The Generation Study question

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Nikki2019
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The Generation Study question

Postby Nikki2019 » Tue Dec 18, 2018 6:23 pm

Hi,

I read and quoted something I came across on the forum... please see below. Does this suggest that 3/4s even if they are age 40s will just have 20-25% risk? Or does it suggest that if you make it to age 60-75 with out any cognitive decline, that you are with in that stat for the next period of life? What about those of us that are late 40s and are 3/4s?

So let me give you some very recent (2017) and very specific news from a large meta-analysis of population-based data on people with ApoE 3/4 ages 60-75, not your age (which I am guessing is 30's or early 40's):
The Generation Study elected to disclose the following “lifetime” risks of [mild cognitive impairment] 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).
APOE-related risk of mild cognitive impairment and dementia for prevention trials: An analysis of four cohorts

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Re: The Generation Study question

Postby NF52 » Thu Dec 20, 2018 6:15 am

Nikki2019 wrote:Hi,

I read and quoted something I came across on the forum... please see below. Does this suggest that 3/4s even if they are age 40s will just have 20-25% risk? Or does it suggest that if you make it to age 60-75 with out any cognitive decline, that you are with in that stat for the next period of life? What about those of us that are late 40s and are 3/4s?

NF52 wrote:So let me give you some very recent (2017) and very specific news from a large meta-analysis of population-based data on people with ApoE 3/4 ages 60-75..:
The Generation Study elected to disclose the following “lifetime” risks of [mild cognitive impairment] 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).
APOE-related risk of mild cognitive impairment and dementia for prevention trials: An analysis of four cohorts
Welcome Nikki2019!

I'm the person who quoted that study, which is one of my favorites for two reasons: 1) I happen to be in the Generation Study and in that age group as an ApoE 4/4 and 2) having read the whole article, I liked the use of 4 large population cohorts which reflect typical people more than those who are studied once they develop Alzheimer's.

So here's what I think the authors would say:
* These predicted risks are MOST relevant to people who are still cognitively healthy and considering enrolling in a study at ages 60-75, since we are predicting out 10-25 years and we know that Alzheimer's and other types of dementia (vascular, Lewy Body, frontal-temporal dementia and mixed dementia) develop very slowly over a period of 10-25 years.
* Alzheimer's is a complex disease with multiple causes that interact, including genes, environment (including pollution, education, social engagement) , history of head trauma, cardiac health, metabolic health, mental health and sleep apnea.
* ApoE 4 is not a dominant gene: it doesn't cause Alzheimer's. It just causes some things that dial up the risk; other things dial down the risk.
* We don't yet have the ability to offer a personalized risk assessment using all the genetic, environmental and lifestyle factors. We also don't yet know if reducing amyloid beta in the brain or preventing it from forming, will also prevent Alzheimer's in people with ApoE 4, or if other processes may still lead to tau tangles or other causes of Alzheimer's. (That's a key part of the Generations Study, which reduces the protein that makes amyloid beta by about 85% and then watches what happens to us for about 5-8 years.)
* Advanced age is itself a risk factor for Alzheimer's, regardless of ApoE, although it looks like a somewhat different disease is people over the age of 85.

My take-away for someone in her late 40's with ApoE 3/4: You are perfectly positioned to use the recommendations that Dr. Stavia has in her PRIMER to keep your brain healthy and to dial down the risk factor below that 20-25% level. If and when some other recommendations or great imaging tools become useful in regular practice, you'll be set to take advantage of those.

Having 3 adult children with ApoE 3/4 in their 30's, I feel confident that they--and you--can look forward to seeing their own grandchildren with a healthy brain.

One more side note: Check out the How-to Guide for tips on how to quote to be sure your post is seen by the author.

Glad you found this community of fellow knowledge-seekers!
Last edited by NF52 on Thu Dec 20, 2018 10:22 am, edited 2 times in total.
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Re: The Generation Study question

Postby mike » Thu Dec 20, 2018 10:11 am

Nikki2019 wrote:Hi, I read and quoted something I came across on the forum... please see below. Does this suggest that 3/4s even if they are age 40s will just have 20-25% risk? Or does it suggest that if you make it to age 60-75 with out any cognitive decline, that you are with in that stat for the next period of life? What about those of us that are late 40s and are 3/4s?


Nikki2019, let me add to what NF52 said. Yes, having a single ApoE4 gene will raise your risk for AD by a small amount - much less than if you have 2, but by far, the largest single risk factor for AD is AGE. Someone who is 85 has more risk of having AD than someone who is 70. And the portion of risk that is ApoE4 (and age) related can be moderated through life-style changes.
Sonoma Mike
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Re: The Generation Study question

Postby Nikki2019 » Thu Dec 20, 2018 12:06 pm

NF52, I am so glad that I have now met someone (online) in this study! That must really be exciting to be a part of that.

I have come across so many different stats. which say different things. I have read that just one out of 50 are 4/4s and that risk of AD is 91% by age 68. I have also read that for 3/4s, its just 10-11% that have just one APOE4, and that by age 75 its a 50% chance of AD. Looking at those stats., its not surprising that my father has AD at such a young age. And, it causes me to prepare for my own care home now. But, other places, I read otherwise. In another journal,

http://www.jpreventionalzheimer.com/280 ... sease.html

I read that the stats. are a lot better. It also has a table which shows that the heterozygous group is a lot more common, at 24% of the general population. That same table shows a third row, which displays " percentage of AD population". I am completely lost on that section. The numbers listed there seem counter intuitive. It lists 4/4s as 10% and non carriers as 51%. I don't get it. Maybe I already have cognitive decline, ha! I better start building those reserves!

By the way, I am making a 2019 New Years Resolution list this year. I am going to have a hell of a time trying to cut out sugar!

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Re: The Generation Study question

Postby NF52 » Thu Dec 20, 2018 1:06 pm

Nikki2019 wrote:...I have come across so many different stats...I have read that just one out of 50 are 4/4s and that risk of AD is 91% by age 68. I have also read that for 3/4s, its just 10-11% that have just one APOE4, and that by age 75 its a 50% chance of AD... In another journal,
http://www.jpreventionalzheimer.com/280 ... sease.html

I read that the stats. are a lot better. It also has a table which shows that the heterozygous group is a lot more common, at 24% of the general population. That same table shows a third row, which displays " percentage of AD population". I am completely lost on that section. The numbers listed there seem counter intuitive. It lists 4/4s as 10% and non carriers as 51%. I don't get it. Maybe I already have cognitive decline, ha! I better start building those reserves!

By the way, I am making a 2019 New Years Resolution list this year. I am going to have a hell of a time trying to cut out sugar!
As Mark Twain once said, "There are lies, damned lies, and statistics!" That doesn't mean you have any cognitive decline; it means you're showing great cognitive reserve to find that article and identify the question!

So that others don't have to go to your helpful link, I've taken a screen shot of it, from an article by some of the key researchers behind the Alzheimer's Prevention Initiative (API), which designed and is running the Generations Trials.

Image

As far as how common having one or two ApoE 4 alleles is in the population, it depends on which population you are testing. 23 & me says about 24% of their users have an ApoE 4 allele, if I remember correctly; while some studies have suggested that in Northern European and Scandinavian countries it's even higher. In general it's safe to say it's not uncommon!

The reason the column of percentages of people WITH Alzheimer's looks so different has to do with how common dementia is with people as they get to be the "oldest old".

Right now about 75% of people have ApoE 3/3 (my husband is one of them), yet they too can develop Alzheimer's or other dementias, but probably do so at later ages. So my mother-in-law, probably also ApoE 3/3, was diagnosed with dementia at about age 85, and died at age 88 and her likely cause was a history of vascular problems including blocked carotid arteries. His father, probably another 3/3, lived to 90 with no sign of dementia. So when you see that 51% of people with Alzheimer's have no ApoE 4, it means that they are under-represented in the disease group based on what you'd expect (51%, not 75% get Alzheimer's).

In contrast, people with ApoE 4/4, who are about 2-3% of the population in the U.S. and Europe, are over-represented in the Alzheimer's group (10%, not 3%). Another way to look at it, my husband has about a 85-90% chance of not getting that diagnosis, while I have a 45-70% chance of not getting it.

As for the age of diagnosis being 68 for ApoE 4/4: that's a very scary statistic that a lot of people see shortly after they get the news. And it's misleading, because lots of people in their 80's are never officially diagnosed with it either before death or on their death certificates (Respiratory failure and heart failure are more commonly listed causes of death).
Someone in their late 60's who is suddenly having memory difficulties is much more likely to be diagnosed officially with the disease. In fact, if people get to the age of 75 with ApoE 4/4 without a diagnosis, it appears the curve of risk drops down some.

So don't start planning for that care home yet. I'm planning a bathroom renovation and a trip to Spain for myself and my husband; the care home can wait!! Start planning to enjoy the journey of life and all that it brings, one day at a time!!
4/4 and still an optimist!

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Re: The Generation Study question

Postby Nikki2019 » Thu Dec 20, 2018 7:09 pm

Hi NF52,

So true what Twain says about stats! The thought came to me that the folks that are looking into the health aspect using " 23 and me" could be more inclined to do so perhaps partially due to a family member with AD, which was the case myself and twin. Maybe that could partially explain the higher percentage than what I read about in some other places. But even if it is just 10-11 %, it is way too common to ignore.

There was a documentary I saw regarding the Early Onset AD. I would like to find out what is going on with the folks that started on the trail. I can't wait so many years to find out the results... the suspense!

My father had no idea that AD would be so soon for him. He had multiple houses with multiple mortgages, which he lost for not remembering to pay. He also forgot to pay taxes and ended up with a bunch of liens on his townhome that was paid off. But, he forgot to pay the HOA fees, so they were garnishing. What a mess. I have his durable POA, better late than never, so now its sort of my mess.. And that is the easy part. The difficult part is seeing how he lives in diapers and can't remember anything. Even though he is a 4/4, his 2 younger brothers still seem ok, but they haven't disclosed their APOE status. Neither of his parents had signs of dementia. One just lived until 67, but the other well into 80s. But, the one that died at 67 did so from pancreatic cancer and her own pa died young from diabetes. They must've had at least one APOE4 each. My father chained smoked many decades, and had an 11 day hospitalization for pneumonia with antibiotics and the works at age 64, then shortly after that it seems he had the cognitive decline.

Since you are doing well, I wonder how your parents did. Have you cut out sugar and how are you feeling ? How long have you been in the study? I also wonder if you did HRT, such as Stavia mentions in the primer. If you go to Spain, then I guess you'll do the shot for the study before or after the trip, assuming its a monthly shot. Feel free to ignore my questions if I am being too nosey! I wonder if you have the placebo or the real one. It is interesting and I tried to sign up for myself or my father, but I was in the wrong age group and my father has AD.

I went to the library and now will read up on the Bredesen book, mentioned in the forum.

Have a good Thursday evening !

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Re: The Generation Study question

Postby NF52 » Sun Dec 30, 2018 6:27 pm

Nikki2019 wrote:Hi NF52,... I would like to find out what is going on with the folks that started on the trail. I can't wait so many years to find out the results... the suspense!

My father had no idea that AD would be so soon for him... Even though he is a 4/4, his 2 younger brothers still seem ok, but they haven't disclosed their APOE status. Neither of his parents had signs of dementia. One just lived until 67, but the other well into 80s. ... My father chained smoked many decades, and had an 11 day hospitalization for pneumonia with antibiotics and the works at age 64, then shortly after that it seems he had the cognitive decline.

Since you are doing well, I wonder how your parents did. Have you cut out sugar and how are you feeling ? How long have you been in the study? I also wonder if you did HRT, such as Stavia mentions in the primer. If you go to Spain, then I guess you'll do the shot for the study before or after the trip, assuming its a monthly shot. Feel free to ignore my questions if I am being too nosey! I wonder if you have the placebo or the real one. It is interesting and I tried to sign up for myself or my father, but I was in the wrong age group and my father has AD.
Hi again Nikki!

I obviously let the holidays get in the way of answering your great questions! Apologies for that, but I'll see if I can do better now. Your dad, like many, probably grew up thinking that he was going to live about as long as his dad (67) and since lots of men died of heart attacks in their 50's and 60's in the generation before me (I'm 66), he may also have felt that it was too difficult to give up chain smoking. (Something else that his generation wasn't told was risky until they were hooked.)

It's possible that his hospitalization with pneumonia for 11 days also involved some hypoxia, a lower level of oxygen to his brain. My own son had asthma as a child, and had too many bouts with pneumonia, which always reduced his ability to breathe deeply and well. At your dad's age, that was like adding kindling to a fire, I'd imagine.

I'm sure he would not have wanted to be either a burden, or to cause you distress, and would be proud of you for being so proactive in your own health. My own dad died at 67 of cardiac arrest and would have been at least a 3/4; I think he would be thrilled that my arteries at almost that age are clear of plaque. My mother lived to 86, but she and her 4 sisters all developed moderate dementia in their 80's, and died of heart or respiratory failure. Her 5 brothers were a mixed bag, but with generally better health.

I am far from sainthood when it comes to avoiding all sugar, but somehow have been lucky enough to have good HbA1c and C-reactive protein scores, and zero coronary artery calcium deposits. I have always enjoyed fresh fruit and vegetables though and rarely eat red meat, and no processed meats (bacon, sausage) anymore. I didn't get HRT because I went through menopause 13 years ago, when it was still verboten for women. (Wish I could have, since it would have helped my sleep and maybe my risk of both AD and osteoporosis.)
But you should figure out what makes you feel healthy and energetic and go with that!

As for the Generations 1 trial, I am glad to answer questions. I'm in the "arm" with either CNP520, a BACE-1 inhibitor, or a placebo. I have a 68% chance of being on the drug and 32% chance of being on the placebo--odds I can live with ;) Neither I, the staff at the study site, or even the pharmacist there know what I am on--that's why it's called a double-blind study. I can still take the supplements I want (and could follow the Bredesen or Gundry or other protocols if I chose) and I only have to "report" 4 times a year; two of those for brief visits and two for more extensive testing. Easy to schedule trips around that.

Enjoy finding purpose in your life; as a parent of 3 adult children with ApoE 3/4 and grandchildren who might have that also, I fervently hope they seek joy and meaning in their lives--we are far more than any gene, or any disease that may come our way.
4/4 and still an optimist!

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Re: The Generation Study question

Postby Nikki2019 » Fri Jan 11, 2019 2:38 pm

Thanks NF52 !
I look forward to continuing to read your posts and hearing about how the trial goes. I read in Bredesen about no single pill and about more of patching up 36 holes...

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Re: The Generation Study question

Postby SusanH » Sun Jan 13, 2019 9:19 am

I was recently tested for the new Navartis Study. I’m a E3/E4. “Your estimated risk of developing mild cognitive impairment or dementia related to Altzheimer’s through the age of 85 is between 20 and 25%.” Those were the exact words in statement. It’s okay. There’s lots we can do like telling the world the truth about statins Eating healthy and exercise (my downfall)

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Re: The Generation Study question

Postby NF52 » Sun Jan 13, 2019 9:50 am

SusanH wrote:I was recently tested for the new Navartis Study. I’m a E3/E4. “Your estimated risk of developing mild cognitive impairment or dementia related to Altzheimer’s through the age of 85 is between 20 and 25%.” Those were the exact words in statement. It’s okay. There’s lots we can do like telling the world the truth about statins Eating healthy and exercise (my downfall)
Welcome SusanH!

I'm so glad that you found our site and hope you will find it a community of eager learners, avid questioners and endless ability to enjoy debating how best to equip ourselves for a long, healthy and purposeful life. Congratulations on beginning the screening process for the Generations 2 Study of 2 different doses of CNP520, a BACE-1 inhibitor. Good to know that my statistic was accurate from the study consent forms !!

Feel free to keep us posted on the process as you go through screening. I'm sure they explained that as a 3/4 you have to "pass" the requirement for a "positive" amyloid PET scan. As a 4/4, I didn't have to, and was not told my results. But I don't worry about the likelihood that I did have a positive result when I took the PET scan. It's just one piece of who I am.

I found it a fascinating (and a few times frustrating) experience to go through the variety of cognitive, motor, blood, imaging and "study partner" tests and felt that I was never discouraged from asking questions. It does take patience--from you and your "study partner". Regardless of the results, such studies add greatly to our knowledge of how Alzheimer's and other dementias develop over years in the "cognitively healthy" population. (For what it's worth; I take 10 mg of atorvastatin myself daily, mostly because heart disease is a major issue on both sides of my family. But reasonable people can come to different conclusions on that.)

Approaching 16 months on the study, I can say that it interfere little with my daily life (including eating and exercise choices!). Even now, as I recover from bunion surgery with a lovely walker for a month, I have found that the study staff at the highest levels care about my health, checking to make sure that I am okay and that there are no possible drug interactions that my doctor and I need to take into account. (The study site does not know if I am on CNP520 or a placebo; they simply use an abundance of caution and assume everyone is on the drug to address any possible interactions.)

Hope you share more about how you decided to start the testing process and what brought you to this forum on Our Stories.
4/4 and still an optimist!


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