Exposure to environmental toxins and the risk of sporadic motor neuron disease: an expanded Australian case-control study.
ABSTRACT It remains unclear what role environmental toxins play in sporadic motor neuron disease (SMND) and its most common subtype, amyotrophic lateral sclerosis (SALS). Most previous studies of this issue have contained only small numbers of SMND cases. We sought to re-examine possible associations between toxins and SMND in a large Australian case-control study.
Questionnaire data were available from 787 patients with SMND (614 with SALS) and 778 non-related controls. Individuals were asked whether they had been exposed to metals or chemicals/solvents at work or to herbicides/pesticides. Chi-square tests with odds ratios and 95% confidence intervals were calculated for responses, and significance levels were corrected for multiple testing.
Men were more likely to acquire SALS if they worked with metals (OR = 1.95, 95% CI = 1.24-3.07) or chemicals/solvents (OR = 1.96, 95% CI = 1.46-2.61) or if they had been exposed to herbicides or pesticides (OR = 1.77, 95% CI = 1.30-2.39). Women who had worked with chemicals or solvents also appeared to be at increased risk of acquiring SALS (OR = 1.71, 95% CI = 1.22-2.40).
These results support previous reports that exposures to metals or chemicals are associated with SMND. A suggested protocol for future multinational studies of environmental toxins and SMND is presented.
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ABSTRACT: There has been a steep increase in the prevalence of dementia in recent decades, which has roughly followed an increase in pesticide use some decades earlier, a time when it is probable that current dementia patients could have been exposed to pesticides. This raises the question whether pesticides contribute to dementia pathogenesis. Indeed, many studies have found increased prevalence of cognitive, behavioral and psychomotor dysfunction in individuals chronically exposed to pesticides. Furthermore, evidence from recent studies shows a possible association between chronic pesticide exposure and an increased prevalence of dementia, including Alzheimer's disease (AD) dementia. At the cellular and molecular level, the mechanism of action of many classes of pesticides suggests that these compounds could be, at least partly, accountable for the neurodegeneration accompanying AD and other dementias. For example, organophosphates, which inhibit acetylcholinesterase as do the drugs used in treating AD symptoms, have also been shown to lead to microtubule derangements and tau hyperphosphorylation, a hallmark of AD. This emerging association is of considerable public health importance, given the increasing dementia prevalence and pesticide use. Here we review the epidemiological links between dementia and pesticide exposure and discuss the possible pathophysiological mechanisms and clinical implications of this association.Toxicology 02/2013; · 4.02 Impact Factor
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ABSTRACT: Damage to the locus ceruleus, with a subsequent decrease of CNS noradrenaline, occurs in a wide range of neurodegenerative, demyelinating and psychiatric disorders. The cause of the initial locus ceruleus damage remains unknown. Recently, inorganic mercury was found to enter human locus ceruleus neurons selectively. This has led to the formulation of a new hypothesis as to the cause of these disorders. Toxicants enter locus ceruleus neurons selectively, aided by the extensive exposure these neurons have to CNS capillaries, as well as by stressors that upregulate locus ceruleus activity. The resulting noradrenaline dysfunction affects a wide range of CNS cells and can trigger a number of neurodegenerative (Alzheimer's, Parkinson's and motor neuron disease), demyelinating (multiple sclerosis), and psychiatric (major depression and bipolar disorder) conditions. This hypothesis proposes that environmental toxicants entering the locus ceruleus can give rise to a variety of CNS disorders. Proposals are made for experiments to gain further evidence for this hypothesis. If it is shown that toxicants in the locus ceruleus are responsible for these conditions, attempts can be made to prevent the toxicant exposures or to remove the toxicants from the nervous system.Medical Hypotheses 11/2013; · 1.18 Impact Factor
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ABSTRACT: A slow but steady increase in neurodegenerative disorders has been noted in recent decades. Degenerations in the nervous system are found in Alzheimer´s disease, Parkinson´s disease and motor neuron diseases. Amyotrophic lateral sclerosis (ALS) is the most common of the motor neuron diseases. It is often considered a model disorder of neurodegeneration. Early symptoms of ALS are limb weakness or weakness in muscles of speech and swallowing. Muscle atrophy follow and a slowly progressing paralysis spreads to respiratory muscles invariably leading to death in respiratory failure. Neurophysiological investigations are necessary for proper diagnosis, and it is important to rule out treatable diagnostic alternatives such as myopathies or polyneuropathies. The cause of ALS is unknown. Prevailing theories include genetic, viral, inflammatory, oxidative or toxic mechanisms. Some indications point toward metallotoxic etiologies. Clusters of ALS have been observed in regions where geological conditions cause elevated metal concentrations in water and soil. Several studies show increased frequency of ALS in certain occupations. ALS-like conditions are found in animals, notably in horses, where metal exposure can be suspected. In addition animal metal exposure experiments show accumulations of metals in the spinal cord. The aim of this thesis project is to clarify the role of metals in ALS. The hypothesis tested is that neurotoxic metals contribute significantly to the pathogenesis of ALS. To study this we have measured concentrations of 22 metals in cerebrospinal fluid (CSF) and plasma from patients with ALS and from controls, and correlated findings to literature data to suggest a model for ALS pathogenesis. Increased concentrations were found for the metals manganese, aluminum, cadmium, cobalt, copper, zinc, lead, vanadium and uranium in CSF from patients with ALS compared to controls. Manganese showed the most prominent correlation. Simultaneous sampling from plasma did not show these elevated concentrations, indicating metal accumulations in ALS CSF. Most of the metals detected in CSF from ALS patients are neurotoxicants. Studies of mercury distribution in a monkey showed mercury accumulations in the spinal cord after respiratory exposure to mercury. Motor neurons of the spinal cord seem to be more vulnerable to metal toxicity then surrounding cells, as they lack protection from the metal-binding protein metallothionein. Patient exposure to metals, distribution by the bloodstream, penetration of protective barriers and direct toxic effects on neurons of the spinal cord is suggested to be causative in ALS. It is concluded that neurotoxic metals can reach and affect the anterior horn cells of motor neurons and thereby contribute to the pathogenesis of ALS.03/2013, Degree: MD PhD, Supervisor: Professor Monica Nordberg