive symptoms among persistently or became food-insecure individuals may have the potential to slow premature cognitive aging.

Prenatal polychlorinated biphenyl exposure is associated with decreased gestational length but not birth weight: archived samples from the Child Health and Development Studies pregnancy cohort.

BACKGROUND: Polychlorinated biphenyls (PCBs), known endocrine disruptors, were banned in 1979 but persist in the environment. Previous studies are inconsistent regarding prenatal exposure to PCBs and pregnancy outcomes. We investigated associations between prenatal exposure to PCBs and gestational length and birth weight. METHODS: In a sample of 600 infants (born between 1960 and 1963) randomly selected from Child Health and Development Studies participants followed through adolescence we measured 11 PCB congeners in maternal post partum sera (within three days of delivery). Length of gestation was computed from the reported first day of the last menstrual period (LMP) and delivery date. Linear regression was used to estimate associations between PCB exposure and gestational age and birth weight, adjusting for potential confounders. PCBs were grouped according to hypothesized biological action (1b (sum of weak phenobarbital inducers), 2b (sum of limited dioxin activity), and 3 (sum of CYP1A and CYP2b inducers)) or degree of ortho- substitution (mono, di, tri). Secondary analyses examined associations between total PCB exposure and exposure to individual congeners. RESULTS: Each unit increase in mono-ortho substituted PCBs was associated with a 0.30 week decrease (95% confidence interval (CI) -0.59, -0.016), corresponding to a 2.1 (95% CI -4.13, -0.11) day decrease in length of gestation. Similar associations were estimated for di-ortho substituted PCBs, (1.4 day decrease; (95% CI -2.9, 0.1)) and group 3 PCBs (0.84 day decrease; (95% CI -1.8, 0.11). We found similar associations in congener specific analyses and for the sum of congeners. CONCLUSIONS: Our study provides new evidence that PCB exposure shortens length of gestation in humans. This may have public health implications for population exposures.

Could maternal thyroid function during pregnancy affect daughters' age at menarche through child growth? A mediation analysis.

Early menarche is associated with adverse health outcomes during adolescence as well as breast and other reproductive cancers later in adulthood. However, the causes of early menarche and the pathways through which they operate are not fully understood. Though maternal thyroid function during pregnancy affects child growth, and rapid childhood growth is associated with a decreased age at menarche, the relationship between prenatal maternal thyroid function and daughters' age at menarche has not been examined. We conducted a mediation analysis in a historical cohort of 260 mother-child pairs to estimate the total and indirect effects of maternal prenatal thyroid function on daughters' age at menarche. No association was observed between thyroid stimulating hormone (TSH) or anti-thyroid peroxidase antibodies (ATPO) and daughters' age at menarche. Using a sample-specific, a-priori cutoff at the 10th percentile, low levels of maternal free thyroxine (FT4) were associated with earlier daughter age at menarche, with a hazard ratio (95 % CI) of 1.70 (1.02, 2.84) comparing the bottom 10th percentile with the top 90th percentile of exposure levels. Higher maternal FT4 was associated with rapid child weight gain from ages 5-9, and rapid child weight gain from ages 5-9 was associated with earlier age at menarche; the estimated indirect effect of this pathway was null. While maternal FT4 is associated with earlier age at menarche in daughters, this is not mediated by rapid weight gain in our study population, suggesting that maternal FT4 is operating through a different pathway.