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Biomedical subjects

Roberta F White

Publications and source records attributed to Roberta F White.

15 recordsLinked to original sources

Impact of prenatal methylmercury exposure on neurobehavioral function at age 14 years.

A cohort of 1022 consecutive singleton births was generated during 1987-1988 in the Faroe Islands, where increased methylmercury exposure occurs from traditional seafood diets that include pilot whale meat. The prenatal exposure level was determined from mercury analyses of cord blood, cord tissue, and maternal hair. At age 14 years, 878 of 1010 living cohort members underwent detailed neurobehavioral examination. Eighteen participants with neurological disorders were excluded. Blood and hair samples obtained from the participants were analyzed for mercury. The neuropsychological test battery was designed based on the same criteria as applied at the examination at age 7 years. Multiple regression analysis was carried out and included adjustment for confounders. Indicators of prenatal methylmercury exposure were significantly associated with deficits in finger tapping speed, reaction time on a continued performance task, and cued naming. Postnatal methylmercury exposure had no discernible effect. These findings are similar to those obtained at age 7 years, and the relative contribution of mercury exposure to the predictive power of the multiple regression models was also similar. An analysis of the test score difference between results at 7 and 14 years suggested that mercury-associated deficits had not changed between the two examinations. In structural equation model analyses, the neuropsychological tests were separated into five groups; methylmercury exposure was significantly associated with deficits in motor, attention, and verbal tests. These findings are supported by independent assessment of neurophysiological outcomes. The effects on brain function associated with prenatal methylmercury exposure therefore appear to be multi-focal and permanent.

Journal Article↗

Effects of sarin and cyclosarin exposure during the 1991 Gulf War on neurobehavioral functioning in US army veterans.

BACKGROUND: During the Gulf War (GW), in early March 1991, a munitions dump at Khamisiyah, Iraq, was destroyed. Later, in 1996, the dump was found to have contained the organophosphate chemical warfare agents, sarin and cyclosarin. METHODS: Data collected in a study conducted between 1994 and 1996, before the Khamisiyah incident was publicly disclosed, were used to examine neurobehavioral task performances of GW veterans (n=140) categorized as having received high, moderate, or low-to-no exposure dose levels to sarin and cyclosarin at Khamisiyah, Iraq. Exposure levels were based on modeled estimates of the exposure plume and on troop location information at the time of the Khamisiyah event. Based on recent findings observed in follow-up studies of persons exposed to sarin during the 1995 terrorist attacks in Japan, we hypothesized that exposure to sarin and cyclosarin would be associated with poorer performances on objective neurobehavioral tasks in specific functional domains (particularly in visuospatial abilities and psychomotor functioning) in a dose-dependent manner. RESULTS: Sarin and cyclosarin exposure was significantly associated with less proficient neurobehavioral functioning on tasks involving fine psychomotor dexterity and visuospatial abilities 4-5 years after exposure. CONCLUSIONS: Findings suggest a dose-response association between low-level exposure to sarin and cyclosarin and specific functional central nervous system effects 4-5 years after exposure.

Adult↗

Neuropsychological outcomes of army personnel following deployment to the Iraq war.

CONTEXT: The effects of war-zone deployment on neuropsychological health remain poorly understood. Neuropsychological performance deficits serve as sensitive measures of neural dysfunction and are often associated with psychosocial and occupational problems. Previous studies have not conducted objective neuropsychological assessments both before and after a major war-zone deployment. OBJECTIVE: To examine objective neuropsychological outcomes of Iraq War deployment in a large military cohort. DESIGN, SETTING, AND PARTICIPANTS: The Neurocognition Deployment Health Study, a prospective, cohort-controlled study conducted at military installations. This report centers on 961 male and female active-duty Army soldiers drawn from the larger cohort. Deploying Army soldiers (n = 654) were examined prior to deployment to Iraq (April-December 2003) and shortly after return (within a mean of 73 days [median, 75 days]; January-May 2005) from Iraq deployment. A comparison group of soldiers (n = 307) similar in military characteristics but not deploying overseas during the study was assessed in sessions timed to be as close as possible to the assessment of deployers. Military unit sampling procedures facilitated representation of combat, combat support, and combat service support functions among both deployers and nondeployers. MAIN OUTCOME MEASURES: Individually administered, performance-based neuropsychological tasks. Estimates (beta; the unstandardized parameter estimate) for the absolute differences in adjusted mean outcome scores between deployed and nondeployed groups were determined using generalized estimating equations. RESULTS: Multiple linear regression analyses adjusted for battalion membership revealed that Iraq deployment, compared with nondeployment, was associated with neuropsychological compromise on tasks of sustained attention (beta = 0.11; P<.001), verbal learning (beta = -1.51; P = .003), and visual-spatial memory (beta = -3.82; P<.001). Iraq deployment was also associated with increased negative state affect on measures of confusion (beta = 1.40; P<.001) and tension (beta = 1.24; P<.001). In contrast, deployment was associated with improved simple reaction time (beta = 4.30; P = .003). Deployment effects remained statistically significant after taking into account deployment-related head injury and stress and depression symptoms. CONCLUSIONS: Deployment to Iraq is associated with increased risk of neuropsychological compromise. Findings point to the need to investigate further the impact of deployment on neural functioning. Public health implications include consideration of neuropsychological compromise in health prevention and postdeployment clinical and occupational management.

Adult↗

Impact of prenatal methylmercury exposure on neurobehavioral function at age 14 years.

A cohort of 1022 consecutive singleton births was generated during 1987-1988 in the Faroe Islands, where increased methylmercury exposure occurs from traditional seafood diets that include pilot whale meat. The prenatal exposure level was determined from mercury analyses of cord blood, cord tissue, and maternal hair. At age 14 years, 878 of 1010 living cohort members underwent detailed neurobehavioral examination. Eighteen participants with neurological disorders were excluded. Blood and hair samples obtained from the participants were analyzed for mercury. The neuropsychological test battery was designed based on the same criteria as applied at the examination at age 7 years. Multiple regression analysis was carried out and included adjustment for confounders. Indicators of prenatal methylmercury exposure were significantly associated with deficits in finger tapping speed, reaction time on a continued performance task, and cued naming. Postnatal methylmercury exposure had no discernible effect. These findings are similar to those obtained at age 7 years, and the relative contribution of mercury exposure to the predictive power of the multiple regression models was also similar. An analysis of the test score difference between results at 7 and 14 years suggested that mercury-associated deficits had not changed between the two examinations. In structural equation model analyses, the neuropsychological tests were separated into five groups; methylmercury exposure was significantly associated with deficits in motor, attention, and verbal tests. These findings are supported by independent assessment of neurophysiological outcomes. The effects on brain function associated with prenatal methylmercury exposure therefore appear to be multi-focal and permanent.

Adolescent↗

Repeated split sample validation to assess logistic regression and recursive partitioning: an application to the prediction of cognitive impairment.

Screening strategies play an important part in the identification and diagnosis of illness. Testing of such strategies in a clinical trial can have important implications for the treatment of such illnesses. Before the clinical trial, however, it is important to develop a practical screening/classification procedure that accurately predicts the presence of the illness in question. Recent published studies have shown a growing preference for classification tree/recursive partitioning procedures.This paper compares the application of logistic regression and recursive partitioning to a neuropsychological data set of 252 patients recruited from four Veterans Affairs Medical Centers. Logistic regression and recursive partitioning was used to predict cognitive impairment in 12 randomly selected exploratory/validation samples. We assessed the effect of sampling on variable selection and predictive accuracy.Predictive accuracy of the logistic regression and recursive partitioning procedures was comparable across the exploratory data samples but varied across the validation samples. Based on shrinkage, both classification procedures performed equally well for the prediction of cognitive impairment across the twelve samples. While logistic regression provided an estimated probability of outcome for each patient, it required several mathematical calculations to do so. However, logistic regression selected one or two less predictors than recursive partitioning with comparable predictive accuracy. Recursive partitioning, on the other hand, readily identified patient characteristics and variable interactions, was easy to interpret clinically and required no mathematical calculations. There was a high degree of overlap of the predictor variables between the two procedures.In the context of neuropsychological screening, logistic regression and recursive partitioning performed equally well and were quite stable in the selection of predictors for the identification of patients with cognitive impairment, although recursive partitioning may be easier to use in a clinical setting because it is based on a simple decision tree.

Cognition Disorders↗

Effects of breast feeding on neuropsychological development in a community with methylmercury exposure from seafood.

Breastfeeding has been associated with an advantage to infant neurobehavioral development, possibly in part due to essential nutrients in breast milk. However, breast milk may be contaminated by environmental neurotoxicants, such as methylmercury. In the Faroe Islands, where maternal consumption of pilot whale may cause transfer of marine toxicants into breast milk, a cohort of 1022 consecutive singleton births was generated during 1986-87. Methylmercury exposure was assessed from mercury concentrations in cord blood and in the hair of the child at age 12 months, and the duration of breastfeeding was recorded. At approximately 7 years of age, 917 (90%) of the children underwent detailed neurobehavioral examination. After adjustment for confounders, breastfeeding was associated with only marginally better neuropsychological performance on most tests. These associations were robust even after adjustment for cord-blood and hair mercury concentration at age 1 year. Thus, in this cohort of children with a relatively high prenatal toxicant exposure and potential exposure to neurotoxicants through breast milk, breastfeeding was associated with less benefits on neurobehavioral development than previously published studies though not associated with a deficit in neuropsychological performance at age 7. Although the advantage may be less, Faroese women can still safely breastfeed their children.

Adult↗

Consequences of exposure measurement error for confounder identification in environmental epidemiology.

Non-differential measurement error in the exposure variable is known to attenuate the dose-response relationship. The amount of attenuation introduced in a given situation is not only a function of the precision of the exposure measurement but also depends on the conditional variance of the true exposure given the other independent variables. In addition, confounder effects may also be affected by the exposure measurement error. These difficulties in statistical model development are illustrated by examples from a epidemiological study performed in the Faroe Islands to investigate the adverse health effects of prenatal mercury exposure.

Bias↗

[Environmental epidemiology research leads to a decrease of the exposure limit for mercury].

The central nervous system is particularly vulnerable to prenatal exposure to methylmercury. Due to the widespread exposure to methylmercury from fish, several prospective environmental epidemiology studies have been initiated, in which the maternal exposure during the pregnancy is related to the neurobehavioural development of the children. We have studied a Faroese birth cohort prenatally exposed to methylmercury from maternal intake of contaminated pilot whale meat. At seven years of age, clear dose-response relationships were observed for deficits in attention, language, and memory. An increase in blood pressure was also associated with the prenatal exposure level. The exposure limit for mercury has therefore been decreased.

Animals↗

Neuropsychological screening for cognitive impairment using computer-assisted tasks.

The aim of this study was to validate a computer-assisted screening battery for classifying patients into two groups, those with and without cognitive impairment. Participants were all patients referred to the neuropsychology clinics at four VA medical centers during a 1-year period. Patients meeting the study inclusionary criteria (N = 252) were administered the Neurobehavioral Evaluation System-3 (NES3) computer-assisted battery. A detailed neuropsychological examination was carried out by an experienced neuropsychologist, who diagnosed the patient as cognitively impaired or not impaired. The neuropsychologist's diagnosis was the gold standard. Recursive partitioning analyses yielded several classification procedures using the NES3 data to predict the gold standard These procedures produced a set of six NES3 tasks that provide good sensitivity and specificity in predicting di- agnosis. Sensitivity and specificity for the least random classification procedure were 0.87 and 0.67, respectively. The results suggest that computer-assisted screening methods are a promising means of triaging patients.

Adult↗

Interrater reliability of neuropsychological diagnoses: a Department of Veterans Affairs cooperative study.

This study examined the interrater reliability of neuropsychological diagnoses produced by clinical neuropsychologists across 4 medical centers. These diagnoses were based on evaluations using a comprehensive battery of commonly used neuropsychological test instruments, interview, history and medical chart review. The diagnoses of individual neuropsychologists were compared to those made by members of an external review panel for each patient evaluated. Patients were first diagnosed as showing cognitive impairment versus no cognitive impairment. If a patient was diagnosed as impaired, a specific neuropsychological diagnosis was assigned. The diagnostic classification for cognitive impairment was moderately reliable [kappa = .48 +/- s.e.(kappa) = .062]. The interrater reliability for specific diagnoses was in the fair to good range [kappa = .44 +/- s.e.(kappa) = .029]. These levels of reliability are comparable to those found for other psychiatric and neurologic specialties and for medical diagnoses made by other health care disciplines.

Adult↗

MRI and neuropsychological correlates of carbon monoxide exposure: a case report.

A 45-year-old woman experienced long-term, chronic exposure to carbon monoxide in the restaurant kitchen where she was employed as a cook. After returning to the restaurant after 5 days off work, she noticed that her symptoms returned immediately; she then aired out the room and called the gas company. Approximately 6 hr after a leak was detected, the patient went to the hospital, where her carboxyhemoglobin was found to be within normal limits and results of a neurologic examination were described as normal. Based on her symptoms, the patient believed she had been exposed to CO for at least 1 year before the leak was discovered. Initially, she experienced flu-like symptoms, which eventually resolved. At the time of her first neuropsychological evaluation (17 months after the exposure was identified), her persisting complaints included difficulties in reading, writing, speaking and word retrieval. The test results were consistent with secondary frontal lobe dysfunction associated with subcortical disorders such as those seen after CO exposure. Results of a subsequent neuropsychological examination (29 months postexposure) showed slight improvement in performance, but her performance was still consistent with mild frontal/subcortical dysfunction. Although the initial screening of a brain magnetic resonance image (MRI) performed 15 months after the exposure was interpreted as being within normal limits, two subsequent blind reviews of the same scans identified multiple bilateral lesions in the basal ganglia, which were consistent with chronic CO exposure. We present this case as an example of the utility of MRI and neuropsychological examinations in detecting central nervous system dysfunction secondary to CO exposure.

Basal Ganglia↗

Neurobehavioral performance of Inuit children with increased prenatal exposure to methylmercury.

Exposure to methylmercury from marine mammals and other seafood may affect the development of the central nervous system. In a traditional Inuit community in Qaanaaq, Greenland, mercury concentrations in cord blood and maternal hair have been examined in connection with all births. We examined 43 children at age 7-12 years with a battery of neurobehavioral tests. The average mercury concentration in hair was 5.0 microg/g and 1.5 microg/g in children and mothers, respectively. Clinical neurological examination did not reveal any obvious deficits. However, neuropsychological tests showed possible exposure-associated deficits, though only in a few cases reaching statistical significance. In conjunction with data from other studies, peak latencies on brainstem auditory evoked potentials tended to be prolonged at increased exposure levels. The data from the present study therefore appears in accordance with other evidence that prenatal or early postnatal exposures to methylmercury may cause subtle neurobehavioral deficits.

Brain Stem↗

Neurotoxic risk caused by stable and variable exposure to methylmercury from seafood.

OBJECTIVES: To examine whether the dose-effect relationship for developmental mercury neurotoxicity is affected by variable mercury exposure during pregnancy. METHODS: The study was based on a birth cohort of 1022 children born in the Faroe Islands between March 1986 and December 1987. Neurobehavioral performance of 917 children (90%) was assessed at age 7. Intrauterine methylmercury exposure was determined from mercury concentrations in cord blood and 2 sets of maternal hair. Complete exposure information was available for 614 children (67%). RESULTS: In children with complete exposure data, 8 of 16 neuropsychological tests showed deficits significantly associated with the cord-blood mercury concentration after confounder adjustment. Variable intrauterine exposure was suggested by disagreement between mercury concentrations in the 2 maternal hair samples. Removal of the 61 children (10%) with the greatest degree of variable exposure had a minimal effect on most exposure-effect relationships. However, the effect of the cord-blood concentration on verbal learning and memory was greater after this exclusion. CONCLUSION: The study supports previous findings from this cohort study that maternal mercury exposure during pregnancy is associated with neuropsychological deficits detectable at age 7 years and that this association is evident in women with stable exposures throughout pregnancy. Thus the association is not the result of variable exposures.

Child↗