Bone Manganese as a Potential Biomarker of Cumulative Manganese Exposure and Predictor of Neurological Decline
Date of Award
Doctor of Philosophy (PhD)
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Committee Member 2
Committee Member 3
Research into the health effects of cumulative exposure to manganese (Mn) has been limited due to the lack of a biomarker that adequately represents cumulative exposure. In this cross-sectional study, we assessed the usefulness of bone Mn (BnMn) as a biomarker of cumulative Mn exposure and as an indicator of neurological decline. Our research group utilized a novel, transportable, in vivo Neutron Activation Analysis (NAA) system to analyze BnMn in a group of Chinese workers (N=60). In addition to bone, blood and fingernail samples were also collected from participants and analyzed for Mn. Participants completed a questionnaire that included work history and demographic information as well as a battery of cognitive, motor, and olfactory tests. Using participants’ work history, a cumulative exposure index (CEI) was created to represent long-term, occupational Mn exposure. Years of Mn exposure (MnYears) were also determined from participants work history. The relationship between BnMn and 1) Mn exposure variable (CEI and MnYears), 2) blood Mn (BMn), and 3) fingernail Mn (FMn) were assessed to investigate which biomarkers were more strongly associated with BnMn. The relationships between blood, fingernail, and bone Mn and the battery of cognitive (Animal Naming, Fruit Naming, UCLA/WHO Audio Verbal Listening Test (AVLT)), olfactory (University of Pennsylvania Smell Identification Test (UPSIT)), and motor (Purdue Pegboard, CATSYS Motor System) tests
were also assessed to investigate which biomarker was most sensitive to changes in neurological function. Median (interquartile range) BMn, FMn and BnMn were 14.1 (4.0) g/L, 6.1 (39.8) g/g, and 2.6 (7.2) g/g respectively. In regression models adjusted for age and education, BnMn was significantly associated with increased FMn (=1.38; 95% confidence interval (CI)=0.75, 2.00), Mn CEI over the past 15 years (MnCEI15) (=5.33; 95% CI=2.07, 8.59) and Years of Mn exposure over the past 15 years (MnYears15) (=1.73; 95% CI=0.17, 3.30), but not other measures. In regression models adjusted for age, education and current factory of employment, BnMn was significantly associated with decreasing average AVLT scores over the first 5 trials [ (95% CI) = -0.6 (-1.2, -0.09)] along with decreasing Animal Naming scores [ (95% CI) = -1.5 (-3.0, -0.7)]. FMn was also significantly associated with decreases in average AVLT scores [ (95% CI) = -0.4 (-0.7, -0.03))] as well as decreases in a difference in AVLT scores [ (95% CI) = -0.4 (-0.7, -0.02)]. BMn was not significantly associated with any test scores. Out of the three Mn biomarkers, BnMn was the greater predictor of decreasing function in 5 out of the 9 scores. Continuous ln(BnMn) was associated with several CATSYS outcomes such as decreasing Rhythmic P/S fast (Non-dominant hand) (β = -0.019; 95% C.I. = -0.036, -0.002), decreasing Rhythmic F-Tap fast (Non-dominant hand) (β = -0.027; 95% C.I. = -0.045, -0.008), increasing Center frequency (Dominant hand) (β = 0.443; 95% C.I. = 0.029, 0.858), and increasing tremor intensity (β = 0.011; 95% C.I. = 0.0001, 0.022). Overall these results suggest BnMn could be a useful biomarker of cumulative Mn exposure over the span of the past 15 16 years. They also demonstrate the association o f BnMn with cognitive and motor outcomes .
Rolle-McFarland, Danielle A., "Bone Manganese as a Potential Biomarker of Cumulative Manganese Exposure and Predictor of Neurological Decline" (2017). Open Access Dissertations. 1626.