Marin-based study reports insights on dementia

A national medical journal has published details of a Marin-based study focused on people with mild dementia symptoms 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, of 25 people in the nine-month trial, 84% showed improvement in cognitive functioning from their prior mild dementia or pre-Alzheimer’s state. Ten of the 25 participants were based in Marin.

Over the nine months, the participants committed to rigorous changes in diet, exercise, stress reduction and detoxification. The treatments included taking multiple vitamin, mineral, hormonal and herbal supplements, doing brain training exercises and monitoring sleep.

Each participant’s regimen was created from results of a battery of blood and urine tests and brain scans to identify which of 150 factors might 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,” Dr. Dale Bredesen, the lead researcher in the trial, said in an email. “But this latest milestone will ultimately create a paradigm shift in the way we evaluate, prevent and treat neurodegenerative diseases such as Alzheimer’s, Lewy body disease, macular degeneration and ALS (Lou Gehrig’s disease).”

Bredesen, a Marin resident, is the former founding president of the Buck Institute for Research on Aging in Novato. He was joined on the lead research team by Dr. Ann Hathaway, a physician in San Rafael; Dr. Kat Toups of Bay Area Wellness in 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 do a large-scale clinical trial of Bredesen’s protocol at six sites across the country. They are San Rafael, Walnut Creek, Folsom, Ohio, Tennessee and Florida, Hathaway said. The trial is expected to start later this year.

The 2019 early-stage trial, as detailed in the article, came under some criticism in recent months because it lacked a control group. All 25 participants were following 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 scientific full-scale clinical trial.

Bredesen, however, has said the early-stage trial was what is called a “proof of concept” trial, which he said is the traditional precursor to a large-scale scientific clinical trial with a control group.

The large-scale clinical trial that the team will start later this year does have a control group, Hathaway said. The trial will include 48 people who have mild cognitive decline and who will be using the Bredesen protocol, and 24 people with some cognitive decline but who are in the “no treatment” category, or control group, Hathaway said.

People in the “no treatment” category will commit to staying with the same lifestyle routines and diet they are already doing, Hathaway said. They will not be able to make any of the changes recommended in the protocol until after the large-scale trial is done.

“After nine months, if they don’t make any changes, we will then provide them with the full protocol at no cost, if they wish,” Hathaway said.

At this point, there has been no treatment or drug that has showed any promise of a cure or reversal of Alzheimer’s disease or dementia — afflictions affecting 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 down the cognitive decline, Bredesen said. Some of the drugs are designed to remove amyloid or plaque that builds up in the brain, but they do not remedy the root cause of why the brain is downshifting in the first place, Bredesen said.

“The only real question here is whether this is better than what is currently available — and it’s clear that it is much better,” Bredesen said, referring to his protocol. “The critics have nothing to offer themselves, except ineffective drugs.”

The targeted treatments in Bredesen’s protocol are based on the identification of specific areas where a person’s brain is shrinking — or involuting — due to what Bredesen calls a “network insufficiency.”  The shrinking could be due to assaults such as toxins, molds, inflammation, viruses or stress, or because of a lack of nutrients or hormones, poor exercise or sleep habits or too much junk food and sugar.

Bredesen has been researching the origins of Alzheimer’s since about 1993. It wasn’t until 2006, however, that “the light bulb suddenly came on,” when his research team realized that “many different pathways” were involved in the brain cells’ switch to Alzheimer’s, not just one factor, Bredesen said.

“We realized that the genetics, toxicology, microbiology, epidemiology — indeed, everything reported in the over 150,000 papers published on Alzheimer’s — fit neatly into a model in which Alzheimer’s disease could be conceptualized as a network insufficiency, one that could potentially be corrected by identifying and addressing the many contributors,” he said.

The team sought to test its “network insufficiency” theory in a clinical trial, but was turned down repeatedly until 2019, when it was finally approved to launch a small, early-stage, “proof-of-concept” trial.

Denise Martini, a 59-year-old somatic therapist and movement practitioner in Sonoma, was one of those who joined the nine-month trial in 2019.

At the time, Martini, who participated out of Hathaway’s office in San Rafael, was on a downward spiral, she said. She was gradually losing her ability to do day-to-day tasks, manage her business or even book appointments.

“When I went into menopause at 55, my cognitive decline just plummeted,” Martini said. “I remember I was packing up supplies to go to my office in San Francisco, and I just sat there and said to myself, ‘Now, what is it that am I doing?”

She spent nine months on a strict, individualized protocol including a ketogenic diet, high-intensity interval training exercises, supplements, bio-identical hormone replacements, brain training and detoxing 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 has continued to improve, she said, now even expanding her life to include new ventures such as teaching.

Hathaway says that the protocol, while effective, can be difficult for some people. For example, a ketogenic diet involves eating few or no complex carbohydrates such as bread or grains, little or no sugar, moderate protein and a generous amount of high-quality healthy fats such as coconut oil or avocado.

“It’s not easy — there’s a lot you have to do,” Hathaway said. “I had one person come in and say, ‘I eat really healthy — I eat four pieces of fruit a day.’ That’s way too much sugar.”

Marin experts on anti-aging and Alzheimer’s said the Bredesen team’s published article and the upcoming full-scale clinical trial will be helpful in moving the research forward.

“Precision medicine tailored to individuals offers tremendous opportunity to shape the future of health care,” said Anne Grey, the chief executive officer of Vivalon, a San Rafael-based nonprofit serving Marin seniors.

“Although this proof-of-concept trial lacks an untreated control group which would add validity to this study, it is an encouraging affirmation that the healthy aging programs offered at Vivalon play a significant role in improving cognitive health,” said Grey, a previous executive director of the Alzheimer’s Association Orange County chapter.

“The importance of human clinical trials with a diverse population cannot be understated and are key to progress in preventing and curing Alzheimer’s disease,” Grey said.

Dr. Eric Verdin, president and chief executive 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 studies which will bring more evidence to bear on this personalized and precision approach to deal with mild cognitive impairment and Alzheimer’s disease,” Verdin said.

“We all live complex lives with different genetic backgrounds, lifestyle choices and environmental exposures,” he said. “I think most efforts to tackle age-related diseases will involve personalized medicine, which is just beginning to get some traction 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 connections between aging cells and age-related dementias such as Alzheimer’s disease. The grant is from the National Institutes of Health.