Let's solve ALZ. APOE4--Nature's/God's Original Design

Alzheimer's, cardiovascular, and other chronic diseases; biomarkers, lifestyle, supplements, drugs, and health care.
AnnieV
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Let's solve ALZ. APOE4--Nature's/God's Original Design

Post by AnnieV »

Dr. Bredesen's stated hope, his goal is that ALZ will be solved via this website forum. Let's reach toward his objective. Toward that end, a starting thread on APOE4 historical context from Dr. Bredesen's book is shown.

This image is from Dr. Bredesen's book. I think many people unnecessarily suffer under the mental burden that APOE4 is a "predisposition", even a predestination, to ALZ. While it's certainly accurate to state APOE4 is correlated to ALZ this reminder image of APOE4 history over 7 million years shows its probably more accurate to state APOE4 is just less adaptable than other APOE variants to today's (corrupted) consumables rather than a "predisposition". I assert this descriptive refinement because this image reminds us all that APOE4 was Nature's/God's original design, that for the overwhelming vast majority of humanity's time on the planet everyone was APOE4/4, that APOE4 still exists today, and not in insignificant numbers. That fact seems to indicate the original design wasn't flawed at all--the original design, one that endures to the present, would most likely not have a built-in "predisposition" for failure of the body's most important organ, it's central headquarters. Instead, what seems to be the basis for ALZ "predisposition", especially in modern times and especially for "developed" countries, is how "advanced" humanity has corrupted its formerly natural food and drinks, creating corrupted consumption habits. The modern corruption of consumables, serving business models not health models, most dramatically accelerated post-Industrial Revolution (starting circa 1870) and especially in the last 40 or so years as obesity rates have also skyrocketed. This assessment is consistent with Dr. Bredesen's early chapter called, "How to give yourself Alzheimer's" where he details a typical poor nutrition diet among industrialized countries.

Having listened to a number of ALZ podcasts, having seen countless ALZ Association ads, the general vector for addressing ALZ appears far more on the "management" side rather than on the prevention/cure side. It appears the "cure" is in the systemic, habit pattern prevention path not the pill path. Our American society appears specifically vulnerable to the deception a pill will fix a problem, that a pill will override structurally flawed (addictive) consumption habits.
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Re: Let's solve ALZ. APOE4--Nature's/God's Original Design

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Our American society appears specifically vulnerable to the deception a pill will fix a problem, that a pill will override structurally flawed (addictive) consumption habits.
Great post. We all wish it were that easy! ApoE4 must have some redeeming qualities or it wouldn't evolutionarily still be around. We often see those with E4, who are practicing a clean diet/lifestyle, actually thriving compared to their non-E4 counterparts. I agree that if we could learn to overcome the genetic mismatch that occurs in our modern world, we may be able to minimize the pathology associated with our risky allele.

Dr. Bredesen suggests that AD results from an imbalance in neuroplasticity signaling. When the damaging forces (insulin resistance, hypoxia, nutrient deficiencies, etc.) overtake the repair forces in the brain, it begins to downsize and cognitive decline results. By identifying and addressing the various insults, he has demonstrated that neuroplasticity — the ability to heal by reorganizing synaptic connections— can be restored. He sees the role of abeta very differently than those in the amyloid hypothesis camp. They suggest that abeta has has a causal role, whereas he thinks it's the result of the various insults. He agrees that there may be a role for anti-amyloid therapies once the various contributors have been identified and addressed. It would be great to see these theories merged and trialed. IMO, pitting diet/lifestyle against pharma oversimplifies a complex disease and does a disservice to us all.
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Re: Let's solve ALZ. APOE4--Nature's/God's Original Design

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This is a just a starting thread on the solving discussion, one that starts literally from the beginning.

"...overcome the genetic mismatch that occurs in our modern world, we may be able to minimize the pathology associated with our risky allele." The APOE4 chart over 7 million years of evolution seems to show we don't have a genetic mismatch, that in the modern world we have a corrupted consumables mismatch, that we don't have a risky allele, we have a risky consumption environment for that allele.

What causes a neuroplasticity imbalance if not possibly for a lifestyle habit of corrupted consumables (in the last 150 years or so)? If corrupted consumables is at least a contributing cause (which Bredesen himself seems to finger in that initial chapter) then its not surprising ALZ can be prevented, reversed if the consumption habit pattern returns to consuming only what Nature designed the body to consume. I suggest that because we see that fundamental thesis made evident in Sub Saharan African countries that have very high APOE4 "predispositions" but studies like the Nigerian Paradox state indigenous APOE4 Nigerians have no, repeat no, correlation to ALZ at all (their words, not mine). Their diets are not only not corrupted like those of "advanced" nations, they also regularly/daily consume fermented foods (grains, milks, vegetables) which we no longer do as societal habit post-Industrial Revolution. Accordingly, I sense the "diet" discussion in the ALZ solution searching framework is far too simplified, broad-brushed, it does not adequately address key specifics of specific corrupted consumable staples that may be aggravating the ALZ problem (see Finland's own reporting showing exploding ALZ rates over the last 40 years. Where is the critical thinking applied here to explain this disaster? The answer cannot simply be that Finnish people are living significantly longer than they were just 40 years ago or that molds are unique to Finland and respect geographic borders). Yes, ALZ is a very complex disease. Unfortunately, we may be making it even more complex by trying to navigate a solution around key corrupted consumables that few want to question. We seem to want our corrupted cakes and our neurons too. I sense that pursuit just won't work, I sense it's a false hope many Americans have. There's an underlying reason why Sub Saharan African countries (and all of the so called "blue zones" of long healthy, mentally intact lives too) are not plagued by ALZ in the rates we "advanced" nations are. I sense that "paradox" is poorly analyzed.
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Re: Let's solve ALZ. APOE4--Nature's/God's Original Design

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We seem to want our corrupted cakes and our neurons too....

Truer words were never spoken ( written )....
[/quote]
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Re: Let's solve ALZ. APOE4--Nature's/God's Original Design

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Julie G wrote: Wed Apr 10, 2024 1:04 pm [He sees the role of abeta very differently than those in the amyloid hypothesis camp. They suggest that abeta has has a causal role, whereas he thinks it's the result of the various insults.
Hi Julie. With the success of current trials, I'm thinking that ApoE4s may actually fit into the amyloid camp, whereas other variants who get AD would fall under Bredesen's multifactor causation model. Of course ApoE4's could be subject to both if their life styles have been poor...

Have we yet gone beyond thinking that the ApoE3 variant was an adaptation to eating meat? Man has been eating meat far beyond when that mutation came about. It has to be as a result of eating carbohydrates on a more regular basis. This could be prior to farming - after man discovered how to treat tubers to make them edible by soaking and then cooking. Maybe E2 came about to deal with the added sugar?
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Re: Let's solve ALZ. APOE4--Nature's/God's Original Design

Post by AnnieV »

Julie is correct in saying Dr. Bredesen believes, per his published research, abeta is the RESULT of various insults. Without being a biologist or neuroscientist myself, logically Bredesen's theory makes sense, that abeta appears as a possible defense response mechanism to various insults (attacks) against the brain. It appears the belief that abeta is at least a partial cause, rather than a direct result as Bredesen’s theory goes, might be attributed to the fact that the abeta defense response mechanism is not designed for long term sustained-habit-driven insults (attacks) on the brain, that abeta’s defensive mission may be designed for shorter term attacks and that abeta’s sustained presence driven by the sustained habit-driven insults (attacks) over decades might further aggravate ALZ by its own waste products. I have heard it explained like a military operation—that theoretically abeta is like using trench warfare to defend the brain against attack, that initially the trenches forestall the attack but if the attack is relentless over a long time the trenches, sustained by living organisms within those trenches, become toxic themselves in a manner not unlike how sanitary conditions cause secondary toxic problems among troops engaged in long term trench warfare.

It might appear that it could be more important to somehow assess blood brain barrier degradation rather than evidence/non-evidence of abeta, etc. Correspondingly, it might be more helpful if science focuses on what harms the BBB and focus on BBB damage prevention means.

The APOE3 and APOE2 evolution causes remain unknown. NIH based theories seem to generally point to human migratory trends northward with accompanied changes in diets and climates as basis from evolving from APOE4. That theory seems to align with factors like Vitamin D production in the body that is a function of optimized UVB exposure at midday timing and skin covering, both of which would be notably different by northern migration. But meat consumption has been constant over the entire human timeline, millions of years, along with nuts, seeds, and berries. Grain consumption so far is theorized to have started much later than when APOE3 and APOE2 emerged.
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Re: Let's solve ALZ. APOE4--Nature's/God's Original Design

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Hi Julie. With the success of current trials, I'm thinking that ApoE4s may actually fit into the amyloid camp, whereas other variants who get AD would fall under Bredesen's multifactor causation model. Of course ApoE4's could be subject to both if their life styles have been poor...
What leads you to believe that abeta CAUSES Alzheimer's for E4 carriers only? You mention that the "success" of the current trials plays into your theory. Are you aware that anti-amyloid therapies do not work for E4 heterozygotes and they worsen cognition for E4 homozygotes? See more here.
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Re: Let's solve ALZ. APOE4--Nature's/God's Original Design

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AnnieV wrote: Wed Apr 10, 2024 3:14 pm ... (see Finland's own reporting showing exploding ALZ rates over the last 40 years. Where is the critical thinking applied here to explain this disaster? The answer cannot simply be that Finnish people are living significantly longer than they were just 40 years ago or that molds are unique to Finland and respect geographic borders). Yes, ALZ is a very complex disease...
Hi Annie,

I'm not a biologist or neuroscientist either, but I have been able to meet with them during discussions of grant applications on research into the epidemiology, pathology, genetics, diagnosis and health disparities in Alzheimer's as a Consumer Reviewer. What I have come away with is a deep appreciation for the complexity you mentioned--especially in epidemiology research, when researchers may be looking at records over period of decades when they were on paper, kept only for the diagnosis at death, and when the average person was lucky to make it to age 65, when late-onset Alzheimer's becomes more prevalent.

As an example, neither my mother, nor her 4 older sisters, nor her two older brothers had "Alzheimer's" or "vascular dementia" put on their death certificates, since the immediate cause of death was heart and/or respiratory failure. My paternal grandmother, who spent the last 7 years of her life in a nursing home with moderate dementia (she thought President Nixon was bringing her ice cream every day) died of "colon cancer"--which lasted about 2 months. Now, most people with Alzheimer's are diagnosed at the MCI or mild AD stage in high income countries.

Here's what a geriatrician, neurologist and primary care doctor in Finland said in 2010 about their rates after studying 70% of the residents in a rural area (and Finland has very little systematic poverty, so the rural folks have access to health care). More recent articles on Google Scholar don't appear to tell a different story:
Population and method
A total population based clinico-epidemiological study was carried out covering all of the 1680 inhabitants aged 60+ in the rural municipality of Haapajärvi in Northern Finland. Registers of health and social welfare, and population interviews using Mini Mental State Examination followed by clinical examinations for those scoring less than 25 points, were used for screening and diagnosing dementia, which was made according to the DSM-IV criteria.

Results
Among all eligible subjects, 70.8% were participating in the study. The prevalence of dementia was 8.8% in a total population aged 60+. The prevalence was associated with advanced age giving the prevalence-rate of 43.8% among the people aged 90+.

Discussion
The systematic auditing for dementia among the total population of people aged 60+ discovered new cases yielding higher prevalence numbers than found earlier in Finnish or in European studies.

Conclusion
The results refer to the fact that active measures are needed in order to improve the access to diagnostics and care for the demented. Assuming no changes in mortality, and that no effective prevention strategies or curative treatment take place, the number of demented persons in the study area will increase due to the population development by 39% by the year 2020, and by 90% by the year 2030.
Prevalence of dementia – a rising challenge among ageing populations
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Re: Let's solve ALZ. APOE4--Nature's/God's Original Design

Post by AnnieV »

NF52,

Is this 2010 Finnish study trying to say their high ALZ rates are a function of (increased/improved) diagnostic reporting?
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Re: Let's solve ALZ. APOE4--Nature's/God's Original Design

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AnnieV wrote: Sat Apr 13, 2024 12:50 pm NF52,

Is this 2010 Finnish study trying to say their high ALZ rates are a function of (increased/improved) diagnostic reporting?
I think it is saying two factors are affecting the prevalence rate:
  • An increasing number of 90+ year olds, which they predicted in 2010 would increase the prevalence (overall number of people living with AD) by 90% between 2010 and 2030, as Finnish baby boomers age.
  • Better diagnosis of people in rural areas (and willingness to let researchers test them for a possible diagnosis).
Alzheimer's is a disease whose prevalence (overall number or % of people living with it) is growing rapidly as people live longer. At the same time it appears in high and middle-income countries to be a disease whose incidence (i.e. risk of it at any given age) is dropping. Here's an explanation of the drop in incidence vs. prevalence:
Although the number of people living with dementia is expected to rise as the world’s population ages, dementia incidence rates appear to be falling, driven by healthier lifestyles that are improving cardiovascular health, according to new research.

Albert Hofman, chair of the Department of Epidemiology and Stephen B. Kay Family Professor of Public Health and Clinical Epidemiology at Harvard T.H. Chan School of Public Health, presented preliminary data at an Alzheimer’s research conference in the UK suggesting that the incidence rate of dementia in Europe and North America has declined by about 15% per decade for the past 30 years, according to a March 21, 2019 article in the Independent. Hofman said that declining incidence is more pronounced among men than women and that it’s likely driven by lifestyle changes that boost cardiovascular health.
Dementia rates may be falling by 15% per decade.

Prevalence refers to how many people in a society at a certain point in time have a condition or disease, regardless of how long they have lived with the disease. Incidence refers to how many people first have a condition or disease in any given time period.

If a disease is age-related, the prevalence in the overall population (percent of the total population) will change as groups reach that age, especially if they live longer than their parents and grandparents. The incidence (% risk at any given year) may be stable or fall with better health care, education and reductions in risk factors like smoking, alcohol use, head injuries and exposure to toxins, and access to post-high school education and continued learning as an adult.

Baby Boomers, born between 1946 and 1964, are now a huge group of people ages roughly 60 to 78. [My siblings and I along with 20 cousins all arrived during those years.] Those same Baby Boomers are now in the years for Late-Onset AD risk, which rises significantly in the oldest-old, reaching about 50% of 85 year olds by most U.S. estimates. The Finnish people over 90 actually may be healthier, since only 43.8% of those over 90 had a diagnosis in this careful study, and only 8.8% of ALL people over the age of 60.

On a side note, this abstract makes a strong case to not blame individuals (which I don't think you're doing) and to look instead as population-level efforts to change both incidence and prevalence.
Dementia is a leading global public health challenge. Prevention approaches have traditionally focused on individual-level strategies. However, such approaches have limited potential, particularly for resource-constrained populations in which exposure to risk factors is greatest, and exposure to protective factors is lowest. A population-level approach to dementia risk reduction is therefore essential to meet the scale of the challenge and to tackle global inequalities in risk and incidence of disease. Such approaches can be highly cost effective. In this viewpoint article, we describe what such an approach should look like, barriers and facilitators to success, and how we should go about achieving it. We include 10 strategic goals to achieve population-level dementia risk reduction and protection enhancement, targeted at researchers, professionals, funders, science communicators, governments, businesses, and policy makers. If we are to significantly reduce the prevalence of dementia there must be increased emphasis on population-level approaches.
https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/alz.12985. It's in the Alzheimer's Association journal. Although the Alz Assn. does way too much advertising IMO, they also do focus much more than realized on prevention.

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