Understanding your risk of Alzheimer's, including the ApoE4 allele

[Sara]

Hi Della66, If I recall correctly I recently heard one of our lecturer's at the FMCA (Functional Medicine Coaching Academy) say something along the line of it's about 20% genetics and 80% lifestyle factors - very generalized but an interesting perspective.

[RJones]

The link below, referenced in another thread, claims that at age 75, the incidence of any form of dementia is

6% if no APOE4
11% if 1 copy of APOE4
18% if 2 copies of APOE4

https://www.alzheimers.org.uk/DementiaRisk

So at age 75, even if you are homozygous APOE4, that website claims there is an 82% chance that you will NOT have any form of dementia, Alzheimer's or otherwise.

I'm going to make a wild guess that the incidence at age 75 of *non*-Alzheimer's dementia is 3%, regardless of APOE4 status. If that's true, then the chance of having specifically Alzheimer's dementia at age 75 would be:

[begin guesswork]
3% if no APOE4
8% if 1 copy of APOE4
15% if 2 copies of APOE4
[end guesswork]

The website doesn't look at APOE4 at other ages. HOWEVER, they do say that the incidence of dementia for the full population in age range 85-89 is 18%. Now we know that at age 75, 6% of non-carriers of APOE4 had dementia. It's safe to assume that *at least* 6% of non-carriers also have dementia >10 years later at age 85-89. Non-carriers are 70% of the population, so that 6% would be 4% of the total population. If that's all true then the remaining ~30% of the population that is APOE4-carrying would include a number of cases of dementia representing 14% of the full population.

Now 14/30 is less than 1/2, so that means that even at age 85-89, there is less than a 50% chance for APOE4 carriers to have dementia of any kind.

However, I think it's better than that.

A paper by Ungar, Altmann, and Greicius writes that "In studies with long-lived subjects the APOE4 effect is detectable in age of onset but is diminished in terms of overall risk attributable to APOE4." If by age 85-89 there's NO additional risk to APOE4 carriers, then their frequency of dementia would be equal to that of the general population at that age, which (as mentioned above) is 18%.

SO, I'd say that at age 85-89, the probability of an APOE4 carrier having some form of dementia is greater than 18% but less than 50%.

[Harrison]

There are now 3+ threads discussing this, so maybe we can consolidate on one?

The Alzheimer's UK numbers are much lower than what is typically reported. Here are some numbers from the Banner Institute, who are running an ApoE4/4 clinical trial (The Generation Study) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5360223/

The Generation Study elected to disclose the following “lifetime” risks of MCI or dementia to its potential participants: 30%–55% for individuals with APOE-e4/e4; 20%–25% for individuals with APOE-e3/e4 and -e2/e4 (with a note that risk might be lower for those with APOE-e2/e4); and 10%–15% for individuals with APOE-e3/e3, -e3/e2, and -e2/e2 (with a note that risk might be lower for those with APOE-e2/e3 and -e2/e2). These values are consistent with our findings, but use round numbers for intelligibility, and broader ranges to reflect statistical and other sources of uncertainty.

The point of this is not to alarm anybody, just as I don't want the Alzheimer's UK numbers to give a false sense of security. Only a few years ago, the risk for E4/4 was considered to be over 75%. My own personal expectation is that as more and more people use services like 23andMe, the numbers will continue to go down.

[Searcher]

Are there any statistics that estimate what percentage of total APOE3/4 and 4/4 carriers never go on to develop Alzheimer's by age group?

Della, that depends largely on the

a) lifestyle of each individual carrier
b) family history of each individual carrier

Summary statistics mask the important effects of lifestyle choices. What each individual carrier might want to know is:

Given my lifestyle and family history, what are my chances of evading Alzheimer's?

I would love to see reports that help answer that specific question.

[Julie G]

There are now 3+ threads discussing this, so maybe we can consolidate on one?

Done. Apologies for any ensuing confusion... a side effect of reigning in chaos .

[Stavia]

Thanks Susan, this is so helpful!

From the Wiki link-

"Here's some background on the idea of modifiable risk. According to the Lancet Journal (2017):

Alzheimer's includes about 65% non-modifiable risk (meaning genetic) including only 7% contributed by the ApoE4 allele, so about 58% of your AD risk is attributable to OTHER genes."

I find this so helpful to know. Some of the articles we see online make out APOE4 to be the be all and end all, but it's not, and this helps get that in context.

This is the main problem I'm having reading about APOE4. I'm so tired of reading articles that say it is "the greatest genetic risk factor that we know of"; I find it all to be terribly upsetting. Even Dr. Bredesen writes in his book that the presence of even one APOE4 causes your risk for Alzheimer's to "soar". I just find reading these types of things counterproductive to my health efforts. Makes me just want to give up.

Della I agree completely.
I chose to live my life with hope that if I do as much as I can with ALL the strategies, I will be one of the lucky ones. I find statistics for E4 very unhelpful. Yes the risk of AD is much higher for me as a 4/4. But no - the risk is not 100% like Huntingdon's chorea.
Nitpicking statistics is IMO unhelpful as they are just a blunt average of a large group of people. It is completely irrelevant to me if my risk at age 85 is 20% or 80%. All I care about is that it's not 100%.
Della - don't panic. Just do your best with what you can do.

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[floramaria]

Are there any statistics that estimate what percentage of total APOE3/4 and 4/4 carriers never go on to develop Alzheimer's by age group?

Dear Della66, Please don't be discouraged by statistics. Just think, they have not been able to factor in this amazing healthy group of people in our community. Though it can't be said YET that the people here who are being conscientious about diet, exercise, sleep, reducing stress, balancing hormones, taking beneficial supplements, kickboxing, piano playing, TaiChi-ing, learning new things....just to name some of what we are doing to minimize our risk...will never go on to develop Alzheimer's, I believe that we, and people like us, will shift the statistics. The statistics can't yet reflect the tremendous gains that have been made in understanding and addressing the factors that drive cognitive decline in ApoE4 carriers. I feel so fortunate to be living now with not only hope but also confidence that my genes will not determine my long term health and well-being. Take heart, Della. Sending best wishes to you.

[Searcher]

It is completely irrelevant to me if my risk at age 85 is 20% or 80%. All I care about is that it's not 100%.
Della - don't panic. Just do your best with what you can do.

Yes, the 4 big points are:

1) Your lifestyle alters your risk. You are powerful.

2) APOE4 amplifies the effects of lifestyle on Alzheimer's risk. This is good news. Because it amplifies the beneficial effects of a healthy lifestyle too. People without APOE4 get smaller benefits from shifting to a healthier lifestyle. APOE4 not only opens your eyes to the attractions of a healthy lifestyle but also rewards you disproportionately for shifting toward a healthier lifestyle.

3) Stress-inducing statements by physicians are counter-productive, because they tend to boost stress, cortisol levels and neurodegeneration. Cortisol wipes out many benefits conferred by tweaks to lifestyle. You can plug holes in the roof all day, but cortisol can destroy the whole roof. Many physicians are naive about how the mind works and how people can thrive despite adversity. They need education and gentle but firm correction when they make careless, counter-productive remarks.

4) No human being need define themselves in terms of one aspect of themselves. We may have blond hair, but there's more to us than that. We may have paraplegia, but that does not fully define us. We may have diabetes, but there's more to us than that. So it is with any aspect of ourselves. We are more than that. In claiming that wider, bigger identity, we open the door to a full and meaningful life despite any challenge. We may be E4 carriers, but there is more to us than that. There's more to life than cowering from challenges. Incidentally, we rise above stress when we claim this full personhood.

Take heart, Della. Live with courage. Do what you can and congratulate yourself for doing it.

[Stavia]

Nicely said Searcher.
We are not numbers. We are people.
And I chose to live my life with balance and hope.

viewtopic.php?f=2&t=687&p=6098&hilit=Musings#p6098

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[Searcher]

Thanks for the link, Stavia. Powerful musings!

I'm mentoring a lady who has quadriplegia due to an accident. Her mother has dementia and has had to be moved to a care home.

It is an eye-opening experience for both of us. Our superficial definitions of who we are fall away. We are forced to understand who a human being really is, what's important and less important in life, and how to live a full and meaningful life in the face of challenges.

This lady is making the most of life. Anyone can learn how to live more fully in the present moment, with more calm confidence, purpose and joy despite adversity.