Neurobehavioral Test Performance Research Articles

Therapeutic potential of deuterium-stabilized (R)-pioglitazone-PXL065-for X-linked adrenoleukodystrophy.

X‐linked adrenoleukodystrophy (ALD) results from ABCD1 gene mutations which impair Very Long Chain Fatty Acids (VLCFA; C26:0 and C24:0) peroxisomal import and β‐oxidation, leading to accumulation in plasma and tissues. Excess VLCFA drives impaired cellular functions (e.g. disrupted mitochondrial function), inflammation, and neurodegeneration. Major disease phenotypes include: adrenomyeloneuropathy (AMN), progressive spinal cord axonal degeneration, and cerebral ALD (C‐ALD), inflammatory white matter demyelination and degeneration. No pharmacological treatment is available to‐date for ALD. Pioglitazone, an anti‐diabetic thiazolidinedione, exerts potential benefits in ALD models. Its mechanisms are genomic (PPARγ agonism) and nongenomic (mitochondrial pyruvate carrier—MPC, long‐chain acyl‐CoA synthetase 4—ACSL4, inhibition). However, its use is limited by PPARγ‐driven side effects (e.g. weight gain, edema). PXL065 is a clinical‐stage deuterium‐stabilized (R)‐enantiomer of pioglitazone which lacks PPARγ agonism but retains MPC activity. Here, we show that incubation of ALD patient‐derived cells (both AMN and C‐ALD) and glial cells from Abcd1‐null mice with PXL065 resulted in: normalization of elevated VLCFA, improved mitochondrial function, and attenuated indices of inflammation. Compensatory peroxisomal transporter gene expression was also induced. Additionally, chronic treatment of Abcd1‐null mice lowered VLCFA in plasma, brain and spinal cord and improved both neural histology (sciatic nerve) and neurobehavioral test performance. Several in vivo effects of PXL065 exceeded those achieved with pioglitazone. PXL065 was confirmed to lack PPARγ agonism but retained ACSL4 activity of pioglitazone. PXL065 has novel actions and mechanisms and exhibits a range of potential benefits in ALD models; further testing of this molecule in ALD patients is warranted.

The Effect of Neurobehavioral Test Performance on the All-Cause Mortality among US Population.

Evidence of the association between global cognitive function and mortality is much, but whether specific cognitive function is related to mortality is unclear. To address the paucity of knowledge on younger populations in the US, we analyzed the association between specific cognitive function and mortality in young and middle-aged adults. We analyzed data from 5,144 men and women between 20 and 59 years of age in the Third National Health and Nutrition Examination Survey (1988–94) with mortality follow-up evaluation through 2006. Cognitive function tests, including assessments of executive function/processing speed (symbol digit substitution) and learning recall/short-term memory (serial digit learning), were performed. All-cause mortality was the outcome of interest. After adjusting for multiple variables, total mortality was significantly higher in males with poorer executive function/processing speed (hazard ratio (HR) 2.02; 95% confidence interval 1.36 to 2.99) and poorer recall/short-term memory (HR 1.47; 95% confidence interval 1.02 to 2.12). After adjusting for multiple variables, the mortality risk did not significantly increase among the females in these two cognitive tests groups. In this sample of the US population, poorer executive function/processing speed and poorer learning recall/short-term memory were significantly associated with increased mortality rates, especially in males. This study highlights the notion that poorer specific cognitive function predicts all-cause mortality in young and middle-aged males.

A follow-up study of neurobehavioral functions in welders exposed to manganese

Welders may be exposed to high amounts of manganese (Mn). In this study 63 welders and 65 referents were followed up with neurobehavioral tests approximately 6 years after the initial examination at baseline. The welders were exposed to the geometric mean (GM) Mn concentration of 116μg/m3 at baseline and 148μg/m3 at follow-up. Their mean duration of employments as welders was 19.5 years at follow-up. Being exposed as a welder was associated with a decline between baseline and follow-up in the performance on the Static Steadiness Test, Finger Tapping Test and Grooved Pegboard Test. However, the decline was also associated with having high concentrations of carbohydrate deficient transferrin in serum (sCDT), indicating high alcohol consumption. When subjects with sCDT above the upper reference limit of the laboratory (≥1.7%) were excluded from the analyses, no difference in the decline in performance was observed between welders and referents for any of the applied neurobehavioral tests. Three welders had developed bradykinesia at follow-up, as assessed by a substantial decline in their Finger Tapping Test performance. They had also experienced a severe decline in Foot Tapping, Grooved Pegboard and Postural Sway Test scores (while blindfolded), while postural tremor as assessed with the CATSYS Tremor 7.0 was normal. Their neurobehavioral test performance at baseline 6 years previously had been normal.

Effects of exposure to mixed volatile organic compounds on the neurobehavioral test performance in a cross-sectional study of US adults

While the environmental exposure to multiple volatile organic compounds (VOCs) is ubiquitous, its neurobehavioral effects are not well understood. We assessed the associations between short-term exposure to VOC mixtures and neurobehavioral test performances on 497 participants in the Third National Health and Nutrition Examination Survey, using quantile and ordinary least squares regression models. We grouped 10 blood VOCs into 3 mixtures based on the principal component analysis, where Mix1 included benzene, toluene, ethylbenzene, m-/p-xylene, o-xylene, and styrene; Mix2 included chloroform and tetrachloroethene; and Mix3 included 1,1,1-trichloroethane and 1,4-dichlorobenzene. We found a general lack of significant adverse effects with exceptions limited to those with the worst performance (i.e. the top 10 percent) in the simple reaction time test, suggesting that these people were potentially more susceptible to impacts of VOC mixtures. However, further research is needed to clarify the neurobehavioral effects of chronic low-level exposure to VOC mixtures among the general population.

The Relationships Between Pesticide Metabolites and Neurobehavioral Test Performance in the Third National Health and Nutrition Examination Survey

ABSTRACT Regression analysis was used to estimate and test for relationships between urinary pesticide metabolites and neurobehavioral test performance in adults, 20 to 59 years old, participating in the third National Health and Nutrition Examination Survey. The 12 pesticide metabolites included 2 naphthols, 8 phenols, a phenoxyacetic acid, and a pyridinol. The 3 neurobehavioral tests included in the survey were simple reaction time, symbol-digit substitution, and serial digit learning. As the 2,4-dichlorophenol, 2,5-dichlorophenol, and the pentachlorophenol concentrations increased, performance on the serial digit learning test improved. As the 2,5-dichlorophenol concentration increased, performance on the symbol-digit substitution test improved. At low concentrations, the parent compounds of these metabolites may act at acetylcholine and γ-aminobutyric acid synapses in the central nervous system to improve neurobehavioral test performance.

Working hours, sleep, salivary cortisol, fatigue and neuro-behavior during Mars analog mission: Five crews study

The buoyancy of humans in exploring extreme space environments has been established during missions to the moon. Long duration missions like mission to Mars however, requires humans to adapt to systemic and complex environments beyond the human body's capacity. Astronauts will encounter both physiological and psychological extremes during this trip. Very few studies are conducted on effect of long duration work and sleepiness on cognitive performance. So, this study was planned to find out effects of leadership responsibility, sleepiness and long duration working hours on cognitive performance. The 30 members (leadership: normal; 10:20) were selected from MDRS crews (Mars Desert Research Station, USA). Neurobehavioral test performance, self-ratings of fatigue and sleepiness, and salivary cortisol levels were evaluated during first day, mid and end day of mission. The leadership group did not show any signs of reduced test performance, even in elevated fatigue and sleepiness. The leadership group had faster reaction times on end of mission as compared to first and after 7day of mission. Salivary cortisol levels were significantly higher in leadership group as compared to normal group. The results suggest that long duration work and sleepiness does not affect the cognitive performance of crew member. Further study is required while taking into account all factors and large sample size to prove this fact.

Neurobehavioral function and organophosphate insecticide use among pesticide applicators in the Agricultural Health Study

Although persistent decrements in cognitive function have been observed among persons who have recovered from clinically overt organophosphate (OP) pesticide poisoning, little is known about the cognitive effects of chronic OP exposures that do not result in acute poisoning. To examine associations between long-term pesticide use and neurobehavioral (NB) function, NB tests were administered to licensed pesticide applicators enrolled in the Agricultural Health Study (AHS) in Iowa and North Carolina. Between 2006 and 2008, 701 male participants completed nine NB tests to assess memory, motor speed and coordination, sustained attention, verbal learning and visual scanning and processing. Data on ever-use and lifetime days of use of 16 OP pesticides were obtained from AHS interviews conducted before testing between 1993 and 2007 and during the NB visit. The mean age of participants was 61years (SD=12). Associations between pesticide use and NB test performance were estimated with linear regression controlling for age and outcome-specific covariates. NB test performance was associated with lifetime days of use of some pesticides. Ethoprop was significantly associated with reduced performance on a test of motor speed and visual scanning. Malathion was significantly associated with poor performance on a test of visual scanning and processing. Conversely, we observed significantly better test performance for five OP pesticides. Specifically, chlorpyrifos, coumaphos, parathion, phorate, and tetrachlorvinphos were associated with better verbal learning and memory; coumaphos was associated with better performance on a test of motor speed and visual scanning; and parathion was associated with better performance on a test of sustained attention. Several associations varied by state. Overall, we found no consistent evidence of an association between OP pesticide use and adverse NB test performance among this older sample of pesticide applicators. Potential reasons for these mostly null results include a true absence of effect as well as possible selective participation by healthier applicators.

Association of Prenatal Exposure to Methylmercury and Fatty Acids with Neurobehavioral Test Performance at Ages 7 Years and 10 Years

Association of Prenatal Exposure to Methylmercury and Fatty Acids with Neurobehavioral Test Performance at Ages 7 Years and 10 Years

Blood lead, serum homocysteine, and neurobehavioral test performance in the third National Health and Nutrition Examination Survey

Regression analysis was used to estimate and test for relationships between blood lead, serum folate, red blood cell folate, serum vitamin B12, serum homocysteine, and neurobehavioral test performance in adults, 20–59 years old, participating in the third National Health and Nutrition Examination Survey. The three neurobehavioral tests included in the survey were simple reaction time, symbol–digit substitution, and serial digit learning. Serum folate, red blood cell folate, and serum vitamin B12 decreased as the blood lead concentration increased. Serum homocysteine increased as the blood lead concentration increased. Serum homocysteine decreased as the serum folate and serum vitamin B12 concentrations increased. Neurobehavioral test performance was not related to the blood lead, serum folate, or serum vitamin B12 concentrations. In adults 20–39 years old, performance on the serial digit learning test improved as the serum homocysteine concentration increased. In adults 40–59 years old, neurobehavioral test performance was not related to the serum homocysteine concentration. Homocysteine may impair cognitive function by acting at N-methyl- d-aspartate receptors, and improve cognitive function by acting at N-methyl- d-aspartate or γ-aminobutyric acid receptors.

The Relationship between Blood Lead Levels and Neurobehavioral Test Performance in NHANES III and Related Occupational Studies

The goals of this study were two-fold: (1) to assess the relationship between blood lead levels and neurobehavioral test performance in a nationally sample of adults from the third National Health and Nutrition Evaluation Survey and (2) to analyze the results from previously published studies of occupational lead exposure that used the same neurobehavioral tests as those included in the survey. Regression models were used to test and estimate the relationships between measurements of blood lead and performance on a simple reaction time, a symbol-digit substitution, and a serial digit learning test in adults aged 20-59 years who participated the survey. Mixed models were used to analyze the data from the occupational studies. The blood lead levels of those participating in the survey ranged from 0.7 to 41.8 microg/dl. The estimated geometric mean was 2.51 microg/dl, and the estimated arithmetic mean was 3.30 microg/dl. In the survey, no statistically significant relationships were found between blood lead concentration and performance on the three neurobehavioral tests when adjusted for covariates. In the occupational studies, the groups exposed to lead consistently performed worse than control groups on the simple reaction time and digit-symbol substitution tests. The results from the survey and the occupational studies do not provide evidence for impairment of neurobehavioral test performance at levels below 25 microg/dl, the concentration that the Centers for Disease Control and Prevention define as elevated in adults. The average blood lead level of the exposed groups in the occupational studies was 41.07 microg/dl, less than 50 microg/dl, the minimum concentration that the Occupational Safety and Health Administration requires for medical removal from the workplace. Given the evidence of impaired neurobehavioral performance in these groups, the 50 microg/dl limit should be reevaluated.

Homocysteine and Cognitive Function in a Population‐Based Study of Older Adults

To assess the relations between homocysteine levels and neurobehavioral test scores representing a broad range of cognitive domains in a population-based study of older adults. Cross-sectional analysis of first-visit data of subjects in the Baltimore Memory Study, a longitudinal study. Specific neighborhoods in Baltimore. Participants were 1,140 randomly selected residents aged 50 to 70 with a mean age+/-standard deviation of 59.3+/-5.9; 65.9% were female, and 54.2% were white and 41.1% African-American. Twenty neurobehavioral test scores in eight cognitive domains. Linear regression models revealed that homocysteine was consistently and strongly associated with worse neurobehavioral test performance, in crude analysis and after control for a large set of important covariates. Associations were observed in all eight cognitive domains assessed but were strongest and most consistent in the domains of simple motor and psychomotor speed, eye-hand coordination/manual dexterity, and verbal memory and learning. On average, an increase in homocysteine levels from the 25th to the 75th percentile, all in the generally accepted normal range, was equivalent in its association with neurobehavioral test scores to an increase of 4.2 years of age. Logistic regression models revealed that, on average, for the neurobehavioral tests associated with homocysteine, subjects in the highest quartile of homocysteine levels were more than two times as likely to be in the lowest quartile of neurobehavioral test scores as those in the lowest quartile. Higher homocysteine levels were associated with worse function across a broad range of cognitive domains, and the magnitude of the associations was large. The data suggest that homocysteine may be a potentially important modifiable cause of cognitive dysfunction.

Effects of the implementation of an 84-hour workweek on neurobehavioral test performance and cortisol responsiveness during testing

This study examined whether long workhours in combination with an extended workweek (12 hours/7 days), as requested by the workers, impaired attention and cognitive performance and whether the degree of hypothalamic-pituitary-adrenal (HPA) activation was related to the response to the performance tasks. A group of 41 male construction workers between 21 and 60 (mean 39) years of age who worked 84 hours a week, with alternate weeks off, was compared with a group of 23 male construction workers between 24 and 65 (mean 43) years of age who had a traditional 40-hour work schedule. Neurobehavioral test performance, self-ratings of fatigue and sleepiness, and salivary cortisol levels were evaluated in a counterbalanced repeated-measures design. The 84-hour group did not show any signs of reduced test performance or elevated fatigue and sleepiness. The 84-hour group had faster reaction times on day 7 than on days 1 and 5. Although the expected activation of the HPA axis was only found in the total study sample when workdays 1 and 5 were collapsed, the HPA activation can be considered normal. The results suggest that an 84-hour work regimen in response to requests from workers does not induce more performance deficits than an ordinary 40-hour workweek. An extended work schedule of 84 hours cannot in the short-term be considered to affect basic mental capabilities negatively.

Cross-Cultural Comparison of Neurobehavioral Performance in Asian Workers

Widely-used neurobehavioral tests have been developed and standardized on Western populations, but studies on subject factors for Asian populations have been very limited. For the effective application and interpretation of neurobehavioral tests in Asian populations, an evaluation of the effects of subject factors, including cultural background, is necessary. A cross-cultural study was conducted to evaluate the effects of cultural background and the interaction between cultural background and education on neurobehavioral tests in Asian populations. The Korean version of the Swedish Performance Evaluation System (Simple Reaction Time, Symbol Digit, and Finger Tapping Speed) and a pegboard test were administered to 537 workers who were not exposed to chemicals at work from Fareast (Korea and Chinese), Central (Uzbekistan and Tajikistan), and South Asia (Sri Lanka and Indonesia). The Fareast Asian group exhibited better performance in adjusted test scores than other Asian groups, achieving significance for Symbol Digit and Finger Tapping Speed in both genders. The magnitude of the effect of cultural background on Symbol Digit was comparable to the effect of about 10 years of education. Cultural background did not modify the relation between years of education and Symbol Digit in either males or females. This study may provide the first evidence that cultural background has a large impact on neurobehavioral test performance, even within Asian populations, and suggests that cultural background is a critical confounding factor that must be controlled in epidemiologic studies which include Asian populations in the sample.

Neurobehavioral test performance in the third National Health and Nutrition Examination Survey

The third National Health and Nutrition Examination Survey (NHANES III) contained three computerized neurobehavioral tests from the Neurobehavioral Evaluation System (NES): simple reaction time, symbol–digit substitution and serial digit learning. The neurobehavioral data that were collected came from a nationally representative sample of adults 20–59 years old. Performance on the tests was related to sex, age, education level, family income and race-ethnicity. Performance decreased as age increased, and increased as education level and family income increased. Differences in performance between sexes, levels of education and racial-ethnic groups tended to decrease as family income increased. The relationship between age and performance on the symbol–digit substitution test varied by education level and by racial-ethnic group. The relationship between age and performance on the serial digit learning test varied by racial-ethnic group. Questionnaire variables that were related to performance on one or more of the tests included the reported amount of last night's sleep, energy level, computer or video game familiarity, alcoholic beverages within the last 3 h and effort. Persons who took the tests in English or Spanish performed differently on the symbol–digit substitution and serial digit learning tests. Performance on all the tests decreased as test room temperature increased.

Feasibility of the Use of Eye Movement Data in the Analysis of Neurobehavioral Test Performance

Better understanding of the functions and abilities underlying some neurobehavioral tests would assist the assessment of the consequences to the health or well-being of exposed populations for which decrements in such tests have been found. Eye movements, which can be useful in evaluating specific theories of visual and cognitive processes, were measured while a single participant completed the NES Symbol-Digit Substitution test. Relationships between the durations and the frequencies of eye fixations within different parts of the test material and overall test performance were examined. The overall pattern of eye-movement behavior observed was as predicted: fixations within three regions of visual interest were made, usually in the order lower matrix, upper matrix, keyboard. Both the upper matrix fixation latency and the number of regional fixations made per item were found to be strongly associated with overall item response latency. This suggests that speed and efficiency of searching and the ability to maintain concentration appeared to be key attributes related to test performance for this participant. For suitable tests, eye-movement data may be useful for assessing and measuring the latencies of subtask components in a real test situation. Monitoring eye movement represents an alternative methodology to using sub test composites, or factor analysis, as a means of tapping into the functions underlying neurobehavioral test performance.

Neurobehavioral Deficits in Persian Gulf Veterans: Additional Evidence from a Population-Based Study

Reports of low-concentration nerve gas exposures during the Gulf War (GW) have spurred concern about possible health consequences and symptoms reported by many returning veterans. The Portland Environmental Hazards Research Center is studying veterans from the northwest United States who report persistent, unexplained "Gulf War" symptoms (cases) and those who do not report those symptoms (controls). An epidemiological survey focused on exposures and symptoms was mailed to a random sample of GW veterans from Oregon and southwestern Washington. Volunteers recruited from survey respondents agreed to undergo a thorough medical examination and psychological and neurobehavioral assessment. Persistent symptoms with no medical explanation associated with Persian Gulf service (e.g., fatigue, muscle pain, memory deficits) beginning during or after the war qualified respondents as cases. The 239 cases with unexplained symptoms and the 112 controls without symptoms were administered a computerized assessment battery of 12 psychosocial and 6 neurobehavioral tests. Replicating and extending previous interim findings, a subgroup of veterans emerged from the initial analysis in the form of extreme outliers which produced a visually and quantitatively obvious bimodal distribution. This led, as it had previously, to analyses of the outliers as a separate group (labeled "slow ODTP"), which confirmed the initial findings of neurobehavioral differences between the outliers and the other cases and controls and provided more convincing evidence that the majority of cases who report neurobehavioral symptoms have no objective evidence of neurobehavioral deficits. However, the larger group of symptomatic veterans do have highly significant and compelling evidence of psychological distress based on scores from 11 separate psychological tests. Whereas the cases differed from the controls by poorer neurobehavioral test performance, extraction of the slow ODTP participants (almost all cases) eliminated neurobehavioral performance differences between the remaining cases and the controls and provided support for the hypothesis that the slow ODTP cases might have been from the unhealthy end of the GW population prior to the war. However, there was no evidence of poor motivation, pre-GW educational differences, or greater association with abnormal psychological function in this group than in other cases or controls.

Neurobehavioral test performance among apprentice painters: baseline data.

In the debate on chronic effects of solvent use, it is often difficult to find information on the cerebral health status of subjects before any exposure has occurred. The objective of this study was to obtain baseline data by examination of workers at the beginning of their occupational lives. This study compares the performance of 57 apprentice painters, mean age 16.6 +/- 1.2 years, with that of 62 apprentices, mean age 16.2 +/- years, drawn from other manual trades involving no significant exposure to solvents. Their performances were compared twice over a period of 3 years using a series of behavioral tests chosen from a translated version of the Neurobehavioral Evaluation System (NES). There were no major differences in performance between the apprentices, except for the verbal ability test, which showed lower results for painters. This can be explained by factors such as socioeconomic background, previous schooling, or mother tongue, and raises the question of whether it is appropriate to use such a test to adjust for the influence of premorbid ability in elderly exposed workers.

Effect of overtime work on cognitive function in automotive workers

The present investigation examined whether increased overtime work predicts impairment in cognitive performance in the domains of attention, executive function, and mood. The behavioral and cognitive functions of 248 automotive workers were measured by a neurobehavioral test performance. Overtime, defined as number of hours worked greater than 8 h a day or greater than 5 d a week, was calculated from company payroll records for the week before the test day. The number of consecutive days worked before the test day was also determined. Cross-sectional data analysis by multiple linear regression, after adjustment for the effects of age, education, gender, alcohol intake, repeated grade in school, acute petroleum naphtha exposure, shift worked, job type, number of consecutive days worked before the test day, and number of hours worked on the test day before the testing, demonstrated that increased overtime was significantly associated with impaired performance on several tests of attention and executive function. Increased feelings of depression, fatigue, and confusion were also associated with increased overtime work. In addition significant interaction effects were observed for job type but not for naphtha exposure. The findings support the hypothesis that overtime work results in impaired cognitive performance in the areas of attention and executive function and that both overtime hours and the number of consecutive days worked prior to a test day affect mood.

Decrements in neurobehavioral performance associated with mixed exposure to organic and inorganic lead.

In 1990, 222 current employees of a chemical facility in the eastern United States that manufactured tetraethyl lead were administered a neurobehavioral test battery, tests of olfactory function and peripheral vibration threshold, and questionnaires that assessed neuropsychiatric symptoms. A cumulative variable of exposure to inorganic and organic lead was derived from 12 years of personal industrial hygiene sampling data and an occupational history interview that assessed work in each of 29 exposure zones in the lead area. The range of assigned exposure intensities in these 29 zones was 4-119 micrograms/m3 for organic lead and 1-56 micrograms/m3 for inorganic lead. Cumulative lead exposure and exposure duration were defined as categorical variables (four groups) in multiple linear regression models. The adjusted mean differences in neurobehavioral test scores were estimated by comparing the average scores of the moderate, high, and highest exposure groups with the low exposure (reference) group. After adjustment for premorbid intellectual ability, age, race, and alcohol consumption, neurobehavioral test scores were poorer as measures of both cumulative lead exposure and exposure duration increased; many of the associations evidenced dose-response relations. Associations were observed in most cognitive and functional domains tested, but were most common in two domains: manual dexterity and verbal memory/learning. On the affected neuropsychologic measures, the groups with the highest exposure averaged scores 5-22% lower than those of the reference groups. Overall, the data revealed generally consistent and coherent associations between two measures of lead exposure and poorer neurobehavioral test performance.