Neuroinflammation and white matter alterations in occupational manganese exposure assessed by diffusion basis spectrum imaging.

OBJECTIVE: To evaluate in-vivo neuroinflammation and white matter (WM) microstructural integrity in occupational manganese (Mn) exposure. METHODS: We assessed brain inflammation using Diffusion Basis Spectrum Imaging (DBSI) in 26 Mn-exposed welders, 17 Mn-exposed workers, and 26 non-exposed participants. Cumulative Mn exposure was estimated from work histories and the Unified Parkinson's Disease Rating Scale motor subsection 3 (UPDRS3) scores were completed by a movement specialist. Tract-based Spatial Statistics allowed for whole-brain voxel-wise WM analyses to compare WM DBSI-derived measures between the Mn-exposed and non-exposed groups. Exploratory grey matter region of interest (ROI) analyses examined the presence of similar alterations in the basal ganglia. We used voxelwise general linear modeling and linear regression to evaluate the association between cumulative Mn exposure, WM or basal ganglia DBSI metrics, and UPDRS3 scores, while adjusting for age. RESULTS: Mn-exposed welders had higher DBSI-derived restricted fraction (DBSI-RF), higher DBSI-derived nonrestricted fraction (DBSI-NRF), and lower DBSI-derived fiber fraction (DBSI-FF) in multiple WM tracts (all p < 0.05) in comparison to less-exposed workers and non-exposed participants. Basal ganglia ROI analyses revealed higher average caudate DBSI-NRF and DBSI-derived radial diffusion (DBSI-RD) values in Mn-exposed welders relative to non-exposed participants (p < 0.05). Caudate DBSI-NRF was also associated with greater cumulative Mn exposure and higher UPRDS3 scores. CONCLUSIONS: Mn-exposed welders demonstrate greater DBSI-derived indicators of neuroinflammation-related cellularity (DBSI-RF), greater extracellular edema (DBSI-NRF), and lower apparent axonal density (DBSI-FF) in multiple WM tracts suggesting a neuroinflammatory component in the pathophysiology of Mn neurotoxicity. Caudate DBSI-NRF was positively associated with both cumulative Mn exposure and clinical parkinsonism, indicating a possible dose-dependent effect on extracellular edema with associated motor effects.

Solvent exposed occupations and risk of Parkinson disease in Finland.

INTRODUCTION: Epidemiologic and toxicology studies suggest that exposure to various solvents, especially chlorinated hydrocarbon solvents, might increase Parkinson disease (PD) risk. METHODS: In a population-based case-control study in Finland, we examined whether occupations with potential for solvent exposures were associated with PD. We identified newly diagnosed cases age 45-84 from a nationwide medication reimbursement register in 1995-2014. From the population register, we randomly selected non-PD controls matched on sex, along with birth and diagnosis years (age). We included 11,757 cases and 23,236 controls with an occupation in the 1990 census, corresponding to age 40-60. We focused on 28 occupations with ≥ 5% probability of solvent exposure according to the Finnish Job Exposure Matrix. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) by logistic regression modeling, adjusting for age, sex, socioeconomic status, and smoking probability. RESULTS: Similar proportions of cases (5.5%) and controls (5.6%) had an occupation with potential exposure to any solvents. However, all occupations with a point estimate above one, and all significantly or marginally significantly associated with PD (electronic/telecommunications worker [OR = 1.63, 95% CI 1.05-2.50], laboratory assistant [OR = 1.40, 95% CI 0.98-1.99], and machine/engine mechanic [OR = 1.23, 95% CI 0.99-1.52]) entailed potential for exposure to chlorinated hydrocarbon solvents, specifically. Secondary analyses indicated exposure to polycyclic aromatic hydrocarbons and some metals might contribute to the association for mechanics. CONCLUSION: PD risk might be slightly increased in occupations with potential exposure to chlorinated hydrocarbon solvents. Confirmation is required in additional studies that adjust for other occupational exposures and smoking.

Nicotine from edible Solanaceae and risk of Parkinson disease.

OBJECTIVE: To test whether risk of Parkinson disease (PD) is associated with consumption of nicotine-containing edibles from the same botanical family as tobacco, Solanaceae, including peppers, tomatoes, and potatoes. METHODS: In a population-based study with 490 newly diagnosed idiopathic PD cases diagnosed during 1992-2008 at the University of Washington Neurology Clinic or Group Health Cooperative in western Washington State and 644 unrelated, neurologically normal controls, we examined whether PD was associated with self-reported typical frequency of consumption of peppers, tomatoes, tomato juice, and potatoes during adulthood, while adjusting for consumption of other vegetables, age, sex, race/ethnicity, tobacco use, and caffeine. RESULTS: PD was inversely associated with consumption of all edible Solanaceae combined (relative risk [RR] = 0.81, 95% confidence interval [CI] = 0.65-1.01 per time per day), but not consumption of all other vegetables combined (RR = 1.00, 95% CI = 0.92-1.10). The trend strengthened when we weighted edible Solanaceae by nicotine concentration (ptrend = 0.004). An inverse association was also evident for peppers specifically (ptrend = 0.005). The potentially protective effect of edible Solanaceae largely occurred in men and women who had never used tobacco or who had smoked cigarettes < 10 years. INTERPRETATION: Dietary nicotine or other constituents of tobacco and peppers may reduce PD risk. However, confirmation and extension of these findings are needed to strengthen causal inferences that could suggest possible dietary or pharmaceutical interventions for PD prevention.

A method to model season of birth as a surrogate environmental risk factor for disease.

Environmental exposures, including some that vary seasonally, may play a role in the development of many types of childhood diseases such as cancer. Those observed in children are unique in that the relevant period of exposure is inherently limited or perhaps even specific to a very short window during prenatal development or early infancy. As such, researchers have investigated whether specific childhood cancers are associated with season of birth. Typically a basic method for analysis has been used, for example categorization of births into one of four seasons, followed by simple comparisons between categories such as via logistic regression, to obtain odds ratios (ORs), confidence intervals (CIs) and p-values. In this paper we present an alternative method, based upon an iterative trigonometric logistic regression model used to analyze the cyclic nature of birth dates related to disease occurrence. Disease birth-date results are presented using a sinusoidal graph with a peak date of relative risk and a single p-value that tests whether an overall seasonal association is present. An OR and CI comparing children born in the 3-month period around the peak to the symmetrically opposite 3-month period also can be obtained. Advantages of this derivative-free method include ease of use, increased statistical power to detect associations, and the ability to avoid potentially arbitrary, subjective demarcation of seasons.