Characterization of bone aluminum, a potential biomarker of cumulative exposure, and the association between olfactory and cognitive function tests with aluminum biomarkers in an occupationally exposed population

Abstract

Aluminum (Al) is the third most abundant metal on the earth’s surface. An association of Al with Alzheimer’s disease has been suggested, but, given limited human evidence, is controversial. It is possible that exploration of long-term, or cumulative, exposure to Al will help clarify this debate. Therefore, our study hypothesis was that occupational exposure to Al, particularly long-term exposure, is associated with adverse cognitive and olfactory outcomes. Biomarkers are important tools in epidemiologic research; however, the reliability and quality of various biomarkers may vary. Therefore, in Chapter 2, we reviewed current evidence on Al biomarkers with the goal to synthesize current understanding regarding their utility for use in research. Our review evaluated 78 papers which discussed various biomarkers of Al exposure. Limited evidence is currently available for Al in nails, hair, breastmilk, saliva and semen. Although they have more daily variation than other biomarkers, blood Al concentrations may differentiate between exposed and non-exposed groups. Unlike blood Al, Al concentrations in both urine and bone are not subject to daily fluctuations. Bone Al appears able to quantify long term Al exposure. Therefore, the use of in vivoneutron activation analysis (IVNAA), a novel bone biomarker, can potentially represent cumulative Al exposure. In Chapter 3, we evaluated the hypothesis that the correlation between bone and CEI measurements will be higher than the correlation between bone with fingernail. A cross-sectional cohort of 61 ferroalloy and manufacturing factory workers from Zunyi, China were used in this secondary analysis. Correlations of bone Al with other Al measures (fingernail and cumulative exposure index (CEI)) were assessed for 43 of the factory workers who had bone Al samples. Fingernail samples were analyzed using inductively coupled plasma mass spectrometry. Bone measurements were taken with a compact IVNAA developed by our research team. CEI was calculated as CEIi=, where Ciis estimated Al exposure based on job title (low/medium/high) and Yiis the years employed. The CEI was calculated for the prior 5, 10, 15, 20 years and lifetime work history. Median Al values were: 34.4 mg/g (IQR=46) fingernail; 15 mg/g (IQR=28) bone; and 26 (IQR=21) total CEI. Adjusting for age and education, the linear regression model suggests that bone Al is reflective of 15 years of exposure based off the significant association between bone Al and 15-year CEI (b=0.91, p