Risk Factors for Alzheimer’s Disease

Alzheimer’s is characterized primarily by the loss of neurons in certain areas of the brain. So while there is neuron loss throughout the brain, there are specifically a few areas that show an abnormally high loss of neurons; these include the highest-order areas of the neocortex. The primary areas are left intact, so the individual can see, can hear, and can walk, but simply can’t do the higher-order processing that’s necessary to live in the world as a normal human being.

illustration of three trees shaped like human heads that have fewer and fewer leaves - symbolizing alheimers

For most cases of Alzheimer’s there is no cause known; only a small percentage can be inherited. For all cases, there is no cure. So at this point, the medications simply try to replace some of the neurotransmitters that have been lost from the loss of the neurons. But neuroscience is discovering which factors increase, or decrease, the risk of developing Alzheimer’s.

image of a elderly woman and her family
The number one risk factor for Alzheimer’s Disease is age.

The most important, number one factor that increases your risk for getting Alzheimer’s is age. One in eight people 65 or older have this disease, and for those individuals older than 85, as many as one-half will be diagnosed with this disorder. But we want to live a long life, so obviously we don’t want to do anything about that one.

Another risk factor is the inheritance of what are called E4/E4 alleles for apolipoprotein E. Alleles are simply gene variants for a particular molecule that’s produced. In this case, the alleles are for apolipoprotein E, which is a normal molecule found in the brain that’s involved in lipid and cholesterol transport. You inherit one gene from each parent, and for apolipoprotein E, there are three different alleles, or variants, of that gene that you could inherit. Inheriting E4/E4 alleles for apolipoprotein E increases your risk of getting Alzheimer’s disease, or at least certain forms of Alzheimer’s disease, and so it’s a very critical one. There are companies that will look at your allele and determine whether or not you have the E4 alleles for apolipoprotein E—but you can’t really alter it, you can’t change it. So, in general, most physicians do not recommend that people do that.

image of two boxers in a ring
Head injuries from sports like Boxing can be a risk factor for Alzheimer’s.

Head injuries are also associated with an increased risk for Alzheimer’s, either at a concussion or more severe level—anytime that a head injury has significantly interfered with neuronal activity. Scientists discovered this because it turns out that professional boxers, who can sustain more than 50,000 hits to the head in their professional careers, have a significantly increased incidence of Alzheimer’s disease. The consensus is yes, you want to protect your head; this is really, really important.

High-fat diets, elevated cholesterol levels, and obesity are also risk factors. This is under our control, so having this as a finding is very significant. There are also a number of chronic disorders that increase the risk—atherosclerosis, for example, diabetes, hypertension. Some individuals have genetic proclivities to have these disorders, and there may not be a lot they can do about that. You can take medicines. But for other people, it’s due to lifestyle, so changes can be made. For example, Type II diabetes is related to obesity; that’s something an individual has some control over. If a person can get rid of the diabetes, he or she would also decrease his or her risk for Alzheimer’s disease.

Smoking is a risk factor for Alzheimer’s.

Smoking has been shown to increase the risk of Alzheimer’s. Not only does it cause lung cancer and many other chronic disorders like emphysema, but also it actually is a risk factor in developing Alzheimer’s disease. So if there wasn’t enough of a motivation to quit this habit …

Another factor that increases the risk for Alzheimer’s disease is a history of clinical depression. Individuals who are chronically depressed or have a history of having true unipolar depression actually have an increased risk of developing Alzheimer’s.

A diagnosis of what is called mild cognitive impairment (MCI) is a fairly significant risk factor. This used to be thought of as an entity in itself, and is defined as a disorder that involves short-term memory loss but no other cognitive deficits. Originally it was thought that it was a disease that just probably involved the hippocampus, but now it is believed that it’s more than likely the earliest stage of Alzheimer’s. Long-term studies have shown that 80 percent to 100 percent of individuals diagnosed with MCI will, in fact, go on to develop Alzheimer’s disease. So most experts now believe those individuals have just been diagnosed at an early stage that doesn’t normally occur.

Hormone replacement therapy—individuals, women, who are over 65 years of age who start either taking estrogen alone, or estrogen and progesterone, have an increased risk of dementia and of developing Alzheimer’s disease. There are still studies going on about what happens if the woman is younger when she starts the regimen; all this is an active area of research for obvious reasons.

The majority of risk factors that increase the risk of developing Alzheimer’s disease are exactly the same risk factors that increase your risk for heart disease and increase your risk for stroke and heart attack.

It is worth noting that the majority of risk factors that increase the risk of developing Alzheimer’s disease are exactly the same risk factors that increase your risk for heart disease and increase your risk for stroke and heart attack.

Now, that was the bad news. So what factors actually decrease the risk of Alzheimer’s? Well, inheritance of E2/E2 alleles for apolipoprotein E actually protects you from ever getting Alzheimer’s disease. This is a very active area of research, for obvious reasons.

image of a salmon steak
Foods rich in Omega 3 Fatty acids, such as this salmon steak, actually decreases the risk of developing Alzheimer’s disease.

Another factor that decreases your risk is eating omega-3 fats, found in cold-water fish like salmon. Eating omega-3 actually decreases the risk of developing Alzheimer’s disease. The word is still out on whether or not taking supplements has the same effect; it isn’t always true that the body can be fooled by supplements.

Other factors include maintaining a normal weight and avoiding obesity and its associated disorders like diabetes. These are things that are under our control and that we can do something about, and it’s very, very important. Eat low-fat foods, keep your low-density lipoproteins low, and do all the things that are recommended to help you with heart disease, and this will help you stave off Alzheimer’s disease. Drinking fruit juices and vegetable juices, eating fruits and vegetables, and drinking certain kinds of teas that are high in antioxidants are definitely implicated in decreasing the risk of developing Alzheimer’s. Again, these are simple changes we can make in our lives that may not prevent us from getting the disease, but certainly play a role.

image of a woman jogging
When you are physically active, you actually generate more new neurons in the structure that’s involved in memory in your brain.

The next factor is exercise. In some of the cutting-edge research that’s going on in neuroscience right now, recent studies have shown that the hippocampus is one of the few areas of the brain that continues to undergo mitosis throughout life. Furthermore, the most recent studies have shown that exercise increases mitosis in the hippocampus. So by staying physically active, you actually generate more new neurons in the structure that’s involved in memory in your brain, so this is just unbelievably important. It’s not going to replace your old memories to generate new neurons, but it will allow you to form new memories, and so this is a very, very positive thing. We become so sedentary, we need to keep ourselves active, and this is going to help us, even if we don’t develop a disorder like Alzheimer’s; it’s going to help us maintain our memory and mental activity into old age.

One of the other factors that’s been shown to be important is continuing mental “challenge.” Continually challenging your mind—and it has to be something that challenges you, like taking a course, learning a new language, learning how to play the piano, or doing something similar—is a major way of decreasing the risk of developing Alzheimer’s disease.

Now, even if you follow everything and you do everything the way you are supposed to, it doesn’t mean that you might not get this disease; Alzheimer’s is the number one neurological disease in the United States. But it matters that we identify factors, particularly those under our control, that might help us be able to decrease the risk of getting this terrible disease.

From the lecture series Understanding the Brain
Taught by Professor Jeanette Norden, Vanderbilt University School of Medicine

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