Apr. 13, 1998 By testing older adults repeatedly for up to 15 years, researchers have shown that a sudden decline in mental ability is not a normal part of aging but can signal the onset of Alzheimer's disease.
In the March 1998 issue of the Archives of Neurology, researchers at Washington University School of Medicine in St. Louis report that cognitive performance in elderly adults remains stable over many years unless and until a dementing illness such as Alzheimer's disease develops. When such an illness attacks, there is a deterioration in cognitive performance that often is detectable over a relatively short period of time.
"People without the disease can look forward to good mental function in old age," says Eugene H. Rubin, M.D., Ph.D., professor of psychiatry. "Unfortunately, those with Alzheimer's disease usually face a sharp decline."
The investigators studied 82 healthy people who were between the ages of 64 and 83 when the study, which was funded by two grants from the National Institute on Aging, began. As the volunteers aged, their cognitive functions tended to remain intact. Although 40 percent of them developed cognitive deterioration within 12 years of an initial examination, the other 60 percent remained stable.
The majority of people with cognitive changes were in the beginning stages of an Alzheimer-type dementia.
Starting in 1979, the researchers enrolled people who had no evidence of any memory or thinking difficulties. Then they followed them with assessments about once every year.
The assessments consisted of a comprehensive clinical evaluation including a neurological exam and rigorous psychometric tests. The latter included many pen and paper tests measuring memory function, vocabulary function and other types of cognitive performance. Clinicians also interviewed a close friend or relative of each volunteer.
The clinicians assigned each participant a score on the Clinical Dementia Rating (CDR) scale, which was developed at Washington University in St. Louis and now is used worldwide. A CDR of zero is considered normal. A rating of 0.5 usually indicates very mild dementia, and 1, 2 and 3 denote mild, moderate or severe dementia. The study participants were assessed every year until they died or were clinically diagnosed with a CDR rating greater than zero. The researchers therefore were able to study aging over the course of many years and to distinguish normal cognitive performance from the impaired performance that results from Alzheimer's disease.
Stability over time was key to distinguishing normal aging from dementia. Although participants who were older when they first took the psychometric tests did not perform as well as those who were younger, both groups tended to remain stable over time.
"On average, someone who takes the tests for the first time at age 80 won't do as well as a person who is 70 or 60," Rubin says. "But our most important finding was that when someone takes the tests each year, they maintain their performance over time. Those who develop Alzheimer's disease experience an abrupt decline between one test and the next."
Comparing test performance to grades in school, Rubin explained that the subjects who were younger when first tested might get A's on average, while older ones might be B students. But over several years, the A students continued to perform at about the same level. So did the B and C students. When dementia developed, however, the A students suddenly started doing B or C work on the tests. Those whose initial scores were lower fell lower still.
"Also, we found that there is a greater chance that C students will eventually develop symptoms of Alzheimer's disease than A students," Rubin explains. "However, many C students remained at that level of performance and did not develop dementia. And many A students did change -- though perhaps only to the B level -- and that's when we also found clinical evidence that they were developing Alzheimer's disease. The change in performance is what is critical."
As test scores declined, subtle behavioral changes also occurred. Some participants had more trouble balancing their checkbooks, remembering where they parked their cars or calculating tips. "When we started to see consistent memory changes involving many different aspects of function, and those changes started to interfere with daily life, we made a clinical diagnosis of dementia," Rubin says.
As clinicians were diagnosing that dementia, the psychometric testers in the other arm of the study also were independently noticing a slip in performance at about the same time. One exception was a memory test that required people to recall information from a paragraph. Scores on that particular test tended to decline six months to a year before those on other cognitive tests in those participants who were to develop dementia. But Rubin says just giving that specific test would not be enough to predict the presence of Alzheimer's disease.
"We followed these people over many years," he explains. "Only by comparing a person's performance to itself over time were we able to pick out the subtle changes that appear to signal the onset of Alzheimer's disease."
The changes that occur before diagnosis may indicate that the brain damage in Alzheimer's disease may occur shortly before symptoms appear, Rubin says. "If this turns out to be correct, then early intervention, even at the very onset of symptoms, may be very helpful," he says.
Note: For more information, refer to Rubin EH, Storandt M, Miller JP, Kinscherf DA, Grant EA, Morris JC, Berg L, "A Prospective Study of Cognitive Function and Onset of Dementia in Cognitively Healthy Elders," Archives of Neurology, 55, 395-401, March 1998.
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