linear regressions were used to test the associa- tion between each MRS measure and each lead parameter, with adjustment for sex, age, and smoking status. Because the units of blood and bone lead levels were different, we compared the effect using standardized regression coeffi- cients. All statistics operations were performed with SPSS software (version 14.0.0; SPSS, Inc., Chicago, IL, USA). p-Values < 0.05 (two- tailed) were considered significant. Results Table 1 shows all the blood and bone (tibia and patella) lead levels. The mean ± SD of blood and bone lead levels in exposed group were 16.99 ± 10.38 µg/dL, 61.55 ± 30.21 µg/g tibia bone minerals, and 66.29 ± 19.48 µg/g patella bone minerals, respectively, and in the nonexposed controls, 3.4 ± 1.11 µg/ dL, 18.51 ± 22.4 µg/g tibia bone minerals, and 7.14 ± 9.81 µg/g patella bone minerals, respectively. The Pearson correlation coeffi- cients were 0.588 (p < 0.001) between patella and tibia lead, 0.685 (p < 0.001) between patella and blood, and 0.544 (p < 0.001) between tibia and blood lead levels. The exposure and nonexposure groups had similar age, BMIs, and life habits. Although the study group had a higher prevalence of smoking (45.4%), alcohol drinking (13.6%), and betel nut chewing (13.6%), the differ- ences by chi-square tests were insignificant. Both the lead-exposed and nonexposed participants had normal neurologic imaging findings and no clinical evidence of neural diseases. The frontal gray and white matter of the lead-exposed group had a significantly lower Cho:tCr ratio than the nonexposed group. In the occipital lobe, all Cho:tCr ratios of gray, subcortical, and white matter in the lead-exposed group were significantly lower than those of the nonexposed group. That ratio in basal ganglions was also lower in the exposed group than in those measured in the nonexposed group, although not significant. Similarly, all the frontal lobe NAA:tCr ratios in the exposed group were lower than those of the nonexposed group. In the occipital lobe, only white matter in the exposed group had significantly lower NAA:tCr ratios compared with those of nonexposed. In the basal gan- glion, the NAA:tCr ratios of those exposed to lead were significantly lower than those found in the controls (Table 2). Table 3 shows the association between human brain MRS measurements and lead biomarkers (including blood, patella, and tibia lead) with 42 multiple regressions. The dependent variables were the MRS measure- ments; the main predictors of interest to us were the lead biomarkers (blood, patella, and tibia lead levels), adjusting for sex, age, and smoking status (yes vs. no). Because the units of blood and bone lead levels were different, Environmental Health Perspectives • volume 117 | number 6 | June 2009 we compared effects using standardized regression coefficients in Table 3. Decreases in Cho:tCr ratios were significantly associated with increases in blood and bone lead levels, especially in the occipital lobe where all gray, subcortical, and white matter values were significant. These data suggest that Cho and Cho-containing compounds in the occipital lobe, compared with the other areas of brain, were the most sensitive to all blood and bone lead levels in these workers. However, the NAA:tCr ratios in every layer of the frontal brain were significantly inversely associated with blood and patella lead levels, suggesting that NAA in the frontal lobe might be the most sensitive to recent and subcumulative lead exposure. One of the strongest regres- sion coefficients was –0.023 (SE = 0.005, p < 0.001, standardized coefficient = –0.764) The effect of lead on brain proton MRS for the NAA:tCr ratio in frontal gray matter and blood lead. Discussion This MRS study comparing the brain metabolism of middle-age workers chroni- cally exposed to lead with matched nonex- posed controls revealed a negative correlation between blood and bone lead and brain NAA and Cho levels, especially in the frontal and occipital lobes. The effects of lead toxicity have been examined in the context of neurobehav- ioral evaluations (Balbus-Kornfeld et al. 1995; Chuang et al. 2005; Shih et al. 2007). Although the adverse effect of lead exposure on neurobehavioral functioning is one of the most consistently reported impairments associated with lead exposure, little is known Table 1. Characteristics of participants, and blood and bone lead levels. Nonexposed (n = 18) Exposed (n = 22) Table 2. Comparisons of brain magnetic resonance between lead-exposed workers and the nonexposed group. Characteristic Age [years (mean ± SD)] Working duration [years (mean ± SD)] BMI [kg/m2 (mean ± SD)] Lead Blood [µg/dL (mean ± SD)] Tibia [µg/g bone (mean ± SD)] Patella [µg/g bone (mean ± SD)] Sex [n (%)] Female Male Years of education [n (%)] ≤ 9 9–12 > 12 Smoking [n (%)] No Yes Drinking [n (%)] No Yes Chew betel nut [n (%)] No Yes at-Test. bChi-square test. MRS measures Cho:tCr ratio Frontal lobe gray matter Subcortical white matter White matter Basal ganglion Occipital lobe gray matter Subcortical white matter White matter NAA:tCr ratio Frontal lobe gray matter Subcortical white matter White matter Basal ganglion Occipital lobe gray matter Subcortical white matter White matter at-Test. p-Value 0.92a 0.99a < 0.001a < 0.001a < 0.001a 0.731b 0.788b 0.09b > 0.99b 0.613b p-Valuea 0.002 0.247 0.042 0.889 < 0.001 < 0.001 0.006 0.001 0.004 0.046 0.038 0.331 0.051 0.001 943 46.06 ± 10.14 — 24.48 ± 2.42 3.40 ± 1.11 18.51 ± 22.40 7.14 ± 9.81 5 (27.8) 13 (72.2) 4 (22.2) 9 (50.0) 5 (27.8) 15 (83.3) 3 (16.7) 15 (83.3) 3 (16.7) 17 (94.4) 1 (5.6) 45.71 ± 11.72 12.95 ± 8.34 24.49 ± 3.07 16.99 ± 10.38 61.55 ± 30.21 66.29 ± 19.48 5 (22.7) 17 (77.3) 7 (31.8) 10 (45.5) 5 (22.7) 12 (54.5) 10 (45.5) 19 (86.4) 3 (13.6) 19 (86.4) 3 (13.6) Nonexposed (n = 18) (mean ± SD) 1.430 ± 0.312 1.292 ± 0.273 1.467 ± 0.222 1.026 ± 0.183 1.137 ± 0.240 1.148 ± 0.239 1.417 ± 0.320 1.702 ± 0.314 1.566 ± 0.272 1.684 ± 0.334 1.107 ± 0.263 1.543 ± 0.293 1.451 ± 0.237 1.602 ± 0.306 Exposed (n = 22) (mean ± SD) 1.159 ± 0.121 1.198 ± 0.232 1.276 ± 0.329 1.017 ± 0.207 0.805 ± 0.290 0.821 ± 0.276 1.092 ± 0.369 1.390 ± 0.214 1.342 ± 0.185 1.477 ± 0.297 0.950 ± 0.199 1.431 ± 0.405 1.290 ± 0.265 1.162 ± 0.409