Alpert Medical School, Brown University
Neuropathologist, Rhode Island Hospital
Although we’ve always known that Alzheimer’s disease is typically associated with numerous tangles and plaque in the brain, the exact cause of these abnormalities has been hard to pin down. Now, we may be closer to an answer.
In many respects, Alzheimer’s is a brain form of diabetes. Even in the earliest stages of disease, the brain’s ability to metabolize sugar is reduced. Normally, insulin plays a big role in helping the brain take up sugar from the blood. But, in Alzheimer’s, insulin is not very effective in the brain. Consequently, the brain cells practically starve to death.
How is that like diabetes?
These days, most people with diabetes have Type 2 diabetes mellitus. Basically, cells throughout the body become resistant to insulin signals. In an effort to encourage cells to take up more sugar from the blood, the pancreas increases the output of insulin. Imagine having to knock louder on a door to make the person inside open up and answer. The high levels of insulin could damage small blood vessels in the brain, and eventually lead to poor brain circulation. This problem could partly explain why Type 2 diabetes harms the brain. In Alzheimer’s, the brain, especially parts that deal with memory and personality, become resistant to insulin.
Why does the brain need insulin?
As in most organs, insulin stimulates brain cells to take up glucose or sugar, and metabolize it to make energy. Insulin also is very important for making chemicals known as neurotransmitters, which are needed for neurons to communicate with each other. Insulin also stimulates many functions that are needed to form new memories and conquer tasks that require learning and memory.
Where does the insulin come from in the brain?
Very sensitive tests showed that insulin is made in the brain. It’s made in neurons, and the hormone made in the brain is the same as that produced in the pancreas. This point may seem surprising, but if you consider the fact that every other gut hormone is also made in the brain, it only makes sense that insulin would be among them. Insulin that’s made by the pancreas and present in blood does gets into the brain as well.
Are people with diabetes more likely to get Alzheimer’s?
Absolutely. Their risk is doubled, at least. Obesity also increases the risk of cognitive impairment, or mental decline. This doesn’t mean that everyone who has diabetes will develop Alzheimer’s or that all people with Alzheimer’s have diabetes. The important thing to recognize is that there is considerable overlap between Alzheimer’s and diabetes.
I’ve never heard that. Is this idea new?
In reality, before about 1980, there was very little overlap between Alzheimer’s and diabetes. In fact, up until about 1980, deaths from diabetes were declining in the United States. That’s probably because of the improvements in medical treatment. But, between 1980 and now, the deaths from Alzheimer’s and diabetes have skyrocketed at alarming rates. The diabetes story is especially frightening because, everyone agrees that today we have much better medical treatments for diabetes than we did in the 1960s and 1970s – so, why should the death rates be so high now?
Maybe people are just living longer. Isn’t that the case?
People are living longer, but more important, they are surviving with various diseases that used to be fatal. On the surface, this argument might explain the increasing death rate trends for diabetes and Alzheimer’s. But, closer examination of the data demonstrated something entirely different and, in fact, surprising.
We compared the Alzheimer’s death rates in 1980, to those in 2005, but instead of looking at the entire population as a single group, we examined the death rates according to age group. We looked at Alzheimer’s death rates in people between 45 and 54 years old, 55 and 64, 65 and 74, and so on. We found that within every single age group, the Alzheimer death rate was much higher in 2005 than it was in 1980. In other words, deaths from Alzheimer’s were considerably higher for 60 year olds in 2005 than they were in 1980. Worse yet, over that time period and until these days, the Alzheimer’s death rates continued to climb, year by year. Diabetes death rates increased sharply within each age group, just as they did for Alzheimer’s.
Most people think Alzheimer’s is caused by a gene problem.
Alzheimer’s disease occurrences are not strictly genetic. In fact, the vast majority of Alzheimer’s occurs sporadically.
If it’s not genetic, what else could be the cause of Alzheimer’s?
Truly genetic diseases do not change over a 30-year period. That interval is too short to affect rates of genetic diseases that arise only in middle-aged or elderly people. The human breeding, growth, development and aging cycle is much longer than 30 years. In contrast, disease like HIV/AIDS and lung cancer are clearly exposure-related, so their mortality rates can be modified within a short period if the exposure to the disease-causing agents are reduced.
Could diabetes and Alzheimer’s be caused by some types of exposures?
We have reasonable evidence that human exposure to nitrosamines is at the root cause of not only Alzheimer’s, but several other insulin-resistance diseases, including Type 2 diabetes, fatty liver disease, also known as NASH, and visceral obesity.
The elimination of local farms in favor of mega-farms requires transport of food for long distances. To prolong shelf-life, preservatives are added. The problem is worsened with transport of “fresh” foods from across the Pacific Ocean. Nitrites are added to meats and processed foods for flavor and coloring. High levels of nitrates added to fertilizers can be incorporated into produce and then converted to nitrites and finally nitrosamines in the body.
Nitrosamines contaminate many processed foods, including fish, cheeses, hotdogs, ground beef, smoked meats like bacon, smoked turkey and ham, and beer. Originally, nitrites were added to food as preservatives to prevent salmonella infection from contaminated meet. The policy remains in place. Although efforts have been made to reduce the levels, nitrites are still added as preservatives. Over time, Western societies, particularly in the US, have been chronically exposed to increasing amounts of nitrosamines due to continuous consumption of processed foods.
Nitrosamines are well-recognized cancer-causing agents. In high doses, they cause cancers in many organs. One of the main toxins in tobacco is a nitrosamine. However, low chronic exposures have cumulative effects.
Years ago, a few scientists suggested that nitrosamines might cause diabetes. The concept was not pursued until now. We performed experiments in the laboratory and showed that very low, limited exposures to nitrosamines (the type found in food) cause Alzheimer’s-type brain degeneration, dementia, diabetes, fatty liver disease and obesity. Adding high fat to the diet made the disease-causing effects of nitrosamines much worse.
How were these findings reached?
We were working on the idea that insulin resistance in the brain was an important cause of disease and injected another drug into the brain to see what would happen. Instead of getting what we were looking for, we found Alzheimer’s. Very soon after that, I realized that the drug I used was a nitrosamine. A bell went off in my head and suddenly I understood the problem. All of the major diseases related to insulin resistance, which are now epidemic in the United States, could be caused by exposure to low doses of nitrosamines over a period of years.
How can I reduce my risk?
For now, the main message is to stop getting exposed. There are small steps and larger ones. Protect yourself by looking for sodium nitrite on food labels. Avoid processed foods. Eat organically grown foods. Push policies to return farming back to local environments to gain control over how food is produced and eliminate requirements for toxic preservatives. Educate children and provide only healthful food choices. Learn to cook and teach cooking in public schools. Pack a healthful lunch the night before for easy grab-and-go in the morning.