There is growing evidence that an epidemic of Alzheimer's Disease may be around the corner. People are justifiably concerned. Many distraught individuals have come to my Psychiatry office asking if their elderly parent's or grandparent's diagnosis of Alzheimer's has doomed them as well to a future of dementia. The answer is, "Probably not."
There are two major forms of Alzheimer's Disease, an early and a late onset form. Auguste Deter was 51 years old in 1901 when her distraught husband, Karl, brought her to see Dr. Alois Alzheimer in Frankfurt, Germany. She was the first person to be diagnosed with what we now refer to as Alzheimer's Disease. Over a period of only a few years, she had developed problems with her memory and dramatic changes in her behavior. She had become insanely jealous of her husband. She had fits of screaming and hallucinations. She was described as dragging bedclothes and other items through the house, sometimes hiding them from people she suspected were out to steal them. Her ability to perform her usual daily functions had drastically deteriorated. In one of his evaluations of Auguste, Dr. Alzheimer asked her to simply write her name. In his clinical notes Alzheimer wrote, "The patient is not able to progress in writing and repeats, "Ich hab mich verloren" ("I have lost myself".)
Such severe an illness in a relatively young woman led Dr. Alzheimer to study Auguste Deter's brain to determine what was responsible for the untimely disintegration of her mind. He noted that her brain was remarkably shrunken, and through the microscope he saw that its tissue was riddled with plaques and tangles of unknown material. Modern research has determined that the plaques of Alzheimer's Disease are formed from build up of an aberrant protein called amyloid. The tangles are abnormal knots of the protein tau, which is a substance naturally found in neurons.
Auguste Deter suffered from the early onset form of Alzheimer's. This form of Alzhiemer's can occur well before the age of 65. It is strongly determined by genetics and is likely difficult to avoid. Thankfully, the early onset form accounts for only a small percentage of cases of the illness. Genes can also contribute to the development of the late onset form of Alzheimer's, which is the predominant form of the illness. However, scientific evidence shows that genes are neither necessary nor sufficient to cause late onset Alzheimer's Disease. The evidence suggests that in most, perhaps not all, but most cases, Alzheimer's can be prevented or at least delayed and diminished in severity. Most of us can avoid the mind ravaging effects of Alzheimer's by healthy changes in lifestyle, diet, exercise, remaining active, achieving ideal weight, reducing stress, and in some cases, supplementing with certain vitamins, herbs and nutraceuticals.
The genes responsible for early onset Alzheimer's are directly involved with the production and processing of amyloid precursor protein (APP). When those genes are faulty, sticky forms of amyloid are produced and accumulate as plaque. The tangles of tau are not so easily explained, but have classically been thought to be secondary to the development of plaque. There can also be genetic contribution to late onset Alzheimer's. The only gene that has consistently been found to increase the risk of this most common form of Alzheimer's is the APOE4 gene. Like brown, blue and green eyes, the APOE gene comes in three main varieties. The APOE3 type is most common and benign. The APOE2 gene may reduce some risk for Alzheimer's. However, the APOE4 form of the gene, which is found in 12% of our population, can double the risk of developing Alzheimer's. Inheritance of two APOE4 genes, one from each parent, is seen in 2% of the population and can increase the risk by up to 20 fold.
The question remains as to how the APOE4 gene increases the risk of developing Alzheimer's. It does not appear to be directly involved in the production and processing of APP. Rather, it is one of the body's house keeping proteins. Indeed, most APOE protein in the body is made in the liver, not the brain. Presence of the APOE4 variety of the gene leads to too much fat and cholesterol in the blood. It increases the risk of heart disease, hardening of the arteries, and stroke. APOE4 also predisposes to inflammation and oxidative damage in the body, including the brain. A major part of how APOE4 increases risk of Alzheimer's is likely its exacerbation of other conditions that are known to be risk factors. In fact, the best evidence indicates that the bad things the APOE4 gene does can be overcome by healthy living.
Amyloid plaques and tangled tau disrupt brain tissue. However, scientists have begun to recognize that plaques and tangles may be equally deleterious in their initiating subsequent pathological processes that damage tissue and diminish brain function. Such processes include inflammation, oxidative stress, insulin resistance, damage to mitochondria that produce the energy neurons use to function, disruption of chemical messenger systems, deposition of amyloid in blood vessels, and other changes. Some of these secondary effects are themselves known to increase deposition of amyloid and disruption of tau, thus forming a vicious cycle that can spiral out of control.
To prevent Alzheimer's, it is imperative to avoid the major risk factors for the illness, which include heart disease, diabetes, obesity, high blood pressure, high cholesterol and triglycerides. The means to do this are to improve the diet, exercise, get adequate sleep, reduce stress, and follow a health maintenance plan with the help of your doctor. Good dental care is a critical component of any plan to avoid Alzheimer's, as tooth and gum disease predispose to heart disease and stroke. It is also essential to maintain levels of nutrients, such as vitamins B12, folic acid, C, D, and others that the brain and organs of the body require to maintain their function and tissue integrity. The brain, like muscles in the body, requires exercise to remain strong in function. Stimulation of the brain increases the growth of neurons that support cognitive function, and these beneficial effects can be seen in people of all ages. Thus, it is important to pursue intellectually challenging activity throughout life. A good education and lifelong intellectual pursuits are known to decrease the risk of dementia as well as to diminish the deleterious effects of amyloid plaque and tangles that may accumulate. There are a variety of herbs and nutraceuticals, that is, substances that the body produces but in insufficient amount, that are likely to reduce the risk of Alzheimer's and other forms of dementia. Many possess anti-oxidant and anti-inflammatory effects that protect the brain and help break the cycle of degenerative processes that result in late-onset Alzheimer's Disease. Such substances can also increase the birth of new neurons in the recently discovered process of neurogenesis, stimulate nerve growth factors, increase the levels of important chemical messengers, and enhance the activity of insulin in brain tissue. We now know that adequate insulin activity can prevent the formation of abnormal tangles of tau protein. Some herbs and nutraceuticals may even help the brain rid itself of amyloid and tangles of tau that have already accumulated. However, no single measure can stop Alzheimer's. Moreover, since the degenerative effects of Alzheimer's begin as many as 15 years before any symptoms appear, it is necessary to start early.
An epidemic of dementia is looming before us. Some of us may be genetically destined to develop dementia, and it is not the job of a physician to peddle false hopes. However, there is abundant evidence that the unhealthy lifestyles of modern society have brought many of us to the doorstep of dementia. For most of us, Alzheimer's and other forms of dementia can be prevented.
Dr. Mendelson is the author of the new book, Beyond Alzheimer's.