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The authors evaluated the association between lead burden and psychiatric symptoms and its potential modification by a delta-aminolevulinic acid dehydratase (ALAD) polymorphism. Lead measurements in blood or bone and self-reported ratings on the Brief Symptom Inventory from 1991 to 2002 were available for 1,075 US men participating in the Department of Veterans Affairs (VA) Normative Aging Study. The authors estimated the prevalence odds ratio for the association between interquartile-range lead and abnormal symptom score, adjusting for potential confounders. An interquartile increment in tibia lead (14 microg/g) was associated with 21% higher odds of somatization (95% confidence interval of the odds ratio: 1.01, 1.46). An interquartile increment in patella lead (20 microg/g) corresponded to a 23% increase in the odds of global distress (95% confidence interval of the odds ratio: 1.02, 1.47). An interquartile increment in blood lead (2.8 microg/dl) was associated with 14% higher odds of hostility (95% confidence interval of the odds ratio: 1.02, 1.27). In all other analyses, lead was nonsignificantly associated with psychiatric symptoms. The adverse association of lead with abnormal mood scores was generally stronger among ALAD 1-1 carriers than 1-2/2-2 carriers, particularly regarding phobic anxiety symptoms (p(interaction) = 0.004). These results augment evidence of a deleterious association between lead and psychiatric symptoms. [ABSTRACT FROM AUTHOR]

Persistent endocrine-disrupting chemicals (EDCs) can dysregulate the stress response. We evaluated associations between persistent EDCs and perceived stress among participants in the Study of Environment, Lifestyle, and Fibroids (n = 1394), a prospective cohort study of Black women. Participants completed the Perceived Stress Scale 4 (PSS-4) at baseline and every 20 months through 60 months (score range: 0-16); higher scores indicate higher stress. Endocrine-disrupting chemicals, including per- and polyfluoroalkyl substances, polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides, were quantified in plasma samples at baseline. We fit bayesian kernel machine regression and linear mixed-effects models to estimate associations of EDCs (as a mixture and individually) with PSS-4 scores at baseline and at each follow-up visit, respectively. Increasing percentiles of the mixture were not strongly associated with PSS-4 scores at baseline, and no interactions were observed among EDCs. Several individual EDCs (eg, perfluorodecanoic acid, PCB 118, PBDE 99) were associated with higher PSS-4 scores at baseline or follow-up, and other EDCs (eg PCB 138/158) were associated with lower PSS-4 scores at baseline or follow-up. The directionality of associations for individual EDCs was inconsistent across follow-up visits. In conclusion, specific EDCs may be associated with perceived stress in Black women. This article is part of a Special Collection on Environmental Epidemiology., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Alzheimer disease (AD) is a progressive disorder common among older adults and culminating in profound cognitive impairments and high mortality risk. The US Food and Drug Administration (FDA) recently provided accelerated approval for Aduhelm, a medication for AD treatment. Aduhelm (Biogen Inc., Cambridge, Massachusetts) has been described as the first disease-modifying treatment for AD but has not been demonstrated to improve patients' cognitive or functional outcomes. In this commentary, we describe why Aduhelm approval was controversial and aspects of the current evidence of special pertinence to epidemiologists. The FDA decision was based primarily on 2 randomized controlled trials (RCTs), both terminated early, with conflicting findings about the cognitive benefits of Aduhelm. Both RCTs showed important adverse effects of the medication. The FDA cited the documented reduction in brain amyloid, an AD biomarker hypothesized as a surrogate outcome, to justify accelerated approval. Despite lack of racial/ethnic diversity in the RCT participants, concerns about health disparities have been invoked to argue for public funding of this expensive medication. The Centers for Medicare and Medicaid Services recently made a "Coverage with Evidence Development" determination for Aduhelm and similar medications. We end by describing how innovative study designs could accelerate postapproval research and evaluate the proposed surrogate outcomes., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to repetitive head impacts such as those from American football. Our understanding of this association is based on research in autopsied brains, since CTE can only be diagnosed postmortem. Such studies are susceptible to selection bias, which needs to be accounted for to ensure a generalizable estimate of the association between repetitive head impacts and CTE. We evaluated the relationship between level of American football playing and CTE diagnosis after adjusting for selection bias. The sample included 290 deceased male former American football players who donated their brains to the Veterans Affairs-Boston University-Concussion Legacy Foundation (VA-BU-CLF) Brain Bank between 2008 and 2019. After adjustment for selection bias, college-level and professional football players had 2.38 (95% simulation interval (SI): 1.16, 5.94) and 2.47 (95% SI: 1.46, 4.79) times the risk of being diagnosed with CTE as high-school-level players, respectively; these estimates are larger than estimates with no selection bias adjustment. Since CTE is currently diagnosed only postmortem, we additionally provide plausible scenarios for CTE risk ratios for each level of play during the former players' lifetime. This study provides further evidence to support a dose-response relationship between American football playing and CTE., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Using web-based survey data collected June - August 2018 from the Society for Epidemiologic Research (SER) members, we characterized numerous dimensions of social identity and lived experience, and assessed relationships between these characteristics and perceptions of inclusion and society participation. We quantified associations between characteristics, feeling very welcomed, high (top 25th percentile) self-initiated participation, and any (top 10th percentile) society-initiated participation. Racial/ethnic and religious minority categories were blinded to preserve anonymity and we accounted for missing data. Most 2018 SER members (n = 1631) were white (62%) or female (66%). Females with racial/ethnic non-response were least likely, while white males were most likely to report feeling very welcomed. Members who did not report race, identified with a specific racial/ethnic minority, or were politically conservative/right-leaning were less likely than white or liberal/left-leaning members to have high self-initiated participation. Women and individuals of a specific racial/ethnic minority or minority religious affiliations were less likely to participate in events initiated by the society. These data represent a baseline for assessing trends and the impact of future initiatives aimed at improving diversity, inclusion, representation and participation within SER., (Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2020.)

Bias due to selective mortality is a potential concern in many studies and is especially relevant in cognitive aging research because cognitive impairment strongly predicts subsequent mortality. Biased estimation of the effect of an exposure on rate of cognitive decline can occur when mortality is a common effect of exposure and an unmeasured determinant of cognitive decline and in similar settings. This potential is often represented as collider-stratification bias in directed acyclic graphs, but it is difficult to anticipate the magnitude of bias. In this paper, we present a flexible simulation platform with which to quantify the expected bias in longitudinal studies of determinants of cognitive decline. We evaluated potential survival bias in naive analyses under several selective survival scenarios, assuming that exposure had no effect on cognitive decline for anyone in the population. Compared with the situation with no collider bias, the magnitude of bias was higher when exposure and an unmeasured determinant of cognitive decline interacted on the hazard ratio scale to influence mortality or when both exposure and rate of cognitive decline influenced mortality. Bias was, as expected, larger in high-mortality situations. This simulation platform provides a flexible tool for evaluating biases in studies with high mortality, as is common in cognitive aging research., (© The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Biologic mechanisms underlying associations of periodontal disease with cancers remain unknown. The authors propose that both conditions share common genetic risk factors. They analyzed associations between baseline periodontal disease, measured by questionnaire-recorded tooth mobility, and incident cancers, identified by linkage with national registries, between 1963 and 2004 in 15,333 Swedish twins. The authors used co-twin analyses to control for familial factors and undertook analyses restricted to monozygotic twins to further control for confounding by genetic factors. They observed 4,361 cancer cases over 548,913 person-years. After adjustment for covariates, baseline periodontal disease was associated with increased risk of several cancers ranging from 15% for total cancer (proportional hazard ratio (HR) = 1.15, 95% confidence interval (CI): 1.01, 1.32) to 120% for corpus uterine cancer (HR = 2.20, 95% CI: 1.16, 4.18). Periodontal disease was also associated with increased risk of colorectal (HR = 1.62, 95% CI: 1.13, 2.33), pancreatic (HR = 2.06, 95% CI: 1.14, 3.75), and prostate (HR = 1.47, 95% CI: 1.04, 2.07) cancers. In co-twin analyses, dizygotic twins with baseline periodontal disease showed a 50% increase in total cancer risk (HR = 1.50, 95% CI: 1.04, 2.17), but in monozygotic twins this association was markedly attenuated (HR = 1.07, 95% CI: 0.63, 1.81). Similar patterns emerged for digestive tract cancers, suggesting that shared genetic risk factors may partially explain associations between periodontal disease and cancers.

In research on the determinants of change in health status, a crucial analytic decision is whether to adjust for baseline health status. In this paper, the authors examine the consequences of baseline adjustment, using for illustration the question of the effect of educational attainment on change in cognitive function in old age. With data from the US-based Assets and Health Dynamics Among the Oldest Old survey (n = 5,726; born before 1924), they show that adjustment for baseline cognitive test score substantially inflates regression coefficient estimates for the effect of schooling on change in cognitive test scores compared with models without baseline adjustment. To explain this finding, they consider various plausible assumptions about relations among variables. Each set of assumptions is represented by a causal diagram. The authors apply simple rules for assessing causal diagrams to demonstrate that, in many plausible situations, baseline adjustment induces a spurious statistical association between education and change in cognitive score. More generally, when exposures are associated with baseline health status, this bias can arise if change in health status preceded baseline assessment or if the dependent variable measurement is unreliable or unstable. In some cases, change-score analyses without baseline adjustment provide unbiased causal effect estimates when baseline-adjusted estimates are biased.