I have had a very personal relationship with Alzheimer’s disease for many years. As a primary care physician I have treated hundreds of patients with this devastating illness for over four decades. My grandmother Amber succumbed to this horrible disease in her 60s and her daughter Pearl (my mother) passed away from this disease a few weeks ago. The medical and research communities have spent a great deal of time searching for possible ways to slow down the progression of Alzheimer’s disease, but to date no effective treatment has been found for this tragic disorder despite the investment of billions of dollars spent on research.
War on Alzheimer’s Isn’t Even a Minor Skirmish
To date the only drugs approved by the FDA for treatment of Alzheimer’s disease are the cholinesterase inhibitors like Aricept and Razadyne, and the glutamate antagonist, Namenda. Although these drugs can offer patients some temporary symptomatic relief for a limited period of time, they do not alter the course of the illness. Currently there are close to a dozen experimental drugs that target Alzheimer pathology in various ways, but despite billions of dollars already spent on these drugs there have been no meaningful breakthroughs. President Obama has declared that our “War on Alzheimer’s Disease” won’t bear fruit until 2025. I don’t know about you but I don’t have that kind of patience.
As a Family Physician with four decades of clinical experience I consider myself to be an empirical scientist or “why guy”. I look around me, make observations and then try to come up with theoretical models that might explain my observations. I then use these models to refine difference therapeutic options that seem to work the best. Most great discoveries in medicine have started with this simple empirical approach, but the details of how things worked out were often quite messy. For example, Ignaz Semmelweis was a physician who is credited with the discovery of infectious diseases in the mid 1800s. He noted that the mortality rate from puerperal sepsis was much higher in women delivered by physicians rather than midwives. He also knew that physicians did autopsies on their patients whereas midwives did not. He postulated that dirty hands from the autopsies were spreading the disease to other patients. He instituted strict hand washing among physicians and the rate of puerperal sepsis dropped dramatically. Despite his rather astounding discovery most of his contemporary physicians ignored his advice and he eventually died in a mental hospital.
What I Have Learned From My Own Family
I also consider myself to be an empirical or observational scientist in Semmelweis’ tradition and to date I have somehow managed to avoid the mental hospital! Over many years I have noticed some interesting trends in the Alzheimer’s patients I was treating and these trends also seemed to extend to my family. In many observational studies Alzheimer’s disease has been clearly associated with vascular problems like heart attacks, strokes and high blood pressure and it also has been strongly tied to metabolic disorders like type 2 diabetes, metabolic syndrome and obesity. My grandmother Welch lived a healthy lifestyle with home cooked meals straight from her large garden but she really loved to bake and whatever she baked she ate. She became obese in her 30’s, developed type 2 diabetes in her 40s, developed Alzheimer’s disease in her 50s and died in her 60s.
Her daughter Pearl (my mother) wasn’t much of a baker and she ate a very healthy Mediterranean style diet throughout her life. She also enjoyed walking every day. She never became obese and didn’t develop type 2 diabetes. She did develop Alzheimer’s disease over 30 years ago, yet her disease has progressed so slowly that her physicians have questioned the diagnosis. To me this illustrates the powerful influence that diet can have on the development and clinical course of Alzheimer’s disease.
The term “type 3 diabetes” has been proposed as a new term for Alzheimer’s disease because of the close associations between insulin resistance in the brain and classical Alzheimer’s disease. Thus to date we have the empirical clinicians looking at Alzheimer’s associations with inflammatory and metabolic disorders while the academic researchers are chasing clues from basic research to come up with targeted treatments but this approach has mainly led to dead ends. In other words, despite tremendous amounts of effort and money thrown at this disease, we have seen little or no progress at actually reversing or effectively treating Alzheimer’s disease.
The Complexity of Biology Often Doesn’t Favor “Magic Bullets”
As an empirical scientist I have also learned another valuable lesson. When dealing with an illness that combines a complex biological picture with multiple genetic factors and a variable clinic course, looking for “magic bullets” when it comes to treatment usually only leads to frustration and less than impressive results. An example might be helpful. Years ago I proposed a new disease model to help explain the clinical picture that I was seeing in many of my patients. Over many years of observation I noticed that many of these patients seemed to develop predictable brain dysfunction symptoms along with progressive metabolic problems like obesity, type 2 diabetes and insulin resistance. It also seemed evident to me that the brain dysfunction symptoms usually occurred prior to most of the metabolic problems suggesting that with this disorder the brain was calling the shots. Over many years it became clear to me that the consumption of highly processed food seemed to be the primary trigger of this disorder which I now call Carbohydrate Associated Reversible Brain syndrome or CARB syndrome.
Science in the Trenches
Because of the complexity of this new disorder it took me years to figure out the most effective way to treat and reverse CARB syndrome. Eliminating highly processed food was of course the core of my treatment protocol but this was easier said than done because of their poorly functioning brains. The lead symptom of CARB syndrome is craving sweet and starchy food so I had to wrestle with ways to suppress these cravings. Patients with significant brain dysfunction also typically had some of the other 22 symptoms of CARB syndrome like difficulty concentrating and focusing, mood swings, poor impulse control, impaired memory and internal restlessness. I learned that if my therapeutic approach simply consisted of telling patients to avoid highly processed food, very few patients could comply because of their other brain dysfunction symptoms. Thus over the years I learned many different methods of improving and restoring good brain function so patients could actually comply with my lifestyle recommendation. I would tell patients that they would need to do at least a dozen things or more to regain their health and sure enough, over time this approach worked remarkably well.
CARB Syndrome: The Elephant in the Room
Here is where things get really interesting. Even though CARB syndrome is a new and unproven disease concept, I have found it to be immensely useful when managing complex patients in the real world. In my opinion this disease stealthily emerged over the past 40-50 years as processed foods took over our diet, yet it was missed by the academic and medical professions. Because the 22 symptoms of CARB syndrome overlap with many traditional brain disorders, this has created a great deal of diagnostic confusion. An example might be helpful. Years ago all patients with major depression lost their appetite and lost weight. You simply couldn’t make a diagnosis of major depression without these defining parameters. Over the past 40-50 years we gradually started to see a lot of depressed patients with an increased appetite and weight gain. The folks at DSM (Diagnostic and Statistical Manual and Mental Disorders) didn’t quite know how to handle this situation when they recently came out with their 5th addition so they punted and changed their criteria to “significant weight change ( >5%) or change in appetite”. This weight category would be one of nine qualifying characteristics of major depression and to make the diagnosis you would need to have five of the nine.
Thus when you really think about it the issue of weight, which was once a key component of depression, was really no longer relevant because you could be diagnosed with depression regardless of what was happening to your weight. They should have thrown the issue of weight out for no longer being relevant, but I think on some level they knew that wasn’t right. In my opinion the “weight gain” type of depression really is CARB syndrome, not true major depression. Because CARB syndrome is extremely common you will usually find it co-mingling with common brain disorders like ADHD, autism, depression, bipolar disorder and dementia. Over the years when I encountered patients who appeared to have both CARB syndrome and another brain disorder I would treat them with the standard treatment for their accepted disorder combined with my dozen or more brain enhancing treatments that were specifically targeted at CARB syndrome. These included everything from dietary changes, relaxation techniques and targeted supplements. When patients complied with most of these treatments they usually responded remarkably well. For example, both their major depression or other classical illness and their CARB syndrome dramatically improved. Their brain function was much better and their metabolic health significantly improved. I refer to this multifaceted treatment of CARB syndrome as my “shotgun” therapy.
Shotgun and MEND: Two Sides of the Same Coin?
Recently I came across a fascinating article that was published in 2014 titled “Reversal of Cognitive Decline: A Novel Therapeutic Program” by Dale E. Bredesen. Dr. Bredesen utilized an approach called “metabolic enhancement for neurodegeneration” or MEND. This approach involves using 36 different factors thought to play a role in Alzheimer’s type dementia. Dr. Bredesen and his team recognized that there was no “magic bullet” on the horizon to treat Alzheimer’s disease so he took the same approach that I used to treat CARB syndrome—throw everything at it but the kitchen sink using factors that are suspected of being involved in the underlying pathology.
This certainly isn’t your mother’s evidence based medicine. The traditional approach to medical research is to isolate one variable and control all the others. In 50% of the patients the variable is then subjected to some type of therapeutic intervention and the other 50% is subjected to a blinded but non-effective intervention. For the intervention to be effective it must have the desired therapeutic outcome in enough cases to reach statistical significance. This “double blind” approach works fairly well for drugs and other well demarcated interventions but it clearly will not work when you are trying to influence complex disorders like Alzheimer’s disease or CARB syndrome.
Dr. Bredesen took a rather radical approach and looked at the biology and basic science of Alzheimer’s disease and then he looked for possible interventions to target specific aspects of dementia. Of course many of these interventions have never been studied in controlled trials so a key element of his approach was to use only interventions with little or no known risk. Although his study was limited to 10 patients over a period of several years all but one of the patients made remarkable recoveries in mental functioning. Several who had quit working were able to return to work. He published a follow up paper this year further documenting the remarkable response to his MEND approach. This approach has 25 distinct elements each targeted a different biological aspects of dementia. It is rather broad and complex so if you are interested in the details I suggest you read his original paper or his follow up paper. Today there are hundreds of patients on the MEND protocol
The Clinical Worlds and Academic Worlds Collide
After reading Bredesen’s papers I immediately recognized his approach because this is almost identical to the approach that I have utilized when managing CARB syndrome. Bredesen has utilized complex computer modeling to come up with some of his protocols whereas I have relied strictly on my knowledge of the literature and decades of empirical observations of my patients. The core of my treatment is getting people off of highly processed food and to do so when patients have advanced disease I need to address their strong cravings for sweet and starchy food by using certain low dose medications and supplements. I also have about 15-20 standard recommendations that I make to patients and many of them are simply targeted to enhancing brain function. After all, people with CARB syndrome by definition have a poorly functioning brain. In choosing my treatment modalities I base my decisions on possible effectiveness from uncontrolled studies and a very low risk of significant side effects. Over years and decades I used empirical observations to monitor how each of these treatments seemed to work in my patients and then I would make appropriate adjustments to my treatment protocols. As this process slowly progressed, I noticed that many patients with CARB syndrome seemed to gradually return to a normal healthy state with no residual evidence of the disease. In other words, I was getting similar results to those obtained by Dr. Bredesen only we were treating two different brain diseases. Or were we?
This is where it gets interesting—and very complex. I have proposed that CARB syndrome is a form of food-induced brain dysfunction that fits the criteria of being a disease, albeit one that was missed by the medical and academic communities. Hudson and Pope first proposed that a group of common brain disorders were actually part of the same disease process that they called Affective Spectrum Disorder (ASD). Because they never identified the triggers or the pathology of ASD, their concept never made it out of academic medicine. The diagnosis of CARB syndrome is based on the presence of many of the 22 typical brain dysfunction symptoms of the illness. It’s interesting to note that dementia was not included in their ASD concept nor in my CARB syndrome concept. So what does this have to do with dementia? Both Alzheimer’s disease and CARB syndrome (or ASD for that matter) are quite common so there are many individuals who have both disorders. The same is true for other common disorders like major depression, bipolar disorder, ADHD, autism, PTSD, anxiety disorders and other conditions. When you mix two diseases together in the same person, they have overlapping symptoms and one of the disorders has yet to be recognized by the scientific community you end up with a real clinical mess. It’s like pouring gas on a fire.
Regardless of Labels Go With the Treatment that Works
I’m going to go out on a limb here and speculate that some of the 10 patients in Dr. Bredesen’s study had both Alzheimer’s disease and CARB syndrome. Many of the interventions that he outlines in the paper are identical to those I have used for treating patients with CARB syndrome who clearly do not have dementia. The good news is that they likely work for both disorders because they are targeted at improving brain function. For example in his study they placed patients on low glycemic and low grain diets combined with intermittent fasting. This combination has been found helpful for treating many different metabolic disorders and it is a key component for reversing or preventing CARB syndrome.
Let me try to summarize what appears on the surface to be a complex issue.
- Both CARB syndrome and Alzheimer’s disease are fairly easy to diagnose over time and they both have their own typical symptoms that sometimes overlap with each other.
- Both conditions respond very well to a program like MEND outlined in Dr. Bredesen’s article or my shotgun approach briefly described in this paper. Although further research is needed, because the treatments in the MEND protocol are extremely low risk, I think they can be integrated into the standard of care for these diseases unless further research suggests that this approach is not effective.
- Because I have been using a MEND like approach to treat thousands of patients over many decades, I am fairly certain that this approach will also be helpful for a long list of common brain disorders including major depression, anxiety disorders, PMS, PTSD, bipolar II, IBS, fibromyalgia, CFS, autism, eating disorders and other related conditions. In my opinion at the present time the benefit/risk ratio is likely favorable for using this approach in all of these disorders in combination with appropriate drug therapy.
I don’t know about you but I believe we are on the cusp of a major revolution in the way we manage common brain disorders and I am very excited to be riding this wave.
