Limitless: APOE revisited

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Jan 24, 2023 | Dona Locke | @DrDonaLocke | Comments (13)

Have any of you watched the recent series "Limitless" with Chris Hemsworth? I found the 6 episode series fascinating! The series was broadly about aging and discussion of contributors to healthy aging and longevity with Chris Hemsworth (of "Thor" superhero fame). The topics of these series are broad--from the impact of stress and our stress response, how muscles and strength may help one live longer, to brain health. It is the latter than brings me to write this blog. In the course of the series, Mr. Hemsworth undergoes many, many medical tests. The doctor in the series calls it, "the million dollar workup". This includes genetic testing. From that testing, Mr. Hemsworth is informed that he is a carrier of two apoeE4 alleles in his genetic analysis. As is explained in the series, this places him at higher risk of developing Alzheimer's disease dementia in the future. Mr. Hemsworth goes on to process, on camera, his reaction to that news in a very moving way. I would encourage you to check it out!

But the additional reason I wanted to write about this series is because it is an opportunity to review what it means to be a carrier of the APOE e4 allele (and what it does not). Dr. Chandler wrote an excellent post on this issue nearly two years ago as well.

Here are a few points of emphasis drawn from her post as well as the medical journal article she references. This article is still a great resource two years later.

1. Having one or two APOE e4 alleles increases your risk of developing Alzheimer's disease in the future, but it does NOT mean you absolutely WILL develop Alzheimer's disease dementia in the future.
2. 1-3% of the population has 2 copies of the e4 allele. For those individuals, their risk is increased 8-12 fold compared to those without the allele. Lifetime cumulative incidence of MCI or dementia in this group is 37-47% (i.e., NOT everyone). That is, somewhere between 37-47% of people with 2 copies of APOE e4 will develop MCI or dementia in their lives (53-63% do not).
3. 20-25% of the population have 1 copy of the e4 allele. For this group, risk is increased 2-3 fold compared to those without the allele. Lifetime cumulative incidence of MCI or dementia in this group is 21-26%.
4. In those without an e4 allele, lifetime cumulative incidence of MCI or dementia is 12-16%.

I encourage you to review Dr. Chandler's full post as well as the article she references there. Those authors (Drs. Chourdhury, Ramanan, and Boeve) put it this way, "APOE e4 is neither necessary nor sufficient for the development of Alzheimer's disease dementia."

My final take-away from the series was this--Live every day. Enjoy every moment. We have no idea what, exactly, is coming around the corner. We can only do our best to take care of ourselves to maximize our quality of life in aging, but after that whatever will be, will be. Worry doesn't help tomorrow; it only reduces our enjoyment of today.

I do not personally know what my genotype is. Nor do I think I want to.  What about each of you?  Would you like to know? Do you already know?  I'd love to hear your thoughts on this in the comments below.