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Dale Bredesen, M.D., is internationally recognized as an expert in the mechanisms of neurodegenerative diseases such as Alzheimer’s disease. He graduated from Caltech, then earned his M.D. from Duke University Medical Center in Durham, North Carolina. He served as chief resident in neurology at the University of California, San Francisco (UCSF) before joining Nobel laureate Stanley Prusiner’s laboratory at UCSF as an NIH postdoctoral fellow. He held faculty positions at UCSF, UCLA, and the University of California, San Diego. Dr. Bredesen directed the Program on Aging at the Burnham Institute before coming to the Buck Institute in 1998 as its founding president and CEO. He is the chief medical officer of MPI Cognition.
Meet Kristin.
Kristin was suicidal. Years before, she had watched in despair as her mother’s mind slipped away, forcing her to enter a nursing home after she could no longer recognize family members, let alone care for herself. Kristin had suffered along with her mother, who at the age of 62 had begun an 18-year decline into Alzheimer’s disease. And at the end Kristin had suffered alone, for her mother was no longer sentient.
When Kristin was 65, she began to experience her own cognitive problems. She got lost when driving on the freeway, unable to remember where to get off and on, even on familiar routes. She could no longer analyze data critical to her job, or organize and prepare reports in a timely fashion. Unable to remember numbers, she had to write down even four digits, not to mention phone numbers. She had trouble remembering what she had read, and by the time she reached the bottom of a page had to start at the top again. Reluctantly, Kristin prepared her resignation. She began to make mistakes more and more frequently, often calling her pets by the wrong names and having to search to find the light switches in her own home, even though she had flipped them on and off for years.
Like many people, Kristin tried to ignore these symptoms. But they got worse and worse. After two years of unremitting cognitive decline, she consulted her physician, who told her she was becoming demented just as her mother had, and there was nothing he could do for her. He wrote “memory problems” on her chart, and because of that, she was unable to obtain long-term care insurance. She underwent retinal scanning, which revealed the Alzheimer’s-associated amyloid. She thought about the horror of watching her mother decline, about how she would live with progressive dementia and no long-term care, about the lack of treatment. She decided to commit suicide.
She called her best friend, Barbara, explaining, “I watched what my mother went through as she slipped away, and there is no way I will allow that to happen to me.” Barbara was horrified to hear Kristin’s saga. But unlike when other friends had fallen victim to dementia, this time Barbara had an idea. She told Kristin about new research she had heard about, and suggested that rather than ending her life, Kristin travel several thousand miles to the Buck Institute for Research on Aging, just north of San Francisco. In 2012, Kristin came to see me.
We talked for hours. I could offer her no guarantee, no example of any patient who had used the protocol—nothing more than diagrams, theory, and data from transgenic mice. In reality, Barbara had been premature in sending her to the Institute. And to make matters worse, the protocol I had developed had just been turned down for its first proposed clinical trial. The review board felt that it was “too complicated,” and pointed out that such trials are meant to test only a single drug or intervention, not an entire program (ah, if only diseases were that simple!). So all I could do was to go over the various parts of the protocol and recommend that she take these to her physician back home, asking him if he would work with her. She did that, and so began what has become the ReCODE protocol.
Three months later, Kristin called me at home on a Saturday to say she could not believe the changes in her mental abilities. She was able to work full-time again, to drive without getting lost, and to remember phone numbers without difficulty. She was feeling better than she had in years. When I put the phone down, what rushed into my mind were the decades of research, the countless hours at the whiteboard with lab members and colleagues, the arguments with myself about each detail of the theory and treatment approach. All of this had not been in vain; it had pointed us in the right direction. Of course Kristin was only one person—as they say, an “n of one”— and we needed to see similar results in thousands and ultimately in millions. I thought back to the doctor who told his patient, “You are just an anecdote; you are not statistically significant.” To which his patient replied, “Well, my family says that I am significant. Besides, I’m healthy once again, so I don’t care about statistics.” Indeed. Every fundamental change needs to start somewhere—every successful approach must start with Patient Zero—and Kristin was Patient Zero.
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