Lifetime air pollution exposure, cognitive deficits, and brain imaging outcomes: A systematic review.

As the amount of air pollution and human exposure has increased, the effects on human health have become an important public health issue. A field of growing interest is how air pollution exposure affects brain structure and function underlying cognitive deficits and if structural and connectivity changes mediate the relationship between the two. We conducted a systematic review to examine the literature on air pollution, brain structure and connectivity, and cognition studies. Eleven studies matched our inclusion criteria and were included in the qualitative analysis. Results suggest significant associations between air pollution and decreased volumes of specific brain structures, cortical thickness and surface area such as in the prefrontal cortex and temporal lobe, as well as the weakening of functional connectivity pathways, largely the Default Mode (DMN) and Frontal Parietal (FPN) networks, as detected by fMRI. Associations between air pollution and cognitive outcomes were found in most of the studies (n = 9), though some studies showed stronger associations than others. For children & adolescents, these deficiencies largely involved heavy reasoning, problem solving, and logic. For young and middle-aged adults, the associations were mostly seen for executive function and visuospatial cognitive domains. To our knowledge, this is the first systematic review to consolidate findings on the associations among air pollution, brain structure, and cognitive function. In the future, it will be important to conduct further longitudinal studies that follow children who have been exposed at a young age and examine associations with brain structure and cognition throughout adulthood.

Low level lead exposure in early childhood and parental education on adolescent IQ and working memory: a cohort study.

BACKGROUND: The independent effect of lead exposure and parental education on children's neurocognition is well-documented. However, few studies have examined the combined effect of childhood lead exposure and parental education on adolescent neurocognition, especially in China. OBJECTIVE: Examine both the combined and interactive effect of childhood blood lead levels (BLLs) and parental education on early adolescent neurocognition. METHODS: 417 children from a longitudinal cohort study in Jintan, China had BLLs measured at 3-5 years and 12 years, parental education levels assessed at 3-5 years, and neurocognitive outcomes tested at 12 years. RESULTS: BLLs at 3-5 years were inversely associated with adolescent IQ (ß -0.55 95% CI: -0.97, -0.13) but not working memory (ß -0.06 95% CI: -0.23, 0.11) and parental education was positively associated with adolescent IQ (ß 0.68 95% CI: 0.19, 1.17) and working memory (ß 0.24 95% CI: 0.04, 0.44). BLLs and parental education evidenced combined effects on neurocognition, where children with higher BLLs and lower fathers' education had mean IQ scores 7.84 (95% CI: -13.15, -2.53) points lower than children with lower BLLs and higher fathers' education. There were significant associations between parental education and working memory, however, not with BLLs. The interaction between mother and father high school education and BLLs was insignificant for effects on IQ and working memory. SIGNIFICANCE: Childhood lead exposure and parental education levels have a combined and long-term impact on IQ, evidence that may partially explain disparities in lead exposure associated outcomes and highlight those children at greatest risk for neurocognitive deficits. IMPACT STATEMENT: Children continue to be exposed to low-levels of environmental lead in China and globally, warranting examination of the impact of such exposures. This paper demonstrates that even relatively low-level lead exposure in early childhood significantly influences adolescent neurocognitive functioning. Furthermore, co-existing social determinant of health-related variables, measured here as parental education, have a combined impact on neurocognition. These results highlight children at greater risk for neurocognitive deficits and demonstrate the need to examine the influence of lead exposure within the broader socio- ecological environment, as these factors work in tandem to influence longer-term neurocognitive outcomes.

Childhood lead exposure and sex-based neurobehavioral functioning in adolescence.

It is well documented that childhood lead exposure is associated with long-term decreases in intelligence quotients (IQ). Lesser known is the relationship with neurobehavioral domains, especially in adolescence. This study sought to identify cross-sectional and longitudinal associations between lead exposure and adolescent executive and visual-motor functioning and examine sex-based differences. Participants were 681 children from Jintan, China who had their blood lead levels (BLLs) assessed at age 3-5 years and 12 years old and neurobehavioral functioning assessed through the University of Pennsylvania Computerized Neurocognitive Battery (PennCNB) platform http://www.med.upenn.edu/bbl at 12 years old. Mean BLLs were 6.41 mcg/dl at age 3-5 years and 3.10 mcg/dl at 12. BLLs at 3-5 years and 12 years were used as predictors for the individual neurobehavioral domains in general linear models while controlling for father and mother occupation and education, residence location, age, and adolescent IQ. Models were run separately for males and females. In adjusted models, males BLLs at 3-5 years were associated with increased time to correctly complete tasks in multiple domains including abstraction/flexibility (ß = 19.90, 95% CI( 4.26, 35.54) and spatial processing (ß = 96.00, 95% CI 6.18, 185.82) at 12 years. For females in adjusted models, BLLs at 3-5 years were associated with increasing time to correctly complete tasks on the episodic memory domain task (ß = 34.59, 95% CI 5.33, 63.84) at 12 years. Two adolescent cross-sectional relationships remained in the adjusted models for males only, suggesting a positive association between BLLs and increasing time for correct responses on the attentional domain task (ß = 15.08, 95% CI 0.65, 29.51) and decreasing time for correct responses on the episodic memory task (ß = -73.49, 95% CI -138.91, -8.06) in males at 12 years. These associations remained with and without controlling for IQ. These results suggest that lead exposure is associated with overall deficits in male and female neurobehavioral functioning, though in different domains and different timing of exposure.

Longitudinal association of early childhood lead exposure and adolescent heart rate variability: influence of parental education.

Lead exposure has been shown to dysregulate physiological stress responses. However, few studies have investigated the effect of lead exposure on later heart rate variability (HRV), an indicator of a stress response, in large samples of children. Furthermore, the interaction between social environmental factors and lead exposure in childhood, which commonly co-occur, remains understudied. This study examined relationships between childhood lead exposure and early adolescent physiological stress responses at different levels of parental education. Participants were 406 children from Jintan, China. Blood lead levels (BLLs) and parental education data were collected at 3-5 years of age, and HRV outcomes assessed at 12 years via frequency domain measures (LF/HF ratio) collected during an induced stress test. Results show a significant interaction between parental education and BLLs at 3-5 years. This relationship was found to be most consistent for the interaction between BLLs and mother's years of education for both the planning (ß = 0.12, p = 0.046) and speaking (ß = 0.11, p = 0.043) phase of the stress task, suggesting that increasing years of mother's education may enhance the deleterious influence of lead exposure on the HRV frequency measure, LF/HF ratio. This research highlights the complexity in lead exposure induced outcomes.

Opioid Taper is Associated with Improved Experimental Pain Tolerance in Patients with Chronic Pain: An Observational Study.

INTRODUCTION: The degree to which opioid-induced hyperalgesia contributes to the pain experience of patients with chronic pain remains relatively undescribed. The objective of this pilot study was to determine if experimental pain responses improve in patients with chronic pain as they undergo a planned opioid taper. METHODS: This was a prospective observational study. Seven patients with chronic neuropathic pain on at least 120 mg morphine equivalents/day were enrolled. The participants were followed over the course of an individualized opioid taper to a lower dose. Measures of experimental pain sensitivity, including indicators of central pain modulation, were collected on a biweekly basis; in addition, measures of function and quality of life were collected monthly. The effect of opioid taper on pain responses and functional outcomes over time were examined using longitudinal mixed-effects regression modeling and general linear regression modeling with regularization as a function of baseline dose, end dose, and taper rate. RESULTS: In this small sample of patients undergoing highly individualized and variable opioid taper, the opioid taper was significantly associated with improved pain responses to the cold-pressor test, with the pain threshold on average increasing by 1.14 s every 6 weeks (p = 0.0084, 95% confidence interval [CI] for 6-week change 0.3039-2.0178) and pain tolerance on average increasing by 2.87 s every 6 weeks (p = 0.0026, 95% CI for 6-week change 1.02-4.7277). Taper-related changes in central pain modulation were not observed, although conditioned modulation trended toward improvement by the completion of opioid taper. Similarly, no declines in function and quality of life were observed with the opioid taper, suggesting stability despite decreased opioid dose. CONCLUSIONS: Opioid taper was associated with improvements in experimental pain responses without a decline in function and quality of life, suggestive of diminished opioid-induced hyperalgesia in this clinical sample. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03912298.

Early childhood lead exposure and adolescent heart rate variability: A longitudinal cohort study.

Lead is a known neurotoxicant with many detrimental health effects, including neurocognitive deficits and cardiovascular and metabolic disorders. However, few studies have tested the association between lead exposure and the physiological stress response, which in and of itself may act as a precursor to and/or underlying mechanism of detrimental health outcomes. The purpose of this study was to examine the influence of early childhood and early adolescent low-level lead exposure on early adolescent heart rate variability, a widely-used measure of physiological stress. Participants were 408 children from Jintan, China for whom blood lead levels were measured between 3 and 5 years (early childhood) and again at 12 years (early adolescence). Heart rate variability was assessed at 12 years while participants underwent an induced stress task utilizing the ratio of low to high frequency (LF/HF) ECG measures. Mean blood lead levels in the cohort were 6.63 mcg/dl and 3.10 mcg/dl at 3-5 years and 12 years, respectively. Blood lead levels at 3-5 years of age (ß 0.06, p = 0.027), but not at age 12 (ß -0.05, p = 0.465), were significantly associated with LF/HF measures while controlling for multiple sociodemographic variables, potentially reflecting a dysregulated stress response with a shift towards sympathetic dominance. These findings suggest that early childhood lead exposure may have a detrimental influence on early adolescent autonomic responses to acute stress, which holds implications for cardiovascular health and overall growth and development.

Dietary Exposure to Toxic Elements and the Health of Young Children: Methodological Considerations and Data Needs.

Concerns have been raised regarding toxic-element (arsenic, cadmium, lead, and mercury) contamination of commercially available infant foods around the world. Young children are vulnerable to the effects of toxic elements, based on higher absorption levels and potentially poorer detoxification capacities. Toxic-element exposures in early life exact high societal costs, but it is unclear how much dietary exposure to these elements contributes to adverse health outcomes. Well-designed epidemiological studies conducted in different geographical and socioeconomic contexts need to estimate dietary toxicant exposure in young children and to determine whether causal links exist between toxicants in children's diets and health outcomes. This commentary outlines the methodological considerations and data needs to advance such research.