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 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.

Venoconstrictive thigh cuffs impede fluid shifts during simulated microgravity.

BACKGROUND: This study determined the efficacy of venoconstrictive thigh cuffs, inflated to 50 mmHg, on impeding fluid redistributions during simulated microgravity. METHODS: There were 10 healthy male subjects who were exposed to a 2-h tilt protocol which started in the standing position, and was followed by 30 min supine, 30 min standing, 30 min supine, 30 min of -12 degrees head down tilt (HDT, to simulate microgravity), 15 min of HDT with venoconstrictive thigh cuffs inflated, a further 10 min of HDT, 5 min supine, and 10 min standing. To increase the sensitivity of the techniques in an Earth-based model, 12 degrees HDT was used to simulate microgravity effects on body fluid shifts. Volume changes were measured with anthropometric sleeve plethysmography. RESULTS: Transition to the various tilt positions resulted in concomitant decrements in leg volume (Stand [STD] to Supine [SUP], -3.0%; SUP to HDT, -2.0%). Inflation of the venoconstrictive thigh cuffs to 50 mmHg, during simulated microgravity, resulted in a significant 3.0% increase in leg volume from that seen in HDT (p < 0.01). No significant changes in systemic cardiovascular parameters were noted during cuff inflation. CONCLUSIONS: We conclude that venoconstrictive thigh cuffs, inflated to 50 mmHg for 15 min during 12 degrees HDT, can create a more Earth-like fluid distribution. Cuffs could potentially be used to ameliorate the symptoms of cephalad edema seen with space adaptation syndrome and to potentiate existing fluid volume countermeasure protocols.

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.

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.

Predictors of verbal fluency (FAS) in the healthy elderly.

The Verbal Fluency Task (FAS), sensitive indicator of brain injury, was examined in a population of healthy elderly (N = 199, aged 40 to 89 years). The present study was conducted to examine the relative contributions of age, sex, education, verbal intelligence, and specific cognitive abilities to FAS performance. Significant effects were found for vocabulary and sex, although no aging effect was found. Separate norms for sex and level of verbal intelligence are presented. Results indicated that ability to quickly organize information and formulate effective recall strategies played a critical role in good FAS performance.