Alzheimer's disease, dementia, and senility are all words that terrify us -- all the more so as people are living longer and therefore at greater risk of losing their mental capabilities. What exactly is Alzheimer's disease? How do we diagnose it? What are researchers doing to combat it? We'll look at these questions below.
What is Alzheimer's disease?
Alzheimer's disease is a form of dementia -- but not all dementias are Alzheimer's disease. A dementia is a global, irreversible loss of cognitive ability. It is typically caused by a degenerative disease that entails progressive loss of brain nerve cells. Other diseases, such as a severely low thyroid level, may cause a reversible loss of selective cognitive functions, but that is not a dementia. Global loss entails a gradual loss of all brain functions, including previously acquired abilities.
Symptoms of Alzheimer's disease
In contrast to the norm for most diseases, complaints to the doctor about problems related to Alzheimer's disease usually come from family members, not the patient. For a cold or a muscle pull, the patient is the only one who feels the symptoms and is therefore is the best source of information about the problem. Not so with Alzheimer's.
Family members see the decline in memory and mental capabilities, but the person with Alzheimer's is largely unaware of the problem and will more than likely deny or minimize it. In fact, this is a symptom of Alzheimer's. Unfortunately, other family members often do not trust or act upon their observations about the person with Alzheimer's, so it is up to an attentive physician to coax crucial information from knowledgeable family members if the physician suspects a problem.
Short-tem memory loss is the most easily recognized symptom. Victims forget what they ate for lunch yesterday, the phone message they took an hour ago or the plot of the movie they watched last night. Family members typically dismiss or ignore their first observations of short-term memory loss in a loved one, excusing forgetfulness with comments such as, "Frank's getting old; he's supposed to forget." Or, "She's under so much stress. I'd have trouble remembering things, too."
Other symptoms relate to the functions our brain performs, usually unconsciously, every day. Alzheimer's victims have difficulty making travel arrangements, which is a planning problem. Activities requiring calculation, organization, sequencing, judgment, insight, executive functioning, spatial understanding, and problem solving also gradually become difficult. People may get lost while driving, be unable to do their taxes or balance a checkbook. They may have difficulty following a recipe, calculating a tip, counting change, or writing a report for the book club.
Later symptoms are more apparent and more incapacitating: forgetting how to operate the TV remote or the microwave oven, being unable to finish a knitting project or put the doorknob back together. Less apparent is the gradual failure to even attempt activities they used to enjoy; many victims resort to watching more TV or taking more naps. If you see a family member fail at a skill he has practiced for years or begin to neglect well-loved activities, then seek a doctor's evaluation.
Diagnosing Alzheimer's disease
This evaluation is similar to other diagnostic procedures. The doctor will question both patient and family member, perform a physical examination, and order blood tests and likely a CAT scan or MRI scan of the brain.
Alzheimer's is most often diagnosed by exclusion -- there are no tests for the disease, only tests to eliminate other conditions that could cause similar symptoms. You cannot see the disease on an MRI scan, so doctors must take a careful history to confirm a decline in mental capacity. The physical examination rules out other illnesses, and the blood tests check for thyroid disorder, B12 deficiency, certain rare infections, blood disorders, and similar problems. Finally, the brain scan checks for indications of stroke, collection of fluid or blood around the brain, and tumors. Once all the information is in, the physician will likely be able to diagnose the cause -- or causes -- of the cognitive decline.
Researcher think that the disease often begins attacking the brain at least a decade before it produces noticeable symptoms. Let's take a look at what we know about its causes.
Causes of Alzheimer's disease
The causes of Alzheimer's disease are varied and multiple; they have not yet been pinned down. But researchers do know something about them.
In 1907, Alois Alzheimer published a paper detailing the progressive dementia of a 50-year-old washer woman. What set this paper apart was Dr. Alzheimer's careful microscopic examination and description of her brain. For under his microscope, he saw the basic pathology that defines Alzheimer's: plaques and tangles.
Plaques are gummy deposits of a protein-like substance called amyloid ; they occur in the millions throughout the Alzheimer's brain, surrounded by a halo of nerve cell loss, cellular debris, and inflammation. Amyloid results when a perfectly normal protein does not get properly metabolized. When it forms a plaque, it appears to cause problems in the surrounding neighborhood, inciting inflammatory activity that likely harms nearby neurons.
The tangles are left-over, collapsed, internal microtubular skeletons of dead nerve cells. Millions of these are scattered throughout the Alzheimer's brain, evidence of previously thriving nerve cells. A microtubule not only forms a structural support system for a nerve cell but also plays an important role in transporting nutritional and maintenance components around the cell. A protein called Tau is also important to this transport system. In the Alzheimer's brain, Tau protein becomes attached to phosphorous atoms, which rapidly and irreversibly paralyze the protein's function. Then, without a way to move important products around the cell, the nerve dies. Its collapsed skeleton leaves the tell-tale tangle that Dr. Alzheimer saw. Alzheimer's causes a gradual but profound loss of neurons -- up to a quarter of the total nerve population.
Scientists have identified a number of "susceptibility genes" that may increase a person's chances of getting Alzheimer's disease. People who are afflicted before age 60 seem to have a dominant gene for the disease.
Treatment strategies and research
When I started out as a young neurologist, there was no treatment to help with Alzheimer's symptoms. Since then, a total of five medications have been approved by the FDA for symptomatic treatment: Cognex, Aricept, Excelon, Razadyne (formerly Reminyl) and Namenda.
All of these medications enhance or modulate certain brain chemicals that improve the function of the surviving neurons. They do not have any effect on the disease itself. Like cold medications, people take them in order to feel better, not because they get rid of the illness. Unfortunately, their ability to control symptoms is also modest and usually temporary. Well-meaning doctors have misrepresented their effect by telling patients that they will slow down the disease's progress, but this creates unrealistic expectations.
Fortunately, many pharmaceutical companies are now conducting clinical trials on treatments and drugs that may have an effect on the underlying disease.
Scientists at one company are using highly targeted antibodies to attack the amyloid plaques and clear them from the brain. This seems to work in rats. Once the antibody attaches to the amyloid in the plaque, the body sends in "garbage truck" cells called microglia to gobble up the antibody-amyloid pairing and gradually reduce the amyloid plaques.
Another company's approach is based on the observation that a hormone system in the body is out of kilter in Alzheimer's patients. Researchers are studying a medication to improve the hormonal balance and help surviving neurons better resist the Alzheimer's processes.
Still another company is looking at a compound that may slow the production of amyloid in the brain. This might allow normal mechanisms to handle elimination of the remaining amyloid.
Other approaches focus on other aspects of Alzheimer's pathology. Like any ambitious scientific endeavor, this one is fraught with potential risks and disappointments. Although researchers are more optimistic than ever before, they are also finding that families of Alzheimer's victims are less willing to have their loved ones participate in clinical trials. The cost of finding qualified patients for research has tripled, and the medication development timelines have more than doubled, which has significantly slowed the pace of research.
What can you do?
Science has spent billions of research dollars to prove that what your grandmother told you was good advice: Eat your vegetables, get plenty of exercise and sleep, and keep your mind and body busy. Higher education, an active life, regular exercise, keeping your mind challenged (more than a crossword a day!), and eating vegetables with antioxidants all seem to stave off the likelihood of getting Alzheimer's disease.
