Cumulative lead exposure in community-dwelling adults and fine motor function: Comparing standard and novel tasks in the VA Normative Aging Study

Abstract

Background and aims

Lead exposure in children and occupationally exposed adults has been associated with reduced visuomotor and fine motor function. However, associations in environmentally exposed adults remain relatively unexplored. To address this, we examined the association between cumulative lead exposure—as measured by lead in bone—and performance on the grooved pegboard (GP) manual dexterity task, as well as on handwriting tasks using a novel assessment approach, among men in the VA Normative Aging Study (NAS).

Methods

GP testing was done with 362 NAS participants, and handwriting assessment with 328, who also had tibia and patella lead measurements made with K-X-Ray Fluorescence (KXRF). GP scores were time (s) to complete the task with the dominant hand. The handwriting assessment approach assessed the production of signature and cursive lowercase l and m letter samples. Signature and lm task scores reflect consistency in repeated trials. We used linear regression to estimate associations and 95% confidence intervals (CI) with adjustment for age, smoking, education, income and computer experience. A backward elimination algorithm was used in the subset with both GP and handwriting assessment to identify variables predictive of each outcome.

Results

The mean (SD) participant age was 69.1 (7.2) years; mean patella and tibia concentrations were 25.0 (20.7) μg/g and 19.2 (14.6) μg/g, respectively. In multivariable-adjusted analyses, GP performance was associated with tibia (β per 15 μg/g bone = 4.66, 95% CI: 1.73, 7.58, p = 0.002) and patella (β per 20 μg/g = 3.93, 95% CI: 1.11, 6.76, p = 0.006). In multivariable adjusted models of handwriting production, only the lm-pattern task showed a significant association with tibia (β per 15 μg/g bone = 1.27, 95% CI: 0.24, 2.29, p = 0.015), such that lm pattern production was more stable with increasing lead exposure. GP and handwriting scores were differentially sensitive to education, smoking, computer experience, financial stability, income and alcohol consumption.

Conclusions

Long-term cumulative environmental lead exposure was associated with deficits in GP performance, but not handwriting production. Higher lead appeared to be associated with greater consistency on the lm task. Lead sensitivity differences could suggest that lead affects neural processing speed rather than motor function per se, or could result from distinct brain areas involved in the execution of different motor tasks.

Introduction

The elderly population in the U.S. is growing rapidly (Rice and Fineman, 2004), and independence in this age group relies on maintaining functional levels of fine motor control that enable bathing, dressing, taking medication, phone usage and more (Christensen et al., 2009). Looking across the entire U.S. elderly population, small changes in fine motor function would shift the distribution such that some portion of the population would move out of independence and into requiring more care. Any factor – such as an environmental exposure – that limits fine motor function would result in changes in the amount of time an elderly individual is independent and subsequently affect medical care and caretaking costs on a large scale (Spillman and Lubitz, 2000).

As one of the most studied neurotoxicants, lead (Pb) has been shown to produce a diverse array of neurological deficits in occupationally exposed adults and environmentally exposed children and adults. In children, studies of lead-related visuomotor effects have helped identify developmentally vulnerable windows of exposure. Occupational exposure studies in adults have provided insight into visuomotor and fine motor deficits resulting from lead exposure occurring at relatively high lead exposure levels (Balbus-Kornfeld et al., 1995, Seeber et al., 2002, Shih et al., 2007). However, there has been limited exploration into the effects of lead on fine motor function in environmentally exposed adults. Deficits in fine motor function can be detrimental occupationally and socially, where daily tasks in the home and at work require fine motor coordination and dexterity. Here, we asked a cohort of elderly men with non-occupational exposure to lead to complete a series of fine motor tasks that included a grooved pegboard task, and two tests (a handwriting task and a signature task) using a novel assessment device.

Lead exposure either prenatally or in childhood has been linked to a spectrum of neurological deficits, including intelligence quotients, memory and other cognitive abilities (Bellinger, 2008, Lanphear et al., 2005, Mazumdar et al., 2011, Needleman and Gatsonis, 1990). Gross motor dysfunction in children, including gait, postural balance, arm control and locomotion has been linked to environmental lead exposure (Bhattacharya et al., 2007, Despres et al., 2005, Fraser et al., 2006, Wasserman et al., 2000). Fine motor function impairment resulting from childhood lead exposure specifically measured with the grooved pegboard task has been shown to be apparent in childhood (Chiodo et al., 2004), adolescence (Ris et al., 2004) and in adulthood (White et al., 1993).

Many cognitive deficits have been attributed to high occupational lead exposure in men, including mood, memory and executive function (Seeber et al., 2002). Studies have incorporated tests of fine motor function, specifically using a pegboard task (Baker et al., 1983, Bleecker et al., 1997, Hanninen et al., 1998, Maizlish et al., 1995, Ryan et al., 1987, Schwartz et al., 2001, Stewart et al., 1999). In each of these studies, pegboard tasks using the grooved pegboard, Purdue pegboard or Santa Ana pegboard showed significant associations with lead measured in blood (Baker et al., 1983, Bleecker et al., 1997, Hanninen et al., 1998, Maizlish et al., 1995, Ryan et al., 1987, Schwartz et al., 2001) and also in bone (Bleecker et al., 1997, Stewart et al., 1999). In one study on low-level occupational exposure, the grooved pegboard task was the only measure found to be associated with blood lead levels out of a battery that also looked at memory, visuospatial ability, learning and attention (Ryan et al., 1987). These associations, as well as similar ones found in Bleecker et al. (1997), were increased at older ages, indicating an enhanced age-related effect of lead on grooved pegboard performance.

Environmental-level exposure to lead—in particular cumulative exposure as measured by lead in bone—has been shown in older populations to affect cognitive function across a number of domains, including measures of attention, executive function, processing speed, memory, language and more (Bandeen-Roche et al., 2009, Glass et al., 2009, Peters et al., 2010, Rajan et al., 2008, Shih et al., 2007, van Wijngaarden et al., 2009, Weuve et al., 2009). To the best of our knowledge, the effects of cumulative lead exposure on fine motor function in a community dwelling group has only been explored in two settings: the Department of Veterans Affairs Normative Aging Study (NAS) and the Baltimore Memory Study (BMS). In our work in the NAS, we have examined the relation between cumulative lead exposure and several domains of cognitive function. In 2003, Wright et al. found that higher lead in blood and patella bone, as well as age, was associated with worse Mini-Mental Status Examination (MMSE) performance (Wright et al., 2003). Patella lead was also associated with greater decline in MMSE performance over time (Weisskopf et al., 2004). When performance on a whole battery of cognitive tests was considered, one interquartile range higher patella bone lead was associated with worse change in scores over time in spatial orientation, memory, attention, language abilities, and figure copying (Weisskopf et al., 2007). The figure copying task—a visuomotor function—had one of the clearest associations with lead exposure. Rajan et al. (2008) subsequently found that the association between lead exposure and performance on the figure copying test was modified by the delta-aminolevulinic acid dehydratase (ALAD) gene polymorphism.

In the BMS, a cohort of community dwelling men and women, ages 50–70 years in the Baltimore, MD area, Shih et al. (2006) examined the association between tibia lead and performance on several cognitive tests, including a composite “hand–eye coordination” score made up of performance on the Purdue grooved pegboard and the Trailmaking A task. They found that after adjusting for age, sex, technician and presence of the APOE-ɛ4 gene mutation, higher tibia lead level was significantly associated with worse hand–eye coordination. Relationships weakened when race/ethnicity, and wealth were included in models. In another study in the same population, tibia lead was significantly associated with progressive decline in the same hand–eye coordination score over time (Bandeen-Roche et al., 2009). However, stratified analysis showed the effect to be significant only in African-American and combined subject pools, but not for white subjects. Thus, the evidence for motor effects of lead exposure at environmental levels is limited, and the data that do exist involve only a couple of motor tests.

In order to further examine the association between cumulative lead exposure and motor function, we explored, in the NAS, the association between bone lead concentration and performance on both a traditional and a novel test of fine motor function: the grooved pegboard and a new handwriting analysis device, the Neuroskill (Verifax Corporation, Boulder, CO). Tests of manual dexterity and fine motor functioning range from simple movements such as finger tapping (where subjects press a button as many times as possible over 10 s), to more complex tasks such as the grooved pegboard that may involve visual integration, executive function and attention. Neuroskill assesses fine motor control through analysis of handwriting and signature dynamics (Shrairman et al., 2005). This device takes a novel approach to assessing the stability of the production of the elemental motor components that make up handwriting, and has been used only once in an environmental context: signature stability measured in welders occupationally exposed to manganese (Mn) showed a negative association with Mn exposure over a work shift (Laohaudomchok et al., 2011). An important unique aspect of the Neuroskill is that the motor assessment is independent of the speed of response, providing information about visuomotor cognitive function that is currently unmeasured in standard test batteries.