August 18, 2020 – Twelve years ago, Jamie Tyrone volunteered to participate in a clinical trial. The researchers wanted to know whether learning your genetic risk for developing some 20 or so different diseases, through a direct-to-consumer genetic test, would prompt you to take up a healthier lifestyle. But Tyrone wanted to get something else out of the study.
The San Diego-based retired nurse, now 59, had been living with mysterious progressive neurological problems for about 15 years. The debilitating weakness and fatigue had pushed her into early retirement. Sometimes she needed a scooter to get around the one-story ranch she and her husband bought to accommodate her increasing physical challenges. But doctors had never made a definitive diagnosis. While brain scans ruled out multiple sclerosis, this clinical trial would tell her if she had a gene that predisposed her to the condition.
So focused on learning her genetic risk for MS, Tyrone didn’t give any thought to the other diseases she’d learn her risk for, including Alzheimer’s disease.
A few weeks after she delivered a vial of saliva to a local lab, Tyrone received her test results in an email from Navigenics. On her home computer screen, she scrolled through a 29-page document until she found the page that laid out her risk for each of the 20-something diseases. Her risk of developing most of the diseases on the list -- lupus, Crohn’s, atrial fibrillation, even MS – was below average. Then she saw it: “Alzheimer’s disease: Average risk 17 percent/Your risk: 75 percent.”
Tyrone had two copies of the e4 variant of the APOE gene -- one inherited from her mother and one from her father. Someone who has one copy of e4 may be three times as likely to develop Alzheimer’s disease as someone who doesn’t have it. Two copies can make you up to 12 times more likely to develop the disease. Tyrone was devastated.
“At one point, I wanted to commit suicide. My great-grandmother, grandmother, two great-uncles, and my dad all died with Alzheimer’s. I just didn’t want to do that.”
The clinical trial aimed to find out whether this news would prompt Tyrone to take better care of herself. But there is no proven way to prevent Alzheimer’s disease -- though a lot of healthy lifestyle choices might help. There’s no screening for early detection either. And, once you get the disease, there is no cure. And the gene test may not be all that informative. Many people who carry the risky variants never develop the disease; and many people who have Alzheimer’s don’t carry these genes. Knowledge of your status, then, can be unnecessarily frightening or falsely comforting. Your genetic risk for Alzheimer’s disease is what health care professionals call “unactionable” information.
These are some of the reasons that the American College of Medical Genetics and Genomics recommends against APOEe4 testing. Nevertheless, in 2017 the FDA authorized direct-to-consumer genetic testing company 23andMe to offer the test. Since then, about 80% of the biotech’s customers have chosen to find out their status. Some are devastated by the news like Tyrone was. Others say the information has transformed their lives.
Know What You’re Getting Into
Learning you have a gene that increases your risk for a serious disease can cause a lot of anxiety and distress. Critics of APOEe4 testing say people may not understand how the information could affect them and may regret finding out.
“If I had had genetic counseling first, I probably wouldn’t have wanted to know,” says Tyrone, who describes the depression this news caused in her book Fighting for My Life: How to Thrive in the Shadow of Alzheimer’s. The lack of support that Tyrone received after learning her APOEe4 status led her to seek help from a therapist, who diagnosed her with post-traumatic stress disorder.
People like Tyrone, who didn’t know they had been tested for this gene, may be most likely to suffer psychological consequences. “The people who are unaware that APOE was on the test come to me a bit panic stricken when they find out their result,” says Scott Weissman, a certified genetic counselor who runs Chicago Genetics.
Genetic counselors educate people on their risk for diseases, including Alzheimer’s, based on the numerous factors that figure into these conditions. After discussing their results with a counselor, Weissman says, people tend to feel better about their APOEe4 status.
Ideally, these counselors meet clients before testing and explain the pros and cons of the information and the distress it could cause. When Weissman speaks to clients before an APOEe4 test, he asks them to think about how they generally handle upsetting news that they can’t change.
“If I’m hearing that they will be very anxious [if they have this gene variant], I tell them, ‘Look, you probably don’t want this information,’” Weissman says.
The trial Tyrone took part in found that 90% of the 2,037 people who completed the study had no real increase in stress or anxiety after getting their results. But, the study did not analyze stress based on which disease the person had a high risk for. Arguably, learning about an increased risk for glaucoma -- which could help you catch the disease early and stop the damage -- would be less stressful than learning about Alzheimer’s risk.
An added stress, Tyrone says, is whether to share your genetic status with family members. On the one hand, the information was unwelcome for her. But on the other hand, would it be unethical to keep it from relatives who might also carry the variant? Or would they also suffer the psychological effects of bad news they weren’t seeking?
While not a substitute for genetic counseling, 23andMe tries to educate customers on the possible consequences of knowing their APOEe4 status before they see the results. Customers must opt in to see their genetic risk for each one of several serious diseases.
“Before you even get the results, we mention that currently there is no known prevention or cure for this disease,” says Shirley Wu, PhD, director of health product science at 23andMe. “It may be emotionally difficult to learn this information. Not everyone wants to know. That’s why we make it a choice.”
The company also points out that having this information might make it difficult to get certain types of insurance, such as life insurance and long-term care. In fact, you may be more likely to get these if you have no knowledge of any elevated risk for diseases of old age. Insurance underwriters comb your medical records for evidence of disease risk. If you share your APOEe4 status with your doctor, it may go in your medical record.
But APOEe4 does not guarantee you’ll have Alzheimer’s one day. “We stress that genetics isn’t the whole story,” Wu says, “and that many other factors, including lifestyle and family history, play a part. Having these gene variants doesn’t mean you’ll definitely develop the disease.”
Not having the gene variants doesn’t mean you won’t. People who have a strong family history of Alzheimer’s likely have other genes at play besides APOEe4.
Is There Anything You Can Do?
Unlike glaucoma, diabetes, or some cancers, there is no early detection screening for Alzheimer’s disease. There’s no definitive way to prevent it either.
“There’s just nothing practical or actionable to do with this information,” Weissman says. “It’s not going to change anyone’s medical management.”
The lifestyle recommendations that might help lower risk for Alzheimer’s, Weissman explains, are the things that doctors encourage their patients to do anyway. Research shows that a healthy diet, plenty of exercise, enough sleep, fewer calories per day or periodic fasting, and brain stimulation (such as puzzles) can all improve your odds of living out your life dementia-free.
But, 23andMe’s Wu argues, “We know these are standard recommendations for staying healthy, but we also know that most people don’t follow them. Genetic information can be the triggering event that gets people motivated.”
It certainly motivated Julie Gregory of Long Beach, IN, to overhaul her lifestyle. Like Tyrone, she took a genetic test for reasons unrelated to her Alzheimer’s risk. When her 23andMe results revealed that she had two copies of APOEe4, she thought of those “senior moments” she’d had since she was 49. She’d forget the names of people she’d known for 20 years when she ran into them at the grocery store. Her test results filled her with dread. Were the wheels already in motion on the road to Alzheimer’s disease?
“It was a dark and terrifying time,” says Gregory, now 58.
But, after the smoke cleared, she thought, “There has to be something we can do. The medical community has to be wrong about this.”
Gregory started to learn everything she could about Alzheimer’s risk and prevention. The Alzheimer’s community on 23andMe’s website became what Gregory calls her “family and lifeline.” There she found pages and pages of information shared by scores of people who had just received the same staggering news that she had. She gathered all the credible information she found on a website she launched, APOE4.info. She put the research to work in her own life as well.
Now, Gregory eats whole, rather than processed, food. Her diet is predominantly plant-based and Mediterranean style, with an emphasis on healthy fats, leafy greens, berries, and wild-caught seafood. She makes sure she gets enough sleep and manages stress. She exercises for an hour or more each day -- and exercises her brain, too, through an online brain training program.
Gregory also practices an extreme form of intermittent fasting in which she only eats during a 4-hour window each day and fasts for the other 20. Some research suggests that calorie restriction and tight control of blood sugar -- both effects of fasting -- may help prevent changes in the brain that lead to Alzheimer’s.
To be sure, Gregory has no confirmation that her memory lapses were an early sign of dementia. Women entering menopause can have the same symptoms. But regardless of the cause, Gregory doesn’t have those lapses anymore.
To Know or Not to Know
Unlike Tyrone, Gregory thinks everyone should learn their APOEe4 status. But also unlike Tyrone, she has not seen family members die of Alzheimer’s disease -- though she learned since her test that she has a strong family history of the condition.
Gregory admits that she still worries about her brain health, and imagines she always will, every time she forgets something. But she has no regrets. “Had I not learned this, I never would have made any of these changes,” she says. “This information has truly saved my life.”
Ultimately, the choice to take an APOEe4 test is a very personal one. But keep in mind, once you know your status, you can’t reverse that knowledge. Whether or not the information saves your life, it’s likely to change it.
“Think hard about your decision,” Tyrone says. “Get your financial house in order first. Think about how the information might affect your family. Talk to a genetic counselor. And ask lots of questions. This is not to be taken lightly.”