Establishment Hostility to Alzheimer's Remediation

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circular
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Re: Establishment Hostility to Alzheimer's Remediation

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Julie G wrote:
So, I have an appointment at UCSF next month to have get some baseline work done. Is this worth doing in light of their attitude?
My guess is that you'd receive a good work-up with quantification of your current cognitive status. As far as prevention or remediation advice; forget about it. This article makes that abundantly clear. It depends what you're looking for...
UCSF is a pretty large institution. I'm not sure I would write off all the practitioners there based on this one commentary, especially in an area as open minded as the Bay Area. I say expect closed mindedness, but be open for open mindedness ;). Now insurance is another matter, and many open minded doctors won't order or prescribe or recommend things they feel are worth a try because they now get warning letters from Medicare and insurance companies telling them if they're putting their patients at risk, etc. etc.
ApoE 3/4 > Thanks in advance for any responses made to my posts.
circular
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Re: Establishment Hostility to Alzheimer's Remediation

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Julie G wrote:FWIW, I just submitted a comment to JAMA; no idea if it'll make it online.
Nice! Not there yet. Did they require you use your real name? I suspect so, darn.
ApoE 3/4 > Thanks in advance for any responses made to my posts.
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Re: Establishment Hostility to Alzheimer's Remediation

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Much better than the knee-jerk response I had. Though in my defense I was in a dementia care unit with my mom and surrounded by people who waited patiently for a treatment that didn't come for them. So the sarcasm came naturally :roll:
Your response was perfection! I'd encourage you to add it to the comments. It underscores the ridiculousness of (some) of their warnings. I'm sorry for you and your Mom, Fiver. I've spent my share of time with loved ones there too... heartbreaking.
Now insurance is another matter, and many open minded doctors won't order or prescribe or recommend things they feel are worth a try because they now get warning letters from Medicare and insurance companies telling them if they're putting their patients at risk, etc. etc.
Yes, because checking for a B12 deficiency is very risky. ;) Sorry, couldn't resist.
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Re: Establishment Hostility to Alzheimer's Remediation

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I'm guessing it is mostly cognitive testing. Apparently no MRI at this initial stage.
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Re: Establishment Hostility to Alzheimer's Remediation

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Fiver wrote: Much better than the knee-jerk response I had. Though in my defense I was in a dementia care unit with my mom and surrounded by people who waited patiently for a treatment that didn't come for them. So the sarcasm came naturally :roll:
I thought that was very artful! :D
ApoE 3/4 > Thanks in advance for any responses made to my posts.
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Re: Establishment Hostility to Alzheimer's Remediation

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I submitted comments as well. Apparently, it takes time for an editor to review and approve them.

I mean, yes, let's defend science and medicine against pseudoscience and fraud. But, really, the authors just don't seem to focus on the important part - that millions suffer from a terrible disease for which there is no cure. It also has a paternalistic tone - that doctors know best - while the reality is that the heath care system is broken and patients need to become educated and take control of their health care. It's just really tone deaf.

And what's the worst that could happen? Some people eat well, exercise, take supplements, and become educated about their health. At a cost which is far less than the cost of the alternative.

Vitamin-popping health nuts are hardly a national health crisis.
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Re: Establishment Hostility to Alzheimer's Remediation

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The establishment knows there is no single present remedy at gold-standard level of evidence. They know that prevention and care must be multicausal. Yet they persist in only monocausal research. It’s great that there are big research teams working on monocausal remedies that could contribute to multicausal treatment. But must that be the only approach? And is it ethical to divert patients who could be or are being treated by mildly supported multicausal approaches into speculative monocausal trials?

Below is a scheme at UCSD that is paid by the feds to recruit subjects for Alzheimer’s trials. That’s not a bad thing. But is it ethical for them to tell the recruited that there are no present options, in order to sign them up for monocausal trials? Drug trials sound great to the naïve, but I would not do one. The treatment is monocausal, likely you would have to give up all other remedies as confounding, it’s probably based on an unsupported or falsified theory, and there’s half a chance you’re thrown into the placebo group.

https://www.sandiegouniontribune.com/ca ... story.html
There is no cure for AD. Current approaches and medications focus on helping patients maintain mental function, manage behavioral changes and slow symptoms of the disease.

For example, drugs like Zoloft, Cymbalta, Wellbutrin and Tofranil may be prescribed to manage AD symptoms such as depression, aggression, restlessness and anxiety, but experts advise using them only after other, non-pharmaceutical strategies have been tried without benefit.

There are only two types of medications currently approved by the U.S. Food and Drug Administration specifically for treating AD. The first, a drug class known as cholinesterase inhibitors (marketed under names like Aricept, Razadyne and Exelon), may help with aspects of mental function by helping prevent the breakdown of a brain chemical called acetylcholine, which is linked to memory and thinking. Cholinesterase inhibitors appear to work best for people in early or middle stages of AD.

The other approved drug is an N-methyl D-aspartate antagonist (Namenda). It is believed to regulate another important brain chemical called glutamate. Too much glutamate in the brain can lead to brain cell death, and diminished brain function.

But AD is confoundingly complex, which is a big reason why no new AD therapeutics have been approved by the FDA since Namenda in 2003. Indeed, it’s not likely that any single drug or intervention can successfully treat AD.

But billions of dollars have been and are being spent on new pharmaceutical possibilities, many with different therapeutic targets, from amyloid plaques and tangled tau proteins to cholesterol and inflammation. According to a survey published in the journal Alzheimer’s & Dementia, there were 112 agents in the AD treatment pipeline in 2018: 25 in phase I clinical trials, 75 in phase II and 35 in phase III.

In San Diego County, the clinicaltrials.gov database reports 19 studies in startup, recruiting or enrolling participants by invitation. Beyond its role as a research center, the Shiley-Marcos center is also a test site for four trials; several are currently enrolling participants. You can find out more about these trials and others by visiting clinicaltrials.ucsd.edu.
I don't mean to pick on UCSD. They are playing by the rules that have been set by national policy makers.
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Re: Establishment Hostility to Alzheimer's Remediation

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bladedmind wrote:The establishment knows there is no single present remedy at gold-standard level of evidence. They know that prevention and care must be multicausal. Yet they persist in only monocausal research... But must that be the only approach? And is it ethical to divert patients who could be or are being treated by mildly supported multicausal approaches into speculative monocausal trials? ...
I don't mean to pick on UCSD. They are playing by the rules that have been set by national policy makers.
I have to respectfully take issue with some of your assertions, which may be true in specific circumstances, but which do not strike me as the rules set by national policy makers. Having spent my career working to support children and their parents in special education, I found they were often rightfully angry, suspicious, frustrated and upset at the quality or availability of interventions or supports for their children with special needs, I have never been a fan of mono-causal or mono-therapy approaches. When I worked with kids and families with traumatic brain injury (TBI) I borrowed a slogan from a great treatment program: "Whatever It Takes".

I apply that same view to having ApoE 4, and value rigor and competing ideas. So while I understand the concerns with being painted with a broad brush (and have been on the receiving end of that), I think we do best when we seek first to find common ground with those who question us. If a parent of a child with severe autism can only agree with me that we both want her child to be happy in school; we have a basis for collaboration. If we can only agree with UCSF that much remains to be proven in prevention of cognitive decline, and that many programs and protocols do in fact use accepted interventions, and gently suggest that doing so in an easy-to-access format does not invalidate their utility, we may make it more possible to partner with health care providers on education about ApoE 4, and with families who need support.

Specifically I have been in the Generations I trial on either a BACE-1 inhibitor study drug or a placebo for almost 18 months--and was in the screening process for several months before that with my husband, who continues to be my study partner. During that time, I have received extensive written consent forms, which could easily fill a notebook, as well as formal and informal verbal conversations about the purpose, methods, requirements, possible risks and reasons why I or the Generations study might decide I want to leave the study.

I was not "diverted" to this study. I found it on Clinical Trials,gov and reached out myself before the study location had even started. Several other members on this site who were screened and/or accepted have done something similar, many through Gene Match. Of those people whose backgrounds I know, all had professional positions during their careers, often with high levels of responsibility. We are not people being diverted away from a healthy intervention; we are people seeking to complement our chosen interventions by contributing to the advancement of knowledge of ApoE 4 in ways that many others are not able to do because of age, location, family commitments or other responsibilities.

Of those people, I know at least one follows the Bredesen Protocol with a trained practitioner, another who follows a very close version of the protocol herself, and additional two who have gained important information about their health and wellness from results of blood and imaging tests shared with them. I myself was told of a low vitamin B-12 level within days of a test for it, even though my own doctors in two states had not been worried about my level, and was able to immediately bring it up with methylcobalamin. I have also been able to take a statin (not a decision everyone would support, but it was my decision) and other supplements.

Every 6 months I have sveral hours of cognitive, motor, daily functioning, and psycho-social assessments, along with blood work. I am also asked very specific questions about my diet, my sleep, my stress and emotional level and my husband is asked about my social engagement and hobbies. It is clear from the questions that the study supports a multi-causal approach to AD, and in fact is seeking to support healthful interventions. The Study Staff member who is my liaison explicitly stated that the researchers believe that eventually many different causal factors will be able to be isolated and treated in people, with some people needing only lifestyle prevention and others needing one or more medical interventions. A BACE-I inhibitor may be one of those; the fact that CRISPR gene editing is working on replacing a faulty APP protein cleavage with correct cleavage suggests it is at least worth a careful assessment.

Here are only a few examples of other studies currently posted on Clinicaltrials.gov that seek to prevent and/or ameliorate the effects of Alzheimers while also seeking to support the health of their participants. The first, the POINTER study, is not yet recruiting, but will be a large, multi-year study of lifestyle interventions at various locations across the U.S. I believe the Alzheimer's Association is funding part of this cost with about $33 million. All of the quotes sections in bold are my emphasis.

U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (POINTER)
Detailed Description:
Lifestyle interventions focused on combining healthy diet, physical activity, and social and intellectual challenges may represent a promising therapeutic strategy to protect brain health. The recent results of the population-based 2-year clinical trial, Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), indicated that a multidomain intervention of physical activity, nutritional guidance, cognitive training, social activities, and management of heart health risk factors protected cognitive function in healthy older adults at increased risk of cognitive decline. As yet, there are no pharmacological treatment options that can rival this effect. Thus, there is an urgent need to expand this work to test the generalizability, adaptability and sustainability of its findings in diverse and global populations. This pivotal U.S. Study to Protect Brain Health through Lifestyle Intervention to Reduce Risk (U.S. POINTER) will test whether a similar 2-year intensive lifestyle intervention, adapted to American culture and delivered within the community, can protect cognitive function in older adults in the U.S. who are at increased risk for cognitive decline and dementia. If successful, the results of this study will have large-scale implications for public policy regarding standard of clinical care and prescriptive practices for a fast-growing and vulnerable population of older adults
.
Atlanta, GA: Tango for Alzheimer's Disease Patients' Caregivers
Detailed Description:
The importance of informal family caregiving in Alzheimer's disease (AD) is well-established. African-American caregivers are most often middle aged adult children of AD patients (vs. spouses), women, and are at higher risk for chronic health problems. AD lifestyle interventions offer an alternative to medication, and are generally affordable, accessible, and adaptable to the lives of caregivers. To date, most non-pharmaceutical interventions have focused on exercise and nutrition, both of which have proven to be highly successful in conferring AD related benefits and decreasing AD risk.
The goal of the project is to determine the extent to which indices of inflammatory biomarkers, cognition and mood, are influenced by a partnered, dance-based intervention vs control condition in African American (AA) female family caregivers, at high risk for Alzheimer's disease.
Dallas, TX Discovery of Novel Biomarkers That Will Lead to the Early Detection of Alzheimer's Disease (BVB)
Brief Summary:
This study will perform a targeted metabolic analysis in blood and urine samples from subjects attending the Baylor AT&T Memory Center. The aim is to identify novel biomarkers that can distinguish normal aging subjects with no cognitive impairment from those with mild, moderate or severe cognitive impairment associated with Alzheimer's disease. Subjects will also be screened for B-vitamin deficiencies that may correlate with other metabolic biomarkers and Alzheimer's disease.
Miami, FL: Alzheimer's Disease Treatment With Combination of 40Hz Light and Cognitive Therapy(AlzLife)
Brief Summary:
Electrical activity in the brain known as "gamma" brainwaves help connect and process information throughout the brain. These gamma waves are diminished in Alzheimer's disease. New research in Alzheimer's disease mouse models shows that exposure to light flickering at the rate of 40 flashes per second or 40Hz increased gamma brainwaves and led to clearing of beta amyloid plaques in the brain, a key abnormality in Alzheimer's disease. This project will test the ability of a novel iPad App ("ALZLIFE") that delivers light therapy at 40 Hz combined with cognitive therapy to improve cognition, function, and quality of life in Alzheimer's disease.
A Dyadic Sleep Intervention for Alzheimer's Disease Patients and Their Caregivers
Los Angeles, CA:
Brief Summary: ...Nighttime sleep disturbance in AD patients is associated with shorter survival, lower quality of life, and decreased social engagement...only a few behavioral sleep intervention studies have targeted community-dwelling AD patients or caregivers. Dyad-based sleep interventions may have better effects on sleep and other health outcomes because of the influence of AD patients on their caregivers and vice versa.
VA Center, Los Angeles, CA:
Curcumin and Yoga Therapy for Those at Risk for Alzheimer's Disease
Brief Summary:
...Drugs developed to stop the underlying disease processes that cause Alzheimer's disease may succeed only with multimodal efforts to stimulate brain function. One purpose of the study is to test the clinical benefits of curcumin...which has been found to inhibit several potential disease pathways in Alzheimer's disease. Another purpose of this study is to determine how the addition of a physical exercise program in individuals with early memory problems may affect memory function....
Mount Sinai, NY, NY
Phase 2 Study to Examine Grape Seed Extract as an Anti-Oligomerization Agent in Alzheimer's Disease (AD)
Detailed Description:
This study aims to establish the safety and pharmacokinetics of Meganatural-Az® GSPE in subjects with Alzheimer's disease. As a secondary goal, clinical and biomarker indices of therapeutic efficacy will also be evaluated. The proposed study will provide the essential human data necessary to guide the design of future studies testing the efficacy of GSPE in mitigating cognitive deterioration in AD patients.
Johns Hopkins, Baltimore, MD and Georgetown, Washington, D.C.:
Rehabilitation and Prophylaxis of Anomia in Primary Progressive Aphasia
Brief Summary:
The goal of this study is to remediate word-finding problems in patients who have Primary Progressive Aphasia (PPA) or Alzheimer's Disease and to delay the further progression of word-finding impairment. The current approach is novel in that it contains a prophylaxis component in which the investigators attempt to strengthen neural connections that remain functional, making them more resistant to degradation as the disease progresses. While the study is specific in its targeting of word-finding problems, a successful outcome would bode well for other studies aimed at prevention or reversal of declining cognitive functions in dementia.
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Re: Establishment Hostility to Alzheimer's Remediation

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Thanks for the correction. At best, I overgeneralized; at worst perhaps I was uninformed and uncharitable. I learned a lot from the trial summaries that you worked to put together for us.

You mentioned the UCSF (UC San Francisco) statement. I think you are referring to my quotation of the UCSD (UC San Diego) statement. That center’s purpose is to recruit people for trials, both in San Diego and elsewhere. It is one of the original six national centers. It also does public health education and other fine things. There are lots of diagnostics, but almost no treating physicians. Its public statement tells recruits for trials that there is no cure for Alzheimer’s. I am overly sensitive, perhaps. When I saw a physician from the UCSD health system several years about my APOE 4/4 status, he told me to accept my fate, nothing can be done. Except, I could sign up for trials. I was doubly a piece of meat for the system.

The trial you are part of does not require that people cease other modes of treatment. Excellent.

The U.S. Pointer trial you quote from is testing a multicausal approach, and states “As yet, there are no pharmacological treatment options that can rival this effect. Thus, there is an urgent need to expand this work to test the generalizability, adaptability and sustainability of its findings in diverse and global populations.” Bravo! Maybe when UC San Diego gets down to actual consent forms they use more accurate language about available treatments. I will find out more about its actual practice. Meanwhile, here’s what UC San Francisco says about an approach like U.S. Pointer:
Recently, detailed protocols to reverse cognitive changes have been promoted, but these protocols merely repackage known dementia interventions (eg, cognitive training, exercise, a heart-healthy diet) and add supplements and other lifestyle changes. Such protocols are promoted by medical professionals with legitimate credentials, offer a unique holistic and personal approach, and are said to be based on rigorous data published in reputable journals. However, when examining the primary data, the troubling and familiar patterns of testimony and cargo cult science emerge. The primary scientific articles superficially appear valid, yet lack essential features, such as sufficient participant characterization, uniform interventions, or treatment randomization with control or placebo groups, and may fail to include sufficient study limitations. Some of these poor-quality studies may be published in predatory open access journals.
If I were a public figure approaching UCSF about its stance, I would strive to build from common ground. But as a private actor in a semiprivate setting I think I am licensed to be frank. I used to be in politics, and I used to write manipulative propaganda statements like the one published by UCSF. I smelled it right away. In my later scholarly life I am cautious and precise, and eschew propaganda and rhetoric. On a board like this I speak as I would casually with a neighbor about a common interest.

The other trials you report divide into alternative interventions and biomarkers. Effects of partner dance measured. Light therapy and cognitive therapy. Curcumin and yoga therapy. Grape seed extract. Strengthen remaining neural connections. Novel biomarkers and B deficiencies. Fair enough. You showed that I overgeneralized.

Here is a graphic of the 2018 Alzheimer’s drug development pipeline -- 114 substances.

https://www.ncbi.nlm.nih.gov/core/lw/2. ... 48_gr1.jpg

Alzheimers Dement (N Y). 2018; 4: 195–214.
Published online 2018 May 3. doi: 10.1016/j.trci.2018.03.009
PMCID: PMC6021548
PMID: 29955663
Alzheimer's disease drug development pipeline: 2018

It looks to me like there is lots of single-bullet research, but nondrug research is not represented in this analysis. Finally, it is correct to say that I have no information about whether any or all of the drug trials forbid patients from following other modes of treatment.
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Re: Establishment Hostility to Alzheimer's Remediation

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bladedmind wrote:Thanks for the correction.
...When I saw a physician from the UCSD health system several years about my APOE 4/4 status, he told me to accept my fate, nothing can be done. Except, I could sign up for trials. I was doubly a piece of meat for the system.

...On a board like this I speak as I would casually with a neighbor about a common interest.

...It looks to me like there is lots of single-bullet research, but nondrug research is not represented in this analysis...

I have a strong sense that you and I would find a great deal to talk about if we were neighbors, bladedmind, and that we would both relish the intellectual give and take! I also believe that the Community Guidelines wisely established by Julie G and the other founders of this forum explicitly support the sort of back-and-forth conversation about topics among members, and that we all benefit from listening closely to differing views. One of the best parts of this forum is that its strength comes from diversity, not uniformity of views, and from constant questioning of received wisdom from "experts".

I appreciate you sharing a bit of your background and how it informs your views. If treated the way you were as UCSD, I would harbor similar feelings. Maybe some health care systems have realized that they are only as effective as their core customers' trust in them, but I suspect it varies widely. I do know that I am thanked each and every time I go to my study site, and am even reminded that at any time I can leave the study.

I recently served as a consumer reviewer on a panel evaluating the merit of applications studying links between TBI and Alzheimer's and other dementias, funded through the Dept. of Defense that explicitly ruled out drug pipeline applications. Consumer reviewers on the AD panel and panels for prostate cancer and epilepsy grants spoke at the plenary session to the scientific and consumer audience of their experiences and were given a significant voice in the decision-making process. The collaboration across titles and positions to innovative, cutting-edge approaches for prevention and treatment of disease to "reduce the burden on individuals, families and caregivers" was heartening. It's that kind of scientific rigor and patient participation that I think would improve the perception of research in the Alzheimer's field.
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