By Paddy Kamen, publisher BetterBrainBetterLife.com
Dale Bredesen Is it possible to turn Alzheimer’s around, to have someone walk back from a diagnosis, return to work, recall foreign languages that were lost to them, and re-grow hippocampal volume? The latest research says yes, but is that research sound? This article covers the details of this groundbreaking research, along with criticism of it.
What constitutes crazy talk with respect to Alzheimer's treatment may be a matter of opinion. Click 'Read More' below to see where the battle lines are being drawn.
What constitutes crazy talk with respect to Alzheimer's treatment may be a matter of opinion. Click 'Read More' below to see where the battle lines are being drawn.
In 2014, Dr. Dale Bredesen, Augustus Rose Professor of Neurology at the David Geffen School of Medicine at UCLA, and founding president of the Buck Institute for Research on Aging, published the results of a small study in which he claimed to have reversed Alzheimer’s in 10 patients. That was exciting news but, understandably, it was cautiously received, as the trial was small and anecdotal, with no control group.[1]
The results of a follow-up study were published in June 2016.[2] This research (again with 10 patients) involved more extensive measuring of objective factors such as hippocampal volume and factors having to do with metabolism, stress and inflammation. Neuropsychological testing, including verbal memory, visual memory, executive function and processing speed were also assessed before and after the protocol.
Bredesen’s treatment approach, known as metabolic enhancement for
neurodegeneration (MEND), is multifactorial and personalized. He justifies this approach in his 2014 paper: “Based on the hypothesis that AD (Alzheimer’s disease) results from an imbalance in an extensive plasticity network, the therapy should address as many of the network components as possible, with the idea that a combination may create an effect that is more than the sum of the effects of many monotherapeutics...Just as for other chronic illnesses such as osteoporosis, cancer, and cardiovascular disease, the underlying network features a threshold effect, such that, once enough of the network components have been impacted, the pathogenetic process would be halted or reversed. Therefore, even though it is not expected that most patients will be able to follow every single step of the protocol, as long as enough steps are followed to exceed the threshold, that should be sufficient.”[3]
And so the MEND protocol aims to address Alzheimer’s by giving the body/mind what it needs to function optimally, including: hormone replacement where indicated, low glycemic, low inflammatory, low grain diets to minimize inflammation and reduce insulin resistance, reducing stress via yoga, meditation and/or music), optimizing sleep (and checking for sleep apnea), exercise, brain stimulation via computerized brain training, vitamin, mineral and anti-oxidant supplementation (to support neurosynaptic health and reduce inflammation, among other things), and improving gastro-intestinal health.
There are some incredible reversals found among the 10 patients involved in the 2016 research. One patient, with a well-documented case of mild cognitive impairment (MCI), had an increase in hippocampal volume from the 17th percentile to the 75th percentile after 10 months, along with a reversal of cognitive decline. One woman regained the ability to speak several languages, another the ability to do complex math in her head, one man went back to running his own business after being on the brink of giving it up. In some cases, previous diagnoses of disease by outside health experts were reversed. These are amazing gains!
As someone who has experienced personal challenges with brain fog throughout my adult life, and who has seen good results from dietary changes, gut-health treatments, brain training, exercise and meditation, I think Bredesen’s approach is bang on. I have also worked with naturopathic doctors who have specialties in neuro-issues and am struck by how similar MEND is to their multifactorial approach to brain health.
Dr. Pamela Hutchison is one such ND. I interviewed her last June at her practice in Victoria B.C., about the Bredensen protocol. She knew of his 2014 paper but had not yet learned about the then-just-published second study. Hutchison works exclusively with patients suffering from mental health challenges, brain injuries and diseases, and cognitive issues. She says the results of Bredesen’s work is, “deeply validating for me. The multi-systems, multi-causal approach makes sense. In wholistic medicine we look at the whole person not just separate systems. The microbiome is a good example of that. Science is now realizing that the gut affects cognition, mood, asthma risk and perhaps even autism.”
Hutchinson was eager to read the latest Bredesen research herself. “I have seen people with Alzheimer’s begin to feel better and improve their memory but to actually reverse it is groundbreaking. Of course, the research will have to be reproduced many times to become believable, but I think he is on the right track.”
Critics of Bredesen’s research include Dr. David Gorski, who blogs as Orac. Dr.Gorski is a surgical oncologist at the Barbara Ann Karmanos Cancer Institute in Detroit, specializing in breast cancer surgery. Dr. Gorski appears to be generally disparaging of what some call ‘integrative medicine’ or ‘functional medicine’ and alternative medicine in general. To my reading, however, he raises some good points, including the fact that the published articles describing Bredesen’s research are very sketchy with respect to details, including describing how decisions were made as to what interventions were given to which patients, how the patients were selected to participate in the study (he wonders if Bredesen cherry-picked patients who showed the best results rather than using a consecutive sample of patients, which is the standard for studies such as these), and the fact that there was no control group. He states: “While a preliminary case series of 10 subjects is not unreasonable as a pilot study, without a clear description of inclusion criteria, how each set of interventions was chosen for each patient, clear descriptions of the exact protocol followed, and predefined criteria for success, a case series like Bredesen’s is virtually worthless, even to tell us if there’s anything worth following up on with a randomized controlled trial.”[4]
As anyone who follows integrative-alternative-functional medicine knows, controlled trials using a multifactorial, personalized approach are difficult to conduct and very costly.[5] In an interview with Chris Kresser, Bredesen says he was close to having a trial approved in Australia but it was turned down by an Independent Review Board (IRB). He recounts: “They said, “Obviously you don’t understand how to do a clinical trial because you’re trying to change more than one variable.” And we said, “Obviously you don’t understand how Alzheimer’s disease works, because it’s not a one-variable disease…. Surprisingly, the very physicians who were on the IRBs that turned it down then turned around and said to us, “Can we use it anyway in our own practices?”
Kresser notes: “Of course, one of the key principles of functional medicine … is that it’s personalized. It’s not single disease, single treatment. This is what your model illustrates so beautifully. You could have three different patients with the same disease label and they’ll get three different treatments because the pathologies that are driving those diseases are different in each of those three patients. Same disease, but different pathologies, so you get a different treatment.”[6]
I realize that the approach of Bredesen and Kresser still sounds like crazy talk to some people deeply embedded in allopathic medicine. But we know now that the determinants of health are many, we understand so much more about the mind-body connection, and systems theory is mounting a vigorous assault on mechanistic thinking in medicine and elsewhere.
It’s important to note that Bredesen did not invent a multifactorial approach to Alzheimer’s. He is building on the research of others and implementing an approach to brain and cognitive health that has received little respect and much criticism until now. Some of the criticism of this systems/holistic approach is valid, and we must also ask if some of it is motivated by resistance to change and a lack of imagination.
One of the great gifts of Bredesen’s research may be that his academic credentials lend validity to the previously unrecognized work of others. He’s clearly willing to go out on a limb and for that I congratulate him. Given the social, economic and personal costs of Alzheimer's disease, many people are, in my view, rightly encouraged by this news.
The results of a follow-up study were published in June 2016.[2] This research (again with 10 patients) involved more extensive measuring of objective factors such as hippocampal volume and factors having to do with metabolism, stress and inflammation. Neuropsychological testing, including verbal memory, visual memory, executive function and processing speed were also assessed before and after the protocol.
Bredesen’s treatment approach, known as metabolic enhancement for
neurodegeneration (MEND), is multifactorial and personalized. He justifies this approach in his 2014 paper: “Based on the hypothesis that AD (Alzheimer’s disease) results from an imbalance in an extensive plasticity network, the therapy should address as many of the network components as possible, with the idea that a combination may create an effect that is more than the sum of the effects of many monotherapeutics...Just as for other chronic illnesses such as osteoporosis, cancer, and cardiovascular disease, the underlying network features a threshold effect, such that, once enough of the network components have been impacted, the pathogenetic process would be halted or reversed. Therefore, even though it is not expected that most patients will be able to follow every single step of the protocol, as long as enough steps are followed to exceed the threshold, that should be sufficient.”[3]
And so the MEND protocol aims to address Alzheimer’s by giving the body/mind what it needs to function optimally, including: hormone replacement where indicated, low glycemic, low inflammatory, low grain diets to minimize inflammation and reduce insulin resistance, reducing stress via yoga, meditation and/or music), optimizing sleep (and checking for sleep apnea), exercise, brain stimulation via computerized brain training, vitamin, mineral and anti-oxidant supplementation (to support neurosynaptic health and reduce inflammation, among other things), and improving gastro-intestinal health.
There are some incredible reversals found among the 10 patients involved in the 2016 research. One patient, with a well-documented case of mild cognitive impairment (MCI), had an increase in hippocampal volume from the 17th percentile to the 75th percentile after 10 months, along with a reversal of cognitive decline. One woman regained the ability to speak several languages, another the ability to do complex math in her head, one man went back to running his own business after being on the brink of giving it up. In some cases, previous diagnoses of disease by outside health experts were reversed. These are amazing gains!
As someone who has experienced personal challenges with brain fog throughout my adult life, and who has seen good results from dietary changes, gut-health treatments, brain training, exercise and meditation, I think Bredesen’s approach is bang on. I have also worked with naturopathic doctors who have specialties in neuro-issues and am struck by how similar MEND is to their multifactorial approach to brain health.
Dr. Pamela Hutchison is one such ND. I interviewed her last June at her practice in Victoria B.C., about the Bredensen protocol. She knew of his 2014 paper but had not yet learned about the then-just-published second study. Hutchison works exclusively with patients suffering from mental health challenges, brain injuries and diseases, and cognitive issues. She says the results of Bredesen’s work is, “deeply validating for me. The multi-systems, multi-causal approach makes sense. In wholistic medicine we look at the whole person not just separate systems. The microbiome is a good example of that. Science is now realizing that the gut affects cognition, mood, asthma risk and perhaps even autism.”
Hutchinson was eager to read the latest Bredesen research herself. “I have seen people with Alzheimer’s begin to feel better and improve their memory but to actually reverse it is groundbreaking. Of course, the research will have to be reproduced many times to become believable, but I think he is on the right track.”
Critics of Bredesen’s research include Dr. David Gorski, who blogs as Orac. Dr.Gorski is a surgical oncologist at the Barbara Ann Karmanos Cancer Institute in Detroit, specializing in breast cancer surgery. Dr. Gorski appears to be generally disparaging of what some call ‘integrative medicine’ or ‘functional medicine’ and alternative medicine in general. To my reading, however, he raises some good points, including the fact that the published articles describing Bredesen’s research are very sketchy with respect to details, including describing how decisions were made as to what interventions were given to which patients, how the patients were selected to participate in the study (he wonders if Bredesen cherry-picked patients who showed the best results rather than using a consecutive sample of patients, which is the standard for studies such as these), and the fact that there was no control group. He states: “While a preliminary case series of 10 subjects is not unreasonable as a pilot study, without a clear description of inclusion criteria, how each set of interventions was chosen for each patient, clear descriptions of the exact protocol followed, and predefined criteria for success, a case series like Bredesen’s is virtually worthless, even to tell us if there’s anything worth following up on with a randomized controlled trial.”[4]
As anyone who follows integrative-alternative-functional medicine knows, controlled trials using a multifactorial, personalized approach are difficult to conduct and very costly.[5] In an interview with Chris Kresser, Bredesen says he was close to having a trial approved in Australia but it was turned down by an Independent Review Board (IRB). He recounts: “They said, “Obviously you don’t understand how to do a clinical trial because you’re trying to change more than one variable.” And we said, “Obviously you don’t understand how Alzheimer’s disease works, because it’s not a one-variable disease…. Surprisingly, the very physicians who were on the IRBs that turned it down then turned around and said to us, “Can we use it anyway in our own practices?”
Kresser notes: “Of course, one of the key principles of functional medicine … is that it’s personalized. It’s not single disease, single treatment. This is what your model illustrates so beautifully. You could have three different patients with the same disease label and they’ll get three different treatments because the pathologies that are driving those diseases are different in each of those three patients. Same disease, but different pathologies, so you get a different treatment.”[6]
I realize that the approach of Bredesen and Kresser still sounds like crazy talk to some people deeply embedded in allopathic medicine. But we know now that the determinants of health are many, we understand so much more about the mind-body connection, and systems theory is mounting a vigorous assault on mechanistic thinking in medicine and elsewhere.
It’s important to note that Bredesen did not invent a multifactorial approach to Alzheimer’s. He is building on the research of others and implementing an approach to brain and cognitive health that has received little respect and much criticism until now. Some of the criticism of this systems/holistic approach is valid, and we must also ask if some of it is motivated by resistance to change and a lack of imagination.
One of the great gifts of Bredesen’s research may be that his academic credentials lend validity to the previously unrecognized work of others. He’s clearly willing to go out on a limb and for that I congratulate him. Given the social, economic and personal costs of Alzheimer's disease, many people are, in my view, rightly encouraged by this news.
[1] Dale E. Bredesen, Reversal of cognitive decline: A novel therapeutic program, AGING, Vol 6, No 9, 2014.
[2] Dale E. Bredesen, Reversal of Cognitive Decline in Alzheimer’s Disease, AGING, Vol 8 No 6, 2016.
[3] ibid
[4] Gorski, David, aka ‘Orac’. Blog post. http://scienceblogs.com/insolence/2016/06/24/the-mend-protocol-for-alzheimers-disease-functional-medicine-on-steroids-revisited/
Gorski also questions possible conflict of interest in Bredesen’s case: “There are other red flags. For instance, Bredesen didn’t disclose some relevant conflicts of interest (COIs). One such COI was that he was one of the founders of Muses Labs. He didn’t disclose this for his 2014 paper. Of course, he is no longer affiliated with Muses Labs, but that doesn’t mean he doesn’t still have a COI.”
[5] Read this article from Nature for a perspective on single patient research, or n-of-1 clinical trials: http://www.nature.com/news/personalized-medicine-time-for-one-person-trials-1.17411
[6] Chris Kresser interview with Dale Bredesen: http://chriskresser.com/prevention-and-treatment-of-alzheimers-from-a-functional-perspective-with-dr-dale-bredese
[2] Dale E. Bredesen, Reversal of Cognitive Decline in Alzheimer’s Disease, AGING, Vol 8 No 6, 2016.
[3] ibid
[4] Gorski, David, aka ‘Orac’. Blog post. http://scienceblogs.com/insolence/2016/06/24/the-mend-protocol-for-alzheimers-disease-functional-medicine-on-steroids-revisited/
Gorski also questions possible conflict of interest in Bredesen’s case: “There are other red flags. For instance, Bredesen didn’t disclose some relevant conflicts of interest (COIs). One such COI was that he was one of the founders of Muses Labs. He didn’t disclose this for his 2014 paper. Of course, he is no longer affiliated with Muses Labs, but that doesn’t mean he doesn’t still have a COI.”
[5] Read this article from Nature for a perspective on single patient research, or n-of-1 clinical trials: http://www.nature.com/news/personalized-medicine-time-for-one-person-trials-1.17411
[6] Chris Kresser interview with Dale Bredesen: http://chriskresser.com/prevention-and-treatment-of-alzheimers-from-a-functional-perspective-with-dr-dale-bredese