A Road Without Signposts
Friends say Robert Citron, the former county treasurer who only two years ago was leading Orange County into bankruptcy, nowadays has periods when his mind fails him.
At age 71, “he has . . . “lapse[s] that go on for quite a while,” says one friend, who asked not to be identified. “He can’t remember names, can’t end sentences, can’t complete conversations. It is quite pronounced and severe when it does occur, and it’s been getting worse over the last year or so.”
One friend says Citron’s case is the perfect example of why we should medically test public officials to weed out the ones headed for dementia, what used to be called senility.
Carl Cotman, director of UC Irvine’s Institute for Brain Aging and Dementia, says the question often pops up when he speaks publicly. “I’ve had several workshops, and someone always says, ‘Shouldn’t Bob Dole be tested?’ ”
Well, why not?
Kansas Sen. Bob Dole, the Republican Party’s presidential nominee, is 73 years old, nearing the age in which the odds are about one in five of developing dementia.
Ronald Reagan’s Alzheimer’s symptoms were diagnosed when he was 83, five years after stepping down as president. Most researchers believe the disease is at work many years, perhaps decades, before symptoms become obvious.
But the question of testing politicians is moot, Cotman says. You can’t screen them for Alzheimer’s, because you can’t screen anyone for Alzheimer’s. For now there is only one conclusive test: an autopsy. It reveals the Alzheimer’s-ravaged brain, shrunken and shriveled by a mass suicide of its cells.
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Even though genes have been found that seem related to Alzheimer’s, they do not necessarily doom a person to the disease. They indicate only that the people who carry them, about 4% of the population, are at five times greater risk. Many people with the genes never develop the disease, and 40% of Alzheimer’s victims do not have the high-risk genes.
This lack of a medical test is the sorest point in Alzheimer’s treatment. A prescription drug, commercially known as Cognex, can lessen Alzheimer’s symptoms in about 30% of cases, and many more drugs are becoming available. But until a reliable diagnostic test is developed, the disease cannot be targeted at its earliest, symptom-free stages, when drugs would do the most good.
The root of the problem is that unlike other organs, the brain is isolated, physically and chemically, and cannot be probed for tissue or fluid samples. Encased in bony armor and walled off by the so-called blood-brain barrier, few of its chemical byproducts leak out. So far, those that do have not proved useful for diagnosis.
Instead, Alzheimer’s now is diagnosed only after symptoms such as memory loss and disorientation have become undeniable. By then, much irreversible damage has been done to the brain. Typically, Alzheimer’s patients are dead within four to eight years after the diagnosis, although some live as long as 25 years.
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“Various people are working on a blood or spinal fluid test for Alzheimer’s,” says Neil Buckholtz, head of Alzheimer’s research at the National Institute on Aging in Bethesda, Md. “Theoretically, there have to be markers--things going on in the body that could be detected and measured.”
Meanwhile, researchers concentrate on learning just how the disease evolves and does its damage.
“I’m very optimistic that within the next five or 10 years we will have a much better understanding of the process,” Buckholtz says. “I think there are eventually going to be some tests, but it’s not clear what they will be.”
Much progress has been made in the last 10 years. Before then, “senility” was popularly believed to be a natural part of growing old. Alzheimer’s disease, first diagnosed in 1907, was considered to be quite rare.
Now researchers believe that except for a slowing of brain processes, aging does not necessarily degrade the brain. Dementia is abnormal, usually caused by disease.
Alzheimer’s is the cause of half of all dementia and is a contributor in another one-fourth of all cases, researchers estimate. They believe there are more than 4.1 million cases of Alzheimer’s in America today, and as the population ages along with the baby boomers, the total is expected to rise dramatically.
Because dementia is at times so difficult to diagnose, the risks of developing it are very rough estimates. According to Malcolm B. Dick, a psychologist who diagnoses dementia at the UCI Alzheimer’s clinic, the risk between ages 65 and 74 is 3% to 10%. The risk about doubles for each additional decade of life, he says. Some estimate it reaches nearly 50% by age 85.
The more than 60 other causes of memory defects--among them depression, thyroid malfunction and vitamin B-12 deficiency--are less common, and in some cases their effects are reversible.
The damage caused by Alzheimer’s, however, is permanent. Driven by a process that is only partially understood, brain cells simply begin dying. By the time the victim dies, the brain has shrunk to about two-thirds its normal size.
Researchers generally agree that brain cells, which do not divide and therefore cannot be replaced, are tricked into committing suicide.
This self-destruction process, called apoptosis, is built into all cells and is normally triggered only to rid the body of defective or unwanted cells. But in Alzheimer’s,a false signal may be given to start a mass suicide in the brain that spans decades and eventually kills its victim. Researchers believe the signal probably comes from an imbalance or concentration of substances that occur normally in the brain.
The disease attacks the parts of the brain involved in memory, language and reasoning. Eventually its victims cannot recognize friends or even family, cannot remember what was done or said a few minutes ago, have difficulty forming and understanding sentences and can become lost only a few yards from home. Personality and behavior are affected as well. Judgment becomes somewhat, then utterly, irrational.
Who is afflicted and who is spared seem to be decided by a combination of genetic and lifestyle factors, Cotman says.
“If you had a head injury and lost consciousness and you’re carrying the wrong genes, the likelihood you’re going to get dementia goes up tenfold,” Cotman says. This makes prizefighting “the craziest profession in the world,” he says.
On the other hand, “if you don’t have the genes, [head injuries] don’t matter.”
There are protective factors as well, Cotman says. “Formal education turns out to be one of them. It’s very clear. Some people say that additional education and training enriches the circuitry in the brain, so when the little losses start to occur, you don’t go down so far because you’re starting from a higher point.”
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Strenuous exercise such as running produces substances in the brain that are known to benefit brain cells, Cotman says.
Other supposed protective factors have downsides, however.
Vitamin E may counteract Alzheimer’s, but only in doses much higher than the usual vitamin supplements. Such high doses can be toxic to some people.
Likewise, tests in women suggest that taking estrogen may inhibit Alzheimer’s but may also increase the risk of breast cancer. “For elderly people, the benefits probably outweigh the risks,” Cotman says.
Such treatment is moot, however, if diagnosis comes too late, as it often does.
Dick says that when symptoms suggesting Alzheimer’s first appear, many people deny that anything is wrong or attribute these changes to normal aging. Many wait to seek help until symptoms are so obvious they’re undeniable, typically a three- to four-year delay.
Even then, diagnosis is difficult. The disease is detected not by specifically identifying it but by eliminating all other likely causes.
At the UCI clinic, patients start by giving a medical history. “We’re looking for a family history of the disease,” Dick says. “Do they have a history of hypertension, strokes, risk factors like head trauma, thyroid problems, low levels of vitamin B-12, combinations of medications that can cause confusion and memory problems? Many of these problems can mimic Alzheimer’s symptoms.”
A physical examination looks specifically for evidence of small strokes that the patient may not even realize occurred. Strokes alone or in combination with Alzheimer’s can cause dementia.
A series of neuropsychological tests are administered to determine which mental skills are intact and which are impaired.
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Finally, patients are sent for brain scans, which can reveal evidence of strokes and unusual gaps in the brain, presumably where brain cells have died and their space filled by spinal fluid.
At present, brain imaging is far from conclusive, Dick says. People in the early stages of Alzheimer’s can show brain scans that appear entirely normal.
“We think we can see the effects [of Alzheimer’s] by the time patients are showing up at the clinic for diagnosis,” Dick says. “But we don’t know how early it begins to show.”
But Buckholtz believes advances in brain imaging are the best hope for early diagnosis in the near future.
At present, three methods are being used.
* PET (positron emission tomography) yields a map of the brain’s metabolism--that is, where brain cells are working at optimum levels and where they are not. PET scanning is expensive and not readily available.
* SPECT (single positron emission computerized tomography) is similar to PET but less detailed, less expensive and more commonly available. Insurance companies generally are more willing to pay for SPECT scans.
* MRI (magnetic resonance imaging) yields a picture of the brain’s physical structure and can show gaps where brain cells have died.
Recent research used PET to scan the brains of people who had high-risk Alzheimer’s genes but no Alzheimer’s symptoms. The scans revealed brain changes that could be developing Alzheimer’s.
Cotman says he is optimistic that Alzheimer’s will be controlled, if not cured. Research is moving at a fast pace, he says.
“It’s a tough problem, but it gets simpler all the time. It is solvable--that I’m convinced of. We just have to get at it early enough.”
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For More Information
Information on Alzheimer’s disease is available from:
* Orange County chapter of Alzheimer’s Assn., (714) 283-1111. Information, counseling, support groups and referrals to local care facilities, physicians and other resources.
* UC Irvine Alzheimer’s Disease Research Center, (714) 824-2382. Information, diagnosis and treatment.
* Alzheimer’s Assn., Chicago, (800) 272-3900 or via World Wide Web at www.alz.org. Information, literature and referrals to local organizations.
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When Cells Die
When Alzheimer’s destroys brain cells, the space is filled by brain fluid. These MRI (magnetic resonance imaging) scans show the fluid cavity (1) is much larger in the Alzheimer’s brain . This is also true in the hippocampus areas (2), which are vital to memory.
The Odds of Alzheimer’s Disease
The difficulty of diagnosing Alzheimer’s makes estimates vary considerably. Estimated risk of contracting the disease:
Age group: 65-74; Risk: 3%-10%
Age group: 75-84; Risk: 19%-22%
Age group: 85 and older; Risk:47%
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Women are slightly more prone to the disease than men are.
Genes that quintuple the risk of Alzheimer’s are carried by about 4% of the population.
* Source: UC Irvine Institute for Brain Aging and Dementia
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Testing for Alzheimer’s Here are simplified versions of tests that psychologists use to help diagnose Alzheimer’s disease. Diagnosing the condition requires many more tests and a psychologist’s expertise. *
Recall
Key
Tire
Chair
Clock
Shoe
Cup
Tree
Dog
Book
Knife
* Read the words aloud. * Put the list aside. How many words can you remember? * Read aloud and try again to remember. Repeat a third time. Did your memory improve each time with practice? * Wait 30 minutes. How many words can you remember now? On average, a person will remember five words the first time, six to seven words the second time, eight words the third time. How quickly that memory fades is an important test for Alzheimer’s. After 30 minutes, a person without Alzheimer’s will still remember almost all he remembered originally. But a person with mild to moderate Alzheimer’s will forget all or most of what was previously remembered.
Recognition Bucket Dog Book Tree Shoe Spoon Window Cat Clock Knife Pencil Horse Fork Tire Broom Table Chair Hammer Telephone Cup * Working from memory, identify from this list the 10 words that were on the original list. The average person will identify all 10 words. A person with mild to moderate Alzheimer’s may get five right but will be unsure of the choices.
Attention “8 6 4 0 7 6 5 2 9” * Have someone speak a series of up to nine numbers. * Repeat the series from memory. The average person will be able to remember seven numbers, the equivalent of a local telephone number. A person with mild or moderate Alzheimer’s will have great difficulty remembering and may forget the first numbers almost as soon as they are spoken.
Shifting Attention Connect the dots in order, alternating between numbers and letters: A-1-B-2, etc. People with mild to moderate Alzheimer’s tend to have difficulty switching concentration between the letters and numbers. They will take longer and make more mistakes.
Visual/Spatial Relationships Arrange the set of cards illustrated in the top row to form the pattern shown in the bottom row. This test can be performed with up to nine cards. People with mild to moderate Alzheimer’s may have increasing difficulty reproducing the pattern as the number of cards increases.
Other tests * Name common objects in a picture. Alzheimer’s patients will frequently have trouble remembering names and may either get them wrong (calling an artist’s palate an “easel”) or describe the objects’ uses (“artists put paint on it”).
* Follow a multiple-step command (“Pick up the pen, turn over the notebook and hand me the coin”). Alzheimer’s patients will have trouble or fail entirely to comprehend.
* Give examples from a wide category, such as fruits. Alzheimer’s patients will think of few examples, perhaps only apples and oranges.
* Identify what related objects--a table and chair, for example--have in common. Alzheimer’s patients will be more literal than conceptual: “They have four legs and are made of wood” rather than “They’re furniture.”
* Respond to a hypothetical situation, such as “What would you do if you came home and found a broken pipe flooding the kitchen?” Alzheimer’s patients may have irrational reactions or may give up when there are obvious solutions. Source: UC Irvine Institute for Brain Aging and Dementia
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Map of Activity
Brain scans show where glucose, the brain’s fuel, is being consumed and at what rate. Called S PECT scans, they indicate high activity in red and yellow, low activity in green and blue. The Alzheimer’s brain has more low-activity because so many brain cells have died.
