Alzheimer’s disease progressively erodes memory. Now Dale Bredesen, M.D. of the UCLA Mary S. Easton Center for Alzheimer’s Disease Research and the Buck Institute for Research on Aging reports a successful therapy that restored memory in 9 of 10 Alzheimer’s patients. He published his findings online, ahead of the print edition, in the journal Aging.
The study is the first to suggest that memory loss may be reversed, and improvement sustained, using a complex, 36-point therapeutic program, which involves comprehensive diet changes, brain stimulation, exercise, sleep optimization, specific medications, vitamin supplements, and multiple other therapies steps that affect brain chemistry. When they joined the study, six patients had stopped working or had been experiencing difficulties at their jobs. All of these patients were able to return to their jobs or continue working with improved performance, and their improvements held up over time. The patient in treatment the longest has been receiving the therapy for two-and-a-half years. One patient who had been diagnosed with late stage Alzheimer’s did not improve.
Patient 1 had experienced two years of progressive memory loss. She was on the verge of quitting her job, which involved analyzing data and writing reports. She became disoriented driving and she mixed up the names of her pets. Patient 2 kept forgetting once-familiar faces at work, forgot his gym locker combination, and relied on his assistants constantly remind him of his work schedule. Patient 3’s memory had deteriorated to a point that she was forced to use an iPad to record everything; then, she forgot her password. Her children noticed she commonly lost her train of thought in mid-sentence, and often asked them if they had completed the tasks that she mistakenly thought she had asked them to do.
Dr. Bredesen, UCLA’s Augustus Rose Professor of Neurology, said that the findings are “very encouraging,” but he added that the results are anecdotal, and a more extensive, controlled clinical trial is needed. No single medication has been found to halt or even slow the progression of Alzheimer’s; furthermore, Alzheimer’s medications have only had modest effects on symptoms. “In the past decade alone, hundreds of clinical trials have been conducted for Alzheimer’s, without success, at an aggregate cost of over $1 billion,” explained Dr. Bredesen.
Dr. Bredesen notes that the use of combination therapies, comprehensive combination therapies have not been evaluated for Alzheimer’s and other memory disorders. However, over the past few decades, genetic and biochemical research has shown that an extensive network of molecular interactions involved in the development of Alzheimer’s. He explained. “That suggested that a broader-based therapeutic 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.”
Dr. Bredesen noted that extensive preclinical studies have identified single targets for potential intervention; however, in human studies, such single target therapeutic approaches have not achieved positive results. He said that it is possible that evaluating multiple targets within the network underlying Alzheimer’s might be successful even when each target is affected in a relatively modest way. He explained, “In other words, the effects of the various targets may be additive, or even synergistic.” (Synergism is when the combination of two therapies work together to produce an enhanced effect.)
Dr. Bredesen’s has found evidence that Alzheimer’s develops from an imbalance in nerve cell signaling. In the normal brain, specific signals promoter nerve connections and memory making, while balancing signals support memory loss; thus, allowing irrelevant information to be forgotten. However in Alzheimer’s sufferers, the balance of these opposing signals is disrupted, nerve connections are suppressed, and memories are lost. His finding contradicts the popular belief that Alzheimer’s is caused by the accumulation of sticky plaques in the brain. He 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 stimulate signals that cause nerve connections to lapse. Therefore, the increase in the peptide that occurs in Alzheimer’s shifts the balance in favor of memory loss.
In view of the foregoing, Dr. Bredesen felt that, rather than a single targeted agent, the solution might be a multiple-component system approach, which is similar to that for other chronic illnesses. He explained, “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,” he said. “The drug may have worked, and a single hole may have been fixed, but you still have 35 other leaks, and so the underlying process may not be affected much.”
Dr. Bredesen’s strategy is personalized to the patient; it is based on extensive testing to determine what is affecting the brain’s plasticity signaling network. In the case of the patient with the demanding job who was forgetting her way home, her therapy consisted of some, but not all, of the components of his program, including: eliminating all simple carbohydrates, gluten and processed food from her diet, and eating more vegetables, fruits and non-farmed fish; meditating twice a day and beginning yoga to reduce stress; sleeping seven to eight hours per night, up from four to five; taking melatonin, methylcobalamin, vitamin D3, fish oil and coenzyme Q10 each day; optimizing oral hygiene using an electric flosser and electric toothbrush; reinstating hormone replacement therapy, which had previously been discontinued; fasting for a minimum of 12 hours between dinner and breakfast, and for a minimum of three hours between dinner and bedtime; and exercising for a minimum of 30 minutes, four to six days per week.
Dr. Bredesen noted that the negative aspects of the program are its complexity and that the burden falls on patients and caregivers to follow it. In the study, none of the patients were able to completely follow the protocol. Their most common complaints were the diet and lifestyle changes, and having to take multiple pills each day. On the plus side, explained Dr. Bredesen, are the side effects: “It is noteworthy that the major side effects of this therapeutic system are improved health and an improved body mass index, a stark contrast to the side effects of many drugs.”
The findings of the small study are encouraging; however, Dr. Bredesen stressed that the results need to be replicated. He explained, “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.”
Cognitive decline is a major concern of seniors; it impacts approximately 5.4 million Americans and 30 million individuals globally. By 2050, without effective prevention and treatment, an estimated 160 million individuals worldwide would have the disease, including 13 million Americans; this could potentially result in the bankruptcy of the Medicare system. Unlike several other chronic illnesses, the incidence of Alzheimer’s is increasing; recent estimates suggest that it has become the third leading cause of death in the U.S. behind cardiovascular disease and cancer.