Why I Want to Know My Genetic Risk for Alzheimer’s
By Kelly O'Brien
Genes are one of many risk factors for Alzheimer’s and related dementias. Science is evolving on the influence of alleles such APOE e4, the most common variant associated with Alzheimer’s disease, across age, gender, race and ethnicity. To date, routine genetic testing in medical care is not widely recommended. It is estimated, however, that more than 100 million people have undergone direct-to-consumer genetic testing, and this market is expected to grow.
UsAgainstAlzheimer’s does not hold a position on consumer genetic testing and recommends consulting with a healthcare provider about brain heath and considering genetic counseling in concert with any DNA test. To learn more about the genetics of Alzheimer's disease and the contribution of the APOE genes, check out the National Institute on Aging's Alzheimer's Disease Genetics Fact Sheet.
I used the direct-to-consumer DNA test 23andMe to learn I have one copy of the APOE e4 gene, the most common genetic variant associated with Alzheimer’s disease. This increases my lifetime risk of developing Alzheimer's disease by a little more than two times, on average. About 10 percent to 15 percent of people carry one copy of APOE4 and 2 percent to 3 percent carry two copies.
Initially I was not interested in unlocking my genetic code. My dad died from Lewy Body Dementia, and all of his siblings lived or are living with Alzheimer’s. What good would it do me to know if this, too, was my fate? After all, I thought, I am doing the best I can, what was the point if it was all going to end with me eating mashed food locked alone in my brain?
This resistance to seeking genetic information was an outlier for me. When I make decisions that impact my health, I like data. I own three smart watches. I track my body fat. I get second clinical opinions. I undergo routine blood panels for nutrient levels and enzyme markers and glucose levels. I’m in my fifties and interested in knowing what steps I can take to increase my health span. For the most part, I try to do these things. I tend to be very Marcus Aurelius about obstacles—they become the way.
But what happens when the impediment cannot be moved? Like many people, I thought that my genes were outsized determinates of my fate and I did not want to look into the genetic crystal ball at something I could not control.
I walked out of the room with hope and a sense of agency, determined to learn my risk and do all I could to reduce it.’
I vividly remember the day I first learned that my genes were in fact not determining factors of my fate but were risk factor data points—just like my blood pressure and my weight. I attended an event to hear Dr. Rudy Tanzi, a pioneer of Alzheimer’s gene discovery, as he explained that only 3 percent to 5 percent of Alzheimer’s is caused by “fully penetrant” genes, and other genes such as APOE e4 are not deterministic. In other words, having the allele does not mean I will definitely develop Alzheimer’s. Many people with APOE e4 never get the disease, and others who develop Alzheimer’s do not have any APOE e4 alleles. And, importantly, there are things we can do to change the way our genes are “expressed.”
I was hit with a wave of tearful relief. I had been living with the idea that my future included dementia. But that day I walked out of the room with hope and a sense of agency, determined to learn my risk and do all I could to reduce it.
Not Powerless
It turns out there is much I can do. Lifestyle interventions can make a difference in more than 95 percent of those at risk for Alzheimer’s disease. Even people with high genetic risk can lower that risk with lifestyle changes that address risk factors that are modifiable. These actions include, among others, engaging in physical activity and cognitively stimulating activities, eating a plant-based diet, getting adequate sleep, and managing conditions including diabetes, hypertension and depression.
Because of the strong case for early intervention, UsAgainstAlzheimer’s also is advocating for a national dementia prevention goal to help raise awareness and fight for more incentives and support in our clinical and public health system.
Science is revealing new insights about the interplay of APOE e4 and estrogen, DHA (Docosahexaenoic acid, an omega-3 fatty acid), hypertension and more, and knowing my status has helped me to ask better questions of my doctor. Understanding the impact of genetic risk and finding effective early treatments for Alzheimer’s means more research is necessary. Clinical trials need more asymptomatic participants. Knowing my risk also means I can help to find a cure.
But behavior change is hard! The pathology of Alzheimer’s starts decades before symptoms, so waiting until symptoms appear is not an optimal strategy. Taking steps to optimize brain health and reduce risk is important throughout life. Knowing my genetic risk is a powerful motivator to invest now in healthy behaviors that pay dividends for my present and future self.
What motivates you? Some research shows that, along with genetic counseling, many who wish to know their genetic information can process their APOE status, without experiencing long-term effects to their well-being. That said, many may find knowing their genetic risk is not psychologically beneficial and the decision to test is personal and optimally made with informed support.
Adopting a brain-healthy lifestyle is going to help increase one’s chances of healthy longevity and reduce risk of dementia whether or not genetic risk is known. Not everyone will find it useful to know their genetic risk; but for me, knowing my genetic risk was an important, empowering data point that has helped me find the way.
Kelly O’Brien is executive director of the Brain Health Partnership at UsAgainstAlzheimer’s in Washington, DC.
Why I Don’t Want to Know My Genetic Risk for Alzheimer’s Disease
By Nora Super
I have studied brain health and risk reduction for Alzheimer’s disease and related dementias for more than ten years. While there is no disease-modifying therapy available on the market today, there is emerging evidence that many common-sense lifestyle choices can improve the resilience of our brains and decrease our risk of developing dementia.
In 2017, the Lancet Commission released a growing body of evidence suggesting that nine risk factors could be modified to help delay or prevent dementia: less education, hypertension, hearing impairment, smoking, obesity, depression, physical inactivity, diabetes and low social engagement. In 2020, the Commission added three more modifiable risk factors (excessive alcohol consumption, traumatic brain injury and air pollution) to its list to make a total of twelve, accounting for around 40 percent of worldwide dementias.
My father and his three siblings all had late-onset Alzheimer’s disease. It is a cruel, mind-robbing disease, and I wish it upon no one. This is why in 2020 I launched the Milken Institute Alliance to Improve Dementia Care, a cross-sector collaborative that includes more than 60 leaders across eight stakeholder groups: advocacy, research, health systems, industry, philanthropy, government, community-based organizations and people living with dementia and their caregivers.
With the number of people living with dementia projected to double by 2040 to nearly 13 million, the Alliance comes at a critical moment to ensure we build workforce capacity and implement collaborative dementia-care models. Our goal is to create the conditions to increase early detection and diagnosis of people with dementia, tailor services to meet their needs and those of their caregivers, and ensure they get the right care at the right time.
‘I’m not sure what I would do differently if I knew I had the APOE e4 gene, so I choose not to be tested.’
Presumably, with my family history of Alzheimer’s disease, I have a genetic risk factor. Still, I’m not interested in being tested for the APOE e4 gene. According to the National Institute on Aging, APOE e4 is associated with an earlier age of disease onset. None of my relatives showed signs of dementia until they were in their 60s and 70s. Plus, genetic testing for APOE cannot determine my likelihood of developing Alzheimer’s disease; it would just confirm or deny another risk factor.
Reducing Risk Already
I have already taken significant steps to reduce my risk factors for dementia based on the Lancet Commission and other evidence-based research. I’m physically active. I don’t have diabetes or hypertension. I keep my weight under control and moderate my drinking. I eat brain-healthy foods and stay socially engaged. I’m not sure what I would do differently if I knew I had the APOE e4 gene, so I choose not to be tested. I fear it might make me more anxious about the future if I tested positive.
Now don’t get me wrong. I fully support annual evidence-based routine cognitive screenings, which can generally be administered in less than five minutes. I believe each of us should be screened annually so we have a baseline to compare any changes to cognition in the future. These cognitive assessments should be viewed as preventive tests, like mammograms and colonoscopies. Most of the time there will be no cause for concern, but if there is a change, that information can be used to pursue an in-depth evaluation that can either identify and treat non-dementia causes for cognitive impairment such as hearing loss or sleep apnea, or lead to a diagnosis of mild cognitive impairment or some form of dementia. Early detection and diagnosis will allow us to take steps to manage symptoms and plan for the future.
I wish we had the opportunity to talk more with my dad about his wishes regarding his end-of-life care and his finances. If he had been diagnosed earlier, we could have had those conversations. And today, the most promising disease-modifying therapies in the pipeline are only effective for people in the early stages of the disease. Thus, it’s more important than ever to receive regular cognitive assessments.
I’m glad the APOE tests are available for those who want to know their genetic risk. But I’m already aware of the risk factors and doing everything I can to reduce them. For me, I don’t think the genetic test would change the way I’m living my life.
Nora Super is the executive director of the Milken Institute Alliance to Improve Dementia Care and the senior director of the Center for the Future of Aging. She previously served as the executive director of the White House Conference on Aging under President Obama.
