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 was diagnosed with MCI many years ago and with advancing age it's hard to tell whether loss of memory etc is due to the age advancement or the MCI or both. My point being that my biggest struggle is fear of dementia. I'm still independent and can take care of myself and fairly intelligent but my powers of intellect are dwindling and it is frightening.
Thank you for sharing this article and I will definitely watch the series.
Art Resnick, 81 years old

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@rezmo

I was diagnosed with MCI many years ago and with advancing age it's hard to tell whether loss of memory etc is due to the age advancement or the MCI or both. My point being that my biggest struggle is fear of dementia. I'm still independent and can take care of myself and fairly intelligent but my powers of intellect are dwindling and it is frightening.
Thank you for sharing this article and I will definitely watch the series.
Art Resnick, 81 years old

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Thank you for your comments Art. I hope the series may help with your fears. Mr. Hemsworth does, I think, a wonderful job of being vulnerable and expressing the reality of his concerns for the future, but also settles into a way forward.

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@DrDonaLocke

Thank you for your comments Art. I hope the series may help with your fears. Mr. Hemsworth does, I think, a wonderful job of being vulnerable and expressing the reality of his concerns for the future, but also settles into a way forward.

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I find this all to be too confusing to deal with. I cannot find a way to
change my settings, so I will be marking this as spam.
My apologies.

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@clarklindh

I find this all to be too confusing to deal with. I cannot find a way to
change my settings, so I will be marking this as spam.
My apologies.

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Hi @clarklindh, if you would like help with setting your notification preferences or turning off emails, send me a message using this form:
https://connect.mayoclinic.org/contact-a-community-moderator/

I can help.

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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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My husband was diagnosed with MCI five years ago. He has a strong family history of Alzheimer’s. Since his diagnosis, we have been on a journey to find a suitable clinical trial. He was recently tested as having 2 ApoE4 allelles and accepted into a trial for the drug ALZ-801.
That knowledge has been daunting. It certainly has implications for our 3 children. How will they use it? Will it be an impetus to follow a healthy lifestyle? I hope so.
I am not familiar with the series "Limitless" and will definitely seek it out.
Thanks for everything that you and the HABIT program have done for us personally and for sharing accurate information with a healthy dose of hope.

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I just watched the trailer to "Limitless." This is definitely not my direction. Taking chance as Mr. Hemsworth does, scares me. It appears that he is coming as close to being killed as he can without crossing the line. My goal is to stay away from the line. Perhaps if I was as buff as Mr. Hemsworth... Nope. Not even then.
Maybe I'm missing the point of "Limitless." can anyone fill me in?

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@liv4now

My husband was diagnosed with MCI five years ago. He has a strong family history of Alzheimer’s. Since his diagnosis, we have been on a journey to find a suitable clinical trial. He was recently tested as having 2 ApoE4 allelles and accepted into a trial for the drug ALZ-801.
That knowledge has been daunting. It certainly has implications for our 3 children. How will they use it? Will it be an impetus to follow a healthy lifestyle? I hope so.
I am not familiar with the series "Limitless" and will definitely seek it out.
Thanks for everything that you and the HABIT program have done for us personally and for sharing accurate information with a healthy dose of hope.

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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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@rfherald

I just watched the trailer to "Limitless." This is definitely not my direction. Taking chance as Mr. Hemsworth does, scares me. It appears that he is coming as close to being killed as he can without crossing the line. My goal is to stay away from the line. Perhaps if I was as buff as Mr. Hemsworth... Nope. Not even then.
Maybe I'm missing the point of "Limitless." can anyone fill me in?

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@rfherald You are correct that there is quite some extreme physical feats in the program. I'm never going to try to climb a rope over a chasm up to a subway car either! My take-away was more the way of thinking about aging. He is doing some extreme things, which I'm sure are somewhat for good TV making, but the message I took away is 1) finding motivation for a healthy lifestyle and 2) acceptance that aging is coming our way even in the most healthy circumstances. The balance between the two (motivation for health vs. inevitability of aging) is one I enjoy pondering and one that I appreciate hearing the series discuss. I hope that others may express their take-aways here if they see the series or have already seen it..

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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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@rfherald First off all, I laughed at your "recovering engineer" description. I appreciate the balanced thoughtfulness of your reflection above, that lands on hope.

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