10-Year Follow-up of the Original Faroese Septuagenarian Cohort: Focus on Frailty and Association With All-cause Mortality.

Little is known about the health status of Faroese people reaching high age. The purpose of this study was to elucidate the health status of older adults in a small-scale society with emphasis on frailty and all-cause mortality. In this 10-year follow-up study, 347 Faroese citizens aged 80 to 84 from the Faroese Septuagenarian cohort participated. A detailed health examination was conducted, in addition to self-reported questionnaire. We constructed a 40-item Frailty Index (FI) to assess frailty. Survival and mortality risks were analyzed using Kaplan-Meier curves and Cox proportional hazard model. Median FI score was 0.28 ranging from 0.09 to 0.7; 71 (21%) individuals were least frail, 244 (67%) moderately frail, and 41 (12%) were most frail. Frailty and sex were statistically significantly associated with mortality; being male was associated with hazard ratio (HR) of 4.05 [CI 1.73, 9.48], and being most frail with HR of 6.2 [CI 1.84, 21.3]. Classification of octogenarians as least/moderately frail may be an opportunity to initiate interventions to prevent or delay frailty in this population stratum.

Working environment and fatigue among fishers in the north Atlantic: a field study.

BACKGROUND: This study investigates how Faroese deep-sea fishers' exposure to work-related stressors affects their sleep, sleepiness, and levels of fatigue. Being constantly exposed to the unpredictable and harsh North Atlantic Ocean, having long work hours and split sleep for up to 40 days consecutively, they will arguably suffer from fatigue. MATERIALS AND METHODS: One hundred and fifty seven fishers participated in this study, and data was gathered throughout 202 days at sea. Subjective data was collected at the start and end of trips via questionnaires, sleep and sleepiness diaries and supplemented by objective sleep data through actigraphs. Ship movements were logged with a gyroscope connected to a laptop. A noise metre measured each work station and resting area, and noise exposure profiles were calculated based on each participant's activity and location. Linear mixed-effect models investigated the effects of work exposure variables on sleep efficiency, and cumulative link mixed models measured effects on the Karolinska Sleepiness Scale and physical fatigue scale. RESULTS: Time of day followed by ship movement were the exposure variables with the highest impact on the outcome variables of sleep efficiency, sleepiness and physical fatigue. The number of days at sea revealed correlations to outcome variables either by itself or interacting with the sleep periods per day. Crew size, shift system or noise did not impact outcome variables when in the model with other variables. Larger catches improved sleep efficiency but did not affect sleepiness and physical fatigue ratings. CONCLUSIONS: The findings indicate a chronically fatigued fisher population, and recommends urgent attention being paid to improving the structure of vessels and installing stabilators for greater stability at sea; work schedules being evaluated for protection of health; and work environments being designed that fulfill human physiological requirements in order to ensure the wellbeing and safety of those at sea.

Impact of work exposure on cognitive performance in Faroese deep-sea fishers: a field study.

BACKGROUND: This study examines the impact of work-related exposure on the cognitive performance of Faroese deep-sea fishers. Faroese fishing crews work long hours in demanding and noisy environments amidst highly uncertain and challenging weather conditions. These factors, together with compromised patterns of rest and sleep, are known to increase fatigue. Our aim was to study if changes could be measured in fishers' cognitive performance at the end of the trip when compared with the baseline measure at the beginning. MATERIALS AND METHODS: Data was collected over 15 months (May 2017 to July 2018) from 157 fishers on 18 fishing trips which involved 202 investigative days on board. Questionnaires and six computerised cognitive tests: Simple Reaction Time, Numeric Working Memory, Corsi Blocks, Rapid Visual Information Processing, Digit Vigilance, and Card Sorting Test were used for data collection at the beginning and end of the trip. Differences between the outcomes on the two test points were analysed with one-way ANOVA comparing the performances at the beginning and end of the voyage, and two-way ANOVA to examine the interactive effect of chronotype and test occasions on the outcomes. Mixed models were used to test for the effects of predictor variables. RESULTS: Significant declines in cognitive performance were observed from the beginning to the end of the trip, with decreases in visuospatial memory and reaction times, and increases in cognitive lapses. Furthermore, slowing in response times was observed in the second half of the Digit Vigilance test when comparing the halves. CONCLUSIONS: Declines in performance were observed from the start to the end of the trip. Furthermore, fishers performed significantly worse in the second half of some parted tests, and evening types seem less influenced by irregular work hours. These findings call for improving the safety of the vessels and their crew.

Sleep, Sleepiness, and Fatigue on Board Faroese Fishing Vessels.

Purpose: Faroese fishers have four times more accidents than workers on land. The aim was to understand fishers' fatigue better and how their work and sleep patterns influenced their sleepiness levels and cognitive performance. Materials and Methods: A total of 157 Faroese fishers wore wrist-worn actigraphs at sea and one week on land and filled in sleep and sleepiness diaries during the trip. Furthermore, a 3-minute simple reaction time (SRT) test was completed at the beginning and end of the trip. The ship's movement and noise were also logged. The actiwatch results were analysed with mixed methods repeated measures. The sleepiness registrations and performance on the SRT-test were analysed with paired t-test. The ship movements (Pitch and roll) were divided into approximately three same-sized groups (lowest 1/3, medium 1/3, and highest 1/3) and compared against the Karolinska Sleepiness Scores (KSS ranging from 1-9) ≥7 and physical tiredness (ranging from 1-9) scores ≥7. Chi-square tests were used to determine the significance of these differences. Mean sleepiness scores at sea, and the proportion of sleepiness scores ≥7 were calculated, as well as sleepiness scores as a function of the time of day. Results: While at sea, fishers had more split sleep, slept less, and had lower sleep efficiency than onshore. Sleepiness was higher at the end of the trip, and cognitive decline was found. The number of major lapses was higher at the end of the trip, but with no significant difference between the median reaction times. Conclusion: The crew on-board the freezer longliner, who worked 8-8 shifts, slept the most, had the longest continuous sleep periods, the highest sleep efficiency, the lowest sleepiness levels, and the highest noise exposure during their time off.

Incidence, gender influence, and neuropsychological predictors of all cause dementia in the Faroe Islands-the Faroese Septuagenarian cohort.

BACKGROUND: Using the Faroese Septuagenarian cohort, we aimed to describe the incidence of dementia and assess the validity of neurocognitive tests to predict subsequent dementia diagnosis. METHODS: In this population-based cohort, 713 Faroese septuagenarians aged 70-74 years without dementia, underwent clinical and neuropsychological examinations. After 10-years of follow-up, information was collected on all participants referred for cognitive evaluations and diagnosed with dementia. Incidence rates were calculated and presented with 95% confidence intervals (CIs), assuming a Poisson distribution. We then performed discriminant analysis to determine the best set of neuropsychological tests to identify those who would develop dementia. RESULTS: Over the 10-years, 65 participants (9.1%) were diagnosed with dementia, with a 10-year incidence rate of 1063 cases per 100,000 person years (95% CI 825, 1343). Women had a greater incidence than men (incidence rate ratio (IRR) = 1.58; 95% CI 0.93, 2.71). After stepwise selection, gender and six neuropsychological measures were selected to discriminate between those who would and would not develop dementia. Overall, the model was able to correctly identify 82% of those who would not develop dementia (specificity) and 71% of those who would (sensitivity). CONCLUSIONS: These results indicate that among a greater number of tests covering a broad range of cognitive abilities, tests reflecting verbal and visual learning and recall, visuospatial function, attention, and encoding into and retrieval from long-term memory may be helpful in identifying patients in the pre-symptomatic phase of dementia. Thus, helping care-givers identify patients at a higher risk of developing dementia and adjusting management of care accordingly.

Gender differences in cognitive performance and health status in the Faroese Septuagenarians cohort.

The aim was to determine cognitive performance and health status in the Faroese Septuagenarians cohort in relation to gender differences. In this cross-sectional study of 713 Faroese septuagenarians who underwent a clinical, neurophysiological and neuropsychological examinations and questionnaire, women performed better on tests covering the memory domain, while there was no gender difference in other cognitive domains. Men suffered more frequently from cardiovascular events while women more frequently suffered from arthrosis, hypothyroidism and muscle pain. We observed a considerable heterogeneity and gender difference in some cognitive domains and health in Faroese septuagenarians.

Joint and independent neurotoxic effects of early life exposures to a chemical mixture: A multi-pollutant approach combining ensemble learning and g-computation.

BACKGROUND: Exposure to mercury (Hg) is associated with adverse developmental effects. However, Hg occurs with a multitude of chemicals. We assessed the associations of developmental exposure to multiple pollutants with children's neurodevelopment using a novel approach. METHODS: Hg, polychlorinated biphenyls (PCBs), and perfluoroalkyl substances were measured in maternal and children's blood at 5-years (n=449 and 419). At 7-years, children were administered Boston Naming Test (BNT) and the Strengths and Difficulties Questionnaire (SDQ). We used the G-formula combined with SuperLearner to estimate independent and joint effects of chemicals at both ages. We constructed flexible exposure-response relationships and assessed interactions. RESULTS: Most chemicals showed negative relationships with BNT scores. An inter-quartile range (IQR) increase in maternal Hg and perfluorooctanoic acid (PFOA) was associated with 0.15 standard deviation [SD] (95% Confidence Interval [CI]: -0.29,-0.03) and 0.14 SD (95%CI: -0.26,-0.05) lower scores in BNT, whereas a joint IQR increase in the mixture of chemicals was associated with 0.48 SD (95%CI: -0.69,-0.25) lower scores in BNT. An IQR increase in PFOA was associated with 0.11 SD (95%CI: 0.02,0.26) higher total SDQ difficulties scores. Maternal ∑PCBs concentrations were associated with lower SDQ scores (ß=-0.09 SD; 95%CI: -0.19,0), whereas 5-years ∑PCBs showed a negative association (ß=-0.09 SD; 95%CI: -0.21,0). Finally, a joint IQR increase in the mixture was associated with 0.22 SD (95%CI: 0.04,0.4) higher SDQ scores. CONCLUSIONS: Using a novel statistical approach, we confirmed associations between prenatal mercury exposure and lower cognitive function. The potential developmental effects of PFASs need additional attention.

Neurological Deficits After Long-term Pyrethroid Exposure.

Pyrethroid pesticides have been suggested to be a cause of Parkinson disease and other neurodegenerative diseases. To investigate this, a cross-sectional study was conducted among 120 Bolivian public health vector program spray men, primarily exposed to pyrethroids. Pesticide exposure and central nervous system (CNS) symptoms were determined by a structured interview, whereas neuromotor and neurocognitive performance was assessed using the computerized Behavioral Assessment and Research System and CATSYS system. Individuals exposed to higher levels reported significantly more CNS symptoms (adjusted odds ratio per quintile of cumulative exposure = 2.01 [1.22-3.31]). There was no association seen between pyrethroid exposure and neuromotor performance. Higher spraying intensity was associated with significantly worse neurocognitive performance in structural equation models (adjusted ß per quintile = -0.405 [-0.660 to -0.150]), and workers only exposed to pyrethroids performed worse than workers also exposed to other pesticides (adjusted ß = -1.344 [-2.224 to -0.464]). Chronic pyrethroid exposure may cause deterioration in neurocognitive performance, and exposure control is recommended.

Aerobic Fitness and Neurocognitive Function Scores in Young Faroese Adults and Potential Modification by Prenatal Methylmercury Exposure.

BACKGROUND: Exposure to methylmercury was shown to decrease neural stem cell populations, whereas aerobic fitness has beneficial effects on the adult brain that relies on improved neurogenesis in the hippocampus. OBJECTIVES: We examined the association between aerobic fitness and neurocognitive outcomes at young adult age, along with the potential moderating effect of prenatal exposure to methylmercury. METHODS: At age 22 years, 262 members of a Faroese birth cohort, established in 1986-1987, underwent a graded exercise test of aerobic fitness to measure maximal oxygen uptake (VO2Max). Their prenatal methylmercury exposure had been assessed from the mercury concentration in cord blood. We estimated cross-sectional associations between VO2Max and multiple measures of neurocognitive function. In addition, we compared groups with low and high prenatal methylmercury exposure. RESULTS: A 1 standard deviation (SD) increase in VO2Max was associated with better scores on short-term memory and cognitive processing speed by 0.21 SD (95% CI: -0.04, 0.46) and 0.28 SD (95% CI: 0.02, 0.54), respectively. In the group with lower prenatal methylmercury exposure, a 1 SD increase in VO2Max was associated with increased scores on cognitive processing speed by 0.45 SD (95% CI: 0.08, 0.81) and with a slightly lesser benefit in short-term memory. No such association was observed in the group with high prenatal methylmercury exposure. CONCLUSIONS: Higher aerobic capacity was associated with better performance in short-term memory and processing speed. However, prenatal methylmercury exposure seemed to attenuate these positive associations.

Health effects associated with measured levels of contaminants in the Arctic.

The Human Health Assessment Group has over the past decade recommended that effect studies be conducted in the circumpolar area. Such studies examine the association between contaminant exposure in the Arctic populations and health effects. Because foetuses and young children are the most vulnerable, effect studies are often prospective child cohort studies. The emphasis in this article is on a description of the effects associated with contaminant exposure in the Arctic. The main topics addressed are neurobehavioural, immunological, reproductive, cardiovascular, endocrine and carcinogenic effect. For each topic, the association between exposure and effects is described, and some results are reported for similar studies outside the Arctic.

Behavioral difficulties in 7-year old children in relation to developmental exposure to perfluorinated alkyl substances.

BACKGROUND: Perfluorinated alkyl substances (PFAS) are suspected endocrine disruptors that are highly persistent and neurotoxic in animals. Human epidemiological studies of exposure-related deviations of children's behaviors are sparse. We assessed the associations between prenatal, 5- and 7-year PFAS exposures and behavioral problem scores in 7-year Faroese children. METHODS: Concentrations of perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA), perfluorooctane sulfonate (PFOS), and perfluorohexane sulfonic acid (PFHxS) were measured in maternal serum and in serum from children at ages 5 and 7years (n=539, 508, and 491, respectively). We used multivariable regressions and structural equations models to estimate the covariate-adjusted associations between serum-PFAS concentrations and behavioral difficulties, as assessed by the strengths and difficulties questionnaire (SDQ) at age 7. RESULTS: Serum-PFOS and PFHxS concentrations declined over time, whereas PFOA, PFNA, and PFDA tended to increase. No associations were observed between prenatal PFAS concentrations and SDQ scores. However, a two-fold increase in 5-year serum-PFOA, PFNA, and PFDA concentrations was associated with increases in total SDQ scores by 1.03 (95% CI: 0.11, 1.95), 0.72 (95% CI: 0.07, 1.38) and 0.78 points (95% CI: 0.01, 1.55), respectively. For SDQ subscales, significant associations were found in regard to hyperactivity, peer relationship, and conduct problems, as well as internalizing and externalizing problems and autism screening composite scores. Cross-sectional analyses at age 7years showed possible sex-dimorphic associations between PFAS concentrations and SDQ scores, where girls had consistently positive associations with SDQ scores whereas boys exhibited a pattern of negative or null associations. CONCLUSIONS: Higher serum PFAS concentrations at ages 5- and 7-years, but not prenatally, were associated with parent-reported behavioral problems at age 7.

Cognitive deficits at age 22 years associated with prenatal exposure to methylmercury.

Prenatal exposure to mercury has been associated with adverse effects on child neurodevelopment. The present study aims to determine the extent to which methylmercury-associated cognitive deficits persist into adult age. In a Faroese birth cohort originally formed in 1986-1987 (N = 1,022), prenatal methylmercury exposure was assessed in terms of the mercury concentration in cord blood and maternal hair. Clinical examinations of 847 cohort members at age 22 years were carried out in 2008-2009 using a panel of neuropsychological tests that reflected major functional domains. Subjects with neurological and psychiatric diagnoses were excluded from the data analysis, thus leaving 814 subjects. Multiple regression analysis included covariates previously identified for adjustment. Deficits in Boston Naming Test (BNT) and other tests of verbal performance were significantly associated with the cord-blood mercury concentration. Deficits were also present in all other tests applied, although most were not statistically significant. Structural equation models were developed to ascertain the possible differences in vulnerability of specific functional domains and the overall association with general intelligence. In models for individual domains, all of them showed negative associations, with crystallized intelligence being highly significant. A hierarchical model for general intelligence based on all domains again showed a highly significant negative association with the exposure, with an approximate deficit that corresponds to about 2.2 IQ points at a 10-fold increased prenatal methylmercury exposure. Thus, although the cognitive deficits observed were smaller than at examinations at younger ages, maternal diets with contaminated seafood were associated with adverse effects in this birth cohort at age 22 years. The deficits affected major domains of brain functions as well as general intelligence. Thus, prenatal exposure to this marine contaminant appears to cause permanent adverse effects on cognition.

Occupational pesticide exposure in early pregnancy associated with sex-specific neurobehavioral deficits in the children at school age.

Prenatal exposure to pesticides may affect neurodevelopment, while the impact of modern pesticides is unclear. From 1997-2001, women working in greenhouse horticultures were recruited at the beginning of their pregnancy. Based on detailed interview of the women and their employers, those categorized as occupationally exposed to pesticides were moved to unexposed work functions or went on paid leave, while women without any exposure were considered unexposed controls. Of the resulting birth cohort of 203 children, 133 (65%) were examined at age 6 to 11 years together with 44 newly recruited children of same age whose mothers were not occupationally exposed to pesticides in pregnancy. All children underwent a standardized examination including a battery of neurodevelopmental tests. Maternal occupational pesticide exposure in early pregnancy was associated with prolonged brainstem auditory evoked potential latencies in the children as a whole and with impaired neuropsychological function in girls, while no effect was apparent in boys. In girls, language and motor speed functions were significantly inversely associated with prenatal exposure, and a non-significant tendency toward decreased function was also seen for other neuropsychological outcomes. A structural equation model that combined all these test results showed an overall impaired neuropsychological function in girls prenatally exposed to pesticides. Thus, our findings suggest an adverse effect of maternal occupational pesticide exposure on their children's neurodevelopment, despite the fact that the exposures occurred solely during early pregnancy and under well regulated working conditions, where special measures to protect pregnant women were applied.

Neurotoxicity from prenatal and postnatal exposure to methylmercury.

The extent to which postnatal methylmercury exposure contributes to neurobehavioral delays is uncertain. Confounding may occur because the child's dietary exposure likely correlates with the mother's. This conundrum was examined in the Faroese birth cohort 1 born in 1986-1987. Exposure parameters included mercury concentrations in maternal hair at parturition, cord blood, and child blood and hair at the age-7 clinical examination (N=923). In regression analyses, the child's current blood-mercury at age 7 (N=694) showed only weak associations with the neuropsychological test variables, but visuospatial memory revealed a significant negative association. Mutual adjustment caused decreases of the apparent effect of the prenatal exposure. However, such adjustment may lead to underestimations due to the presence of correlated, error-prone exposure variables. In structural equation models, all methylmercury exposure parameters were instead entered into a latent exposure variable that reflected the total methylmercury load. This latent exposure showed significant associations with neurodevelopmental deficits, with prenatal exposure providing the main information. However, postnatal methylmercury exposure appeared to contribute to neurotoxic effects, in particular in regard to visuospatial processing and memory. Thus, addition in the regression analysis of exposure information obtained at a different point in time was not informative and should be avoided. Further studies with better information on exposure profiles are needed to characterize the effects of postnatal methylmercury exposure.

Negative confounding by essential fatty acids in methylmercury neurotoxicity associations.

BACKGROUND: Methylmercury, a worldwide contaminant of fish and seafood, can cause adverse effects on the developing nervous system. However, long-chain n-3 polyunsaturated fatty acids in seafood provide beneficial effects on brain development. Negative confounding will likely result in underestimation of both mercury toxicity and nutrient benefits unless mutual adjustment is included in the analysis. METHODS: We examined these associations in 176 Faroese children, in whom prenatal methylmercury exposure was assessed from mercury concentrations in cord blood and maternal hair. The relative concentrations of fatty acids were determined in cord serum phospholipids. Neuropsychological performance in verbal, motor, attention, spatial, and memory functions was assessed at 7 years of age. Multiple regression and structural equation models (SEMs) were carried out to determine the confounder-adjusted associations with methylmercury exposure. RESULTS: A short delay recall (in percent change) in the California Verbal Learning Test (CVLT) was associated with a doubling of cord blood methylmercury (-18.9, 95% confidence interval [CI]=-36.3, -1.51). The association became stronger after the inclusion of fatty acid concentrations in the analysis (-22.0, 95% confidence interval [CI]=-39.4, -4.62). In structural equation models, poorer memory function (corresponding to a lower score in the learning trials and short delay recall in CVLT) was associated with a doubling of prenatal exposure to methylmercury after the inclusion of fatty acid concentrations in the analysis (-1.94, 95% CI=-3.39, -0.49). CONCLUSIONS: Associations between prenatal exposure to methylmercury and neurobehavioral deficits in memory function at school age were strengthened after fatty acid adjustment, thus suggesting that n-3 fatty acids need to be included in analysis of similar studies to avoid underestimation of the associations with methylmercury exposure.

Neurobehavioral deficits at age 7 years associated with prenatal exposure to toxicants from maternal seafood diet.

To determine the possible neurotoxic impact of prenatal exposure to polychlorinated biphenyls (PCBs), we analyzed banked cord blood from a Faroese birth cohort for PCBs. The subjects were born in 1986-1987, and 917 cohort members had completed a series of neuropsychological tests at age 7 years. Major PCB congeners (118, 138, 153, and 180), the calculated total PCB concentration, and the PCB exposure estimated in a structural equation model showed weak associations with test deficits, with statistically significant negative associations only with the Boston Naming test. Likewise, neither hexachlorobenzene nor p,p'-dichlorodiphenyldichloroethylene showed clear links to neurobehavioral deficits. Thus, these associations were much weaker than those associated with the cord-blood mercury concentration, and adjustment for mercury substantially attenuated the regression coefficients for PCB exposure. When the outcomes were joined into motor and verbally mediated functions in a structural equation model, the PCB effects remained weak and virtually disappeared after adjustment for methylmercury exposure, while mercury remained statistically significant. Thus, in the presence of elevated methylmercury exposure, PCB neurotoxicity may be difficult to detect, and PCB exposure does not explain the methylmercury neurotoxicity previously reported in this cohort.

Thyroid dysfunction as a mediator of organochlorine neurotoxicity in preschool children.

BACKGROUND: Exposure to organochlorine compounds (OCs) can alter thyroid function in humans, and hypothyroidism during early life can adversely affect a child's neurodevelopment. OBJECTIVES: In this study we aimed to assess the relationship between developmental organochlorine exposures and thyroid function and the relationship between thyroid function and subsequent neurodevelopment. METHODS: A population-based birth cohort of 182 children was followed annually up to 5.5 years of age. The assessments included OC concentrations in maternal pregnancy serum and milk, clinical thyroid parameters in maternal and cord serum, and subsequent neuropsychological outcomes of the child, along with sociodemographic cofactors. Resin triiodothyronine uptake ratio (T3RU) was also assessed as an estimate of the amount of thyroxine-binding globulin (TBG) sites unsaturated by thyroxine. The T3RU is high in hyperthyroidism and low in hypothyroidism. RESULTS: The findings showed consistent inverse and monotonic associations between organochlorine exposure and T3RU after covariate adjustments. We observed no associations with other thyroid parameters. T3RU was positively associated with improved performance on most of the neuropsychological tests. For other thyroid parameters, the findings were less consistent. CONCLUSIONS: The results suggest that OC exposures may decrease the T3RU during early life, which is a proxy measure of the binding capacity of TBG. In addition, minor decreases of the thyroid function may be inversely associated with a child's neurodevelopment.

Functional MRI approach to developmental methylmercury and polychlorinated biphenyl neurotoxicity.

Prenatal and early childhood exposure to methylmercury (MeHg) or polychlorinated biphenyls (PCBs) are associated with deficits in cognitive, sensory, motor and other functions measured by neurobehavioral tests. The main objective of this pilot study was to determine whether functional magnetic resonance imaging (fMRI) is effective for visualization of brain function alterations related to neurobehavior in subjects with high prenatal exposure to the two neurotoxicants, MeHg and PCBs. Twelve adolescents (all boys) from a Faroese birth cohort assembled in 1986-1987 were recruited based on their prenatal exposures to MeHg and PCB. All underwent fMRI scanning during behavioral tasks at age 15 years. Subjects with high mixed exposure to MeHg and PCBs were compared to those with low mixed exposure on fMRI photic stimulation and a motor task. Boys with low mixed exposures showed patterns of fMRI activation during visual and motor tasks that are typical of normal control subjects. However, those with high exposures showed activation in more areas of the brain and different and wider patterns of activation than the low mixed exposure group. The brain activation patterns observed in association with increased exposures to MeHg and PCBs are meaningful in regard to the known neurotoxicity of these substances. This methodology therefore has potential utility in visualizing structural neural system determinants of exposure-induced neurobehavioral dysfunction.

Prenatal exposure to lead and cognitive deficit in 7- and 14-year-old children in the presence of concomitant exposure to similar molar concentration of methylmercury.

Few studies have examined the effects of mixed metal exposures in humans. We have evaluated the effect of prenatal lead exposure in a Faroese birth cohort in the presence of similar molar-level exposure to methylmercury. A cohort of 1022 singleton births was assembled in the Faroe Islands during 1986-1987 from whom lead was measured in cord-blood. A total of 896 cohort subjects participated in a clinical examination at age 7 and 808 subjects in a second examination at age 14. We evaluated the association between cord-blood lead concentrations and cognitive deficits (attention/working memory, language, visuospatial, and memory) using multiple regression models. Overall, the lead concentration showed no clear pattern of association. However, in subjects with a low methylmercury exposure, after inclusion of statistical interaction terms, lead-associated adverse effects on cognitive functions were observed. In particular, higher cord-blood lead was associated with a lower digit span forward score on the Wechsler Intelligence Scale for Children-Revised (WISC-R) [beta=-1.70, 95% confidence interval (CI): -3.12 to -0.28] at age 7 and a lower digit span backward score on the WISC-R (beta=-2.73, 95%CI: -4.32 to -1.14) at age 14. Some interaction terms between lead and methylmercury suggested that the combined effect of the exposures was less than additive. The present study indicates that adverse effects of exposure may be overlooked if the effects of a co-pollutant are ignored. The present study supports the existence of adverse effects on cognitive functions at prenatal lead exposures corresponding to an average cord-blood concentration of 16 µg/L.

Structural equation models for meta-analysis in environmental risk assessment.

The potential of structural equation models for combining information from different studies in environmental epidemiology is explored. For illustration we synthesize data from two birth cohorts assessing the effects of prenatal exposure to methylmercury on childhood cognitive performance. One cohort was the largest by far, but a smaller cohort included superior assessment of the PCB exposure which has been considered an important confounder when estimating the mercury effect. The data were analyzed by specification of a structural equation model for each cohort. Information was then pooled based on a joint likelihood function with key parameters constrained to be equal in the different models. Modeling assumptions were chosen to obtain a meaningful biological interpretation of the joint effect parameters. Measurement errors in mercury variables were taken into account by viewing observed variables as indicators of latent variables. Adjustments for measurement error were also included for confounder variables. In particular, this example illustrates how to properly utilize that one study provided superior information about a confounder. A final more advanced model pooled information across different outcomes to gain power and to avoid multiple testing problems. In this model, the mercury effect remained statistically significant, while the effect of PCB was less certain.