The Power of Knowledge

The Power of Knowledge

Does knowing your predisposition to developing Alzheimer’s give you an advantage or just bad news?

By Alex Lubischer

“How will I die?”

Would you want to know the answer to the question? For many, the decision to know or not know would hinge on the answer to a second question: “Can I change my fate?” The battle between fatalism and self-determinism has long been waged in philosophy, science fiction and, more recently, medicine.

With the advent of genetic mapping—creating a graphic representation of the arrangement of a gene or a DNA sequence on a chromosome—science’s ability to predict the onset of future diseases in patients has surpassed its means to preventing them.

In 2013, the procedure has become increasingly affordable and common. (The cost of mapping a person’s entire genome, i.e., his or her complete set of DNA, has fallen to $3,000 or less, down from about $100 million in 2001.)

The National Human Genome Research Institute predicts that, within the next 50 years, individualized analysis based on each person’s genome will lead to a very powerful form of preventive medicine. People will be able to learn about their risks of future illness based on DNA analysis.

Diana Kerwin, assistant professor of medicine–geriatrics at Northwestern University Feinberg School of Medicine, believes that genetic mapping could hold the key to making now-incurable diseases, like Alzheimer’s, a thing of the past.

“Genetics for us right now are a really key research area,” says Kerwin, who is also Northwestern’s principal investigator for the second Alzheimer’s Disease Neuroimaging Initiative (ADNI—currently in its third phase). “We’re trying to identify markers that can tell who might be at an increased risk from their genetics, because those will be the people in the future, when there’s more development of gene-modifying therapy, who are going to be more likely to benefit from the treatment.”

But would you want to know? Consider the following: Illumina, a real global company that sequences and analyzes genomes for its clients, hypothetically emails you a file revealing whether or not you will likely develop Alzheimer’s. Whether or not it’s opened all depends on you.

Dr. Nilufer Ertekin-Taner, MD, PhD, who is a neurogeneticist and neurologist, wrestled with this decision herself after having her genome sequenced as part of a campaign at the Mayo Clinic. Ertekin-Taner already knew which gene could evince a predisposition for developing Alzheimer’s: APOE e4. This adverse allele (or, version of the APOE gene) is present in about 20–30 percent of the population and in about 40 percent of people with late-onset Alzheimer’s.

Although many studies have confirmed that APOE e4 increases the risk of developing Alzheimer’s, how it does so is not yet understood.

“I had to think, ‘Do I really want to know?’” Ertekin-Taner says. “And mind you, even having the risk allele [APOE e4], doesn’t necessarily doom you to having Alzheimer’s disease. It increases your risk. But you might still have a risk variant and not have the disease… At the end of the day, I decided to go for it.”

Ertekin-Taner, who did not reveal the results of her test, stated that learning she didn’t have the risk variant would have brought her profound relief, while learning that she did have APOE e4 would carry its own benefits.

“If I had it, perhaps I could [exercise] more,” says Ertekin-Taner. “I could increase my fish intake. I could do all those things that I tell my patients to do more religiously.”

In addition to those preventative measures, The Alzheimer’s Association cites staying socially and mentally active as key steps to keeping your brain healthier as you age.

“It’s a very personal decision,” says Ertekin-Taner. “And it’s a decision that mustn’t be taken lightly. And I think for anybody, before you make the decision to get your whole genome sequenced, you must have expert medical genetics counseling. Because right now, we do not have a cure for this condition—we’re all fighting for a cure; it is coming, but it’s not here right now. So, a decision regarding whether you would want to know, has to be done in a manner that would be based on full knowledge. You should know what to expect if you have it—and if you don’t have it.”

But physicians disagree about the benefit of prescient knowledge to the individual patient.

“We will get to a point where we will want to do genetic identification to identify high-risk individuals to give them therapies in the future,” says Kerwin. “But at this moment in time, the risk markers are really more at the research level, as far as helping us to further the science. On an individual basis, really, I would advise someone with or without a genetic risk marker to do the same thing.”

When asked whether genome sequencing was beneficial to individual patients at this point, a third researcher, Dr. Andrew Saykin, a psychologist and the director of the Indiana University Center for Neuroimaging and the Indiana Alzheimer Disease Center, says no. “I think the most prudent approach is to assume that you have the risk allele and do all of the things that are widely recommended to enhance one’s cognitive function.”

Saykin stresses that, for many, Alzheimer’s prevention’s eventual goal is comparable to today’s treatment of high cholesterol. Cholesterol-lowering medication wasn’t always available, but once it became a viable option, knowledge of one’s cholesterol acquired new importance; it granted patients the chance to effectively head off future heart attacks or strokes.

“We do not yet have preventative treatments for Alzheimer’s disease, and I do think we’re on the verge of having disease-modifying drugs.” said Saykin. “But we’re not there yet.”

At present, health-conscious consumers are faced with a precarious dilemma. Should we know with a little more certainty how our final years will play out, or is ignorance truly bliss?

Originally published in Chicago Health Summer/Fall 2013