Sarah A. Jewell

Occupation and Risk of Parkinsonism: A Multicenter Case-Control Study

BACKGROUND We examined risk of parkinsonism in occupations (agriculture, education, health care, welding, and mining) and toxicant exposures (solvents and pesticides) putatively associated with parkinsonism. OBJECTIVE To investigate occupations, specific job tasks, or exposures and risk of parkinsonism and clinical subtypes. DESIGN Case-control. SETTING Eight movement disorders centers in North America. PARTICIPANTS Inclusion criteria were parkinsonism (>or=2 cardinal signs), diagnosis within 8 years of recruitment (to minimize survival bias), and ability to participate in detailed telephone interviews. Control subjects were primarily nonblood relatives or acquaintances of patients. MAIN OUTCOME MEASURES This multicenter case-control study compared lifelong occupational and job task histories to determine associations with parkinsonism and certain clinical subtypes (postural instability and gait difficulty and age at diagnosis <or=50 years). RESULTS Findings in 519 cases and 511 controls were analyzed. Work in agriculture, education, health care, or welding was not associated with increased risk of parkinsonism. Unexpected increased risks associated with legal, construction and extraction, or religious occupations were not maintained after adjustment for duration. Risk of parkinsonism increased with pesticide use (odds ratio, 1.90; 95% confidence interval, 1.12-3.21), use of any of 8 pesticides mechanistically associated with experimental parkinsonism (2.20; 1.02-4.75), and use of 2,4-dichlorophenoxyacetic acid (2.59; 1.03-6.48). None of the specific occupations, job tasks, or task-related exposures were associated with younger age at diagnosis (<or=50 years). Ever working in business and finance, legal occupations, construction and extraction, or transportation and material moving was associated with postural instability and gait difficulty subtype of parkinsonism. Tobacco use was inversely associated with parkinsonism risk. CONCLUSION The association of disease risk with pesticides support a toxicant-induced cause of parkinsonism.

Head Injury, Alpha-Synuclein Rep1 and Parkinson’s Disease

To test the hypothesis that variability in SNCA Rep1, a polymorphic dinucleotide microsatellite in the promoter region of the gene encoding α‐synuclein, modifies the association between head injury and Parkinsons disease (PD) risk.

Meeting Report: Consensus Statement—Parkinson’s Disease and the Environment: Collaborative on Health and the Environment and Parkinson’s Action Network (CHE PAN) Conference 26–28 June 2007.

Background Parkinson’s disease (PD) is the second most common neurodegenerative disorder. People with PD, their families, scientists, health care providers, and the general public are increasingly interested in identifying environmental contributors to PD risk. Methods In June 2007, a multidisciplinary group of experts gathered in Sunnyvale, California, USA, to assess what is known about the contribution of environmental factors to PD. Results We describe the conclusions around which they came to consensus with respect to environmental contributors to PD risk. We conclude with a brief summary of research needs. Conclusions PD is a complex disorder, and multiple different pathogenic pathways and mechanisms can ultimately lead to PD. Within the individual there are many determinants of PD risk, and within populations, the causes of PD are heterogeneous. Although rare recognized genetic mutations are sufficient to cause PD, these account for < 10% of PD in the U.S. population, and incomplete penetrance suggests that environmental factors may be involved. Indeed, interplay among environmental factors and genetic makeup likely influences the risk of developing PD. There is a need for further understanding of how risk factors interact, and studying PD is likely to increase understanding of other neurodegenerative disorders.

Muscle mitochondrial ATP production in progressive supranuclear palsy

Abstract: Six patients with progressive supranuclear palsy (PSP) and 12 age‐matched disease‐free subjects participated in this study designed to compare rates of ATP production by intact mitochondria from biopsied skeletal muscle. When pyruvate and malate were used as metabolic substrates, rates of ATP production were 0.184 ± 0.025 μmol/min/U of citrate synthase (CS) activity (a mitochondrial marker) in control subjects and 0.131 ± 0.051 μmol/min/U of CS in PSP patients. In the presence of succinate, rates of ATP formation were 0.137 + 0.02 μmol/min/U of CS in controls and 0.109 ± 0.04 /4mUmol/min/U of CS in patients. With N,N,N′,N′‐tetramethyl‐p‐phenylenediamine (TMPD) and ascorbate, rates were 0.034 ± 0.008 μm Umol/min/U of CS in controls and 0.022 ± 0.01 μmol/min/U of CS in PSP subjects. Differences between the control and PSP populations reached statistical significance with pyruvate/malate and TMPD/ascorbate. No differences in either muscle histopathology or histochemistry were found between patient and control subjects. Results of this study suggest that oxidative phosphorylation defects occur in muscle mitochondria from patients with PSP.

Overview of Neurodegenerative Disorders and Susceptibility Factors in Neurodegenerative Processes

Abstract The classification of neurodegenerative disorders includes human diseases that vary significantly in terms of their incidence, clinical presentation, and prognosis. All of these disorders, however, share the pathological feature of a progressive degenerative process that initially impairs neuronal function and ultimately leads to frank neurodegeneration and brain atrophy. Interestingly, neurodegenerative diseases also have in common another (besides neuronal loss) pathological trait, which is the accumulation of proteinaceous deposits. This intriguing feature may reflect dysfunction of protein-processing mechanisms, involving, for example, proteasomal and/or autophagic degradation pathways. The vast majority of cases of neurodegenerative disorders, such as Alzheimers and Parkinsons diseases, are idiopathic and sporadic. The likely involvement of genetic, environmental, and age-related culprits in disease pathogenesis justifies the appellation of complex disorders. Environmental contribution could arise from factors and mechanisms that include toxic exposures, lifestyle habits (e.g., food consumption and exercising), use of medications (e.g., cholesterol-lowering and anti-inflammatory drugs), and epigenetic modifications.