What is the absolute risk?

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Indyjulie
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What is the absolute risk?

Postby Indyjulie » Tue Jul 31, 2018 10:11 am

Hi All

I understand the relative risk of having APO4 one allele (about 300% or 3x greater) but I have been unable to figure out or locate any info on the absolute risk. Anyone have info on this?

Thanks in advance for your time.

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ccfield
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Re: What is the absolute risk?

Postby ccfield » Tue Jul 31, 2018 12:53 pm

Hello Indyjulie, and Welcome!

As you've probably noticed, the members on this site are quite educated about all things ApoE4 so I will let others with more knowledge specific to risk respond to your question, and they will! There was a good discussion on risk that you can find here: Apolipoprotein E and Alzheimer disease: risk, mechanisms, and therapy.

In the meantime, if you have not yet read the Primer, it is very informative. It was written by physician member Stavia and she continues to update it with new information. You can also use the search feature at the top of the page to see if there are past threads that relate to a topic that you are curious about.

We are glad you are here Indyjulie! If you have any questions please feel free to private message me or post in the forums.

Last, if you would like, you can post your story in the Our Stories forum. We'd love to know more about you!

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Re: What is the absolute risk?

Postby Sara » Tue Jul 31, 2018 4:50 pm

Greetings IndyJulie and welcome to the apoe4.info site! Here is the risk as indicated on page 11 of Dr. Bredesen's book "The End of Alzheimer's". "Carrying one ApoE4 (that is, inherited from one parent) increases your lifetime risk of Alzheimer’s to 30 percent, while carrying two copies (inheriting copies from both parents) increases it to well over 50 percent (from 50 to 90 percent, depending on which study you read). That compares to a risk of only about 9 percent in people who carry zero copies of this allele." So just remember... with one copy of the ApoE4 gene there is a 70% probability that you will not see AD in your lifetime... a factor that is clearly impacted by the decisions you make about lifestyle and nutrition - i.e., healthy living!
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Re: What is the absolute risk?

Postby NF52 » Tue Jul 31, 2018 8:25 pm

Indyjulie wrote:Hi All, I understand the relative risk of having APO4 one allele (about 300% or 3x greater) but I have been unable to figure out or locate any info on the absolute risk. Anyone have info on this? Thanks in advance for your time.
Hi IndyJulie!

Welcome to a place where questions are what we all crowd-source to arrive at some answers--and more questions!

As a 4/4, I have to say that terms like "relative risk" drove me crazy when I first found out my results. Turns out the reason scientists use "relative risk" is that they don't have any easy or accurate way to identify someone's absolute risk. Our genetics (not just ApoE4), our lifestyles, our environments, even access to health care and ability to practice healthy-supporting habits, affect both our "risk" and our "resilience".

In fact, researchers are realizing that it's important to consider both sides of the equation. Things like having one ApoE 4 allele might be a relative risk, but having an education beyond high school, using problem-solving in everyday life and social connections may be associated with "cognitive reserve" or resilience. That's why many of the strategies recommended in Stavia's Primer make sense for everyone.
As an example of how many areas could provide resilience to the effects of amyloid and tau and other forms of neurological injury, here's an overview from Vanderbilt University with some nifty charts, and the statistic that 30% of people in one study who donated their brains to science shows Alzheimer's pathology although the people had been cognitively normal until death. Vanderbilt Memory and Alzheimer's Center Resilience Initiative

But to get an idea of what might be the current range of risk, here's what I use: a meta-analysis of four large cohorts of people followed for years. The researchers looked ONLY at risk for people ages 60-75, who might be participants in a clinical study for those with ApoE 3/4, 2/4 or 4/4. Someone younger may have much different risk, and more interventions possible. Here's a link to the study (jump to the end in the Discussion section for the more readable parts): APOE-related risk of mild cognitive impairment and dementia for prevention trials: An analysis of four cohorts And here's the part relevant to you. Note that it refers to the predicted range of risk for either Mild Cognitive Impairment (MCI) or dementia by age 85.

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.


Hope this helps!
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Re: What is the absolute risk?

Postby apod » Wed Aug 01, 2018 11:50 pm

Indyjulie wrote:I understand the relative risk of having APO4 one allele (about 300% or 3x greater) but I have been unable to figure out or locate any info on the absolute risk. Anyone have info on this?

I've read the average population sees a risk of about 1/10.

At a baseline 9% we have:
    1.0-(0.91^1) = 9% risk (91% odds of avoiding Alzheimer's :D)
If you have a copy of the E4 gene, your risk goes up 2-3x.
    1.0-(0.91^2.5) = 21% risk (79% odds of avoiding Alzheimer's :|)
At two out of two copies of the E4 gene, your risk goes up 12x.
    1.0-(0.91^12) = 67.75% risk (32.25% odds of avoiding Alzheimer's :cry:)
Now, I've read that when you have an E4 and 2/2 copies of C677T (I can put a triple check here), you're looking at upwards of a 35.5x risk.
    1.0-(0.91^35.5) = 96.48% risk (3.52% odds of avoiding Alzheimer's :shock:)
Both my mother and my sister have the 1x E4 + 2x C677T gene combo... so at 3x the 35.5x risk, what's that... something like 99.99% before you round up to 100%? :o

That's some... rough math. Although, other studies show a much less drastic increase with the 1x E4 + 2x C677T gene combo. There are many factors.

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Re: What is the absolute risk?

Postby NF52 » Thu Aug 02, 2018 7:30 am

apod wrote:Now, I've read that when you have an E4 and 2/2 copies of C677T (I can put a triple check here), you're looking at upwards of a 35.5x risk. That's some... rough math. Although, other studies show a much less drastic increase with the 1x E4 + 2x C677T gene combo. There are many factors.


Those numbers are scary--but less so when I saw that the study was from one clinic in Bratislava, Slovakia, and followed only 100 people with AD and 100 without AD over a period of 10 years. So in a population of people identified with AD, in one city in an area that split off from Czechoslovakia due to ethnic rivalries--suggesting this is a very homogeneous population--these people showed a high association of ApoE 4 and C677T. In various books like In Pursuit of Memory: The Fight Against Alzheimer's by neuroscientist and AD grandson Dr. Joseph Jebelli, and A Brief History of Everyone Who Ever Lived: The Stories in Our Genes, by Adam Rutherford, they argue against extrapolating from populations that may have had extensive shared genes through inter-marriage, thus exacerbating the effects of genes that in other populations have less impact. It's possible that in addition to C677T, this Slovakian population has multiple additional shared SNPs that each have an additive effect, which isn't calculated or even known due to the lack of a genome-wide association study (GWAS).

More importantly, this study is silent as to the population-based frequency of AD in Bratislava. How many people are in Bratislava in their 80's with the same genes? Maybe 50% or more of those are not developing AD? As someone whose mother took an astronomical amount of diethylstilbestrol for 4 months early in her pregnancy with me, I read at 18 that I was "very likely" to get a rare vagina cancer in my early 20's. Turns out some DES daughters did get that cancer, but the early news ("100% of women in their early 20's who have vaginal cancer are DES daughters") with more research became "0.001 % of DES daughters develop vaginal cancer, which can be screened for with knowledge of their DES status."

One reason I like population-based studies and meta-analyses of diverse populations, especially healthy populations.
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Re: What is the absolute risk?

Postby Angelheart301 » Sun Aug 05, 2018 12:13 pm

Whoa! What scary statistics! 99.99% risk! I think there must be many of us who have one APOE4 and who are homozygous for C677T. (Me!) I can't even begin to consider that, and choose to believe that study is faulty.

There was a recent study that found that having 5 babies during your lifetime increases your Alzheimer's risk by 70%.(Again me!) A few days later, another study found that having 3 babies deceases your risk by 12% over those who have only given birth once.

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Re: What is the absolute risk?

Postby NF52 » Sun Aug 05, 2018 7:41 pm

Angelheart301 wrote:Whoa! What scary statistics! 99.99% risk! I think there must be many of us who have one APOE4 and who are homozygous for C677T. (Me!) I can't even begin to consider that, and choose to believe that study is faulty.
There was a recent study that found that having 5 babies during your lifetime increases your Alzheimer's risk by 70%.(Again me!) A few days later, another study found that having 3 babies deceases your risk by 12% over those who have only given birth once.
Hi Angelheart,

I agree with your decision to believe that the Bratislava study is, if not faulty, as least fatally flawed when applied to populations other than those already diagnosed with Alzheimer's and living in a small geographic area.
And here's a review of the recent childbirth story that asks if this study got it right in finding a cause of dementia.
Stephen Soumerai, ScD, Professor of Population Medicine at Harvard Medical School and Harvard Pilgrim Health Care Institute, says it’s way too soon to know. “This unpublished abstract should be considered extremely preliminary, but the scientists and news reports would almost have women believe that having three children will protect them from senile dementia decades later... The causal words imply this but the data do not begin to show it.” He said that...household income and dozens of other factors could be responsible for the observed results...

Susan Molchan, MD, a psychiatrist and former NIH clinical researcher who studied Alzheimer’s disease, agreed that there’s “no real information” here. “Many correlations were done and one is bound to find what seems like significant associations that may superficially appear to be causal if one does enough correlations,” she wrote via email. In other words, if you look at enough different outcomes, you’re bound to find some that look interesting due purely to the play of chance.
"... we’re left with the fact that dementia is multi-factorial, that women live longer, and that age is the greatest risk factor for dementia.”
Surprisingly, given this context, you won’t find a single note of caution about the limits of this kind of research in NBC’s coverage. The only source interviewed for the story is a representative of the Alzheimer’s Association, which has a clear stake in amplifying the importance of this study presented at its conference.
{Emphasis added.}HealthNewsReview.Org

A shorter way to describe this is "A post hoc fallacy". Here's the Wikipedia definitions, with my addition of the relevant terms.
Post hoc ergo propter hoc (Latin: "after this, therefore because of this") is a logical fallacy that states "Since event Y (dementia} followed event X (five births), event Y (dementia) must have been caused by event X (five births)." It is often shortened simply to post hoc fallacy.

https://en.wikipedia.org/wiki/Post_hoc_ergo_propter_hoc
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Re: What is the absolute risk?

Postby Starfish77 » Tue Aug 07, 2018 12:53 am

I tried looking up C677T on my 23andme raw data. Nothing came up. I Googled C677T and saw it equated to RS1801131 and RS1801133.
I am RS1801131 = GT and RS1801133 = AG I don't know how to interpret these results.
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Re: What is the absolute risk?

Postby Andru » Mon Aug 13, 2018 4:01 pm

Starfish77 wrote:I tried looking up C677T on my 23andme raw data. Nothing came up. I Googled C677T and saw it equated to RS1801131 and RS1801133.
I am RS1801131 = GT and RS1801133 = AG I don't know how to interpret these results.
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rs1801133 is C677T, according to SNPedia: https://www.snpedia.com/index.php/Rs1801133

With AG, that means you are CT on that page (the orientations there are minus, therefore "A" is "T" and "G" is "C").

So you are heterozygous, which doesn't seem to be that big of a deal.


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