Reversal of cognitive decline: The Bredesen Protocol

Fact or hype?

Introduction

After reading the book “The End of Alzheimer's: The First Program to Prevent and Reverse Cognitive Decline,” by Dr. Dale Bredesen, and listening on the web various talks on it by him, I decided to take the plunge in December 2019 and try the program for my wife, Peg, age 72. Peg had been diagnosed with Dementia two years earlier. As we were advised by her neurologist, she was continuing to decline cognitively. The available medicine (Aracept) may have slowed down the decline. But she was clearly on a downward trajectory.

Like many others in the same boat, I was desperate to try any treatment that offered some hope. In 2019, I enrolled her in an 8-month clinical trial of a drug (Nilotonib), but it ended in failure. In end-2019, as my desperation was growing, I decided to sign on to the treatment recommended by Dr. Bredesen. However, seven months into following rigorously the protocol, Peg had not only not shown any improvement, but showed further decline. The Bredesen practitioner who we had been working with was surprised. He said that he had expected definite improvement and could not explain why my wife had not reacted positively to the Protocol.

Although we still had three months left in the 9-month treatment package that we had signed up for, I decided after consultation with Peg and our family to discontinue the program. It was not only because the program was not working. It was also because having to take 10 or more supplements and detoxicants twice or more a day was becoming too much for her. Our Bredesen practitioner, normally an upbeat and optimist, agreed with our decision

Our six-month experience made me question whether all the talk about the protocol was just hype. As we all know, given the hopeless mainstream medicine prognosis of Dementia, Patients and particularly their caregivers are amenable to jump at anything that offers any hope. But I took the plunge after considerable research. I generally believe in non-traditional medicine, including Homeopathic and Aryuvedic medicine. To me, the Bredesen approach seems close to these. I also think that Dr. Bredesen makes a reasonable case about Alzheimer’s being caused by multiple “holes” (as he puts it) caused by various toxins and deficits in our body that cannot just be cured by a single medication. In his book and various talks, he comes across as someone very credible. But the fact still remains that it did not work for my wife. Why?

While as a layman I do not feel competent to pronounce judgment just based on my one experience, I feel that I can at least share some of my experiences with the protocol that in hindsight I have questioned. I hope these would help those who are considering the protocol to ask questions, something I only wish in hindsight I had done so myself.

The Bredesen Protocol

I don’t exactly recall how I found out about Bredesen. Someone had recommended to me Dr. Bredesen’s book. The book had received quite an acclaim in various magazines and talk shows. I Googled and found several links to talks by Dr. Bredesen. I found his analysis of the disease both understandable and appealing.

While the prevalent medical view for decades has been that it is the plaques on the brain that cause Alzheimer’s, Dr. Bredesen suggests that Alzheimer’s is caused by multiple toxins/deficiencies (or “holes in the roof” as he calls them in the book) and the plaques are but a reaction of the brain - and probably a protective reaction – against these toxins/deficiencies. So in his view, conventional medicine has been wrongly treating the affect and not the cause, and hence without any positive results. The Bredesen Protocol was designed to plug each of these “holes in the roof” for the treatment of Alzheimer’s. Fixing of these holes in the Bredesen Protocol requires getting rid of the toxins and building up the body’s resistance.

During my continuing research, I came across a 2016 paper by Dr. Bredesen, et al, in Open Access Impact Journal on Aging[1] that reported “clear improvements” in cognitive function of some 10 subjects suffering from Alzheimer’s. The paper made quite a convincing case, at least to an educated layman like me.

After more research on the internet and listening to several presentations by Dr. Bredesen, the Bredesen approach seemed appealing. But still I wondered what those in the field thought. I asked the views of two neurologists, a family friend doctor, our primary care physician, and a few others. The responses varied from outright hostile: “it is a scam that preys on people like me who are desperate to find anything to help their loved ones;” “I am very skeptical of the claims made. But if you have money to spend, go ahead,” etc. Only our primary care physician showed a bit of openness. He said that he had a patient who had tried Bredesen protocol and reported some improvement. But I continued to waiver. What tipped me in the end was a talk by Dr. Bredesen at a symposium organized by the Institute for Functional Medicine at Cleveland Clinic[2]. Dr. Bredesen seemed confidant and the Cleveland Clinic host quite receptive. Given the sterling reputation of the Cleveland Clinic, I decided to sign on.

Somewhere in my research, I had discovered that it is important to work with a Bredesen certified practitioner during the course. I went to the Bredesen Institute website that has since been renamed “Apollo Health” to find a practitioner in my area. However, it would not give you any names unless you signed up for the “Recode” that is a detailed blood analysis at a cost of some $1,400. It seemed rather strange, but I went ahead and signed up for Recode in November 2019. It now allowed me access to the list of approved Bredesen practitioners in my area.

Largely based on proximity, I located 5 possible practitioners. All but one of them were what is known as ‘Functional Medicine Specialists’ and the one a Chiropractor. I called each of them to see how they handle the protocol. There was no standard answer. All but one offered an 8-15 month package at a cost of 10-15 thousand Dollars. One wanted the first appointment for a physical and consultation at a cost of $800. No one had the standard way of medical billing for office visit. I realized that since they are not covered by any insurance (or Medicare), they probably design their fees accordingly. It all seemed quite expensive, but I signed up with one of them who had an office close to our home.

We had our first appointment in mid-December, 2019. By then, Apollo had sent the Recode report that included several dozen indicators and a recommended list of a dozen or so different supplements sold by Apollo. At the same time, all the test results seemed to be within the normal range, so I was unclear then of the diagnosis. Which were the “holes” I wondered that the recommended supplements were designed to fix. I found it surprising that they could prescribe treatment simply based on blood testing and without ever having examined the patient. But I still continued largely on faith.

I took the report to my practitioner during our first visit. He said that I did not need to have the tests done in advance and indeed he himself had arrangements with a local lab that provides these tests at a very reasonable cost. Nevertheless, he reviewed the report in some detail and gave us some six different detoxicants and supplements to take, most to be taken twice a day. He said that he does not like the approach of overloading the patient with a whole bunch of supplements at once and instead introduces them gradually. The cost of the supplements was included in the package as an “estimated allowance”. In response to my question about the inference to be drawn from all the indicators being within the recommended range, he said that the goal is to have “optimum” levels. I did not pursue further, although in hindsight I should have. He also suggested that we sign on to Apollo Health and have Peg do the brain games regularly on their platform “BrainHQ” on Apollo’s site (that Apollo requires you to subscribe to for the next 12 months at a cost of $75 per month for a minimum commitment of 12 months)

For the next 6 months we saw him once a week (by telephone after March 2020 with the start of COVID). During this period, he prescribed various combinations of binders, detoxicants, and vitamins, and over the course of the next 4 months he added some and took away others. He requested additional blood and urine tests, as well as tests of saliva and hair follicles. As I recollect, he said he was using these tests to go beyond Recode to look at any issues with heavy metals, mercury, mold, etc. At any one time, we had 8-10 different pills, liquids and powders that had to be taken twice a day, including some detoxicants that were to be taken early-morning at least 45 minutes before the others and late at night at least an hour or two after the evening regiment. It was quite a challenge to keep track of all this, but I managed with the help of a color-coded chart. Peg fortunately was very cooperative throughout, even though it was not easy on her to be taking all these supplements.

The other part of the protocol was a strict “Keto diet” that is largely plant based, and small amounts of protein coming primarily from fish. Certain oils and nuts were added as the source of energy. It sounded similar to the “Mediterranean diet” that our neurologist had suggested three years back, but the Keto version is much stricter. Besides emphasizing a largely vegetables and oily fish diet, it also requires you to have no lactose, carbohydrates, and glutens. There was in addition an exercise regime that required that each day Peg exercises for at least 30 minutes and has at least 5 minutes at a vigorous level to get her heartbeat up to 120. We were to monitor her “Ketosis” level as an important factor for the protocol. For initial few months, Peg’s Ketosis level hovered around 0.7 that our practitioner said was satisfactory, noting that Dr. Bredesen prefers over 1.5 but few he said ever achieve this. Later in the treatment period, he asked her to consume two tablespoons of coconut oil that bumped up her Ketosis level to 1.5. He was very pleased with this.

On the brain exercises on BrainHQ, Peg was unable to do any of the exercises since she could often not get past the instructions. We also found many of the exercises poorly designed and not suitable for a person like Peg who had already significantly diminished cognitive skills. The practitioner tried twice to give her a baseline test but without success for the same reason. Similarly, she could not take the CNS test that the practitioner asked her to take each month.

The Keto diet seemed to agree with Peg. Indeed, her general health during this period had been very good, without her having even a common cold. However, improving cognition, that was our main goal, was another story. She continued to be stable the first three months on the protocol but began to show decline in cognition after the fourth month. Our practitioner was surprised since he said that he should have seen some improvement but continued to encourage us to stay the course. And we did until Month 7 when it became too much to continue. After discussion with the family, we decided to stop participation in the protocol.

I made a small posting on the Apollo Health forum indicating that the protocol had not worked for us. My purpose was to see if there are others who have had similar experience. But soon I received a call from the Customer Support people at Apollo offering to help. A very helpful person called to say that her job was specifically to help us with the protocol. She had rerun our Recode report from December that she said was based on an “improved methodology” and went over it with me in detail. I thought that after our discussion, she will connect with our practitioner to go over all that he had done and see where the gaps may have been and/or what else should be considered (and this time I would have expected to ask why). But what she proposed instead was that I get yet another practitioner, a Functional Medicine Specialist based in the Midwest and a “coach” based in California. It all sounded like starting all over again and that too without any explanation of why trying again the same protocol would give different results. I decided to not follow her recommendation and stick with our decision to stop further participation.

So, does Bredesen work?

While our experience with Bredesen was clearly unsatisfactory, I do not think it is enough of a basis to answer this question definitively. However, I think our experience does lead me to raise some questions and perhaps to provide some guidance to someone seeking to follow the protocol. In retrospect, I at least see some red flags that make me raise some questions about the protocol and how it is administered by Dr. Bredesen’s company, the Apollo Health. I discuss these questions below.

But before going to my own conclusions, I decided to take a look back at the studies Dr. Bredesen cites in making the case. Doing an internet search, I could find two that at least looked sufficiently analytical. The first one was the 2016 paper mentioned earlier, with Dr. Bredesen as the principal author that reported improvements in cognition in some 10 patients. However, on re-reading the paper now, I noted that the reported improvements were largely subjective reports by either the physician responsible or the members of the family. Such subjective observations can be misleading. The “improvements” may just have been because of the subjects learning to become more responsive to the test. They also can reflect aspirations of the observer who were not necessarily objective and without a bias.

A larger study of 100 patients by 18 different practitioners, including Dr. Bredesen, in an open-source journal[3] reported improvements in cognitive ability of most of the subjects. These subjects were under treatment by one of the 18 authors of the paper. However, on closer look at the data reported in the paper, the level of improvement does not seem to have been large. For the 63 patients for whom MoCA scores were reported before and after treatment, scores ranged from 0-27 at the start of the study and 0-30 at the end, with the average score reportedly increasing from 16.8 to 21.5 and the median from 19.0 to 24.0. Not what one would call major improvements. There are of course other issues with this study also. All the authors were themselves practitioners of Bredesen with thus possible bias. There is also the possibility of improvements being temporary from the “placebo effect.” And the testing was not done by an independent third party.

In addition, of course, neither of these two studies can be considered scientific without a control group as is the requirement for trials. A more rigorous and scientific trial was reportedly launched in mid-2019 and expects to report its findings later this year[4]. But as I write this note, I could not find any reported results. More recently, there are reports of scientific trial with a control group was reported to be starting by end-2022. But no details are available as of this writing. We hope it would be more definitive and convincing than the two studies mentioned above.

Given the prominence that Bredesen has received starting with Dr. Bredesen’s bestseller book, I would have expected to see some critical reviews as well. Surprisingly, I could not find any. The only one that I did find from an Internet search was a critique from a Dr. Harriett Hall in Skeptic, on-line journal,[5] raising doubts not only about Bredesen but most other claims of treatment of Alzheimer’s. I cannot claim to judge the validity of the arguments made, but it makes for interesting reading.

But as I began to write this note, I came across a much more recent critique by Dr. Joanna Hellmuth of the Memory and Aging Center of UCSF in the Lancet[6] (and summarized in a blog by Suzanne Leigh, UCSF’s Senior Public Affairs Specialist on the UCSF website[7]. Dr. Hellmuth raises questions about the validity of the two papers mentioned earlier based on a lack of adequate analytical basis, confirming my doubts now about the two studies reported by Dr. Bredesen, et. al.

So, what is my “subjective” conclusion? Despite my negative experience, I still think that the proposition that Dr. Bredesen makes has some logic. Alzheimer’s indeed is a complex disease and I am inclined to share his view that it may not be caused by just one simple thing like plaques on the brain that conventional medicine has been trying to deal with over at least two decades without success. The protocol’s emphasis on nutrition, exercise and staying mentally engaged also makes sense, and is in the same spirit as what conventional neurologists recommend. Also, our experience with Keto diet has been positive.

However, looking back I now have doubts about the array of detoxicants, binders, vitamins, etc. that Bredesen promotes. I can cite several reasons for my doubts:

I would expect a protocol to have defined elements and sequencing of different interventions at different stages, and close monitoring. Bredesen protocol does not have this important requirement of a protocol. As a result, each practitioner who I talked to, had his/her own method. There is no uniformity in how they approach treatment. There is no “protocol.”
Based simply on the Recode report based on your blood analysis, Apollo recommends a number of supplements without having had any discussion with the patient or the caregiver. There is no indication of any sequencing or follow-up, although it does suggest that you should work with a practitioner to follow-up on the Recode report. But the fact that it does prescribe the supplements makes you wonder again as to the underlying protocol.
After you have signed up for the Recode testing, Apollo provides a list of practitioners who reportedly had completed their training in the Protocol. I assumed that these practitioners would have somehow been vetted by Apollo. But I discovered later that this is not so and indeed Apollo does not necessarily vouch for them. Nor does it require an accreditation to be listed. Thus, when an Apollo representative talked to me after my having reported failure with the protocol, I discovered that they had no knowledge of the practitioner I had been working with and went on to recommend a totally different practitioner, as if I was starting afresh.
While I am sure Dr. Bredesen’s initial advocacy was derived from his desire to help people with Alzheimer’s, the formation and promotion of Apollo Health as a company and the way it functions indicates that commercial interest has become more prominent. Why else would it not reveal its list of practitioners until after you have signed up for the Recode report at a cost of $1,400? And it also makes you question their recommendations for supplements that are then offered from their own store. As if the prescribing doctor also owns the pharmacy!
The “support” it provides appears to come from customer service types rather than from trained professionals and is thus not a resource you or your practitioner can call for advice.

So, what is my verdict arising from my experience? It is a hard question to answer. But if I can simplify my answer, I would say that I have gone from being “mildly positive” before starting with the protocol to being “mildly negative and cautious.” I have written this note not to just discourage someone from pursuing the Protocol, but rather to point to a few things that you should keep in mind.

Some Lessons from Experience

In hindsight there are a few lessons I can draw that maybe helpful to anyone who is considering Bredesen Protocol for a loved one.

First, when at the time of Peg’s diagnosis by the neurologist, I wish we had taken his advice on following the Mediterranean diet and focusing on “PMS” (physical/mental/social) more seriously. We tried to follow but not nearly as rigorously as we did when we started on Bredesen. At the same time, I wish the neurologist had some resource persons(s) in his practice or as a referral for us to work with a nutritionist and coach in implementing the recommendation. Such a resource would have been extremely useful as lifestyle changes are often not easy and it would have helped to have someone to help us along.

Second, when we discovered that Peg also had “moderate” sleep apnea, we should have taken the diagnosis more seriously and gotten her fitted with the machine they recommended. We somehow thought that since the diagnosis is only “moderate apnea”, the machine is not that critical. We were wrong. I have since discovered in my research that interruptions in oxygen going to the brain, even if occasional, can be damaging. Again, I wish the neurologist had been stronger in recommending that Peg be fitted with the machine and not make it sound optional.

Third, if you decide to try Bredesen, spend some time selecting the practitioner. Do not assume that just because the name appears on the list provided by Apollo after the Recode report that s/he is somehow accredited. Call Apollo and insist that you need professional advice not just a list of practitioners without any endorsement. And then ask questions from the ones you talk about your Recode report and the sequence of interventions that s/he would implement. Ask about the supplements – how many, which ones, any side effects, etc. And how will s/he monitor progress. I wish I had not just taken the protocol at face value.

Fourth, I would hope that Apollo would become more patient-oriented and not as commercial as it seems to be. It needs to do much more to interact with patients and answer questions. It should not be asking too much for it to have a few trained practitioners on its roster who can advise anyone considering Bredesen and also be a resource to the practitioner in case s/he wished to discuss progress (or lack thereof as in our case).

Finally, while I hope you are successful with your treatment with Bredesen, be prepared for failure as well even after you have worked hard and spent a lot of money. The impression in Dr. Bredesen’s book that you will see definite improvement in cognition, is vastly overstated and perhaps even misleading. Since our experience, I have known of two other cases like Peg’s, where following the Bredesen regime did not help.

[1] Reversal of cognitive decline in Alzheimer's disease, Dale E. Bredesen, Edwin C. Amos, Jonathan Canick, Mary Ackerley, Cyrus Raji, Milan Fiala, and Jamila Ahdidan8 – June 2016