New and not sure where to start

Newcomer introductions, personal anecdotes, caregiver issues, lab results, and n=1 experimentation.
Post Reply
wwbok
Contributor
Contributor
Posts: 3
Joined: Fri Apr 22, 2022 4:03 pm

New and not sure where to start

Post by wwbok »

Hello everyone! I'm new here here!

Short version: I don't know what APOE status my dad and I are yet (I'm going to order 23andMe for both of us), but when looking through our raw DNA file from Ancestry.com, we both have the same DNMT3B gene polymorphism potentially associated with dementia and Parkinson's. My paternal grandfather and his fraternal twin brother, had these two conditions, respectively. I'm now terrified for my dad and myself. What diet and supplements can we start immediately, regardless of APOE status?

Long version:
My paternal grandfather and his fraternal twin brother had dementia and Parkinson's, respectively. My grandfather, the one with dementia, lived until he was 86 and was relatively fine the whole time. The only time he was diagnosed with dementia was after he had been in the nursing home for two years (he'd have trouble remembering what day it was, stumbling over his words, and things like that). He never had issues remembering who we were though. He died from acute kidney failure. He also had a stroke in his early 70s due to unchecked diabetes and blood pressure. His fraternal twin brother died when he was 80 from complications related to Parkinson's. Their older brother died from a heart attack at 88 (not sure if he ever had dementia); and their sister died at the age of 98 (not sure if she had dementia either; however, her son had sundowning syndrome).

My father is 75 (this month!) and overall fine. He has a-fib, but through diet and exercise, has cured his diabetes himself and maintains a 5.2 A1c (which he's trying to lower further) and several years ago lost over 200lbs on his own. He has a PhD and was a professors for over 30 years before retiring. In general, I would say his memory is great for someone his age (it's better than mine!). He remembers dates of appointments without needing to write them down, remembers current and past events (both personal and in the news), recalls things he's read or watched on television just fine, gardens and volunteers as a coordinator for multiple projects, manages his own finances and checkbook just fine, remembers to take his meds, and for his "fun activities" he plays scrabble, speed word games, crosswords, and 200-500 piece puzzles. He sometimes stumbles over his words, but he had a stutter when he was young. All his other labs are normal, including cholesterol, triglycerides, etc. He recently dusted off his old CPAP machine as well.

I have more health problems than he does, but that's for another post, heh.

What brings me here is that a few years ago, before my mother passed away, she, my dad, and I all took DNA tests (from Ancestry.com) so my mother could learn about her ancestry. For 5 years, I never once thought to look at my raw DNA data; partly, at least, because I have a diagnosis of OCD and some health-related OCD hangups, so I didn't want to open that proverbial can of worms. Well, of course, eventually I couldn't leave well enough alone, and I went looking through my our raw DNA files.

Ancestry.com apparently often misreports the SNPs people often use to determine their own APOE status, so I can't use those as being reliable, and I've ordered a 23andMe kit for my dad and I. However, one thing that Ancestry did report on is the DNMT3B gene and polymorphism that's potentially associated with dementia and Parkinson's: https://www.clinicadamemoria.com.br/wp- ... isease.pdf
and https://www.semanticscholar.org/paper/T ... 983ba0f1fa

My father and I have the TGG polymorphism mentioned in the article (technically, Ancestry is reporting a TAA/CGG, but I think we actually have the TGG if I look at Livewello and/or Promethease).

These studies are largely from 2014/2016, with a few updated articles, including one from 2020 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139499/) that states "At this moment, there are not appropriate and reliable epigenetic biomarkers for diagnosis, classification and disease progression..." referring to specific polymorphisms, but given that they specifically mention Parkinson's and dementia, I freaked out. Hardcore.

In fact, I'm terrified.

I'm so overwhelmed. I realize that I don't know our APOE status yet, but my own mental health "doom and gloom" says we'll both be 4/4.

Regardless of APOE status, I have no idea where to start on diet, supplements, etc. Is it too late to alter the course for my father if things are "building" in the background, even though he seems fine now? What should we be doing? We're both on board for fasting and any and all diet changes and supplements. What supplements and diet changes can we start immediately, regardless of APOE status? The Bredesen Protocol?

Thank you to everyone for reading my long (LONG) first post and I hope you're all well. <3
Theresa.J
Contributor
Contributor
Posts: 44
Joined: Fri Jan 21, 2022 3:00 pm
Location: Northern California

Re: New and not sure where to start

Post by Theresa.J »

wwbok wrote: Fri Apr 22, 2022 5:06 pm Hello everyone! I'm new here here!

Short version: I don't know what APOE status my dad and I are yet (I'm going to order 23andMe for both of us), but when looking through our raw DNA file from Ancestry.com, we both have the same DNMT3B gene polymorphism potentially associated with dementia and Parkinson's. My paternal grandfather and his fraternal twin brother, had these two conditions, respectively. I'm now terrified for my dad and myself. What diet and supplements can we start immediately, regardless of APOE status?

Long version:
My paternal grandfather and his fraternal twin brother had dementia and Parkinson's, respectively. My grandfather, the one with dementia, lived until he was 86 and was relatively fine the whole time. The only time he was diagnosed with dementia was after he had been in the nursing home for two years (he'd have trouble remembering what day it was, stumbling over his words, and things like that). He never had issues remembering who we were though. He died from acute kidney failure. He also had a stroke in his early 70s due to unchecked diabetes and blood pressure. His fraternal twin brother died when he was 80 from complications related to Parkinson's. Their older brother died from a heart attack at 88 (not sure if he ever had dementia); and their sister died at the age of 98 (not sure if she had dementia either; however, her son had sundowning syndrome).

My father is 75 (this month!) and overall fine. He has a-fib, but through diet and exercise, has cured his diabetes himself and maintains a 5.2 A1c (which he's trying to lower further) and several years ago lost over 200lbs on his own. He has a PhD and was a professors for over 30 years before retiring. In general, I would say his memory is great for someone his age (it's better than mine!). He remembers dates of appointments without needing to write them down, remembers current and past events (both personal and in the news), recalls things he's read or watched on television just fine, gardens and volunteers as a coordinator for multiple projects, manages his own finances and checkbook just fine, remembers to take his meds, and for his "fun activities" he plays scrabble, speed word games, crosswords, and 200-500 piece puzzles. He sometimes stumbles over his words, but he had a stutter when he was young. All his other labs are normal, including cholesterol, triglycerides, etc. He recently dusted off his old CPAP machine as well.

I have more health problems than he does, but that's for another post, heh.

What brings me here is that a few years ago, before my mother passed away, she, my dad, and I all took DNA tests (from Ancestry.com) so my mother could learn about her ancestry. For 5 years, I never once thought to look at my raw DNA data; partly, at least, because I have a diagnosis of OCD and some health-related OCD hangups, so I didn't want to open that proverbial can of worms. Well, of course, eventually I couldn't leave well enough alone, and I went looking through my our raw DNA files.

Ancestry.com apparently often misreports the SNPs people often use to determine their own APOE status, so I can't use those as being reliable, and I've ordered a 23andMe kit for my dad and I. However, one thing that Ancestry did report on is the DNMT3B gene and polymorphism that's potentially associated with dementia and Parkinson's: https://www.clinicadamemoria.com.br/wp- ... isease.pdf
and https://www.semanticscholar.org/paper/T ... 983ba0f1fa

My father and I have the TGG polymorphism mentioned in the article (technically, Ancestry is reporting a TAA/CGG, but I think we actually have the TGG if I look at Livewello and/or Promethease).

These studies are largely from 2014/2016, with a few updated articles, including one from 2020 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139499/) that states "At this moment, there are not appropriate and reliable epigenetic biomarkers for diagnosis, classification and disease progression..." referring to specific polymorphisms, but given that they specifically mention Parkinson's and dementia, I freaked out. Hardcore.

In fact, I'm terrified.

I'm so overwhelmed. I realize that I don't know our APOE status yet, but my own mental health "doom and gloom" says we'll both be 4/4.

Regardless of APOE status, I have no idea where to start on diet, supplements, etc. Is it too late to alter the course for my father if things are "building" in the background, even though he seems fine now? What should we be doing? We're both on board for fasting and any and all diet changes and supplements. What supplements and diet changes can we start immediately, regardless of APOE status? The Bredesen Protocol?

Thank you to everyone for reading my long (LONG) first post and I hope you're all well. <3
Hello wwbok!

As a Support Team intern, I would like to welcome you the ApoE4.info website. I'm so glad that you found us!

It IS scary and overwhelming to find out that our genes may predispose us to unwanted and debilitating illness, particularly those that involve any form of dementia. Many users on this site have had your experience and can relate. The good news is that our genes are not our destiny. Even if you were to find out that you and/or your father carry the ApoE4 variant, this would not mean that you will for sure develop Alzheimer's disease. On top of that, scientists have determined that adopting certain positive lifestyle behaviors can help prevent ApoE4 from causing Alzheimer's or cardiovascular disease.

The wonderful news is that your father sounds like he is doing extremely well at age 75. Your openness to considering changes to your diet and other lifestyle factors as you gather more genetic information is a great starting point. There is much to explore and learn and you most certainly have time to make positive changes. Your curiosity and desire to learn will serve you well on your health journey.

There is a tremendous amount of information of this site that can help you get started. If you would like to explore the site in more detail, I can share several tools/resources to help you get the most out of your experience here:

First, if would like to learn more about ApoE4, the Primer is a detailed and informative resource written by a practicing M.D. with ApoE4/4. It includes information about the biochemistry of the ApoE4 gene and offers a variety of research-based prevention strategies. A side benefit is that many, if not all, of the recommended strategies will lead to improved overall health in the long term, regardless of ApoE4 status.

In addition, the How to Guide offers tips on how to navigate forums and respond to posts including how to quote members (use the quotation icon in the upper right of any post) so they get an email notification of your post. It also demonstrates how to use the Search function for topics, and how to subscribe to topics of interest in the forums.

Finally, if you would like to learn more about other community members' experiences, you can link to Our Stories.

I hope you find these tools useful as you navigate the site and begin your quest to gather more information.

Take care and be well!

Warmly,
Theresa
Theresa.J, MPH
ApoE4.info Support Team Intern
Functional Medicine Certified Health Coach
wwbok
Contributor
Contributor
Posts: 3
Joined: Fri Apr 22, 2022 4:03 pm

Re: New and not sure where to start

Post by wwbok »

Theresa.J wrote: Fri Apr 22, 2022 7:11 pm The wonderful news is that your father sounds like he is doing extremely well at age 75. Your openness to considering changes to your diet and other lifestyle factors as you gather more genetic information is a great starting point. There is much to explore and learn and you most certainly have time to make positive changes. Your curiosity and desire to learn will serve you well on your health journey.

[...]

Warmly,
Theresa
Hello Theresa! I'm Sarah, btw (I don' think I mentioned that, heh).

Thank you so much for the introduction and the helpful lists of posts/information.

I'm so glad to hear you say that there's still time for my dad to make even more positive and beneficial changes, especially since he's doing so well (he still walks a mile a day for exercise) so we can do everything possible to make sure "our genes are not our destiny."

My big takeaway from your message is that it sounds like it's never too late to start, even for someone at my dad's age?

Thank you so much,
Sarah
User avatar
AnnaM
Contributor
Contributor
Posts: 50
Joined: Fri Feb 04, 2022 7:01 am
Location: West Palm Beach, FL

Re: New and not sure where to start

Post by AnnaM »

Hi Sarah,
My name is Anna and I am also an intern here on the support team. It is not too late to start with the changes recommended in the Primer. In fact, Dr. Bredesen's recent studies show much promise for people following the lifestyle recommended there.
Here is the Chapter 5 section in the Primer that recommends the diet found to be so helpful, plus a few of the books that discuss healthful diets.Chapter 5
Your enthusiasm to learn and help your Dad is very heart-warming, and will continue the positive changes you have already started.
With my best,
AnnaM
Certified Functional Medicine Health Coach
wwbok
Contributor
Contributor
Posts: 3
Joined: Fri Apr 22, 2022 4:03 pm

Re: New and not sure where to start

Post by wwbok »

AnnaM wrote: Sat Apr 23, 2022 7:32 am Hi Sarah,
My name is Anna and I am also an intern here on the support team. It is not too late to start with the changes recommended in the Primer. In fact, Dr. Bredesen's recent studies show much promise for people following the lifestyle recommended there.
Here is the Chapter 5 section in the Primer that recommends the diet found to be so helpful, plus a few of the books that discuss healthful diets.Chapter 5
Your enthusiasm to learn and help your Dad is very heart-warming, and will continue the positive changes you have already started.
With my best,
AnnaM
Hello :) Thank you for the message and the links to the diet information. I'm glad that there's still time to make positive changes for my dad, given that he's showing no overt signs of anything right now (other than is normal for a 75 year old).

We're starting our new diet on Tuesday (the day after his 75th birthday) and a few of our supplements are arriving today.

Thank you again,
Sarah
NF52
Support Team
Support Team
Posts: 2772
Joined: Tue Oct 25, 2016 9:41 am
Location: Eastern U.S.

Re: New and not sure where to start

Post by NF52 »

wwbok wrote: Fri Apr 22, 2022 5:06 pm Hello everyone! I'm new here here!

Short version: I don't know what APOE status my dad and I are yet (I'm going to order 23andMe for both of us), but when looking through our raw DNA file from Ancestry.com, we both have the same DNMT3B gene polymorphism potentially associated with dementia and Parkinson's. My paternal grandfather and his fraternal twin brother, had these two conditions, respectively. I'm now terrified for my dad and myself. What diet and supplements can we start immediately, regardless of APOE status?

Long version:
My paternal grandfather and his fraternal twin brother had dementia and Parkinson's, respectively. My grandfather, the one with dementia, lived until he was 86 and was relatively fine the whole time. The only time he was diagnosed with dementia was after he had been in the nursing home for two years (he'd have trouble remembering what day it was, stumbling over his words, and things like that). He never had issues remembering who we were though. He died from acute kidney failure. He also had a stroke in his early 70s due to unchecked diabetes and blood pressure. His fraternal twin brother died when he was 80 from complications related to Parkinson's. Their older brother died from a heart attack at 88 (not sure if he ever had dementia); and their sister died at the age of 98 (not sure if she had dementia either; however, her son had sundowning syndrome).
...

My father and I have the TGG polymorphism mentioned in the article (technically, Ancestry is reporting a TAA/CGG, but I think we actually have the TGG if I look at Livewello and/or Promethease).

These studies are largely from 2014/2016, with a few updated articles, including one from 2020 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139499/) that states "At this moment, there are not appropriate and reliable epigenetic biomarkers for diagnosis, classification and disease progression..." referring to specific polymorphisms, but given that they specifically mention Parkinson's and dementia, I freaked out. Hardcore.

In fact, I'm terrified.

I'm so overwhelmed. I realize that I don't know our APOE status yet, but my own mental health "doom and gloom" says we'll both be 4/4.

Regardless of APOE status, I have no idea where to start on diet, supplements, etc. Is it too late to alter the course for my father if things are "building" in the background, even though he seems fine now? What should we be doing? We're both on board for fasting and any and all diet changes and supplements. What supplements and diet changes can we start immediately, regardless of APOE status? The Bredesen Protocol?

Thank you to everyone for reading my long (LONG) first post and I hope you're all well. <3
Welcome, Sarah!

You've done a great job researching and presenting a "case history" for your family--suggesting that high cognitive reserve is something shared between you and your dad. As someone with ApoE4/4 who also was terrified when I found that out 8 years ago, I know you can't simply wish that feeling away. You need hard info that supports an alternative view of you and your dad's future.

For some background, I am a member of a Research Participant Advisory Board with people like me who have been in clinical studies for prevention or treatment of Alzheimer's, along with researchers and study coordinators. Beyond seeing how many people are working really hard in this field, I have been able to have free access to several major conferences on Alzheimer's research (COVID forced conference presenters everywhere to switch on a dime to virtual and now "hybrid" conferences) with topics ranging from epidemiology to pathological processes to genetics to caregiving to expanding diversity and access to clinical trials, etc.

I looked at the 2014 article and noticed a few things that suggest it may not be generalizable to you or your dad.
First, the population was described as uniformly low-income people in a Brazilian city, with an average of 6 years of. education--far different than the environment or education you dad and you have had. Second, the authors acknowledge that these results are different than their own earlier research and may be due to environmental factors. (I added emphasis in this quote)
We have studied DNMT3B rs998382, rs2424932 and rs2424913, while a previous study conducted on an Italian sample focused on DNMT3B rs2424932 and rs1569686 [10]. In contrast to our results, no difference in allelic or genotypic frequencies was found for eitherpolymorphism between AD subjects and the healthy control group in this previous investigation [10]...it should be noted that AD has a complex inheritance pattern, which means that the individual is the product of the interaction between genetic inheritances and the environment they live in.
...Some genes may not predispose to disease per se, but rather act through interaction with specific environmental triggers.This...may explain why putative association studies of complex diseases sometimes cannot be replicated in different geographic areas
DNA methyltransferase haplotype is associated with Alzheimer’s disease

I have heard repeatedly in the last few years: "Alzheimer's is complicated" and "Nothing is more rare that "pure Alzheimer's". People over 80 tend to have a slow-progressing loss of abilities that may be caused by "classic" amyloid plaques and tau tangles, but are much more likely to also have cerebrovascular disease, with a history of strokes or TIA's or a history of unstable or poorly controlled high blood pressure. They are also more likely to have signs of other causes of dementia, including "senescent cells"--loss of neurons seen in aging, and possible history of brain injury or systemic inflammation or disease, like kidney disease. They might have signs of Parkinson's, which is a tauopathy and can occur with or without dementia.

Your paternal grandfather had a stoke in his early 70's with a history of diabetes and high blood pressure. Sounds like my dad, who died at age 67 with diabetes seven months after quadruple bypass. But he only knew he had heart disease at age 65, because few in the 1980's ever saw a cardiologist until they had a heart attack and the axiom for blood pressure was "Your age plus 100= a normal blood pressure". Yet none of his four children has any heart disease (or diabetes or high blood pressure) and have lived beyond what he reached.

Since your grandfather was cognitively fine into his 80's, it's likely he vascular issues and damage from his kidney disease that led to his cognition changing. That's not your dad, thanks to his herculean weight loss success and his current great A1C, and not you!

Your grandfather's fraternal twin and his other siblings did not give you any DNA directly--and your grandfather gave you as most 25%. That's why my husband's fraternal twin brothers look nothing alike; one is 6'5" while the other one is 5'10--they don't each have the same grandfather's genes!

Your dad sounds like he'd breeze through the cognitive tests that I have taken as a clinical participant in studies of people with ApoE 4/4 and normal cognition ages 65-80 (and there are lots of us!). Here's a brief excerpt from a 2022 article on the benefit of both education and occupation in reducing risk of dementia, using an international database of over 10,000 participants with a median baseline age of 74:
The meta-analytic results indicated that both education and occupational complexity were independently associated with increased dementia-free survival time, with 28% of the effect of education mediated by occupational complexity.
Education, occupational complexity, and incident dementia: A COSMIC collaborative cohort study

What you can say about your grandfather's family is that they must have had some longevity genes to be born in an era with air and water pollution, coal-fired heating in homes, carcinogens in smoked foods, no vaccines for measles, flu, whooping cough and polio, and yet most lived into their 80's and 90's! (BTW, your great aunt's son with sundowning is likely to have only about 2% of shared DNA with you, from looking at my family's results on 23&me's DNA relatives list.) So plan to have decades of life to enjoy--along with the time to make changes thoughtfully!

You know yourself well, Sarah, so be kind to yourself. If you think that taking that 23&me test will send you into a tailspin, why not just decide to skip it and live with the lifestyle recommendations that make sense for all of us, with or without ApoE4. I don't follow the same diet as my vegan 4/4 friends, or play competitive bridge and golf like another 4/4 friend, and I don't expect to ever handle the financial business for a community nonprofit, like another--because we're all more different than we are alike! I do know that many of us felt adrift and angry for a while, and found solace in learning more and in spending time with people who made us laugh and focus on others. And we asked for help from counselors or tai-chi or meditation or white-water rafting--whatever it takes to feel empowered and strong.

Stay strong, and enjoy your smart, wonderful dad.

Hugs from a 4/4 woman.
4/4 and still an optimist!
Post Reply