Why I won’t test myself for the Alzheimer’s gene

A recent survey of 1200 adults found that Alzheimer ’s disease (AD) is the most feared disease among older Americans, with 44% identifying it as their biggest worry. Cancer was second, with 33% fearing it most. Over 65ers will not be surprised by these findings.

Given the high level of fear, it’s natural and inevitable that many people will want to know their risk for developing AD. The best known risk factor for development of AD is the apolipoprotein E (APOE) gene, which found on chromosome 19. APOE contains the instructions for making a protein that helps carry cholesterol and other types of fat in the bloodstream. One form (allele) of APOE – APOE4 – is associated with increased risk of AD in the over 65 phase of life. Depending in part on whether it is inherited from one or both parents, APOE4 increases the risk for developing AD four to twelve fold. APOE4 is a statistical predictor, not a fate. Having APOE4 does not mean that a person will develop AD, and not having it does not mean they won’t. (A National Institute of Aging fact sheet on the genetics of AD can be found here.)

A recent research report in the American Journal of Psychiatry found that older adults who knew they were positive for the APOE4 gene had more subjective distress about their memory and performed worse on objective tests of memory than a comparable group of adults who had the APOE4 gene but did not know it. The researchers concluded that knowledge of APOE4 status “could have a serious clinical impact by increasing the likelihood of false positive diagnosis of dementia or mild cognitive impairment.” In other words, the test is potentially harmful to mental function. Knowing one’s risk for developing AD made one appear – in self-perception and in external function – more demented!

It’s not unusual for over 65ers or younger folks to say something like “If I developed severe dementia I’d rather be dead than live with it…” In a 2013 article on “Alzheimer disease and pre-emptive suicide,” Dena Davis, professor of Religion Studies at Lehigh University, argued that (a) some people may prefer suicide to developing AD, (b) emerging technologies are making it potentially more possible to diagnose AD before dementia sets in, which, in her view means that (c) , if and when accurate pre-clinical diagnosis of AD becomes possible, those who want to consider pre-emptive suicide will have a legitimate, autonomy-based interest in having access to information like APOE4 status.

The research report and Davis’s article point to a serious moral dilemma. Individuals concerned about developing AD will want to know their APOE4 status. But that Information can harm them by worsening their cognitive capacities. It’s conceivable that someone who would not have developed AD would commit suicide after learning about their APOE4 status. A crystal ball might say – “that unfortunate person missed out on many years of healthy life…” These considerations point to not allowing access to APOE4 status outside of a medical relationship.

But those who are committed to not living with dementia will argue that this information is crucial to their ability to pursue their conception of a good life and they have a right to it. These considerations point to allowing competent adults to have unfettered access to APOE4 status without having to get the approval of a medical gatekeeper.

Until November 22, 2013, when the FDA required 23andme (the largest provider of genetic information to individual consumers) to cease and desist, the company, co-founded by Anne Wojcicki, the (recently estranged) wife of Google co-founder Sergey Brin, offered a kit whereby a person could send a saliva sample for genetic analysis, including APOE4. Although for now 23andme no longer provides that service, as best I can tell from a Google search, the test is still available via other vendors.

I’m torn about what policy recommendations I’d make about direct consumer access to genetic tests like APOE4. The physician in me wants to protect the public from what I see as very real harms from open access. The civil libertarian in me believes that individuals should be able weigh risks and benefits for themselves. If I were in charge of the policy decision I would ban the commercial direct-to-consumer sites.

But the realist in me concludes that genetic cat is out of the bag. Given that even if the U.S. were to prohibit consumer access to genetic testing outside of a medical care relationship testing would be available from overseas sites, in practical terms the most realistic policy will be to regulate the area in terms of quality of testing, clarity of reporting, and truth in advertising. Given that at present an early diagnosis of AD does not point to useful interventions, I would not have myself tested for APOE4 status. But the test is available and consumer demand will ensure that it’s accessible. For better and for worse, health care and biological information are moving rapidly from doctor-centric to “consumer-centric” status.

Jim Sabin, M.D., 75, is an organizer of Over 65, a clinical professor of population medicine and psychiatry at Harvard Medical School, and a Fellow of the Hastings Center.


4 Responses to “Why I won’t test myself for the Alzheimer’s gene”

  1. Steve Moffic

    Your question, Jim, got me thinking about what I would want. It is curious that I’ve never thought of answering that question. Maybe because the tests are not yet reliable or predictive enough. If they were, I think I would like to get it. Like receiving a diagnosis of a terminal illness, it could change how I wanted to live in the near future. Contrary to becoming suicidal, for me it would likely intensify my love of life.

    In a way, too, for Alzheimer’s, it is eventually like a personal death; you end up not knowing who you were or are. Though it is so hard to understand the subjective state of one in the throes of Alzheimer’s, I would assume that once the disease progresses, the mental suffering is limited. The harder future, I believe, is for family and loved ones. So, really, they are the ones I would like to answer that question if better testing emerges. Do they want to know if I am likely to get Alzheimer’s?


    • Jim Sabin

      Hi Steve –
      When and if (a) predictive tests are more accurate and (b) there are steps one can take that one would not otherwise be taking, then (c) I’d answer the question differently. But at this point the “preventive” measures that are best recognized involve getting physical exercise, using one’s mind, and maintaining social connections. These ought to be part of our lives – AD risk or not. For me the clincher in the conclusion I reached was the finding that knowing one’s APOE status was correlated with poorer mental function. That’s a negative placebo effect (“nocebo”) I see no value in incurring.

  2. Carol Eblen

    In the future, as the test is determined to be absolutely accurate and creditable, I imagine the test will be more common practice for the purpose of preparing the “advanced directive” for the family and for the medical professionals.

    I know you don’t like to talk about “advanced directives” in this blog but it seems obvious that those who know that they might suffer brain damage and become a burden to themselves and their families, in a financial and emotional sense, will opt to shorten their lives by some legal means.

    It seems obvious that a legal means will become available in the future in order to solve this growing problem in countries with growing elderly populations.

    • Jim Sabin

      Hi Carol –
      I’m sorry for the delay in responding – I’ve been travelling. I agree that some proportion of those who anticipate the possibility of brain damage would want to shorten their lives. This week I had a conversation with a friend who is undergoing a medical procedure that carries some risk, who wanted to make sure that those close to him clearly understood his wish to “allow nature to take its course” were he to sustain devastating brain damage. But I continue to fear that some folks will rely on inevitably less-than-perfect predictive tests for dementia and choose to shorten a life that would otherwise have continued in acceptable health.