Whole Foods Plant Based Diet/Lifestyle Leads to MCI Improvement

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Plumster
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Whole Foods Plant Based Diet/Lifestyle Leads to MCI Improvement

Post by Plumster »

Small study and possibility of placebo effect, but objective biomarkers confirm the MCI improvement. Research led by Rudolph Tanzi and Dean Ornish.
Effects of intensive lifestyle changes on the progression of mild cognitive impairment or early dementia due to Alzheimer’s disease: a randomized, controlled clinical trial

Dean Ornish, Catherine Madison, Miia Kivipelto, Colleen Kemp, Charles E. McCulloch, Douglas Galasko, Jon Artz, Dorene Rentz, Jue Lin, Kim Norman, Anne Ornish, Sarah Tranter, Nancy DeLamarter, Noel Wingers, Carra Richling, Rima Kaddurah-Daouk, Rob Knight, Daniel McDonald, Lucas Patel, Eric Verdin, Rudolph E. Tanzi & Steven E. Arnold

Alzheimer's Research & Therapy volume 16, Article number: 122 (2024)

Abstract
Evidence links lifestyle factors with Alzheimer’s disease (AD). We report the first randomized, controlled clinical trial to determine if intensive lifestyle changes may beneficially affect the progression of mild cognitive impairment (MCI) or early dementia due to AD.

Methods
A 1:1 multicenter randomized controlled phase 2 trial, ages 45-90 with MCI or early dementia due to AD and a Montreal Cognitive Assessment (MoCA) score of 18 or higher. The primary outcome measures were changes in cognition and function tests: Clinical Global Impression of Change (CGIC), Alzheimer’s Disease Assessment Scale (ADAS-Cog), Clinical Dementia Rating–Sum of Boxes (CDR-SB), and Clinical Dementia Rating Global (CDR-G) after 20 weeks of an intensive multidomain lifestyle intervention compared to a wait-list usual care control group. ADAS-Cog, CDR-SB, and CDR-Global scales were compared using a Mann-Whitney-Wilcoxon rank-sum test, and CGIC was compared using Fisher’s exact test. Secondary outcomes included plasma Aβ42/40 ratio, other biomarkers, and correlating lifestyle with the degree of change in these measures.

Results
Fifty-one AD patients enrolled, mean age 73.5. No significant differences in any measures at baseline. Only two patients withdrew. All patients had plasma Aβ42/40 ratios <0.0672 at baseline, strongly supporting AD diagnosis. After 20 weeks, significant between-group differences in the CGIC (p= 0.001), CDR-SB (p= 0.032), and CDR Global (p= 0.037) tests and borderline significance in the ADAS-Cog test (p= 0.053). CGIC, CDR Global, and ADAS-Cog showed improvement in cognition and function and CDR-SB showed significantly less progression, compared to the control group which worsened in all four measures. Aβ42/40 ratio increased in the intervention group and decreased in the control group (p = 0.003). There was a significant correlation between lifestyle and both cognitive function and the plasma Aβ42/40 ratio. The microbiome improved only in the intervention group (p <0.0001).

Conclusions
Comprehensive lifestyle changes may significantly improve cognition and function after 20 weeks in many patients with MCI or early dementia due to AD.
Open access: https://alzres.biomedcentral.com/articl ... 24-01482-z
Last edited by Plumster on Sat Jun 08, 2024 4:02 am, edited 1 time in total.
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Quantifier
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Re: Whole Foods Plant Based Diet/Lifestyle Changes Leads to MCI Improvement

Post by Quantifier »

I just read the paper. It is so exciting that improvements are possible with a diet that differs in composition from what Dale Bredesen recommends - it seems to me that overall diet quality is more important than a specific ratio of macronutrients.

One caveat is that the researchers worked hard to make compliance to their parameters easy - they sent meals and supplements to the participants, they spent 12 weekly hours in zoom calls for exercise, stress management, support group, and lectures on healthy lifestyle. I expect that people doing it on their own would be somewhat less successful. We need a scaled up support system for introducing and maintaining this kind of lifestyle change.
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Re: Whole Foods Plant Based Diet/Lifestyle Leads to MCI Improvement

Post by Plumster »

Press release from the Preventative Medicine Research Center:

https://www.prnewswire.com/news-release ... 66826.html
Many patients who experienced improvement reported regaining lost cognition and function. For example, several patients in the intervention group reported that they had been unable to read a book or watch a movie because they kept forgetting what they had just read or viewed and had to keep starting over, but now they were able to do so and retain most of this information. One individual reported that it used to take him weeks to finish reading a book, but after participating in the study he was able to do so in only three or four days and was able to remember most of what he read.

A former business executive reported regaining the ability to manage his own finances and investments. "It was so much a part of my life — who I am, and who I was — it was hard saying that part of me was just gone," he said. "I'm back to reconciling our finances monthly; I keep up to date on our investments. A lot of self-worth comes back."

A woman said that for five years she had been unable to prepare their family business financial reports, but now she is able to do so accurately. "A deep sense of identity is returning. It's given me a new lease on life, and yet it's a familiarity and something I've always prided myself on. I'm coming back like I was prior to the disease being diagnosed. I feel like I'm me again — an older but better version of me."

There was a statistically significant dose-response correlation between the degree of lifestyle changes in both groups and the degree of change in most measures of cognition and function testing. In short, the more these patients changed their lifestyle in the prescribed ways, the greater was the beneficial impact on their cognition and function.

This dose-response correlation adds to the biological plausibility of these findings and may help to explain, in part, why some patients in the intervention group improved and others did not (although other mechanisms may also play a role). Other studies have shown that more moderate lifestyle changes such as adopting the Mediterranean diet may slow the rate of progression (worsening) of Alzheimer's disease but may not go far enough to improve cognition and function.

In addition to improvements in cognition and function, the intervention group also demonstrated significant improvements in several key blood-based biomarkers. One of the most clinically relevant biomarkers is called the Aβ42/40 ratio, which is a measure of amyloid, thought to be an important mechanism in Alzheimer's disease. This measure improved in the lifestyle intervention group (with the presumption that this improvement reflected amyloid moving out of the brain and into the blood), but it worsened in the randomized control group, and these differences were statistically significant (p = 0.003).

There was also a statistically significant dose-response correlation between the degree of lifestyle change and the degree of improvement in this amyloid ratio (p = 0.035). This direction of change in amyloid was also a major finding with lecanemab, a drug approved for treating Alzheimer's disease last year.

Also, the gut microbiome in the intervention group showed a significant decrease in organisms that raise the risk of Alzheimer's disease and an increase in organisms that are protective against Alzheimer's disease. These biomarker and gut microbiome results also add to the biological plausibility of the overall findings.

According to renowned Alzheimer's scientist Miia Kivipelto, M.D., Ph.D., "These findings add to the growing body of evidence that moderate multimodal lifestyle changes may help prevent Alzheimer's disease or slow its progression, and also suggest that more intensive multimodal lifestyle changes may have additional benefits for improving cognition in patients with early Alzheimer's disease."
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Re: Whole Foods Plant Based Diet/Lifestyle Leads to MCI Improvement

Post by JD2020 »

I found the 1 hour per day for stress management interesting. I manage 30 minutes... I remember when we were raising the children. I would have come unglued if anyone had suggested that I should find 10 minutes available to meditate.
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Re: Whole Foods Plant Based Diet/Lifestyle Leads to MCI Improvement

Post by rubyd0g 3/4 »

I am trying to find an appropriate diet for my family, 4 sisters which all have APOE3/4 and one with 4/4. Our children are testing and one so far is a 4/4. My mother and grandmother died of Alzheimers. I read this article and many others on dietary interventions. ( I have stacks of research from PUBMed and Clinical Trials.gov)) I am not clear what the meals in this trial contained ( high polyphenol olive oils, crucifers, walnuts, mushrooms?). The problem I have is that most of the lifestyle and diets that have been evaluated in clinical trials are not defined clearly. When it is called a Modified Mediterranean - is it the olive oil, coffee and Omega 3 fish, etc. that are driving the outcome. Was there a caloric/energy max on the daily intake or some fasting. There are so many variables. If the composition is not measured for macros and micronutrients nor is clear on what supplements are included, how can we understand what is the causative factor?
I am new to this, but I have just buried my young daughter who died from breast cancer. I was used to big pharm and clinical trials where everything was measured and no deviations from protocols are allowed. We did multiple lifestyle interventions as well, including a modified keto diet for cancer, daily runs, yoga, etc. But both myself and my daughter understood that these were also therapy/medicine.
There clearly is no pharm available for women APOE4 carriers now and may not be for awhile. None of the amyloid targets appear to have any benefit without high risks for us. Lifestyle interventions and diet will be our therapy, our IV's, our pills. It is not a diet as such. It is our medicine. It is no more optional than chemo was for my child, or insulin is for a diabetic. There is a choice always involving a benefit /risk decision with any therapy. But you have to make that decision with eyes open. We need to understand the science of diet, exercise, sleep, etc. This is not easy without the assistance of multiple experts in many fields. Our regular doctors know very little about this kind of treatment, even the neurologist at the "memory clinic" suggested nothing for intervention. They will not even order the testing that can assist in making a determination on what should be the primary focus of therapy, ie, insulin resistance, lipid metabolism, inflammation, cardiovascular issues, etc. It is not APPROVED by the FDA or insurance will not cover. It is not the gold standard. I am searching for a protocol that helps with this, particularly for APOE4.
I started with the Bredessen protocol as it made sense, but my sister (4/4) immediately complained about the high fat content and said she was going to do an easier Mediterranean diet and maybe could sneak a glass of wine in. I could not insist that her brain might need ketones to survive as I really didn't know the metrics of her brain metabolism; if she had insufficient glucose for energy as we didn't have a PET scan. I couldn't insist that we needed to focus on her brain's hyperlipidemia as I don't know what her lipid/cholesterol levels are in her brain or CSF. I am plodding along as best I can with Bresdesen general plan though not perfect and adapt as needed. It isn't the easiest and is very time consuming. I am hoping it will get easier. (When I make my "bullet coffee" in the morning, I have researched the coffee/ie. caffeine, found a very high polyphenol (1700-2000) olive oil; with a high monounsaturated fat macadamia nut creamer, organic vanilla and cinnamon- all measured and macros figured with Cronometer and I have done basic research on what effect this has on brain) I check my glucose and my ketones daily.
I am searching clinical trials regularly for dietary interventions or a magic bullet. The more I read particularly about the APOE4 gene and its influence on almost everything, the more I believe that the diet needs to focus primarily glucose and lipid metabolism in the brain. I would appreciate any thoughts on how do do this. thank you..
Pam, 76- 3/4
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Re: Whole Foods Plant Based Diet/Lifestyle Leads to MCI Improvement

Post by Lyre Taylor »

rubyd0g 3/4 wrote: Thu Jun 13, 2024 5:08 pm I am trying to find an appropriate diet for my family, 4 sisters which all have APOE3/4 and one with 4/4. Our children are testing and one so far is a 4/4. My mother and grandmother died of Alzheimers. I read this article and many others on dietary interventions. ( I have stacks of research from PUBMed and Clinical Trials.gov)) I am not clear what the meals in this trial contained ( high polyphenol olive oils, crucifers, walnuts, mushrooms?). The problem I have is that most of the lifestyle and diets that have been evaluated in clinical trials are not defined clearly. When it is called a Modified Mediterranean - is it the olive oil, coffee and Omega 3 fish, etc. that are driving the outcome. Was there a caloric/energy max on the daily intake or some fasting. There are so many variables. If the composition is not measured for macros and micronutrients nor is clear on what supplements are included, how can we understand what is the causative factor?
I am new to this, but I have just buried my young daughter who died from breast cancer. I was used to big pharm and clinical trials where everything was measured and no deviations from protocols are allowed. We did multiple lifestyle interventions as well, including a modified keto diet for cancer, daily runs, yoga, etc. But both myself and my daughter understood that these were also therapy/medicine.
There clearly is no pharm available for women APOE4 carriers now and may not be for awhile. None of the amyloid targets appear to have any benefit without high risks for us. Lifestyle interventions and diet will be our therapy, our IV's, our pills. It is not a diet as such. It is our medicine. It is no more optional than chemo was for my child, or insulin is for a diabetic. There is a choice always involving a benefit /risk decision with any therapy. But you have to make that decision with eyes open. We need to understand the science of diet, exercise, sleep, etc. This is not easy without the assistance of multiple experts in many fields. Our regular doctors know very little about this kind of treatment, even the neurologist at the "memory clinic" suggested nothing for intervention. They will not even order the testing that can assist in making a determination on what should be the primary focus of therapy, ie, insulin resistance, lipid metabolism, inflammation, cardiovascular issues, etc. It is not APPROVED by the FDA or insurance will not cover. It is not the gold standard. I am searching for a protocol that helps with this, particularly for APOE4.
I started with the Bredessen protocol as it made sense, but my sister (4/4) immediately complained about the high fat content and said she was going to do an easier Mediterranean diet and maybe could sneak a glass of wine in. I could not insist that her brain might need ketones to survive as I really didn't know the metrics of her brain metabolism; if she had insufficient glucose for energy as we didn't have a PET scan. I couldn't insist that we needed to focus on her brain's hyperlipidemia as I don't know what her lipid/cholesterol levels are in her brain or CSF. I am plodding along as best I can with Bresdesen general plan though not perfect and adapt as needed. It isn't the easiest and is very time consuming. I am hoping it will get easier. (When I make my "bullet coffee" in the morning, I have researched the coffee/ie. caffeine, found a very high polyphenol (1700-2000) olive oil; with a high monounsaturated fat macadamia nut creamer, organic vanilla and cinnamon- all measured and macros figured with Cronometer and I have done basic research on what effect this has on brain) I check my glucose and my ketones daily.
I am searching clinical trials regularly for dietary interventions or a magic bullet. The more I read particularly about the APOE4 gene and its influence on almost everything, the more I believe that the diet needs to focus primarily glucose and lipid metabolism in the brain. I would appreciate any thoughts on how do do this. thank you..
Pam, 76- 3/4
"
Hello Pam,
Welcome to our community. We’re delighted that you’ve joined us. I see you have been through a lot and probably feel like you are on an emotional roller coaster. It’s clear that you’ve put in a lot of effort researching the right dietary choices for both yourself and your family members. I can see you are a true caregiver who dedicates yourself wholeheartedly , and it can be overwhelming to sift through all the information available.
Rest assured, you’re not alone on this journey. Like you, we believe that epigenetics holds the key to success. While making lifestyle changes can be challenging, the effort is undoubtedly worthwhile.

If you haven't already checked out apoe4.info, as a Support Team Intern I'm happy to share several tools & resources to help you get the most out of your experience here. 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.

Some helpful tips to navigate the site include the How-To Guide. It includes topics such as navigating the forum, private messaging, and searching. One great tip is using the quote (") button when replying to a post. Using the button will automatically alert the member of your response.

Wiki Main Page contains a wealth of information.

Blood Sugar from our Wiki contains valuable information about blood sugar management, which may be of particular intrest to you.

If you are interested in learning more about other members check out Our Stories.

Again, I am so glad you joined our forum. Please reach out anytime! We are here to support each other as we navigate this path together.

Warmly,
Lyre
Plumster
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Re: Whole Foods Plant Based Diet/Lifestyle Leads to MCI Improvement

Post by Plumster »

rubyd0g 3/4 wrote: Thu Jun 13, 2024 5:08 pm I am trying to find an appropriate diet for my family, 4 sisters which all have APOE3/4 and one with 4/4. Our children are testing and one so far is a 4/4. My mother and grandmother died of Alzheimers. I read this article and many others on dietary interventions. ( I have stacks of research from PUBMed and Clinical Trials.gov)) I am not clear what the meals in this trial contained ( high polyphenol olive oils, crucifers, walnuts, mushrooms?). The problem I have is that most of the lifestyle and diets that have been evaluated in clinical trials are not defined clearly. When it is called a Modified Mediterranean - is it the olive oil, coffee and Omega 3 fish, etc. that are driving the outcome. Was there a caloric/energy max on the daily intake or some fasting. There are so many variables. If the composition is not measured for macros and micronutrients nor is clear on what supplements are included, how can we understand what is the causative factor?
Pam, 76- 3/4
Hi Pam,
I recommend reading Dr. Dean Ornish's newest book Undo It! It lays out what he means by "lifestyle medicine." The diet is very low fat and low sugar. It is plant-based and uses whole foods--so, yes; cruciferous, nuts in small amounts, mushrooms, all fruits, vegetables, whole grains, and legumes. The book has a chapter on food and a big section with recipes (breakfast, main dishes, soups, desserts, snacks). It's very important to Dean Ornish that the diet is low fat with the fat ideally derived from the whole foods themselves only, a few nuts, low fat plant milk, etc. Most snacks should not contain more than 3-4 grams of fat total, for example. Historically, there's been a turn toward more and more fat in the diet, he says. (see also here.) I am whole foods plant based myself and aim to eat low fat and low sugar as much as possible. Everyone is different, but it really works for me.
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Re: Whole Foods Plant Based Diet/Lifestyle Leads to MCI Improvement

Post by Verbow »

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Re: Whole Foods Plant Based Diet/Lifestyle Leads to MCI Improvement

Post by ellisto »

My brother is in stage 6 of 7 of Alzheimers. I have so far avoided his fate by following the Dale Bredesen Protocol and upping my vitamin D3 and using as much olive oil as possible. Dr Dayan Goodenowe in his book Breaking Alzheimers also has some suggestions I follow to increase my plasmologens.
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Re: Whole Foods Plant Based Diet/Lifestyle Leads to MCI Improvement

Post by Dany_ele »

Plumster wrote: Fri Jun 07, 2024 10:05 am Small study and possibility of placebo effect, but objective biomarkers confirm the MCI improvement. Research led by Rudolph Tanzi and Dean Ornish.
Effects of intensive lifestyle changes on the progression of mild cognitive impairment or early dementia due to Alzheimer’s disease: a randomized, controlled clinical trial

Dean Ornish, Catherine Madison, Miia Kivipelto, Colleen Kemp, Charles E. McCulloch, Douglas Galasko, Jon Artz, Dorene Rentz, Jue Lin, Kim Norman, Anne Ornish, Sarah Tranter, Nancy DeLamarter, Noel Wingers, Carra Richling, Rima Kaddurah-Daouk, Rob Knight, Daniel McDonald, Lucas Patel, Eric Verdin, Rudolph E. Tanzi & Steven E. Arnold

Alzheimer's Research & Therapy volume 16, Article number: 122 (2024)

Abstract
Evidence links lifestyle factors with Alzheimer’s disease (AD). We report the first randomized, controlled clinical trial to determine if intensive lifestyle changes may beneficially affect the progression of mild cognitive impairment (MCI) or early dementia due to AD.

Methods
A 1:1 multicenter randomized controlled phase 2 trial, ages 45-90 with MCI or early dementia due to AD and a Montreal Cognitive Assessment (MoCA) score of 18 or higher. The primary outcome measures were changes in cognition and function tests: Clinical Global Impression of Change (CGIC), Alzheimer’s Disease Assessment Scale (ADAS-Cog), Clinical Dementia Rating–Sum of Boxes (CDR-SB), and Clinical Dementia Rating Global (CDR-G) after 20 weeks of an intensive multidomain lifestyle intervention compared to a wait-list usual care control group. ADAS-Cog, CDR-SB, and CDR-Global scales were compared using a Mann-Whitney-Wilcoxon rank-sum test, and CGIC was compared using Fisher’s exact test. Secondary outcomes included plasma Aβ42/40 ratio, other biomarkers, and correlating lifestyle with the degree of change in these measures.

Results
Fifty-one AD patients enrolled, mean age 73.5. No significant differences in any measures at baseline. Only two patients withdrew. All patients had plasma Aβ42/40 ratios <0.0672 at baseline, strongly supporting AD diagnosis. After 20 weeks, significant between-group differences in the CGIC (p= 0.001), CDR-SB (p= 0.032), and CDR Global (p= 0.037) tests and borderline significance in the ADAS-Cog test (p= 0.053). CGIC, CDR Global, and ADAS-Cog showed improvement in cognition and function and CDR-SB showed significantly less progression, compared to the control group which worsened in all four measures. Aβ42/40 ratio increased in the intervention group and decreased in the control group (p = 0.003). There was a significant correlation between lifestyle and both cognitive function and the plasma Aβ42/40 ratio. The microbiome improved only in the intervention group (p <0.0001).

Conclusions
Comprehensive lifestyle changes may significantly improve cognition and function after 20 weeks in many patients with MCI or early dementia due to AD.
Open access: https://alzres.biomedcentral.com/articl ... 24-01482-z
So, it looks like a small study found that making some serious lifestyle changes can actually improve mild cognitive impairment, and even slow down Alzheimer's disease. The cool thing is that they used objective biomarkers to confirm the results, so it's not just people feeling better - there are real changes happening in their bodies.
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