Alzheimer's Disease Annual Update: To Know or Not to Know
Do you want to know when you're going to die?
A modified version of that question - do you want to know if you're going to get Alzheimer's disease, and when? - is the basis for the ongoing REVEAL study. Dr. Robert Green, a genetics fellow at Harvard Medical School and professor of neurology, genetics and epidemiology at Boston University Schools of Medicine and Public Health, has devoted a good deal of his recent professional life to answering that question.
Dr. Green presented his findings last week at the "Alzheimer's Disease: Annual Update," sponsored by the UW School of Medicine and Public Health and the Wisconsin Alzheimer's Institute. His research showed that first-degree relatives of people with Alzheimer's disease, who have been proven to be at greater risk for developing Alzheimer's themselves, prefer to know their chances even if the news their doctors deliver is bad news.
In the early years of his career, Dr. Green wasn't certain how he should answer the most common question family members of people with Alzheimer's disease asked him - what is my risk?
"I made up a number. Seventeen percent," Dr. Green joked. "We didn't know the answer to that question."
Subsequent research, most pertinently the MIRAGE study, has determined that people who inherit the e4 version of the apolipoprotein E (APOE) gene are at increased risk.
"If you have one copy of the e4, you have three times the risk of Alzheimer's disease," Dr. Green said. "If you have two, you have 15 times the risk. This is a robust risk factor, the most powerful risk factor we know."
But that answer led to yet another question. Should physicians tell their patients of the presence of the e4 version of that gene, and its implications? Stated more simply, should doctors tell people that their genetic disposition makes it likely they will develop Alzheimer's in their later years?
"Is genetic risk information beneficial or is it in some way toxic?" Dr. Green asked and then described the uniqueness of the REVEAL study. "We designed a drug study where information is the pill."
To find out, Dr. Green and his colleagues organized 162 people into a randomization group and compared them to a "gene disclosure" group of 111. The groups were statistically similar in categories beyond their genetic profile, including age, gender (first-degree relatives who are women are at greater risk), race and ethnicity. One group, the second, was told of their Alzheimer's odds. The other wasn't.
The result? Knowledge proved to be no more a burden for the gene disclosure group than it was for the randomization group.
"The results were very clear. There is no change," Dr. Green said. "Basically there is no increase in anxiety or depression symptoms from knowing. That was reassuring. As a group, we were not engendering depression. Every geneticist predicted we would have people who would be devastated by this information. So far it hasn't been the case."
The most statistically significant result of the study, in fact, involved the people in the disclosure group who discovered they had not inherited the e4 gene. That group was understandably relieved. But the converse did not prove true. Those study participants who learned they were at greater risk for future cognitive dysfunction did not experience marked depression. Instead, the information spurred certain changes in lifestyle, some of them demonstrably unreasonable.
The e4-positive people were five times more likely to purchase long-term insurance. They were also more inclined to pursue avenues of health improvement, including exercise and vitamins, even though they were told that such activities would not reduce their odds of developing Alzheimer's.
Nothing wrong with some extra Vitamin C and a Pilates regimen, but Dr. Green warned of some potential negative consequences. People who found out about their genetic disposition for Alzheimer's were more likely to turn to the Internet for supplements purported to help but with no scientific data supporting their claims, which Dr. Green referred to as "a dark lining that we need to watch out for."
Moreover, members of the gene disclosure cohort demonstrated an inability to be convinced of their true risk. If someone came to the study believing they had, say, a 40 percent chance of developing Alzheimer's but learned that their genes in fact suggested 60 percent, they split the difference.
"They'd convince themselves that their risk was about 50 percent," Dr. Green said. "We expected everybody to believe us. They walked in with a perception that anchored their belief, and you can't really move them off that anchor."
So what can be taken away from the REVEAL study? Dr. Green's primary concern - that proof of an increased risk of Alzheimer's disease will throw people into a crippling depression - proved untrue. But while the reactions of study participants weren't pessimistic, they could not be characterized as consistently reasonable.
Date Published: 11/09/2009