New Tests Find Alzheimer’s Before Symptoms Emerge : Health: UCLA study involves imaging and genetics. Researchers say early detection could aid treatment.
A combination of genetic testing and sophisticated imaging techniques can detect brain damage caused by Alzheimer’s disease 20 years before obvious symptoms of the disorder appear, according to UCLA researchers.
Such an early diagnosis, they say, could open the door to treatments that would prevent further deterioration of the brain, staving off the onset of the disease for years or even decades.
Dr. Gary W. Small of UCLA and his colleagues report today in the Journal of the American Medical Assn. that in people who have a gene called ApoE4, the early stages of Alzheimer’s can be detected by an imaging technique called PET scanning.
“The search for an early and accurate diagnostic tool for Alzheimer’s is a critical step in the development of preventative strategies,” said Dr. Zaven Khachaturian, director of Alzheimer’s research at the National Institute on Aging. “This is a major step forward.”
Scientists currently have only one drug for treating Alzheimer’s, and it is only effective in some patients. But a variety of other promising medications are nearing or beginning human trials.
Each of these would be most effective in the earliest stages of the disease, which affects as many as 4 million Americans over the age of 65. “It doesn’t make sense to treat somebody late in the course of the disease, because all the brain cells are already dead,” Khachaturian said. But current techniques usually provide a diagnosis only after the full-blown disease develops.
Researchers have previously reported several potential techniques--including a skin test and an eye test--for diagnosing Alzheimer’s, but none of them has been fully confirmed yet and none appears to diagnose the disease at such an early stage. “I think this (test) is a lot stronger,” Khachaturian said.
The new technique may also prove valuable in distinguishing between Alzheimer’s and other mental disorders that afflict the elderly, such as depression, said Dr. Rex W. Cowdry, acting director of the National Institute of Mental Health. Although advanced Alzheimer’s is not generally treatable, he said, “these other conditions are.”
The study also provides the first direct evidence that the brain damage produced in Alzheimer’s accumulates over a long period before symptoms become evident, which should provide new insights into the mechanisms of the disease, said Sheryl Williams, vice president of medical affairs at the Alzheimer’s Assn. It “is more evidence that we are getting close to understanding Alzheimer’s disease,” she said.
Alzheimer’s is characterized by a progressive deterioration of mental function, including loss of memory, language and the ability to deal with numbers. Victims progress into confusion and a complete inability to handle everyday situations. Eventually, when the brain loses the ability to regulate body functions, victims die of malnutrition, dehydration, infection or heart failure.
Researchers are still not precisely sure what causes Alzheimer’s, but a strong--and surprising--genetic link was discovered in 1992 by Dr. Allen D. Roses and his colleagues at Duke University. They discovered that susceptibility to Alzheimer’s is related to the gene for a protein called apolipoprotein E (ApoE), which is involved in the transport of cholesterol in and out of cells throughout the body.
Every individual has two copies of the ApoE gene, one from each parent. Roses’ team found that there are three slightly different forms of the gene, called ApoE2, 3 and 4, and that the presence of the type 4 form greatly increases the risk of Alzheimer’s. An individual with two copies of ApoE4 has about 15 times the risk of developing Alzheimer’s as someone with no copies of it, while an individual with one copy has five times the normal risk.
In the new study, Small, Roses and their colleagues used PET scans to study seven Alzheimer’s patients, 12 relatives of Alzheimer’s patients who had at least one copy of ApoE4 and 19 Alzheimer’s relatives who had no copies of ApoE4. All the subjects were over the age of 40.
In PET scans, a slightly radioactive form of the sugar glucose is injected into the subjects’ blood. Because glucose is the only form of energy used by brain cells, the radioactively labeled sugars accumulate in the brain cells that are most active, allowing researchers to produce a picture of brain activity.
In the Alzheimer’s patients, the team observed a marked overall lowering of brain functions, with the greatest effect in the parietal lobe, where thought processes are concentrated and which has previously been implicated in Alzheimer’s disease. They also observed that the left side of the brain loses much more of its functioning than the right side.
The key findings came in the relatives who had at least one ApoE4 gene, but no obvious symptoms of the disease. This group showed the same type of changes in their PET scans as the Alzheimer’s patients, but the deviation from normal was less severe, indicating that less damage had occurred.
The relatives without an ApoE4 gene showed normal PET scans.
“The findings suggest that genetic testing and brain function studies may help identify people at risk for the disease,” Small said. “They are also consistent with the view that subtle changes in brain function begin gradually, years before the clinician can make a clinical diagnosis.”
Small cautioned that the tests are not yet ready for widespread use. PET scanning is very expensive and time-consuming, he noted. The group is now working on ways to simplify the procedures and lower the cost, as well as to improve the diagnostic capabilities, he added.
Meanwhile, several groups of researchers are beginning clinical trials of several drugs they hope may delay progression of Alzheimer’s, including such well-known but previously untried drugs as aspirin, prednisone and estrogen. Other groups have identified a growth factor that strongly protects brain cells in animal models of Alzheimer’s, Parkinson’s disease and other disorders.
By the time Small has refined his technique for identifying early stage Alzheimer’s, Khachaturian said, “we should have at least one new drug to slow its progression.”
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Inherited Risk
ApoE, the gene for a protein that transports fats in and out of cells, comes in three different forms, called 2, 3 and 4.
The number of copies of ApoE 4 inherited from your parents defines your risk of developing Alzheimer’s* Two copies: 15 times normal risk One copy: 5 times normal risk ***
The number of copies of ApoE 4 also controls the percentage who develop Alzheimer’s by age 65. No copies: 20% One copy: 60% Two copies: 90% * Only a handful of research laboratories currently can determine how many copies a person has.
