Should You Get Tested for the Alzheimer’s Risk Gene?

Pros and cons of discovering your ApoE4 status

Photo by Szilvia Basso on Unsplash

Hello, brain health ambassadors. All this month on the newsletter we have been talking about ApoE4. We’ve covered a lot! I am really heartened that so many of you opened, read, and shared your thoughts on these posts. It’s an important topic for everyone to understand, but especially those who may be at increased risk for Alzheimer’s. 

ApoE4 is an extremely common gene variant that about 25% of Americans carry. This means that there are potentially millions of people that would find out they had the gene if tested. So why aren’t most health care practitioners recommending getting tested? I’ll go into that, below, along with the pros and cons of ApoE4 testing. And, if you already know your ApoE4 status, there is some new information about testing that will interest you.  

Need to catch up? Start here to read everything from our ApoE4 series and more

• ApoE4 basics + how HRT may be beneficial for female carriers

• What ApoE4 carriers need to know about the 2024 study in Nature Medicine

• 21 thing you can do to lessen the impact of carrying an ApoE4

• How lifestyle shapes genetic risk

• This fun Q and A with

  Vasudha Viswanath
  (my go-to source for protein-packed vegetarian recipes) includes a brain-healthy summer party menu (with recipes!), a lightning round, and the 9 things I want people to know about Alzheimer’s.

The first newsletter of the month is always free. Please share.

Thinking of getting tested? Ask yourself these questions first

If you are thinking about checking your ApoE4 status, consider it from every angle. It may help to ask yourself what you would do differently if you knew you were a carrier. Would you exercise more? Eat more mindfully? Quit drinking? And, how would it affect your mental wellbeing? Would this lead to anxiety and excessive worry that impedes your enjoyment of life? Or, are you someone who is more likely to follow current Alzheimer’s prevention guidelines on the heels of a positive ApoE4 test? There’s no correct, or easy, answer. With that in mind, let’s go through the pros, cons, and possible pitfalls of getting tested.

PROS of ApoE4 testing

Knowing ApoE4 carrier status may help you make better brain care decisions. These five stand out:

1. Create a personalized brain health plan. Knowing ApoE4 status, for many, is an impetus to get serious about self care. This includes everything we talk about on BHK, with heightened focus on the areas in which ApoE4’s benefit most: avoiding alcohol, quitting smoking, exercising, avoiding ultra-processed foods, creating an evidence-based supplement regimen, and following a brain-protective way of eating like the Mediterranean, MIND, or Green MED diet. 

2. Get access to medical care and studies. As interest in ApoE4 grows, there will be more opportunities to enroll in clinical trials, which means you get access to Alzheimer’s prevention experts, new protocols, and drugs. As amyloid-blocking drugs evolve to treat preclinical Alzheimer’s (amyloid accumulation before symptoms), knowing ApoE4 status will help guide the safest and best options.

3. Gain awareness that helps you help others. Knowing your own ApoE4 status can help you be an effective brain health ambassador out in the world. The first circle of influence will be with those you love—your family and friends. The young adults in your life will probably benefit the most with an earlier onset of self care focused on brain health.

4. Guide decisions at menopause. Knowing one’s ApoE4 status can help guide the pros and cons of taking hormone replacement therapy. We now have new studies that suggest ApoE4 carriers may be most helped by taking hormones early in the perimenopausal transition. 

5. Feel empowered. Much is said about the stress and anxiety of knowing one’s ApoE4 status, but choosing to understand your genetic makeup can also be very empowering. The Risk Evaluation and Education for Alzheimer’s Disease (REVEAL) trial looked at the psychological and behavioral impact of knowing one’s ApoE4 status. While there was an initial increase in anxiety and distress following the disclosure of APOE4 status, these effects were typically short-lived and did not result in significant long-term psychological harm. In fact, most participants in this study reported more positive behavioral changes related to diet, exercise, medications, and vitamins compared to those who learned they were non-carriers. 

The overall conclusion of the REVEAL trial is that the benefits of knowing one's APOE4 status, when combined with appropriate support, outweigh the potential psychological risks.

CONS of ApoE4 testing

On the flip side, getting tested for the ApoE4 risk gene doesn’t give you a clear diagnosis. Knowing you have a heightened risk of Alzheimer’s could have negative impacts:

1. Create worry and stress. Even though the data reassuringly says most carriers do not become clinically depressed after knowing their status, only you know how you may react to worrisome health news. The REVEAL study also showed that having a strong support system (family, friends, medical care) was a key factor in avoiding serious psychological fallout. 

2. Finding expert guidance is a challenge. There are just a handful of Alzheimer’s prevention clinics in the U.S. It can be a challenge to assemble a team of health care professionals to guide your care. This puts the impetus on you—ApoE4 carrier—to stay on top of the latest advancements particular to this condition. This means building your own health care team that includes a knowledgeable cardiologist, gynecologist, registered dietician, certified personal trainer, and mental health support. 

3. The list of guidelines for ApoE4 carriers may be overwhelming. It’s good news that there are many lifestyle interventions known to lessen the impact of carrying an ApoE4 risk gene. But this can also be overwhelming. I break down the latest guidelines and help you get started here: 21 science-based recommendations for ApoE4 carriers.

4. Potential insurance discrimination. Can insurance companies exploit ApoE4 carrier status to decline coverage and care? This is a gray area in medicine. Privacy is one reason to choose to test with a home kit instead of through a doctor’s office (see below).

If you know your ApoE4 status, do you have anything to add? What were some of the positive things that came from testing? What were the negatives? If you had the choice, would you do it again?

Most physicians aren’t recommending this test

Photo by Sasun Bughdaryan on Unsplash

Why aren’t physicians more enthusiastic about ApoE4 testing? First, it’s important to know that there are currently no professional guidelines for ApoE4 genetic testing. Physicians tend to follow the written guidelines that have been vetted by their licensing organizations, such as the American Academy of Neurology. It can take decades to update practice guidelines to reflect current research. As a result, these guidelines may be less than cutting edge (as we saw in our discussion of lipid panel recommendations). 

Plus, the medical landscape doesn’t tend to lean into preventative care. There are very few neurologists specialized in Alzheimer’s prevention. Neurologists are trained to diagnose and treat neurological diseases. But preventing disease? That is a relatively new thing. So it’s not surprising that many physicians, including neurologists, are not well-versed in the nuances of Alzheimer’s prevention, especially ApoE4 testing. There’s a shortage of genetic counselors, too, which leaves physicians with inadequate expertise or time to sufficiently counsel patients.

How to get an accurate ApoE4 test

An ApoE4 genetic test entails sampling saliva or blood and sending it off to a specialized laboratory. This can be done at your physician’s office or through a direct-to-consumer kit that is mailed to you at home. When you google “ApoE4 test” pages and pages of results come up. How do you know you what’s best?

Here are a few things to consider:

• Choose a laboratory that is certified by the Clinical Laboratory Improvement Amendments (CLIA) and/or the College of American Pathologists (CAP).

• Home kits have the obvious advantage of privacy because the results do not necessarily become a part of your medical record. The test is mailed to you, done by swabbing saliva from the mouth into a tube, and then mailed to a laboratory. 

• Checking ApoE4 through a health care practitioner’s office means the results will become part of your medical record. On the other hand, there may be an advantage in that your provider has experience with the lab.

• Checking for ApoE4 along with other gene variants that influence Alzheimer’s risk may be more accurate than checking it on its own. Dozens of gene variants have been identified that increase or decrease Alzheimer’s risk. Testing these together as a panel can be used to determine a polygenic risk score (PRS)—a more accurate estimation of Alzheimer’s risk than an isolated ApoE4 test.

• Regardless of the type of test you choose—at home or through your doctor’s office—it’s important to discuss your results with a qualified health care practitioner.

My top picks:

Home testing: ADx Health checks ApoE4 alleles along with 30 other gene variants linked to Alzheimer’s to give you a polygenic risk score. This small company has a lot going for it—a pathologist specialized in Alzheimer’s risk genes at the helm, a nod from top neurologists in the prevention field, excellent customer service (meaning you can get someone on the phone to talk to you), and supportive follow-up. ADx Health is constantly adjusting the gene variants in its panel to accommodate new findings.

Physician’s office: Boston Heart Diagnostics offers ApoE4 testing as part of a polygenic risk score for Alzheimer’s. You’ll need to have a health care practitioner order the test and the results will become part of your medical chart. Boston Heart has an excellent reputation in the field, and is also my top choice for getting tested for cardiovascular risk factors, such as ApoB and Lp (a).

What about 23andme? This company tests ApoE4 along with a long list of other genetic traits. And it is the main reason 1 in 25 people in the U.S. know their ApoE4 status. 23andme initially lost their FDA approval because of inadequate counseling after a positive ApoE4 test but that situation has been resolved. Questions still remain about their false negative and positive rates as they don’t share that data. Plus, sharing results with large databases is a concern. None of the neurologists I have spoken with recommend testing ApoE4 through 23andme.

Discussing ApoE4 on a recent podcast

Last month I was discussing this very topic with Laura Schein on her podcast. Laura, a young woman in excellent health, has a family history of Alzheimer’s. Growing up, she witnessed rapid cognitive decline in both of her grandmothers. It had a huge impact on her. She couldn’t stop thinking that Alzheimer’s was looming in her future, too. So she decided to find out her ApoE4 status by testing with 23andme. In the episode, she goes into how knowing her status has empowered her and become the driving reason she takes good care of her health. Listen to the full episode here. I would love to hear what you think.

June is Brain Health Awareness Month

It’s always brain health awareness month at BHK, but this June I’ll be sharing some handy downloadable guides to help make brain-healthy living easy and fun. Been reading BHK for a while? Follow me over on Instagram to Test Your Brain Health IQ with a series of pop quizzes. Also coming this month: our next Founding Members cooking class happens on Monday, June 24. To join me for this live on zoom class, upgrade your subscription to FM here: 

This part of Italy has more healthy centenarians than anyplace else on earth. Sardinia, Italy.

I just got home from a trip to the Blue Zone villages in Sardinia, Italy—a brain health retreat destination for 2025. Stay tuned! My new jetlag recovery routine is really working for me. Would you like me to share in an upcoming post? I hope your month is off to a great start.

Love,

Annie

Upcoming Brain Health Retreats

Ortigia, Sicily October 13 to 19, 2024: Join me in the ancient city of Ortigia in southeast Sicily on this culinary adventure. We’ll cook with local chefs, tour almond, avocado, and olive farms, and learn all about olive oil.
Palermo, Sicily October 27 to November 4, 2024: Join me in the vibrant city of Palermo and explore less-traveled western Sicily. We’ll visit farms and cook local dishes, while soaking up the beauty of ancient Greek temples, medieval villages, coastal salt flats, and maybe even get to see olive oil pressed!
Costa Rica, January 9 to 14, 2025. If a cozy cabaña nestled in the jungle near the beach is more your style, join me on this 6-day brain health retreat. We’ll enjoy energizing yoga, plant-based cuisine, waterfall walks and a comprehensive brain health education in this jungle oasis.