Hello,
Well, it's been 5 days since I found out I'm 4/4. I bought and read Dr. Bredesen's book, been buying supplements like a crazy man (Amazon Prime is really paying off) and now I have a few more questions.
1. Are there testimonials from 4/4s that have made it through the 75 and 85 hoops? I'd like to have a more concrete hope that my ending up a mindless mass of cytoplasm, is not relegated to little more than a coin toss.
1.a. Are there age related data on 4/4s cognitive impairment? In other words, what % have SCI at 60, 65, 70, 75, 80?
2. The number of conflicting study outcomes and conclusions is mind boggling! One study says do this and another one says do that. Is there a list of studies that have been vetted by the members on this site? Or some other reliable source?
3. Regarding #2, are Dr Bredesen's theories and protocols considered peer approved/agreed and cutting edge? Are there other reads I should be doing?
4. All told, there are a huge number of supplements recommended. One, are the interactions considered safe? Two, are there supplements that combine many ingredients into one capsule for ease of use. Currently, my supplements are beating my spice rack in shear numbers alone.
5. What are members experience with Medicare paying for the recommended "Cognoscopy"?
6. Am I reading right that I should stop my Omega 6 Flax seed oil cuz Omega 6 is inflammatory?!?
7. Here are a few sites I found useful in my quest for knowledge. Healthy foods with nutritional values, http://www.whfoods.com/index.php ; Articles on cognitive health, https://www.alzdiscovery.org/cognitive-vitality ; More info on diet, research and explanations, https://www.geneticlifehacks.com/mthfr/ .
Be strong and carry on....
Steven
Still new and digesting 4/4>>> questions
Re: Still new and digesting 4/4>>> questions
Hi Steven, and welcome. I read your other recent posts and remember what it was like finding out the news. You're asking good questions. I might be able to help with a few of them.
There are some 4/4s around here that are doing well at various ages. Not all 4/4s end up with AD. There are some sources of statistical data. As you suggest, the odds at broken down by age. You'll find that the odds are sometimes listed as percentages, odds ratios, hazard ratios, etc. It's hard to combine all of them into a "gut feeling" for risk. But I've come to accept a rule of thumb that in the past about half of 4/4's have had some cognitive decline, esp if they live long enough. However, that was in the past. Even the most basic health advances we as a society have adopted in recent decades should reduce this risk some. Also, the most recent studies of lifestyle programs seems to indicate that generally healthy diets, exercise, sleep, and stress reduction reduce the risk for 4/4s by about 1/3rd, on average, for the study populations. The greatest risk reductions seem to be by going from poor lifestyles to generally healthy, with some (but less) impact from becoming "very" healthy. This reduced risk significantly but did not quite get the risk for healthy 4/4s to the levels of 3/3s. That's probably about as much as we can reasonably read into the data.
Yep, the studies offer different conclusions and recommendations. Part of the reason is certainly that everyone is different, with different health risks, and will benefit from different interventions. Like D. Bredesen's different sub-types of AD would be treated differently. Part of the process is trying different approaches to see how they work for you. A doctor - maybe a functional medicine doctor - can help. Or you can get blood tests and interpret them more or less on your own. We all find our own winding paths.
D. Bredesen's studies have been published in peer-reviewed journals. The first was a small case study of 10 individuals. Followed later by one with 100 individuals. The field wanted larger clinical studies, of course. And obtaining the funding was frustrating for him. But more recent lifestyle studies have more or less demonstrated that the types of interventions he suggested do indeed reduce risk and even the larger organizations are starting to come around. You'll find some criticism. After all, you have to expect some if the title of your book is "The End of Alzheimer's". But his work and the work of others seems to show that being healthy and fixing health problems makes us.....er......healthier.....anyway it seems to protect our cognition and lower risk, or delay cognitive decline....to a modest degree. That's my interpretation, anyway.
Yes, the number of supplements mentioned is large. But not all patients were on all of them. In D. Bredesen's study the supplements and other health interventions were personalized based on a large amount of testing up front.
I don't know about Medicare paying for a cognoscopy. I have learned, however, that even a general practioner has a lot of flexibility in ordering tests. So the basic tests can be obtained with the help of an understanding family doctor. Other are harder to get, unless you negotiate it with the insurance companies or just pay for them out of pocket. You could make the argument that a couple thousand dollars for a full work up is cheaper than a few months in a memory care facility....but that's if you have the funds handy.
On the fats. I'm a little rusty on this now. But it is the balance of omega-3 and omega-6 fats that is the key. The standard american diet is high in 6's and, hence, pro-inflammatory. 6's are converted into pro-inflammatory mediators, mostly. 3's are anti-inflammatory because they are (mostly) converted into resolvins, which reduce inflammation. But I recall flax being quite good in terms of the 3 / 6 ratio. I used to experiment with flax seed recipes to maximize my intake. Getting this balance into the healthy range actually takes some doing....the cronometer.com food calculator with help you see where you are with this balance. You can also check your inflammation markers to see if this is a problem for you and determine how serious you want to be about balancing these fats.
Hope this helps!
There are some 4/4s around here that are doing well at various ages. Not all 4/4s end up with AD. There are some sources of statistical data. As you suggest, the odds at broken down by age. You'll find that the odds are sometimes listed as percentages, odds ratios, hazard ratios, etc. It's hard to combine all of them into a "gut feeling" for risk. But I've come to accept a rule of thumb that in the past about half of 4/4's have had some cognitive decline, esp if they live long enough. However, that was in the past. Even the most basic health advances we as a society have adopted in recent decades should reduce this risk some. Also, the most recent studies of lifestyle programs seems to indicate that generally healthy diets, exercise, sleep, and stress reduction reduce the risk for 4/4s by about 1/3rd, on average, for the study populations. The greatest risk reductions seem to be by going from poor lifestyles to generally healthy, with some (but less) impact from becoming "very" healthy. This reduced risk significantly but did not quite get the risk for healthy 4/4s to the levels of 3/3s. That's probably about as much as we can reasonably read into the data.
Yep, the studies offer different conclusions and recommendations. Part of the reason is certainly that everyone is different, with different health risks, and will benefit from different interventions. Like D. Bredesen's different sub-types of AD would be treated differently. Part of the process is trying different approaches to see how they work for you. A doctor - maybe a functional medicine doctor - can help. Or you can get blood tests and interpret them more or less on your own. We all find our own winding paths.
D. Bredesen's studies have been published in peer-reviewed journals. The first was a small case study of 10 individuals. Followed later by one with 100 individuals. The field wanted larger clinical studies, of course. And obtaining the funding was frustrating for him. But more recent lifestyle studies have more or less demonstrated that the types of interventions he suggested do indeed reduce risk and even the larger organizations are starting to come around. You'll find some criticism. After all, you have to expect some if the title of your book is "The End of Alzheimer's". But his work and the work of others seems to show that being healthy and fixing health problems makes us.....er......healthier.....anyway it seems to protect our cognition and lower risk, or delay cognitive decline....to a modest degree. That's my interpretation, anyway.
Yes, the number of supplements mentioned is large. But not all patients were on all of them. In D. Bredesen's study the supplements and other health interventions were personalized based on a large amount of testing up front.
I don't know about Medicare paying for a cognoscopy. I have learned, however, that even a general practioner has a lot of flexibility in ordering tests. So the basic tests can be obtained with the help of an understanding family doctor. Other are harder to get, unless you negotiate it with the insurance companies or just pay for them out of pocket. You could make the argument that a couple thousand dollars for a full work up is cheaper than a few months in a memory care facility....but that's if you have the funds handy.
On the fats. I'm a little rusty on this now. But it is the balance of omega-3 and omega-6 fats that is the key. The standard american diet is high in 6's and, hence, pro-inflammatory. 6's are converted into pro-inflammatory mediators, mostly. 3's are anti-inflammatory because they are (mostly) converted into resolvins, which reduce inflammation. But I recall flax being quite good in terms of the 3 / 6 ratio. I used to experiment with flax seed recipes to maximize my intake. Getting this balance into the healthy range actually takes some doing....the cronometer.com food calculator with help you see where you are with this balance. You can also check your inflammation markers to see if this is a problem for you and determine how serious you want to be about balancing these fats.
Hope this helps!
Re: Still new and digesting 4/4>>> questions
Maybe. Omega -6's are important but they do tend to be more prevalent in today's diet and they compete for the same conversion enzymes. We have a wiki on the subject. Fats, Omega -3(ω-3) & -6(ω-6), DHA and More?IForgot wrote:6. Am I reading right that I should stop my Omega 6 Flax seed oil cuz Omega 6 is inflammatory?!?
We have lots of information for APOEe4s on this site, have you found the PRIMER: An introduction to ApoE4, biochemistry, and possible prevention strategies
There's also lots of info in our Wiki including a good starting point "How-To" Get the most out of the ApoE4.info website. That particular subheading will instruct you how to search the site and maybe answer some of your questions.
-Theresa
ApoE 4/4
ApoE 4/4
Re: Still new and digesting 4/4>>> questions
Hi Fiver,Fiver wrote:Hi Steven, and welcome. I read your other recent posts and remember what it was like finding out the news. You're asking good questions. I might be able to help with a few of them.
There are some 4/4s around here that are doing well at various ages. Not all 4/4s end up with AD. There are some sources of statistical data. As you suggest, the odds at broken down by age. You'll find that the odds are sometimes listed as percentages, odds ratios, hazard ratios, etc. It's hard to combine all of them into a "gut feeling" for risk. But I've come to accept a rule of thumb that in the past about half of 4/4's have had some cognitive decline, esp if they live long enough. However, that was in the past. Even the most basic health advances we as a society have adopted in recent decades should reduce this risk some. Also, the most recent studies of lifestyle programs seems to indicate that generally healthy diets, exercise, sleep, and stress reduction reduce the risk for 4/4s by about 1/3rd, on average, for the study populations. The greatest risk reductions seem to be by going from poor lifestyles to generally healthy, with some (but less) impact from becoming "very" healthy. This reduced risk significantly but did not quite get the risk for healthy 4/4s to the levels of 3/3s. That's probably about as much as we can reasonably read into the data.
Yep, the studies offer different conclusions and recommendations. Part of the reason is certainly that everyone is different, with different health risks, and will benefit from different interventions. Like D. Bredesen's different sub-types of AD would be treated differently. Part of the process is trying different approaches to see how they work for you. A doctor - maybe a functional medicine doctor - can help. Or you can get blood tests and interpret them more or less on your own. We all find our own winding paths.
D. Bredesen's studies have been published in peer-reviewed journals. The first was a small case study of 10 individuals. Followed later by one with 100 individuals. The field wanted larger clinical studies, of course. And obtaining the funding was frustrating for him. But more recent lifestyle studies have more or less demonstrated that the types of interventions he suggested do indeed reduce risk and even the larger organizations are starting to come around. You'll find some criticism. After all, you have to expect some if the title of your book is "The End of Alzheimer's". But his work and the work of others seems to show that being healthy and fixing health problems makes us.....er......healthier.....anyway it seems to protect our cognition and lower risk, or delay cognitive decline....to a modest degree. That's my interpretation, anyway.
Yes, the number of supplements mentioned is large. But not all patients were on all of them. In D. Bredesen's study the supplements and other health interventions were personalized based on a large amount of testing up front.
I don't know about Medicare paying for a cognoscopy. I have learned, however, that even a general practioner has a lot of flexibility in ordering tests. So the basic tests can be obtained with the help of an understanding family doctor. Other are harder to get, unless you negotiate it with the insurance companies or just pay for them out of pocket. You could make the argument that a couple thousand dollars for a full work up is cheaper than a few months in a memory care facility....but that's if you have the funds handy.
On the fats. I'm a little rusty on this now. But it is the balance of omega-3 and omega-6 fats that is the key. The standard american diet is high in 6's and, hence, pro-inflammatory. 6's are converted into pro-inflammatory mediators, mostly. 3's are anti-inflammatory because they are (mostly) converted into resolvins, which reduce inflammation. But I recall flax being quite good in terms of the 3 / 6 ratio. I used to experiment with flax seed recipes to maximize my intake. Getting this balance into the healthy range actually takes some doing....the cronometer.com food calculator with help you see where you are with this balance. You can also check your inflammation markers to see if this is a problem for you and determine how serious you want to be about balancing these fats.
Hope this helps!
Thank you for taking the time to write this comprehensive response. I'll sort out the tests with my GP. Once I have the results, I have to start figuring out which levers to pull. Some are fairly obvious, for example, Homo-cysteine. Others, like DHEA sulfate, not so much. Also, I'd like to get my nutrients from food sources as opposed to bottles.
Thanks,
Steven
Last edited by IForgot on Fri Aug 02, 2019 6:23 pm, edited 2 times in total.
Re: Still new and digesting 4/4>>> questions
Hello Theresa,TheresaB wrote:Maybe. Omega -6's are important but they do tend to be more prevalent in today's diet and they compete for the same conversion enzymes. We have a wiki on the subject. Fats, Omega -3(ω-3) & -6(ω-6), DHA and More?IForgot wrote:6. Am I reading right that I should stop my Omega 6 Flax seed oil cuz Omega 6 is inflammatory?!?
We have lots of information for APOEe4s on this site, have you found the PRIMER: An introduction to ApoE4, biochemistry, and possible prevention strategies
There's also lots of info in our Wiki including a good starting point "How-To" Get the most out of the ApoE4.info website. That particular subheading will instruct you how to search the site and maybe answer some of your questions.
Thank you for the helpful info. Yes, I've read the primer 2x. It's very good but can't answer everything. And I have looked at how to get the most out of this site. I may still need some practice on the search function, as I did not find answers to the questions I was asking.
Regards,
Steven
Re: Still new and digesting 4/4>>> questions
Dear Steven,
You're running very fast and I would suggest you slow down a bit. I am now 79 and luckily have known my 4/4 status for a number of years. So far everything is good for me and I started slowly with meditation, gradually added supplements, have always been active and so forth. But what I'm experiencing is the currently rapid explosion of info that was not available just a short time ago. I am thinking the future few years will bring a great deal of new research into how we master our cognition. So my words of wisdom are to slow down, take some deep breaths often, enjoy whatever you can in your daily life and slowly and steadily adjust your lifestyle based on your information gathering and listening to your body.
You're running very fast and I would suggest you slow down a bit. I am now 79 and luckily have known my 4/4 status for a number of years. So far everything is good for me and I started slowly with meditation, gradually added supplements, have always been active and so forth. But what I'm experiencing is the currently rapid explosion of info that was not available just a short time ago. I am thinking the future few years will bring a great deal of new research into how we master our cognition. So my words of wisdom are to slow down, take some deep breaths often, enjoy whatever you can in your daily life and slowly and steadily adjust your lifestyle based on your information gathering and listening to your body.
Re: Still new and digesting 4/4>>> questions
Hello rrmolo,rrmolo wrote:Dear Steven,
You're running very fast and I would suggest you slow down a bit. I am now 79 and luckily have known my 4/4 status for a number of years. So far everything is good for me and I started slowly with meditation, gradually added supplements, have always been active and so forth. But what I'm experiencing is the currently rapid explosion of info that was not available just a short time ago. I am thinking the future few years will bring a great deal of new research into how we master our cognition. So my words of wisdom are to slow down, take some deep breaths often, enjoy whatever you can in your daily life and slowly and steadily adjust your lifestyle based on your information gathering and listening to your body.
Thank you for your input. Me and slow have never been in the same sentence. I'm active and have a generally healthy life style.(BMI=23) To be honest, finding out I inherited 4/4 was quite unexpected and rather like getting a diagnosis of cancer. That said, I'm past that stage and taking steps to hone my "healthiness" to the next level.
Best regards,
Steven
Re: Still new and digesting 4/4>>> questions
Hi again, Steven!IForgot wrote:Hello,
Well, it's been 5 days since I found out I'm 4/4. I bought and read Dr. Bredesen's book, been buying supplements like a crazy man (Amazon Prime is really paying off) and now I have a few more questions.
1. Are there testimonials from 4/4s that have made it through the 75 and 85 hoops? I'd like to have a more concrete hope that my ending up a mindless mass of cytoplasm, is not relegated to little more than a coin toss.
1.a. Are there age related data on 4/4s cognitive impairment? In other words, what % have SCI at 60, 65, 70, 75, 80?
2. The number of conflicting study outcomes and conclusions is mind boggling! One study says do this and another one says do that. Is there a list of studies that have been vetted by the members on this site? Or some other reliable source?
...5. What are members experience with Medicare paying for the recommended "Cognoscopy"?...
Be strong and carry on....
Steven
Here's some hopeful news for your fast-paced neurons: anyone who can joke about himself and Amazon Prime in the same sentence has some fine functional brain connectivity--and a dose of self-deprecation that helps to sort the more from less reliable sources. Second, anyone who is planning a journey to not end up with a "mindless mass of cytoplasm" is at about the top 3% of the public in language skills (I used to test kids as part of my job; trust me on this one.) That's called "cognitive reserve" which provides you with a deep bench and a great offense/defense team of resistance/resilience to the effects of ApoE 4.
Here's a couple of articles talking about that with selected quotes (emphasis added by me). The first is from June 2019 and references a very recent model of a new tau-related subtype of AD, seen possible more in men, with the acronym "LATE", which does not appear to be associated with ApoE 4, from the little I've read.
Resistance and resilience to Alzheimer’s disease pathology are associated with reduced cortical pTau and absence of limbic-predominant age-related TDP-43 encephalopathy in a community-based cohortLimbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) was robustly associated with clinical dementia and was more prevalent in cases with high pTau burden, supporting the notion that resilience to ADNC may depend, in part, on resistance to pTDP-43 pathology.Therefore, what appears to be cognitive resilience to ADNC may, in part, be due to resistance to developing comorbid neuropathologies. Mechanisms underlying these processes are unknown, but some studies have identified relationships of resilience and resistance to ADNC with systemic exposures and disorders including smoking, cardiovascular disease, diabetes, and medication history [50, 56], as well as lifetime experiences [15, 24, 28, 44, 72, 75, 89], such as educational level, occupation, intelligence, degree of involvement in socially, physically, and cognitively stimulating activities, socioeconomic status, and early life environment.
Note: This study also illustrates a few things to look for when judging quality:
* in general, a population or community-based study will have more typical distribution of risk than a "convenience sample" or case-control study in which people who self-referred to a memory clinic were assessed for risk. Here's an explanation of why that might be, from a study quoted below:
APOE-related risk of mild cognitive impairment and dementia for prevention trials: An analysis of four cohortsWhile higher education is associated with lower risk of dementia overall, more educated individuals with memory concerns actually have higher risk of developing dementia than their counterparts with less education [59], and this may be particularly true for the highly educated individuals who form a substantial fraction of the NACC cohort...Thus, baseline cognitive symptoms and preexisting subthreshold decline, both likely to be more frequent in the highly educated NACC cohort, have a substantial impact on short-term onset of MCI and even dementia. This phenomenon may underlie the higher risk of cognitive decline noted earlier for more versus less educated individuals among those with subjective cognitive concerns
In other words, people with a high education level can often "coast" for a long period of time with some level of cognitive changes which don't change their MOCA score but which do cause them subjective concern. Since studies often skew high on average achievement levels (with 14-16 years of education typical), the people who sign up may have underlying concerns that seem to show a lower age of MCI and AD than would be seen in population-based study.
* A study that combines imaging (MRI/ PET) and/or autopsy studies with in-depth neuro-psychological assessment using multiple measures of cognition and behavior is likely to have more accurate diagnoses of true Alzheimer's than one that used primary care doctors' assessment using a MOCA or other brief assessment, or diagnoses from decades ago which have been estimated to have error rates of up to 30%.
* Study authors affiliated with a major AD research university may be more likely to be building on previous accepted research, using computer modeling, statistics and genetically-bred mice that have been documented to closely parallel specific traits (ex. ApoE 4 mice, tau-mice, mice that developed AD-like spatial and memory loss, etc.) than those who do not specify their methodology clearly.
And here's another type of study, a meta-analysis, which can either be well-designed (I'm biased to think this one is, as a former participant in the recently ended Generations Trial) or may be simply a collection of small, poorly designed studies showing "garbage in; garbage out." This one is easy-to read, and addresses your question 1a. It points out that short-term risk varies hugely based on the selection of participants. The short-term risk of a diagnosis of AD is far higher for people who self-refer for a comprehensive memory assessment study than it is for a group of people who are being followed for the Framingham Heart Study, for example.
Here's the chart of that info:Short-term risk is more subject to variability due to details of how a particular study is conducted than longer-term risk.... Five-year incidence of MCI/dementia was higher in the highest age stratum, particularly among APOE-e4/e4 homozygote individuals (38% in NACC and 18%–23% in Framingham and Rotterdam). Five-year incidence of dementia alone was negligible at younger ages[60-65], even in APOE-e4/e4 homozygote individuals, but rose among older individuals [ages 70-75], particularly among those with APOE-e4/e4 (12% in NACC and 7%–12% in Framingham and Rotterdam)...These pooled estimates..[rose] to a high of 26.70% for individuals aged 70–75 y with two copies of APOE-e4/e4 in all four cohorts. APOE-related risk of mild cognitive impairment and dementia for prevention trials: An analysis of four cohorts
Cumulative incidence curves, adjusting for competing risk of mortality, for dementia by baseline age and APOE-e4 dose.
And as for Question 5: It depends--on your Medicare plan, your doctor and your reported symptoms. You can probably get a full assessment for a regional Memory Assessment Clinic with "subjective complaints", although if they are subtle, the results may not tell you much. You may be able to get some of the recommended blood test in the Primer from your primary care doctor, including insulin resistance, homocysteine, a comprehensive lipid panel, Vitamin B-12, and D3, thyroid, etc. Other tests may not cost too much using direct-to consumer testing. Here's our Wiki on that Direct to Consumer Lab Testing Options
Even with a turbo-charged brain, rrmolo's advice is wise; in spite of disappointing clinical trials; basic research is also turbo-charged and focusing on what you can control (and improve) while watching the science improve is a good plan!
4/4 and still an optimist!
Re: Still new and digesting 4/4>>> questions
Hello NF52,NF52 wrote:
Here's a couple of articles talking about that with selected quotes (emphasis added by me). The first is from June 2019 and references a very recent model of a new tau-related subtype of AD, seen possible more in men, with the acronym "LATE", which does not appear to be associated with ApoE 4, from the little I've read.
In other words, people with a high education level can often "coast" for a long period of time with some level of cognitive changes which don't change their MOCA score but which do cause them subjective concern. Since studies often skew high on average achievement levels (with 14-16 years of education typical), the people who sign up may have underlying concerns that seem to show a lower age of MCI and AD than would be seen in population-based study.
And here's another type of study, a meta-analysis, which can either be well-designed (I'm biased to think this one is, as a former participant in the recently ended Generations Trial) or may be simply a collection of small, poorly designed studies showing "garbage in; garbage out." This one is easy-to read, and addresses your question 1a. It points out that short-term risk varies hugely based on the selection of participants. The short-term risk of a diagnosis of AD is far higher for people who self-refer for a comprehensive memory assessment study than it is for a group of people who are being followed for the Framingham Heart Study, for example.
Even with a turbo-charged brain, rrmolo's advice is wise; in spite of disappointing clinical trials; basic research is also turbo-charged and focusing on what you can control (and improve) while watching the science improve is a good plan!
Thank you again for yet another very thorough response. Based on the referenced data, It looks like the slope definitely changes at 70 and not in a good direction.
I definitely agree with comments that sample population need to be carefully screened for comorbidity that affects cognitive decline.
Also agree that the pace of discovery, ergo potential solutions, has definitely picked up. Gene therapy efforts, in particular, are very exciting.
Best regards,
Steven
Re: Still new and digesting 4/4>>> questions
Take a look here and see if anything is relevant for you: https://synapsevibe.com/are there supplements that combine many ingredients into one capsule for ease of use.
Also:
https://optimallivingdynamics.lpages.co/optimal-brain/
e3/4 MTHFR C677T/A1298C COMT V158M++ COMT H62H++ MTRR A66G ++ HLA DR
