Impact of cognitive reserve on the relationship of lead exposure and neurobehavioral performance.

BACKGROUND: Cognitive reserve (CR)--a construct studied in many neurologic disorders--refers to the maintenance of cognitive performance in spite of ongoing underlying brain pathology. OBJECTIVE: We hypothesized that a dose-effect relationship would exist between chronic occupational lead exposure and cognitive effects in workers with low CR but not in workers with high CR and identical lead exposure, and that level of CR would not influence the relationship between lead exposure and motor performance. METHODS: We stratified currently employed lead smelter workers by Wide Range Achievement Test-R for reading (WRAT), a recognized measure of CR, into loCR and hiCR groups. From these two groups we matched 56 pairs on working lifetime weighted blood lead (TWA). We performed a factor analysis on 14 neuropsychological outcome variables. Within each CR group regression analyses after adjusting for age, alcohol use, and depression scale score tested for dose-effect relationships between TWA and outcome variables. RESULTS: Both CR groups had comparable age, years employed, alcohol use, and current blood lead levels. Factor analysis provided three factors and five tests used in the regression analyses. Significant dose-effect relationships between TWA and cognitive tests present only in the loCR group included Attention Factor and Digit Symbol. Both CR groups demonstrated significant dose-effect relationships on the Motor Factor. CONCLUSION: This study found that cognitive reserve protects against the effect of chronic lead exposure on select measures of cognitive performance but not on motor performance.

Differential effects of lead exposure on components of verbal memory.

AIMS: To determine if verbal learning and memory requiring acquisition and retention of information is differentially affected by lead exposure. METHODS: The Rey Auditory Verbal Learning Test (RAVLT), a test of verbal learning and memory, was administered to 256 English speaking lead smelter workers who had a mean (SD) age of 41 (9.4) years and employment duration of 17 (8.1) years. Lead exposure variables, based on up to 25 years of prior blood lead data, included a mean (SD) current blood lead (PbB) of 28 (8.8) microg/dl, working lifetime time weighted average blood lead (TWA) of 39 (12.3) microg/dl, and working lifetime integrated blood lead index (IBL) of 728 (434.4) microg-y/dl. Associations of these chronic and recent lead exposure variables with measures from the RAVLT were modelled through multiple linear regressions after controlling for age and educational achievement. RESULTS: PbB was not associated with any of the RAVLT variables. However, TWA and IBL contributed significantly to the explanation of variance of measures of encoding/storage and retrieval but not to immediate memory span, attention, and learning. Grouping study participants by RAVLT performance according to three recognised clinical memory paradigms showed significantly higher TWA and IBL in the group with "generalised memory impairment" after adjusting for age and educational achievement. We examined recall mechanisms in each group by serial position in the word list and found stronger primacy (recall of words from the beginning of the list) in the "no impairment" and "retrieval difficulties" groups while the "generalised memory impairment" group had better performance on recency (recall of words from the end of the list). CONCLUSIONS: Lead exposure over years and not PbB interfered with the organisation and recall of previously learned verbal material. Chronic lead exposure affects encoding/storage and retrieval of verbal information.

The role of quantitative neurological examination in clinical neurotoxicology.

The use of the clinical neurological examination to document abnormal signs in suspected neurotoxic disorders is described, recognizing that identifying an abnormal examination does not establish the cause of the problem. Several forms of quantitative tests of neurological function are discussed, and their application to the evaluation of neurotoxic disorders is reviewed. Although results of such testing are rarely specific for toxic exposure, these measures have important application in sequential evaluations to document small changes in neurologic function over time.

The factor structure of the Profile of Mood States (POMS) and its relationship to occupational lead exposure.

The Profile of Mood States (POMS) is an instrument composed of six mood scales that were developed using clinical populations. This study examines the replicability of the POMS factor structure in lead-smelter workers and its association with demographic variables and lead exposure. Four hundred sixty-seven current and retired smelter workers completed the POMS, and a factor analysis was performed on the individual items. Two multiple regressions in the currently employed workers (n = 340) with a mean age of 40 years (range, 20-63 years) were used to compare the relationship of the resulting POMS factors with demographic characteristics and two measures of occupational lead exposure: current blood lead level (mean, 28 micrograms/dL; range, 4-62 micrograms/dL) and working-lifetime integrated blood lead level (mean, 711 micrograms-yr/dL; range, 1-1537 micrograms-yr/dL). Factor analysis produced one factor, labeled "general distress," that was composed mainly of items from five of the six POMS subscales (anger, confusion, depression, fatigue, and tension) and a second factor labeled "psychological adjustment." Demographic variables, including education, age, and alcohol use, were significantly related to the "general distress" factor score. After the effects of the demographic variables were accounted for, the "general distress" factor was significantly related to integrated blood lead level but not current blood lead level. Integrated blood lead level, a measure of cumulative lead exposure that included prior high exposure, was significantly related to the POMS "general distress" factor, while a current blood lead level that was relatively low was unrelated. As expected, POMS psychological adjustment was not related to lead exposure. Factor analysis did not support the use of six separate POMS subscales in this occupational population.

Curvilinear relationship between blood lead level and reaction time. Differential association with blood lead fractions derived from exogenous and endogenous sources.

Prior studies demonstrate an inconsistent relationship between occupational inorganic lead exposure and simple reaction time (SRT) performance. In this study, we administered a computerized SRT test to 78 currently employed lead smelter workers and then investigated the relationship between different measures of blood lead and components of SRT performance. The measures of blood lead included current blood lead (PbB) and mathematically derived blood lead fractions from the environment (PbB-env) and from bone (PbB-bn). Measures of SRT performance, obtained from 44 trials with interstimulus intervals (ISIs) ranging from 1 to 10 seconds, included median SRT (SRT-md), mean SRT for ISIs between 1 and 5 seconds (SRT-1-5), and mean SRT for ISIs between 6 and 10 seconds (SRT-6-10). Multiple regression analysis after adjustment for age and education revealed a curvilinear relationship between PbB and SRT-md. As PbB increased from 0 to 30 micrograms dl-1, SRT-md decreased, and only with PbB levels above 30 micrograms dl-1 did SRT-md increase. PbB terms accounted for 13.7% of the variance in this SRT measure (P < 0.01). The longer ISI variable, SRT-6-10, was found to be more strongly related to PbB, to have lesser variability across ISIs, and to be unrelated to age. Additional multiple regression analysis to examine the relationship between components of SRT and the PbB fractions, PbB-env and PbB-bn, showed only PbB-env to account for significant variance in SRT-md, (14.4%, P < 0.01), SRT-1-5 (9.7%, P < 0.03), and SRT-1-6 (15%, P < 0.01). We conclude that the relationship between PbB and SRT is U-shaped, that the SRT measure SRT-6-10 has properties that make it the preferred measure of SRT performance in future studies, and finally that only PbB-env, and not PbB-bn, is related to components of SRT.

Differential contribution of current and cumulative indices of lead dose to neuropsychological performance by age.

We examined measures of lead dose that reflect intensity of exposure and cumulative exposure for differential association with neuropsychological functional domains and with neuropsychological performance by age. Eighty active lead smelter workers assessed for verbal memory and visuomotoric skills had a mean (range) age of 44 (24-64) years, duration of employment of 20 (4-26) years, education of 8 (0-13) grades, current blood lead (B-Pb) of 26 microgPb dl(-1) (13-43), working lifetime weighted average blood lead (TWA) of 42 microgPb dl(-1) (17-57), working lifetime integrated blood lead (IBL) of 903 microgPb-yr dl(-1) (81-1,436) and bone lead (bone-Pb) of 41 microgPb (g bone mineral)(-1) (-12-90). Multiple linear regression after adjusting for age and education showed a significant amount of variance in verbal memory (Rey Auditory Verbal Learning Test and Verbal Paired Associates) explained only by measures of lead dose intensity, B-Pb, and TWA. Visuomotoric ability (Grooved Pegboard [GP] and Digit Symbol) had significant variance accounted for by measures of both lead dose intensity, TWA, and of cumulative lead dose, IBL, and bone-Pb. The relationship between bone-Pb and GP was curvilinear in older workers, with increasingly slower performance above a bone-Pb threshold of 20 microgPb (g bone mineral)(-1). Examination of age-related change in GP with exposure using IBL, a surrogate for cumulative lead dose in the brain, showed enhanced age-related change in older workers with high IBL. These findings suggest that the older nervous system provides a substrate more susceptible to the effects of chronic lead exposure.

Relation of cumulative exposure to inorganic lead and neuropsychological test performance.

OBJECTIVES: To determine if measures reflecting chronic occupational lead exposure are associated with performance on neuropsychological tests. METHOD: 467 Canadian male lead smelter workers (mean (SD) age 43.4 (11.00) years, education 9.8 (3.18) years, years of employment 17.7 (7.43), and current blood lead concentration (B-Pb) 27.5 (8.4) micrograms dl-1) were given a neuropsychological screening battery. Time weighted average (TWA) and time integrated blood levels (IBL) were developed from B-Pb records obtained through regular medical monitoring (mean (range) TWA 40.1 (4.0-66.4) micrograms dl-1, mean IBL 765.2 (0.6-1625.7) micrograms-y dl-1). 14 neuropsychological variables were included in three multivariate analyses of covariance, with each exposure variable as the grouping variable (high, medium, and low) and age, education, score on a measure of depressive symptoms, and self reported alcohol use as the covariates. Groups did not differ in history of neurological conditions. RESULTS: Neither the B-Pb, TWA, nor IBL was significant by multivariate analyses of covariance (MANCOVA). When years of employment, a suppressor variable, was included as a covariate, IBL exposure groups differed significantly on digit symbol, logical memory, Purdue dominant hand, and trails A and B. CONCLUSIONS: A dose-effect relation was found between cumulative exposure (IBL) and neuropsychological performance at a time when current B-Pb concentrations were low and showed no association with performance.

Relationship between bone lead and other indices of lead exposure in smelter workers.

The relationship between blood lead (B-Pb) indices and bone lead was determined in 81 smelter workers. Lead exposure had changed dramatically since the smelter opened 27 years ago; therefore, workers were stratified by years employed. Seventy workers, hired prior to 1979 (Group 1), had a mean (range) age of 46 years (35-64), mean years of employment 23 (16-27), mean years of education 8 (0-13), mean B-Pb 26 micrograms dl-1 (13-43), mean time-weighted average (TWA) B-Pb 44 micrograms dl-1 (23-57) and mean integrated blood lead index (IBL), 983 micrograms Pb year dl-1 (537-1437). Eleven workers, hired after 1978 (Group 2), had a mean age of 34 years (24-55), mean years of employment 11 (5-14), mean years of education 11 (8-12), mean B-Pb 26 micrograms dl-1 (8-13), mean TWA 33 micrograms dl-1 (17-44) and mean IBL 378 micrograms year dl-1 (81-555). Bone lead measured in the mid-tibia used K-X-ray fluorescence. Mean bone lead in Group 1 and Group 2 was 45 (-7-90) and 11 (-12-33) micrograms Pb (g bone mineral)-1, respectively. Linear regression analysis demonstrated a significant relationship between bone lead and B-Pb indices. B-Pb accounted for 10.8%, years employed 12.7%, TWA 31.4% and IBL 36% of the bone lead variance. Using a previously established relationship, the mean bone lead predicted a mean B-Pb content of approximately 8 micrograms dl-1 in Group 1 as compared to 2 micrograms dl-1 in Group 2. The mean B-Pb was 26 micrograms dl-1 in both groups despite differences in contribution from bone stores. Differential contribution of ambient air lead to B-Pb in the two groups of current workers with similar job titles may reflect use of personal protective equipment.

Carotid high-low flow ratio most accurately predicts significant stenosis.

The Doppler quantitative carotid blood flow technique is a dynamic, physiologic tool that measures carotid blood flow, velocity, and vessel diameter. A high-low flow ratio that reflects variation in side-to-side carotid flow is calculated. We determined the accuracy of this method for the detection of carotid stenosis in 70 patients with cerebrovascular disease in whom cerebral angiography was the gold standard. The most sensitive measure proved to be high-low flow ratio, which was abnormal in 19 of 23 patients (82.6% sensitivity). The patients with high-grade stenosis had contralateral elevated flow compared with that of patients without high-grade stenosis and age-specific normal subjects. The quantitative carotid blood flow technique reflects compensatory alterations in flow produced by significant carotid disease, with an abnormal high-low flow ratio having the highest positive predictive value. This technique can be used independently to screen for carotid stenosis and as an adjuvant to carotid duplex scanning in the investigation of extracranial carotid disease.

The influence of weight reduction and exercise regimes upon the personality profiles of overweight males.

In the present study, the MMPI was used to detect personality changes in 53 overweight, yet otherwise healthy, males who were participating in either a weight reduction or an aerobic exercise conditioning program. Analysis of pre- and post-intervention scores revealed that only the participants in the aerobic conditioning group demonstrated the predicted desirable psychological changes. More specifically, this group displayed significant clinically desirable changes on the Hs, PD, and HEA scores. Similar to the weight loss participants, a demographically matched nonintervention comparison group showed none of these desirable changes and actually yielded a significant increase on the D scale. However, when compared to this "normal" group, both intervention programs showed statistically significant differences on at least two MMPI scales.

Comparison of computerized and examiner-administered neurobehavioral testing techniques.

To better understand the relationship of newly developed computerized neurobehavioral tests to their examiner-administered counterparts, performance on four pairs of tests was compared among 185 solvent-exposed workers in the paint manufacturing industry. Two approaches to the comparison of the test methods (computer or examiner) were employed: (1) the multitrait-multimethod correlation matrix and (2) linear regression modeling of the difference scores between pairs of tests (same functional domain, different test formats). The data revealed that the validity criteria of the multitrait-multimethod technique were met for the tests of simple visual reaction time and attention-concentration (digit symbol substitution). Linear regression analyses demonstrated that the digit symbol substitution and visual memory test pairs were differentially affected by age, vocabulary, solvent exposure, or manual dexterity. Overall, this latter approach holds promise as a means of understanding test format similarities and differences.

Current perception threshold screening for carpal tunnel syndrome.

Screening for the onset of carpal tunnel syndrome (CTS), which is associated with excess ergonomic stresses of the wrist and hand, is a major concern in occupational medicine. CTS questionnaires, physical examinations, and quantitative sensory function determination through neuroselective current perception threshold (CPT) measurements were obtained from the median digital nerves of 16 assembly line workers who were symptomatic with hand pain. Median nerve evaluations by CPT detected sensory abnormalities in 75% of the workers, and abnormalities in 50% of the workers were detected by clinical evaluations (p less than .05, df = 22). CPT abnormalities were characterized as "hypoesthetic" in 25% and hyperesthesic in 42% of the workers. The noninvasive, nonaversive CPT technique provided sensitive and easily obtained quantitative measures. Regular use of this procedure in the occupational setting may assist in preventing the development of advanced CTS for it provides early detection of median nerve abnormalities.

Solvent-associated olfactory dysfunction: not a predictor of deficits in learning and memory.

OBJECTIVE: The aim of the study was to evaluate associations between olfactory dysfunction and aberrations in learning and memory after chronic occupational exposure to mixed hydrocarbon solvents. METHOD: This was a cross-sectional, epidemiologic study of 187 paint manufacturing workers. The authors administered quantitative tests of olfactory function (the University of Pennsylvania Smell Identification Test) and neurobehavioral function (eight computer- and examiner-administered tests of learning and memory) to workers for whom detailed information was available on lifetime occupational exposure to solvents. RESULTS: Olfactory function test scores were positively correlated with performance on seven of eight of the tests of learning and memory in bivariate analyses. After adjustment for important confounding variables (i.e., age, vocabulary score, and cumulative exposure to hydrocarbon solvents) with multiple linear regression, olfactory function scores predicted performance only on the Wechsler Memory Scale Delayed Logical Memory test. CONCLUSIONS: Overall, the data did not reveal that olfactory dysfunction was correlated with decrements in various memory functions.

Relationship of obesity and physical fitness to cardiopulmonary and metabolic function in healthy older men.

The relationship of obesity and physical fitness (VO2max) to cardiopulmonary and metabolic function was examined in 132 healthy obese, nonsmoking men age 45-79. Obese men with higher VO2max had lower % body fat and waist-to-hip ratio (WHR) than obese men with low VO2max. The obese subjects with high WHR (upper body fat distribution) had higher systolic blood pressure, hyperinsulinemia and impaired glucose tolerance, lower high density lipoprotein cholesterol (HDL-C), and higher triglyceride (TG). VO2max (ml/kg FFM.min) was lower in the older men (r = -0.54, p less than .001), and 32% of the variation was accounted for by age and the one-second forced expiratory volume. Although pulmonary function was normal, 50% of the variability was predicted by age, height, and VO2max or WHR. Glucose tolerance and insulin correlated better with VO2max and indices of body composition than with age, while plasma TG and HDL-C correlated with body composition, not VO2max or age. Thus, while age affects the cardiopulmonary and metabolic function of obese older men, physical inactivity, obesity, and an abdominal body fat distribution (increased WHR) contributed significantly to their reductions in physiological function.

Dose-related subclinical neurobehavioral effects of chronic exposure to low levels of organic solvents.

One hundred eight-seven workers (mean age +/- SD; 42 +/- 8.8 years) in two paint manufacturing plants were examined to determine if sustained low-level exposure to mixed organic solvents resulted in the painters' syndrome (a psycho-organic syndrome). The test battery consisted of a medical and occupational questionnaire, the Present State Examination, the Zung Depression Scale, the Scandinavian Questionnaire 16, a neuropsychological battery, and vibration thresholds. Solvent exposure, expressed as total hydrocarbon of combined selected solvents, was quantitated using 13-15 years of personal breathing zone samplings. Linear regression analysis controlling for several confounding variables demonstrated significant correlations between increasing exposure to mixed organic solvents and neurobehavioral performance for vibration threshold and several neuropsychological tests. Dose-related effects of chronic solvent exposure on neurobehavioral outcomes (all subclinical) were shown, but "typical" symptoms characteristic of the painter's syndrome were not found.

Memory complaints in older adults. Fact or fiction?

Complaints of poor memory by patients may be an early symptom of a pathologic process like Alzheimer's disease. It is therefore important to determine if patients' complaints of memory impairments are an accurate reflection of real memory disturbance. The relationship between memory complaints (metamemory) and objective memory performance, mood, age, verbal intelligence, and sex was examined in a group of 199 healthy, community dwelling adults (39 to 89 years old). Memory complaints demonstrated a stronger association with depressed mood than with performance on memory tests. Increasing reports of depressive symptoms were associated with more overall memory complaints. Verbal intelligence, age, and sex also contributed to memory complaints. Patients with higher verbal intelligence reported fewer complaints and placed less emphasis on forgetting. Older individuals reported greater frequency of forgetting and greater frequency of using memory techniques. Specific types of memory complaints, seriousness of forgetting, and types of memory aids employed are also described. These results showed that self-rating of memory disturbance by older adults may be related more to depressed mood than to poor performance on memory tests.