The Connection Between Environmental Exposures And The Development Of Alzheimer Disease

Today, an estimated 50 million people in the world are living with some form of dementia, with roughly two thirds of them having Alzheimer’s – a neurodegenerative disease characterized by progressive memory loss, decline of neurological abilities, and, eventually, the inability to perform day-to-day tasks. In 2017, Alzheimer’s was responsible for an estimated 1. 54 million deaths worldwide, and that number is projected to increase dramatically as the global population ages. There is currently no known cure, and Alzheimer’s Disease International reports that out of over a hundred tested drug treatments, only four have been approved for sale. These drugs may help to manage common symptoms, but they often have little to no effect on life expectancy, as the typical life expectancy after being diagnosed with Alzheimer’s remains a meagre four to eight years. In Canada, the national prevalence of Alzheimer’s and other forms of dementia is rising sharply, and the Alzheimer Society of Canada estimates that there are over 564 000 Canadians living with dementia today. In addition to that, an excess of 25 000 new cases are being diagnosed every year, and by 2031, the national prevalence of dementia is projected to rise up to 937 000 cases. That increase in cases would put a significant strain on Canada’s economy, as it would increase Canada’s dementia-related health care costs from $10. 4 billion per year to $16. 6 billion per year. Therefore, it is imperative that we enact primary prevention methods to decrease the incidence of dementia-related diseases in our population. In this review, we will focus on the common form of dementia, which is Alzheimer’s. The purpose of this paper is to identify and explore the relationship between environmental exposures and the development of Alzheimer’s in various locations around the world, in hopes that the results may be generalizable to the Canadian population.

Once we have identified the relationship between exposures and outcomes, we need to explore the underlying causes for the relationship and determine whether any interventions are needed to mitigate environmental risks. Then, we can use the supporting evidence to promote better health outcomes by influencing policy decisions related to environmental and occupational health and safety. In conducting this review, we hope to elucidate contentious areas in the existing body of knowledge surrounding Alzheimer’s disease and environmental exposures by identifying the interactions between different exposures and how we can design studies that appropriately address all of them.

Review of Literature

There are many risk factors that can contribute to the development of Alzheimer’s, including aging, genetic predispositions, and environmental exposures. Out of those factors, the only one we can actively change is our exposure to environmental hazards, and a quick literature search reveals that the main exposure of concern is heavy metals. People are mainly exposed to heavy metals in the environment by soil and water contamination, as well as airborne pollutants generated by industrial waste from mining operations, mills, and battery factories. For instance, lead, aluminum, mercury, and cadmium are heavy metals that are utilized extensively in industrial processes, and while acute exposures may generate little to no risk, the bioaccumulation of these metals over time has been proven to lead to toxic effects. Because of this, workers in industrial facilities are at high risk for developing neurodegenerative disorders later in life. Of course, all humans are at risk due to the ubiquitous nature of airborne pollutants and soil and water contamination, but occupational exposures are far more significant. Workers in battery factories are often exposed to much higher levels of heavy metals compared to average adults, and one meta-analysis showed that being chronically exposed to aluminum increased lifetime risk of developing Alzheimer’s by nearly 70%. This phenomenon makes sense biologically, as a comprehensive review paper by Chen et al. (2016) confirms that the cellular damage inflicted by the toxic accumulation of heavy metals may result in a number of neurological impairments, which may result in Alzheimer’s. In fact, multiple epidemiological studies have linked chronic exposure to heavy metals with neurodegenerative effects such as memory loss and reduction of brain volume. Until the early 2000s, this ‘toxic metal hypothesis’ was highly contentious among researchers, for while the majority of studies had observed higher blood levels of heavy metals in Alzheimer’s patients compared to normal patients, there were other studies with no statistically significant difference between groups.

In recent years, however, findings from key studies have been more consistent, and researchers seem to be reaching a consensus about the risks of environmental and occupational exposure to heavy metals. This year, a meta-analysis of 42 studies showed that blood levels of mercury, aluminum, and cadmium were significantly higher in Alzheimer’s patients than in controls. The individual studies involved each focused on a single metal and its relationship to Alzheimer’s. For example, a post-mortem case-control study of a family that had been exposed to high levels of methylmercury throughout their lives proved that exposure to methylmercury leads to a buildup of mercury in the brain, which inflicts progressive damage on neurons. Additionally, a prospective study conducted on zebrafish found that long-term exposure to cadmium resulted in decreased head sizes at maturity, along with strange subdivisions in one region of the brain.

There are limited prospective studies involving human subjects, but one retrospective cohort study showed that exposure to arsenic in early stages of development significantly impaired brain growth in a group of children, as the neural damage led to them having lower brain weights at maturity, which is believed to put them at a greater risk for developing neurodegenerative diseases later in life.