Memory Loss Associated with Alzheimer’s Reversed for First Time

Small trial from UCLA and Buck Institute succeeds using systems approach to memory disorders.

Patient one had two years of progressive memory loss. She was considering quitting her job, which involved analyzing data and writing reports, she got disoriented driving, and mixed up the names of her pets. Patient two kept forgetting once familiar faces at work, forgot his gym locker combination, and had to have his assistants constantly remind him of his work schedule. Patient three’s memory was so bad she used an iPad to record everything, then forgot her password. Her children noticed she commonly lost her train of thought in mid-sentence, and often asked them if they had carried out the tasks that she mistakenly thought she had asked them to do.

Since its first description over 100 years ago, Alzheimer’s disease has been without effective treatment. That may finally be about to change: in the first, small study of a novel, personalized and comprehensive program to reverse memory loss, nine of 10 participants, including the ones above, displayed subjective or objective improvement in their memories beginning within 3-to-6 months after the program’s start. Of the six patients who had to discontinue working or were struggling with their jobs at the time they joined the study, all were able to return to work or continue working with improved performance. Improvements have been sustained, and as of this writing the longest patient follow-up is two and one-half years from initial treatment. These first ten included patients with memory loss associated with Alzheimer’s disease (AD), amnestic mild cognitive impairment (aMCI), or subjective cognitive impairment (SCI; when a patient reports cognitive problems). One patient, diagnosed with late stage Alzheimer’s, did not improve.

The study, which comes jointly from the UCLA Mary S. Easton Center for Alzheimer’s Disease Research and the Buck Institute for Research on Aging, is the first to suggest that memory loss in patients may be reversed, and improvement sustained, using a complex, 36-point therapeutic program that involves comprehensive changes in diet, brain stimulation, exercise, optimization of sleep, specific pharmaceuticals and vitamins, and multiple additional steps that affect brain chemistry.

The findings, published in the current online edition of the journal Aging, “are very encouraging. However, at the current time the results are anecdotal, and therefore a more extensive, controlled clinical trial is warranted,” said Dale Bredesen, the Augustus Rose Professor of Neurology and Director of the Easton Center at UCLA, a professor at the Buck Institute, and the author of the paper.

This image shows a drawing of a brain slice shrunken due to Alzheimer's disease.
The study is the first to suggest that memory loss in patients may be reversed, and improvement sustained, using a complex, 36-point therapeutic program that involves comprehensive changes in diet, brain stimulation, exercise, optimization of sleep, specific pharmaceuticals and vitamins, and multiple additional steps that affect brain chemistry. This image is for illustrative purposes only. Credit NIH/NIA.

In the case of Alzheimer’s disease, Bredesen notes, there is not one drug that has been developed that stops or even slows the disease’s progression, and drugs have only had modest effects on symptoms. “In the past decade alone, hundreds of clinical trials have been conducted for Alzheimer’s at an aggregate cost of over a billion dollars, without success,” he said.

Other chronic illnesses such as cardiovascular disease, cancer, and HIV, have been improved through the use of combination therapies, he noted. Yet in the case of Alzheimer’s and other memory disorders, comprehensive combination therapies have not been explored. Yet over the past few decades, genetic and biochemical research has revealed an extensive network of molecular interactions involved in AD pathogenesis. “That suggested that a broader-based therapeutics approach, rather than a single drug that aims at a single target, may be feasible and potentially more effective for the treatment of cognitive decline due to Alzheimer’s,” said Bredesen.

While extensive preclinical studies from numerous laboratories have identified single pathogenetic targets for potential intervention, in human studies, such single target therapeutic approaches have not borne out. But, said Bredesen, it’s possible addressing multiple targets within the network underlying AD may be successful even when each target is affected in a relatively modest way. “In other words,” he said, “the effects of the various targets may be additive, or even synergistic.”

The uniform failure of drug trials in Alzheimer’s influenced Bredesen’s research to get a better understanding of the fundamental nature of the disease. His laboratory has found evidence that Alzheimer’s disease stems from an imbalance in nerve cell signaling: in the normal brain, specific signals foster nerve connections and memory making, while balancing signals support memory loss, allowing irrelevant information to be forgotten. But in Alzheimer’s disease, the balance of these opposing signals is disturbed, nerve connections are suppressed, and memories are lost.

The model of multiple targets and an imbalance in signaling runs contrary to the popular dogma that Alzheimer’s is a disease of toxicity, caused by the accumulation of sticky plaques in the brain. Bredesen believes the amyloid beta peptide, the source of the plaques, has a normal function in the brain – as part of a larger set of molecules that promotes signals that cause nerve connections to lapse. Thus the increase in the peptide that occurs in Alzheimer’s disease shifts the memory-making vs. memory-breaking balance in favor of memory loss.

Given all this, Bredesen thought that rather than a single targeted agent, the solution might be a systems type approach, the kind that is in line with the approach taken with other chronic illnesses—a multiple-component system.

“The existing Alzheimer’s drugs affect a single target, but Alzheimer’s disease is more complex. Imagine having a roof with 36 holes in it, and your drug patched one hole very well—the drug may have worked, a single “hole” may have been fixed, but you still have 35 other leaks, and so the underlying process may not be affected much.”

Bredesen’s approach is personalized to the patient, based on extensive testing to determine what is affecting the plasticity signaling network of the brain. As one example, in the case of the patient with the demanding job who was forgetting her way home, her therapeutic program consisted of some, but not all of the components involved with Bredesen’s therapeutic program, and included:

(1) eliminating all simple carbohydrates, leading to a weight loss of 20 pounds; (2) eliminating gluten and processed food from her diet, with increased vegetables, fruits, and non-farmed fish; (3) to reduce stress, she began yoga; (4) as a second measure to reduce the stress of her job, she began to meditate for 20 minutes twice per day; (5) she took melatonin each night; (6) she increased her sleep from 4-5 hours per night to 7-8 hours per night; (7) she took methylcobalamin each day; (8) she took vitamin D3 each day; (9) fish oil each day; (10) CoQ10 each day; (11) she optimized her oral hygiene using an electric flosser and electric toothbrush; (12) following discussion with her primary care provider, she reinstated hormone replacement therapy that had been discontinued; (13) she fasted for a minimum of 12 hours between dinner and breakfast, and for a minimum of three hours between dinner and bedtime; (14) she exercised for a minimum of 30 minutes, 4-6 days per week.

The results for nine of the 10 patients reported in the paper suggest that memory loss may be reversed, and improvement sustained with this therapeutic program, said Bredesen. “This is the first successful demonstration,” he noted, but he cautioned that the results are anecdotal, and therefore a more extensive, controlled clinical trial is needed.

The downside to this program is its complexity. It is not easy to follow, with the burden falling on the patients and caregivers, and none of the patients were able to stick to the entire protocol. The significant diet and lifestyle changes, and multiple pills required each day, were the two most common complaints. The good news, though, said Bredesen, are the side effects: “It is noteworthy that the major side effect of this therapeutic system is improved health and an optimal body mass index, a stark contrast to the side effects of many drugs.”

The results for nine of the 10 patients reported in the paper suggest that memory loss may be reversed, and improvement sustained with this therapeutic program, said Bredesen. “This is the first successful demonstration,” he noted, but he cautioned that the results need to be replicated. “The current, anecdotal results require a larger trial, not only to confirm or refute the results reported here, but also to address key questions raised, such as the degree of improvement that can be achieved routinely, how late in the course of cognitive decline reversal can be effected, whether such an approach may be effective in patients with familial Alzheimer’s disease, and last, how long improvement can be sustained,” he said.

Cognitive decline is a major concern of the aging population. Already, Alzheimer’s disease affects approximately 5.4 million Americans and 30 million people globally. Without effective prevention and treatment, the prospects for the future are bleak. By 2050, it’s estimated that 160 million people globally will have the disease, including 13 million Americans, leading to potential bankruptcy of the Medicare system. Unlike several other chronic illnesses, Alzheimer’s disease is on the rise–recent estimates suggest that AD has become the third leading cause of death in the United States behind cardiovascular disease and cancer.

Notes about this Alzheimer’s disease research

Multiple entities provided support for the study including the National Institutes of Health (AG16570, AG034427 and AG036975). Please see paper for the complete list.

Contact: Mark Wheeler – UCLA
Source: UCLA press release
Image Source: The image is credited to NIH/NIA and is in the public domain
Original Research: Full open access research for “Reversal of cognitive decline: A novel therapeutic program” by Dale E. Bredesen in Aging. Published online September 27 2014

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  1. Like the Prof said; this is just a descriptive piece of research – but all good ideas start with careful observation and it’s certainly worth following this up in proper trials. Of course the population studied here were very “early” and atypical; if further study shows this approach really works it will be important to tease out which parts of the combination are most important. In addition we must do TWO other things. FIRST take a major public health initiative on diet and exercise which which we already KNOW protect cardiovascular as well as brain health and SECOND continue to refine EARLY accurate diagnosis of the different types of dementia and their prodromal stages.

  2. Donn G….as a personal trainer I share your views…don’t know of anyone who has practiced proper diet, aerobic and anaerobic exercise on a sustained basis who has Alzheimer’s …I’m sure there may be some…but bet the incidence rate is extremely low

    1. Ok that’s just ignorant. My mother went to the gym 4 times a week, ate very healthy overall & still got this beast of a disease. Her BMI was on point and physically her body is still holding up. Ever hear of the APOE4 gene? Well it’s in our family. Not everyone with the gene has it go into effect..that is still a mystery as well other genes. It’s a given that one should exercise and eat right, it’s another given that you will be far more likely to avoid issues….but sometimes that has no bearing on if you have an unfortunate genetic hand or not

      1. Thanks for your unfortunate example of the rare incidence the trainer speaks about from his years working with people. The trainer adds hope to all of us that we can play the odds — and genes not withstanding — the odds are fare better of having our minds into our latest years. You merely contribute, alas, that your mother did all the active and healthy living and the genes got her mind. That is worth sharing, thank you, but why in the world post as though you were calling the trainer’s experience untrue or dumb?

  3. This finally surfaces with corroborating “science” from the general collection of correlations (much less memory loss and such in folks who are very active, who haven’t relied on Xanax and such for “anxiety”, who stay socially engaged, who drink three cups of coffee daily, et all) . . . the collection one of the first centers for gerontology (at Johns Hopkins) has been offering on its website for a long, long while. My first use of Johns Hopkins information was from its gerontology journal when my 70 something father was diagnosed with dementia at the University of Iowa hospital after routine prostate surgery and his family practice doctor took the file and simply kept him on all kinds of suppressing and sedative medications, even after I used the Iowa medical library to find Gerontology joural article about evidence that older patients ‘going crazy’ after surgery was theoretically related to having doctors prescribe drugs at levels too high for how older people process them. The drug testing was mainly on males and much younger. Even the Iowa head neurologist whom I finally reached by rattling at the PR department called the information from the Gerontology journal ‘bad medicine.’ I finally researched enough to phase out the two most likely causes of my father becoming so trembly he could hardly walk and beginning to shout and yelp in the middle of the night . . . two of the medications. I watched him for three weeks. With in days the trembling phased down and he stopped shouting at night and I culd take him back to his hometown to visit his old farmer friends. He lived another 10 years with a pretty high quality of life. And my 80 something brother has had non-geriatric family practice and neurologists sedate him and medicate for this and that, including years of Xanax, so that he has no short term memory and the doctors tell the family not to be “in denial” instead of encouraging my brother to play the odds of cutting back on the wine and ice cream he depends on and drink coffee in the mornings and get up before noon to four p.m. . . . In commonsense theory, if you dampen down your brain activity with sedatives, alcohol, and such and don’t use the brain to move around, the cells will not continue to develop. Of course commonsense says there are other causes in some patients related to genes or whatever, but in general for our entire physical system, including the brain, it is probably a good idea to take the maxim; use it or lose it; start using it again and it will probably begin to grow again.

    1. Elderly patients frequently get confused in hospitals. I have had a number who would be really confused but once they got home, they were fine. I used minimal sedation. The best treatment is familiar surroundings. I am getting old myself and having some memory lapses, minor at present. My wife and I plan to start doing crossword puzzles as therapy. It has worked for elderly colleagues. The diet changes sound questionable but activity and less TV seems basic.

      1. The diet changes sound questionable? Read ‘Grain Brain’ and ‘Stop Alzheimer’s Now.’

      2. You are kidding yourself if you think diet is not worth very careful consideration! Of course fads come and go and that confuses things. However, do a bit of research on sugar. We consume vast quantities of it and its harmful effects pave the way for many chronic illnesses–heart disease, diabetes, etc. Gluten sensitivity does not have to be of the severity that leads to celiac disease. There are levels of sensitivity to gluten and it’s worth eliminating it, even for a period of time, to guage effects.

  4. Interesting that patients would call the program “complex” and complain about certain aspects. Does the benefit not outweigh the alternative of extremely decreased quality of life?

    1. I believe the complex part is the diet and maybe the pills. Going through a similarly extensive diet calibration myself, I can confirm that it is very difficult. I need to basically modify current eating habits and fight food preferences. This is not easy as that would mean learning entirely different menus and adjusting to different food lifestyles.

    2. When people are used to relying on pills, they often rebel against taking control of their own health. They want simple solutions. Of course the benefits outweigh the hassle of embracing a multi-faceted health regime. But it amazes me (as a practitioner) how difficult it can be for people to understand this.Older people in particular are very attached to dietary habits. It’s a difficult adjustment.

  5. Instead of trying to recover brain health after decades of unhealthy behavior, we need to adopt healthy behaviors before brain health decline begins (University of Virginia research estimates brain health begins to decline at age 27).
    Acuity Games is a family of iOS brain games that measures long term changes to brain health. Once we start measuring changes to our brain health, it will nudge us to the healthy behaviors that maintain brain health.

  6. I love the objections people have to changing their life for the better: “The downside to this program is its complexity. It is not easy to follow, with the burden falling on the patients and caregivers, and none of the patients were able to stick to the entire protocol.” Simply put, this describes taking responsibility for your well being.

    As for the results being “anecdotal” another term I have come to ‘love’…I have been applying these fixes into my life for over 24 years. My mother had Alz and I am Vegan, work out almost every day and avoid putting processed ‘food’ in my body and I challenge my brain with new information.

    Studies have shown that nothing improves cognition of people with Alz more than exercise. High Intensity Interval Training is the best thing you can do for your body and brain.

    My friends, take responsibility for your health. There will be no pill that will solve Cancer, heart or brain problems. The power is in your hands to begin healing today..with the next bite of food..will it be health or illness you serve up? A healthful lifestyle will make you happier and more complete in all ways imaginable. Save yourself and your family the financial and emotional burdens of prolonged illness. You can begin today, right now! Eat an apple or have tea with see, it is not complicated as they make you think. Your body craves for the bnatural foods that are healthy and reparative.

    Check out these resources:
    Forks over Knives
    Dr Joel Fuhrman
    Dr Neal Barnard
    Dr. John McDougall

    To just name a few reliable people attuned to helping us all achieve maximum health.

    1. Its better to let problems happen, actually to PROMOTE health problems. So treatments can exist. All about control over you. No prevention. No study of cause. Just plain old treatment, to keep you under the power structure..

    2. Agree with all the points but Forks Over Knives and McDougall are anything but reliable. McDougall wouldn’t know science if it smacked him in the head. And why service a vegetarian agenda when you just said a ‘varied’ approach is healthy??

    3. I agree DonnG, I’ve been doing the elimination diet and feel much better. Alzheimer’s runs in my family and I’m beginning to show some signs in myself. It’s nice to know there are some possible solutions and that I can be proactive. I’m cutting out all processed foods and gluten and also milk, Exercising daily and losing weight. That seems to be the hard part. I’m glad I’m on to a good start, Now to get on to the rest of the program.

    4. Anecdotal has a meaning. This study of ten patients included at least one who only subjectively had symptom improvement. In other words, he or she thought she/he was doing better. There is a great difficulty in diagnosing Alzheimers in the first place. There are other forms of dementia. This article does not state what criteria they used to determine the form of dementia they treated. Right now, nothing has been found to slow or stop alzheimer’s disease. It is common sense to take good care of ourselves with a good diet and exercise; we can hope that will help. But no amount of crossword puzzles, diet change, exercise change, has yet been shown to have any effect.

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