Executive function modifies the relationship between occupational lead exposure and complex figure test performance.

OBJECTIVES: To determine if chronic lead exposure is associated with non-verbal memory performance and if this association is affected by organisation strategies, a component of executive functions. METHODS: We administered the Rey-Osterrieth Complex Figure (ROCF) test, both copy (ROCF-C) and 30-min delayed recall (ROCF-DR), to 358 current lead smelter workers with a mean (SD) age of 41 (9.1) years, education of 11 (2.7) years, and working lifetime-weighted average blood lead (TWA) of 39 (12.0) µg/dl. Copy and delay organisation scores, surrogates for executive functions, were developed for ROCF-C and ROCF-DR. We used multiple regression analyses to examine the relationship between TWA and ROCF performance, organisational scores, and the interaction of organisational scores and TWA after adjusting for relevant covariates. RESULTS: Organisational scores, while not associated with years of education, were significantly correlated with ROCF-C and ROCF-DR performance. We found a significant relationship between TWA and ROCF-DR but not with ROCF-C performance. The interactions of TWA by copy organisation and TWA by delay organisation were significant for ROCF-DR with a significant dose-effect relationship only in participants with lower organisational scores. CONCLUSIONS: Chronic lead exposure was significantly associated with complex figure test delayed recall but not copy performance. Organisational strategies, a component of executive functions, served as effect modifiers of the relationship between lead exposure and non-verbal memory. With increasing TWA exposure workers with good organisational strategies maintained performance on the complex figure test while workers with poor organisational strategies demonstrated decreasing performance.

The association of lead exposure and motor performance mediated by cerebral white matter change.

The goals were to determine if lead exposure is associated with cerebral white matter changes (WMC) and if so, does WMC mediate the relation between lead and psychomotor slowing as measured by Grooved Pegboard (GP). In the literature, age is the strongest predictor of WMC and therefore 61 lead smelter workers age 50 and under were included in the study population. Mean (range) age was 40 (23-50) years, years of education was 9 (0-13), duration of employment was 19 (1-26), current blood lead (PbB) was 29 (16-42) microg/dl, working lifetime weighted integrated blood lead (IBL) was 826 (65-1451) microg year/dl, working lifetime weighted average blood lead (TWA) was 42 (17-59) microg/dl, and bone lead (PbBn) was 39 (-12-90) microg Pb/g bone mineral. WMC, recorded as hyperintensities on T2-weighted MRI of the brain were graded. Lead variables were entered in a logistic regression attempting to differentiate normal versus abnormal MRI, after controlling for age and cerebrovascular risk factors. Direct effects of lead on GP and indirect effects of lead on GP through WMC was modeled using multiple linear regression analyses after controlling for the covariates. WMC were present in 23% of MRIs. Logistic regression of WMC on lead exposure metrics demonstrated significantly elevated odds ratios for IBL, TWA, and PbBn after the covariates. Of the lead exposure variables, IBL (beta=0.339, p<0.10) had a larger direct effect on GP after adjusting for the covariates than PbBn (beta=0.265, p<0.10). After adjusting for the lead term and covariates WMC accounted for an additional effect on GP performance after PbBn (beta=0.261, p<0.10) and after IBL (beta=0.278, p<0.05). Path analysis demonstrated that some of the relationship of both PbBn and IBL with GP is mediated by WMC.

Effect of lead exposure and ergonomic stressors on peripheral nerve function.

In this study we investigated the effect of recent and chronic lead exposure, and its interaction with ergonomic stressors, on peripheral nerve function. In a cross-sectional design, we used retrospective exposure data on 74 primary lead smelter workers. We measured blood and bone lead levels and, from historical records, calculated lead dose metrics reflecting cumulative lead exposure: working-lifetime integrated blood lead (IBL) and working-lifetime weighted-average blood lead (TWA). We additionally created five metrics related to IBL that cumulated exposure only above increasing blood lead levels ranging from 20 to 60 microg/dL (IBL20-IBL60). Current perception threshold (CPT) assessed large myelinated (CPT2000), small myelinated (CPT250), and unmyelinated (CPT5) sensory nerve fibers. Using multiple linear regression, we modeled CPT on the different measures of lead dose after adjusting for relevant covariates. CPT had a curvilinear relationship with TWA, with a minimum at a TWA of 28 microg/dL. Both TWA and IBL accounted for a significant percentage of the variance of CPT2000 (DeltaR2 = 8.7% and 3.9%, respectively). As the criterion blood lead level increased from IBL20 through IBL60, so did the percentage of CPT2000 variance explained, with DeltaR2 ranging from 5.8% (p < 0.03) for IBL20 to 23.3% (p < 0.00) for IBL60. IBL60 also significantly contributed to the explanation of variance of CPT250 and significantly interacted with ergonomic stressors. Measures of chronic blood lead exposure are associated with impairment of large and small myelinated sensory nerve fibers. This effect is enhanced at the highest doses by ergonomic stressors.

Association of chronic and current measures of lead exposure with different components of brainstem auditory evoked potentials.

Current blood lead (PbB) affects brainstem auditory evoked potentials (BAEPs) in children but whether a similar association exists in lead-exposed adults remains unclear. During an investigation of the neurobehavioral effects of occupational lead exposure we performed BAEPs on 359 English- and French-speaking, currently exposed, male, lead smelter workers having a mean (S.D.) age of 41 (9.0) years, employment duration of 17 (7.9) years, PbB of 28 (8.4)microg/dl, working-lifetime weighted average blood lead (TWA) of 39 (11.9) microg/dl, and working-lifetime integrated blood lead (IBL) index of 719 (421.0) microg.year/dl, the latter a measure of cumulative lead dose. BAEPs were performed at a click stimulation of 10s(-1) for 1000 repetitions, at an intensity 75dB above the threshold of the ear tested. Right-sided latencies for peak waves I, III, and V and the corresponding interpeak intervals (IPI) I-V, I-III, and III-V were chosen for analyses. Age correlated significantly with BAEPs, PbB, TWA, and IBL. Partial correlation analyses adjusting for age found PbB and TWA significantly associated with wave I latency r=0.13, P<0.01 and r=0.11, P<0.05, respectively, and IBL significantly associated with wave III latency r=0.16, P<0.01. The contribution of age, PbB, TWA and IBL to the variances of different BAEPs was assessed using multiple regression analysis. In the regression model of the full group, after the contribution of age, PbB and TWA accounted for significant variance of wave I, Deltar(2)=1.8, P<0.01 and Deltar(2)=1.2%, P<0.04, respectively, and IBL accounted for significant variance of wave III latency, Deltar(2)=2.8%, P=0.00 and I-III interpeak interval, Deltar(2)=1.4%, P<0.03. Four groups similar in age were created with increasing abnormalities based upon clinical cut-off scores for wave I latency and I-V interpeak interval. PbB, TWA, and IBL were significantly higher in the group with abnormalities of both latency in wave I and IPL I-V. Lead exposure interferes with BAEPs in a dose-dependent manner. Current lead exposure in this population of lead smelter workers preferentially affected conduction in the distal auditory nerve while chronic lead exposure appeared to impair conduction in the auditory nerve and the auditory pathway in the lower brainstem.

Pattern of blood lead levels over working lifetime and neuropsychological performance.

The authors examined the impact on neuropsychological performance of past high lead exposure, followed by lower proximate lead exposure, in 2 groups of smelter workers selected on the basis of their patterns of blood lead levels (BLLs) over time. Prior to 1980 (past exposure), both groups had more than 90% of their BLLs > or = 40 microg/dl. During and subsequent to 1980 (proximate exposure), those subjects with more than 90% of their BLLs remaining at > or = 40 microg/dl were assigned to the high-high (H-H) pattern group (n = 40); whereas those with 90% of levels below 40 microg/dl were assigned to the high-low (H-L) pattern group (n = 40). Means (and standard deviations) for pre-1980 time-integrated blood lead (IBL) levels were similar for the H-H pattern [633.2 (202.2) microg/yr-dl] and the H-L pattern [556.5 (144.8) microg/yr x dl]; however, IBLs from 1980 on were significantly different [H-H pattern = 646.9 (58.70) microg/yr x dl and H-L pattern = 408.8 (46.37) microg/yr x dl; p < 0.0001]. Age, education, and years of employment were similar for both groups. Examination of 5 neuropsychological measures revealed that verbal memory was significantly better in the H-L pattern group than in the H-H group. Multivariate examination of the data showed that pattern of exposure contributed significantly to verbal memory performance, after adjustment for the covariates, current BLL, and IBL. A partial correlation analysis between verbal memory and IBL for past high exposure showed an association with H-H pattern, but none with H-L pattern. Pattern of BLLs over a working lifetime contributed unique variance to verbal memory. Absence of an association between past high lead exposure and verbal memory in the H-L pattern group suggests that reversibility of function may occur when proximate BLL is maintained below 40 microg/dl.

The interaction of education and cumulative lead exposure on the Mini-Mental State Examination.

The effect of lead exposure on neurobehavioral performance is modified by age. Whether educational achievement can serve as an effect modifier on the lead-cognitive performance relationship is examined. The Mini-Mental State Examination (MMSE) and the reading section of the Wide Range Achievement Test-Revised (WRAT-R), a measure of educational achievement, were administered to 256 lead smelter workers. The workers had a mean (standard deviation) age of 41 (7.9) years, education of 10 (2.8) years, employment duration of 17 (8.1) years, current blood lead of 28 (8.8) micrograms/dL, and working lifetime integrated blood lead index (IBL) of 725 (434) micrograms-yr/dL. The median (range) MMSE score was 29 (19 to 30). Multiple linear regression assessed the contribution of age, WRAT-R, education, alcohol intake, cigarette use, IBL, and IBL x WRAT-R on MMSE performance. A significant IBL x WRAT-R interaction examined by stratification found a significant dose-effect relationship between IBL and MMSE, but only in the 78 workers with a WRAT-R reading grade level below 6 years. Workers with higher educational achievement compensated for the effect of lead on cognitive performance.