Limitless: APOE revisited

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.

 

Interested in more newsfeed posts like this? Go to the Mild Cognitive Impairment (MCI) blog.

I have 1 ApoE4 allele and I have a family history of Alzheimer’s (Grandma, Aunt and uncle). I am 58 years old and have just been diagnosed with MCI. I am a health care professional and still working, but it is very hard.
I am glad that I know my ApoE4 status. It helped motivate me early on to make lifestyle changes that can help with brain health, it also had me somewhat prepared for the diagnosis of MCI.
I love the show Limitless! I’ve only watched the first few episodes. I will definitely be checking out episode 5! Thanks so much.

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@DrDonaLocke

Thank you so much @liv4now. I'm curious, do your children know of his genotype? Perhaps Limitless would be helpful for all of you as a family. The series is on Disney+, but here is a trailer: https://www.youtube.com/watch?v=4AxfL9Y4boE

Episode 5 is the one where this is addressed, but I think the whole series is great.

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Yes, they are aware. Our daughter is a biology teacher and understands the implications. She is also interested in joining a clinical trial for people without memory deficit. Our 2 sons are younger and less inclined to think about the future.
My husband's family also had a strong history of cardiovascular disease. I think ultimately it will be determined that inflammation is the connection and possible causative agent of both cvd and Alzheimer’s. And for now, lifestyle is all we can control.
I will share the series with all of them.

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@rfherald

In reply to @DrDonaLocke, I have 1 copy of the e4 allele. I am 76 years old. I am a recovering engineer and remember some statistics. A ~ 25% chance of developing Alzheimer's is enough to keep me aware of any loss of acumen. A neuropsycology exam showing srandard memory loss for my age helps with acceptance, but not the frustration. Sleep disruption from BPH increases the probability of Alzheimer's and my anxiety. As time passes and no serious symptoms of Alzheimer's are revealed, I believe I am in the 75% group.

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I’m am 73 and have developed MCI. There is a question of whether some is related to general anesthesia of 8 months ago. So potentially some degree of it may ”clear” but I’m doubtful. I’m a statistically-based test designer to evaluate regulatory compliance by vocation.
My chief complaint is word retrieval. Not just names, though frankly I haven’t been very good at remembering people’s names for my whole life. But I’m also aware I am experiencing a more generalized loss of acuity. I feel executive function is intact, but not necessarily supporting functions. So I know that to solve a gap in compliance the necessary requirements are … but I may not retrieve what they are called or specific interdependence.

So I’m trying to learn what my state of brain health is.

Like you, I have one copy of the APOE4 variant.

MRI shows
Only age-consistent changes and no atrophy of brain volume beyond that.

The new ATN blood Test for presence of Alzheimer’s pathology revealed:

Reduced Beta Amyloid 42/40 ratio, and elevated p-Tau-181, has been associated with presence of Alzheimer's Disease pathology.

So two views look ok to good, one is worrisome. With my profound family history of Alzheimer’s, it’s more than worrisome.

I haven’t had the psychological testing or a PET scan. But I’m not one that doesn’t want to know. I want to know everything there is to know.

I don’t want drug trials but I would want to be in trials that are more procedural. That said, I have comorbidities like RA that would likely preclude me.

So I’ve spent the last 18 months retiring, planning my estate docs and designating responsibilities. So I am free to control what I can for as long as I can. Try to exercise and eat well and try to keep laying down new neuronal pathways.

Glad to find this discussion. Family members are kind but don’t really want to discuss this.

Thanks for ‘listening’
And if you haven’t watched it, this was the most exciting research result I could imagine.
https://rni.wvumedicine.org/60minutes/

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