A national medical journal has published details of a Marin-based study that focuses on people with mild symptoms of dementia or pre-Alzheimer’s disease.
The peer-reviewed article “Precision Medicine Approach to Alzheimer’s Disease: Successful Pilot Project” was published July 4 in the Journal of Alzheimer’s Disease.
According to the article, 84% of the 25 people in the nine-month study showed improvement in cognitive function over their previous mild dementia or pre-Alzheimer’s state. Ten of the 25 participants were stationed in Marin.
Over the nine months, participants committed to rigorous dietary changes, exercise, stress reduction and detoxification. Treatments included taking several vitamin, mineral, hormone and herbal supplements, brain training exercises and sleep monitoring.
Each participant’s regimen was created from the results of a series of blood and urine tests and brain scans to determine which of 150 factors could be causing the cognitive decline. Such targeted therapy is referred to as “precision medicine,” according to the article.
“It took us 30 years to get here,” said Dr. Dale Bredesen, the study’s lead researcher, in an email. “But this latest milestone will ultimately bring about a paradigm shift in how we assess, prevent and treat neurodegenerative diseases such as Alzheimer’s, Lewy body disease, macular degeneration and ALS (Lou Gehrig’s disease).”
Bredesen, a resident of Marin, is the former founding president of the Buck Institute for Research on Aging in Novato. He was on the senior research team of Dr. Ann Hathaway, a doctor in San Rafael; dr Kat Toups of Bay Area Wellness at Walnut Creek; and dr Deborah Gordon, the Founder and Medical Director of Northwest Memory Care in Ashland, Oregon.
The research team has secured funding to conduct a large-scale clinical trial of the Bredesen protocol at six sites across the country. They are San Rafael, Walnut Creek, Folsom, Ohio, Tennessee and Florida, Hathaway said. The process is scheduled to begin later this year.
The early-stage 2019 study described in the article has been criticized in recent months for lacking a control group. All 25 participants followed the treatment protocol, and there was no parallel group of people who received either no treatment or a placebo, as is generally required for a large-scale scientific clinical trial.
But Bredesen said the early-stage study is what he calls a “proof of concept” study, which he says is the traditional precursor to a large-scale scientific clinical trial with a control group.
The large-scale clinical trial the team will start later this year will have a control group, Hathaway said. The study will include 48 people who have mild cognitive decline and will use the Bredesen protocol, and 24 people with some cognitive decline but who are in the no treatment or control group, Hathaway said.
People in the “no treatment” category will commit to sticking to the same lifestyle habits and diets they already do, Hathaway said. You cannot make any of the changes recommended in the protocol until the large-scale study is complete.
“If they don’t make any changes after nine months, we’ll provide them with the full log free of charge if they want,” Hathaway said.
To date, there has been no treatment or drug that promised to cure or reverse Alzheimer’s disease or dementia – conditions that affect millions of Americans and older adults worldwide.
While some prescription drugs have been touted in recent years, the best these drugs can do is slow cognitive decline, Bredesen said. Some of the drugs are designed to remove amyloid, or plaque, that builds up in the brain, but they don’t address the root cause of why the brain shuts down in the first place, Bredesen said.
“The only real question here is whether this is better than what’s currently available – and it’s clear that it’s a lot better,” Bredesen said, referring to his transcript. “The critics have nothing to offer themselves except ineffective drugs.”
The targeted treatments in Bredesen’s protocol are based on identifying specific areas where a person’s brain is shrinking – or curling up – due to what Bredesen calls a “network insufficiency”. Shrinking can be due to assaults like toxins, mold, inflammation, viruses, or stress, or it can be due to a lack of nutrients or hormones, poor exercise or sleeping habits, or too much junk food and sugar.
Bredesen has been researching the development of Alzheimer’s since around 1993. But it wasn’t until 2006 that “the light bulb suddenly went on” when his research team found that “many different pathways” are involved in the brain cell switch to Alzheimer’s, not just one factor, Bredesen said.
“We realized that genetics, toxicology, microbiology, epidemiology – in fact everything reported in the more than 150,000 articles published on Alzheimer’s – fit seamlessly into a model in which Alzheimer’s disease could be conceptualized as a network insufficiency, one that… could potentially correct identifying and addressing the many contributors,” he said.
The team attempted to test their “network insufficiency” theory in a clinical trial, but were repeatedly rejected until finally being approved in 2019 to start a small, early-stage “proof-of-concept” study.
Denise Martini, a 59-year-old somatic therapist and movement practitioner in Sonoma, was one of those who participated in the nine-month study in 2019.
At the time, Martini, who was attending from Hathaway’s San Rafael office, was on a downward spiral, she said. She gradually lost her ability to complete everyday tasks, manage her business, or even make appointments.
“When I went into menopause at 55, my cognitive decline just took off,” Martini said. “I remember packing supplies to go to my office in San Francisco and I just sat there and said to myself, ‘Well, what am I doing?’
She spent nine months on a strict, individualized protocol that included a ketogenic diet, high-intensity interval training exercise, nutritional supplements, bioidentical hormone replacement, brain training, and detoxification from mold, plastics, and gasoline additives.
“I was more like myself,” Martini said. “I was back at work. And I was physically stronger than I’ve ever been in my life.” She’s continued to improve, she said, even now expanding her life to include new endeavors like teaching.
Hathaway says that while the protocol is effective, it can be difficult for some people. For example, a ketogenic diet involves eating few or no complex carbohydrates like bread or grains, little or no sugar, moderate protein, and a generous amount of quality healthy fats like coconut oil or avocado.
“It’s not easy — there’s a lot to do,” Hathaway said. “One person walked in and said, ‘I eat really healthy food — I eat four pieces of fruit a day.’ That’s way too much sugar.”
Marin experts in anti-aging and Alzheimer’s said the Bredesen team’s published paper and upcoming full-scale clinical study will be helpful in advancing research.
“Precision medicine tailored to the individual offers tremendous opportunity to shape the future of healthcare,” said Anne Gray, chief executive officer of Vivalon, a San Rafael-based nonprofit that supports Marin seniors.
“Although this proof-of-concept study lacks an untreated control group that would lend validity to this study, this is encouraging confirmation that the healthy aging programs offered at Vivalon play a significant role in improving cognitive health,” said Grey, a former executive director of the Orange County chapter of the Alzheimer’s Association.
“The importance of human clinical trials in a diverse population cannot be underestimated and is key to advancing progress in preventing and curing Alzheimer’s disease,” said Gray.
dr Eric Verdin, president and executive director of the Buck Institute for Research on Aging, agreed.
“I am encouraged by the results of the small clinical trial and look forward to the larger trials that will provide more evidence for this personalized and precise approach to treating mild cognitive impairment and Alzheimer’s disease,” said Verdin.
“We all live complex lives with different genetic backgrounds, lifestyle choices and environmental pressures,” he said. “I think most of the effort to combat age-related diseases will involve personalized medicine, which is just beginning to gain a foothold in biomedical research and clinical practice.”
Late last year, two professors at the Buck Institute were awarded a $14.3 million grant to look for links between senescent cells and age-related dementias such as Alzheimer’s disease. The grant is from the National Institutes of Health.