July 16, 2009 -- For people with a common genetic variation, researchers have discovered signs of the possible onset of Alzheimer's before a patient would be clinically diagnosed by a doctor.
In people with the ApoE4 gene variation, one previously implicated as affecting the likelihood of Alzheimer's, researchers have been able to pinpoint some signs of memory loss beginning in the person's mid- to late-50s -- without the patient having full-blown Alzheimer's disease or dementia.
"[One could argue] we really captured for the first time the onset of Alzheimer's disease," explained Dr. Richard Caselli, a neurologist at the Mayo Clinic in Scottsdale, Ariz.
"What's passing as normal aging itself correlates with the most common genetic risk factor for Alzheimer's disease," he said, adding that the symptoms are noticeable in a clinical setting, but not in everyday life.
"It's not the sort of thing that you can look at somebody or they can look at themselves and know."
Researchers caution that when in interpreting the findings, one should keep in mind that people who had shown some memory loss were still functioning normally and having the gene did not impair anyone at an earlier age.
For the study, researchers followed and looked at data for 815 subjects, 317 of whom had the ApoE4 variant. They administered a variety of neuropsychological tests to the patients and found that memory was affected in some patients with the ApoE4 gene as they reached their late 50s and into their 60s.
The study results are published in the most recent issue of the New England Journal of Medicine.
"You can start to see cognitive impairment, memory decline, in ApoE4 carriers early, although they're not clinically diagnosed with dementia or mild cognitive impairment," said Rudy Tanzi, director of the genetics and aging unit at Massachusetts General Hospital. "I think it's important that this study has elegantly confirmed what many of us have been dancing around for years."
But researchers caution that ApoE4 is not a gene that by itself determines the fate of a person's brain.
"ApoE4 is not sufficient to give you the disease. It works together with not only your lifestyle and environmental factors…but it works together with other genetic factors, some of which confirm risk…but some of which confirm protection," said Tanzi.
Dr. Richard Lipton, professor and vice chair of neurology at the Albert Einstein College of Medicine concurred.
"Not everyone who carries the E4 gene develops Alzheimer's disease," he wrote in an e-mail to ABC News. "We have 100-year-olds in one of our studies who carry the gene and have no evidence of memory decline. And not everyone who develops Alzheimer's disease has an E4 gene; only about half of people who develop Alzheimer's disease carry an E4 gene."
Genetic Testing for an Alzheimer's Future?
While another Alzheimer's study published in the most recent New England Journal issue found patients who underwent testing for the ApoE4 gene and received counseling handled it well, researchers generally advised against getting such a genetic test.
"I do not recommend that people go out and have this test," said Caselli. "I think it's an important tool for research right now, but as of this moment there isn't any routine benefit people would get from this information.
"There's many different considerations…unless there's a compelling reason a person should know [such as research], then no, I would not recommend that people go out and get this test."
Caselli noted that a number of problems could arise from getting the test, in the forms of employer discrimination, insurance discrimination, and children who might learn of an increased risk to themselves.
"I argue that until we have the entire set of genetic risk factors for Alzheimer's…and look a them as a group, in the end you're cumulative risk involves hundreds, if not thousands of risk factors," said Tanzi, whose own research has focused on finding all of the genes connected with Alzheimer's.
He notes, however, that a study such as this could be easily misinterpreted.
"You don't want to risk that kind of discrimination when it's not really warranted. It's not warranted," Tanzi said. "Just because you carry an E4, you're not cognitively different from anyone else. Importantly, there's no correlation between ApoE4 and intellectual achievement.
"There is no effect on E4 as measure by your occupation or educational success or outcomes. It's just saying the disease is starting before you see symptoms, but it's pretty close to when the symptoms occur."
The Next Step
Caselli said one effect of this study is that it adds to the knowledge that Alzheimer's might affect the elderly, but does not begin then.
"The age group that we're talking about is pre-retirement," he said.
While people may typically think of Alzheimer's as an "old person's disease," he said, "actually, the earliest stages of it happen where we're still employed.
"It's important to keep in mind that this could start to have an effect on people in very intellectually demanding jobs as they age, as they try to remain employed."
Most research going on, Caselli said, is targeted at people who are much older. He believes that as we move towards experimental trials for prevention, "we really have to shift the spotlight to a younger age."
But while the disease might have its roots in that age group, he said, it does not generally have its symptoms then.
"I'm hoping that we don't generate a lot of panic in a lot of people in this age group," said Caselli.
"The dangerous way to look at it is to say people who carry E4 are cognitively deficient, even earlier in life," said Tanzi. "You don't want to invite discrimination when they're in the prime of their lives, when they're just fine."