Alan H. Lockwood, MD, is Emeritus Professor of Neurology and Nuclear Medicine at the State University of New York at Buffalo as well as the lead author of the Physicians for Social Responsibility report on coal’s adverse health effects. In The Silent Epidemic (MIT Press, 2012), Lockwood describes and documents the adverse health effects of burning coal by examining every aspect of coal, from its complex chemical makeup to details of mining, transporting, burning and disposal — each of which generates significant health concerns. Relatively few people are aware of the health threats posed by coal-derived pollutants, and those who are aware lack the political clout of the coal industry. Read the scientific studies that connects burning coal and other air pollution with neurological diseases such as Alzheimer’s Disease, Parkinson’s Disease and Diabetes Mellitus. This excerpt is taken from chapter 11, “Health Effects on the Horizon.”
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There are things we don’t know we don’t know.
— Donald Rumsfeld
It is hard to imagine that there was a time when chimneys belching clouds of black acrid smoke were seen as a sign of industrial prowess and economic vigor rather than a threat to health. At one time physicians appeared in advertisements touting the benefits of smoking cigarettes! Advances in knowledge change the way we look at our environment and how it impacts health. Where are the holes in our vision and what surprises are ahead? This chapter addresses that question using very early, sometimes provocative data to discuss what might emerge in the future and be placed on the growing list of health effects of the pollutants generated by burning coal.
Inflammation and oxidative stress are important in the pathogenesis of respiratory and cardiovascular diseases, as discussed in earlier chapters. Emerging data suggest that these two processes may affect the brain and metabolic pathways and play a role in the production of neurodegenerative diseases, particularly Alzheimer’s disease (AD) and type 2 diabetes mellitus. If the early studies suggesting these links are upheld by adequately powered (i.e., large enough) more rigorous investigations that utilize contemporary epidemiological methods, there will be enormous public health implications.
Particulates and Neurodegenerative Disease
Alzheimer’s disease is the most common form of dementia. In 2007 it was the sixth leading cause of death among Americans, claiming over 82,000 individuals. It is the only disease among the top 10 for which there is no effective treatment to halt its progression. In addition to the human suffering by patients and caregivers, AD is also very expensive to manage. According to the Alzheimer’s Disease Association more than 14 million Americans who are among the family or friends of AD patients provide over $200 billion in uncompensated care each year.
Alzheimer's Disease is characterized by the gradual loss of memory plus loss of function in at least one other aspect of mental capacity, such as judgment, language, or the ability to organize and execute tasks. These deficits must represent a decline from an earlier state and must be severe enough to interfere with social or occupational functions, or both. Although there are several drugs that are approved by the Food and Drug Administration for the treatment of AD, they all treat the symptoms of the disease but do nothing to halt the progression of its characteristic brain lesions.
Animal data suggest strongly that very small particles, those with a diameter of 2.5 microns or less, cross the membranes of the nose and enter the brain via the olfactory nerve. This is the nerve that mediates the sense of smell. The endings of this nerve begin in the nose and travel through many small holes in the skull (the cribiform plate) and enter the brain, forming the olfactory nerve. This nerve and its connections in the brain form part of what is known as the limbic system, which plays a key role in the mediation of memory, emotions, and other basic neural functions. The hippocampus is an important part of the limbic system. Pathological changes in the hippocampus and other parts of the brain, specifically deposition of a protein known as β-amyloid, the loss of neurons and synapses (connections between neurons), and the presence of neurofibrillary tangles, are the neuropathological hallmarks of Alzheimer’s disease.
Doty reviewed what he calls the “olfactory vector hypothesis of neurodegenerative disease,” namely the hypothesis that environmental toxicants or other agents enter the brain via the olfactory nerve leading to the production of diseases such as Alzheimer's Disease and idiopathic Parkinson’s disease (PD). In support of the hypothesis, he notes that numerous studies have shown that tests of olfactory function are abnormal in as many as 90% of all patients with early stages of AD and PD. Pathological changes that are characteristic of both PD and AD are found in the olfactory pathways, providing further support of the hypothesis. Hawkes et al. expanded this theory by proposing a “dual-hit” hypothesis, suggesting that offending agents may gain entry to the nervous system via the nose and collections of nerves (neural plexuses) in the stomach. From the stomach, the agents could ascend into the brain in the fibers that form the vagus nerve.
Some of the most intriguing and potentially important data linking coal-derived air pollution and neurological disease have come from studies comparing brains of dogs and humans living in highly polluted versus nonpolluted cities in Mexico. In Mexico City, airborne particulate matter levels (as well as those of other pollutants) regularly exceed US air quality standards. This is shown in figure 3.3. In a study of the brains of 26 dogs from Mexico City, the concentration of the 42 amino acid form of β-amyloid and the expression of cyclooxygenase were increased compared to levels in the brains of dogs from regions with low pollutant levels. These findings may be relevant because β-amyloid deposits are characteristic of AD neuropathology in humans and cyclooxygenase is an enzyme that is found in inflammatory conditions. Similar results were found in a second study of 10 human brains (age 51.2 ± 4.9 years, standard deviation) from individuals who had lived in high-pollution areas compared to 9 brains (age 58.1 ± 4.6 years, standard deviation) from those who had lived in low-pollution areas. None of the brains in that study were from patients with known neurological disease or cognitive deficits. The authors suggest that “exposure to urban air pollution may cause brain inflammation and accelerate the accumulation of [ β -amyloid 42 ], a putative mediator of neurodegeneration and AD pathogenesis.” These data are supported by the results of animal experiments in which several strains of transgenic mice were exposed to particulate matter.
To further test the olfactory hypothesis, Calder ó n-Carcidueñas et al. found significant reductions in a test of smell in a cohort of 65 individuals from Mexico City, the pollution-exposed group, when compared to 25 controls, drawn from a less polluted area. In that same publication they reported the results of pathological examinations of the olfactory bulb (a part of the olfactory nerve and the limbic system) in 35 autopsy specimens from residents of Mexico City and 9 controls. The average age was 20.8 years. Ultrafine particles were found in the olfactory bulb of 2 of the specimens from Mexico City residents but none of the controls. Twenty-nine of the Mexico City olfactory bulbs contained β-amyloid whereas none of the control bulbs contained this protein. The authors concluded that air pollution may play a key role in the development of neurodegenerative diseases.
Although there are characteristics of particulate matter that define its origin, at present the EPA treats all particulates similarly (i.e., the Agency does not distinguish effects of particulates that appear to be related to vehicular traffic from those originating from coal and other sources). Thus reports that focus on diesel exhaust particles may be completely relevant to particles originating from fossil fuel combustion.
Two reports relating traffic-caused pollution to cognitive function are worthy of consideration. Ranfit et al. studied a group of 399 women between the ages of 68 and 79 years of age who had lived for 20 or more years at the same address. Particulate exposure was highest among those who lived near busy highways. Mental function was evaluated using a neuropsychological test battery and smell was evaluated with an odor identification test. They report a dose – response function linking decrements in mental function and increases in particulate concentration that survived statistical adjustments for potential confounders. Specifically, the results of tests for mild cognitive impairment, a risk factor for Alzheimer’s disease, were significantly poorer if the participant lived within 50 meters of a highway with a traffic density of 10,000 cars or more per day. A study in which the investigators sought a relationship between nitrogen dioxide levels and cognitive function in 210 children who were 4 years old found a suggestive deleterious effect that was not statistically significant.
The possible link between airborne pollutants and neurodegenerative diseases is still very speculative. However, it may ultimately be extremely important because of the very large and growing number of patients with Alzheimer’s disease and the financial and societal impacts of this terrible illness.
Air Pollution and Diabetes Mellitus
Diabetes mellitus is the seventh leading cause of death in Americans. According to the CDC, 70,610 Americans died because of diabetes in 2008. Diabetes is one of the most debilitating of all chronic diseases, particularly when it is poorly controlled. Diabetes may lead to the development of hypertension and is a risk factor for strokes and heart attacks. Patients with advanced poorly controlled diabetes may develop kidney failure, requiring dialysis or transplantation, and may suffer repeated amputations or become blind.
Diabetes is one of the most common and most frequently undiagnosed chronic diseases. A recent estimate of the worldwide prevalence of diabetes predicts that the prevalence of this condition will continue to increase, particularly in underdeveloped countries. The authors of this report drew on data from 91 countries to estimate the prevalence of diabetes in 2010 and 2030 in 216 nations. They estimated that among adults, aged 20 to 79, the prevalence of diabetes in 2010 would be 6.4%, affecting 285 million individuals. By 2030, the prevalence in developing nations would increase by 69%, and in developed nations the prevalence is expected to increase by 20%. By 2030, they estimated that 7.7% of adults, or 439 million individuals, will be diabetic worldwide.
Diabetes is a disease that is characterized by an elevation of the amount of glucose in the blood. There are two main types: type 1 diabetes, sometimes called juvenile diabetes, is a form of the disease in which the beta cells of the pancreas fail, making patients dependent on insulin. In type 2 diabetes, formerly called adult-onset diabetes, the body fails to respond appropriately to the insulin that is produced by the pancreas. Diabetes in these patients is treated with a combination of medications, diet, weight loss, and exercise. Some women develop diabetes during pregnancy, a condition called gestational diabetes. The symptoms of diabetes include abnormal thirst, frequent urination, increased hunger, weight loss, and fatigue. Diabetes is diagnosed by measuring the amount of glucose in the blood.
The rising prevalence of diabetes mellitus, particularly type 2 diabetes, is a cause for national concern. Many regard this as an epidemic that is out of control. In 2002, I made the serendipitous observation that there was a statistically significant correlation between the by-state prevalence of diabetes and the by-state emission of pollutants discharged into the air as reported via the Toxics Release Inventory ( r = 0.54, p = 0.000054). I speculated that airborne dioxins might be the cause, as others had implicated this class of chemicals as a risk factor for the development of diabetes.
In 2005 Brook postulated several mechanisms by which the inhalation of particulates might lead to the development of insulin resistance, a pre-diabetic condition characterized by an inability to respond normally to insulin. These mechanisms begin with the inhalation of small particles that stimulate pulmonary inflammation and generate reactive oxygen species and oxidative stress. One pathway is suggested to operate via the brain and the autonomic nervous system, leading to stimulation of the adrenal gland with subsequent increases in epinephrine and cortisol. Both of these hormones affect glucose metabolism. A second and perhaps concurrent pathway was suggested that might operate more directly on blood vessels. In concert with autonomic nerves, this could lead to vasoconstriction and insulin resistance.
This hypothetical mechanism gained substantial credence with the publication of a paper linking nitrogen dioxide exposure to diabetes in women. In this study the authors evaluated the records of over 7,500 patients attending clinics for respiratory diseases in Toronto and Hamilton, Ontario. Geographic information systems techniques were used to estimate nitrogen dioxide exposures from networks of air sampling devices in each of the cities. The diagnosis of diabetes was obtained from a provincial medical database. There was a positive relationship between nitrogen dioxide exposure and diabetes in both cities, after controlling for several potential confounding factors such as age and body mass index. When the data from both cities were combined there was about a 17% increase in the odds for diabetes in women between quartiles of exposure (quartiles divide the population into four sections, based on the nitrogen dioxide exposure). Although the authors of this report used nitrogen dioxide levels as a surrogate marker for traffic-related air pollutants, substantial amounts of this pollutant are formed when coal is burned. The authors conclude that their results “suggest that common air pollutants are associated with [diabetes mellitus]. ”
A second study linking exposures to particulates and nitrogen dioxide with diabetes was the result of 16 years of following 1,775 nondiabetic German women who were between the ages of 54 and 55 at the time of enrollment. Using questionnaires that specified physician-diagnosed type 2 diabetes and NO 2 and particulate matter concentrations at locations associated with each patient, the investigators found significant relationships between these two pollutants and the risk of developing diabetes.
The relationship was stronger for NO 2 than for particulates, suggesting to them that traffic may be more important than other sources of pollution. They also measured complement C3c, a marker for low level inflammation, and found that those with the highest levels of the marker had the highest risk for developing diabetes. Finally, a US study of the relationship between fine particles and the prevalence of diagnosed diabetes found a significant relationship between these variables. In counties where the fine particle concentration was within EPA air quality standards, the prevalence of diabetes among those with the highest exposure was more than 20% higher than the prevalence among those with the lowest exposures. They estimated the risk for developing diabetes was on the order of 1% for an increase in the concentration of fine particles of 10 μ g/m 3 .
The evidence linking diabetes with air pollutants that are derived, in part, from burning coal is becoming increasingly convincing. As is the case with neurodegenerative disorders, if this relationship gains strength, the public health implications will be enormous. The observation that the risk for the development of diabetes increases even within the current air quality standards for particulates is especially telling. As is the case with other disease conditions, there may well not be a limit below which one can be free of risk. A re-evaluation of the standard is in order, as mandated by the Clean Air Act. The failure of the EPA to begin this process is the subject of legal action initiated by Earthjustice.
Are Diabetes and Alzheimer’s Disease Linked?
The March 2009 issue of the Archives of Neurology was devoted to a series of papers discussing the possible links between metabolic disorders, such as diabetes and the metabolic syndrome, with Alzheimer’s disease and vascular dementia. Metabolic syndrome is a disorder with several defining characteristics, including abnormal glucose metabolism, elevated blood triglycerides, low blood levels of high-density lipoproteins, hypertension, and central obesity, meaning an elevated waist-to-hip circumference ratio. Metabolic syndrome is an important risk factor for the development of diabetes.
In a summary article in that issue, Craft discusses evidence that insulin resistance is related to Alzheimer’s disease. Insulin resistance is a diabetes risk factor and is characterized in part by elevated blood insulin levels and a lack of responsiveness of various organs and tissues to the effects of insulin. Although the putative pathophysiological mechanisms that link these two diseases are complex, and beyond the scope of this review, inflammation and oxidative stress appear prominently. As discussed throughout this book, these two mechanisms are intimately related to exposure to various air pollutants, particularly fine particles.
Alzheimer’s disease and diabetes are two of the most common and costly chronic diseases in the United States. The prevalence of both is increasing dramatically. It seems quite possible that the list of the many adverse health effects of burning coal will expand beyond the obvious (i.e., respiratory diseases), to include a substantially larger portion of the population. Eventually, burning coal to produce electricity may be seen as an addictive, unacceptable universal threat to health, a modern-day equivalent to smoking cigarettes.
This excerpt has been reprinted with permission from The Silent Epidemic: Coal and the Hidden Threat to Health, published by Massachusetts Institute of Technology, 2012. You can buy this book from our store: The Silent Epidemic.