Why is aging "on earth" the most important risk factor for Alzheimer's disease?
Few things about Alzheimer's disease are crystal clear, except for the relationship between aging and Alzheimer's. Aging is the leading risk factor for Alzheimer's disease, dwarfing all other risk factors (such as head trauma, lifestyle or medical factors). Less than 1% of people under the age of 65 get Alzheimer's disease, and almost all of these cases have a genetic mutation (usually in the amyloid gene) that is the cause. But the number of new cases per year and the total number of cases increases dramatically after age 65. By age 80, up to 40% of people have Alzheimer's disease.
So the intriguing scientific question is why? To better understand the relationship between aging and Alzheimer's disease, some basic knowledge about gerontology, the scientific study of aging, is useful. Gerontology teaches us that there are many factors that contribute to "aging on earth."
Consider a car. One way a car gets old is that it is driven many miles, called "wear and tear." The car might also get into accidents, both minor and major (analogous to "disease"). But a new car, never driven and just put in the garage, would still get "old" with time, quite simply due to "aging on earth,"
These "aging on earth" factors also play a role in human aging. For example, the cumulative effects of environmental factors such as toxins and oxidation from food and UV light alter molecules in the body, including gene expression and protein function. We also suffer the cumulative effects of accidents and injuries, chronic illnesses and inflammation, the "wear and tear" factor.
Of course, the brain is subject to the same factors that also cause aging of other organs like the skin. Indeed, cognitive aging begins at age 20! According to some experts, between age 20 and age 80, humans generally lose up to 70% of their normal cognitive function, such as processing speed and working memory. Along with these clinical findings, the pathology of normal human brain aging is sometimes associated with the same plaques and tangles that we see in the brain of patients with Alzheimer's disease.
Normal brain aging and Alzheimer's disease may be a "continuum," with some individuals ultimately developing dementia. Or, aging may be a contributing factor that is complicated by Alzheimer's disease in some people. Finally, aging and Alzheimer's may be two completely separate and unrelated biologic processes, though this possibility seems least likely (at least to me!)
What are the implications for preventing dementia from Alzheimer's disease? Lifestyle strategies like exercise and Mediterranean diets that prevent other common diseases of aging, such as heart disease, will also likely delay the onset of Alzheimer's disease.
What are the implications for drug discovery? Drugs that address the fundamental processes of aging "on earth" may be useful to prevent or delay the onset of Alzheimer's disease. Indeed, anti-oxidants and anti-inflammatory medications have already been tried (unsuccessfully) for Alzheimer's disease. But these failures do not necessarily mean the theories are wrong, but rather that effective drugs have not been developed---yet.
Copyright 2009: Howard Fillit, MD