Lifestyle Changes Significantly Improve Cognition and Function in Early Alzheimer's Disease for the First Time in a Randomized Controlled Trial

SAN FRANCISCO, June 7, 2024 /PRNewswire/ -- For the first time, a randomized controlled clinical trial has demonstrated that an intensive lifestyle intervention, without drugs, significantly improved cognition and function after 20 weeks in many patients with mild cognitive impairment or early dementia due to Alzheimer's disease. The multisite clinical study was published today in the leading peer-reviewed Alzheimer's translational research journal, Alzheimer's Research and Therapy.

This peer-reviewed study was directed by lifestyle medicine pioneer Dean Ornish, M.D., founder and president of the nonprofit Preventive Medicine Research Institute and clinical professor of medicine at the University of California, San Francisco, in collaboration with other renowned scientists and neurologists from leading academic medical centers. These include:

• Harvard Medical School / Massachusetts General Hospital (Rudolph E. Tanzi, Ph.D.; Steven E. Arnold, M.D.; Dorene Rentz, Psy.D.)
• Karolinska Institute (Miia Kivipelto, M.D., Ph.D.)
• Preventive Medicine Research Institute (Dean Ornish, M.D.; Catherine Madison, M.D.; Colleen Kemp, R.N.; Anne Ornish, B.A.; Sarah Tranter, R.N.; Nancy DeLamarter, M.S.W.; Noel Wingers, M.S.; Carra Richling, R.D.)
• University of California, San Francisco (Dean Ornish, M.D.; Charles E. McCulloch, Ph.D.; Jue Lin, Ph.D.; Kim Norman, M.D.)
• Renown Health Institute of Neurosciences (Jon Artz, M.D.)
• University of California, San Diego (Douglas Galasko, M.D.; Rob Knight, Ph.D.; Daniel McDonald, Ph.D.; Lucas Patel, B.S.)
• Duke University Medical Center (Rima Kaddurah-Daouk, Ph.D.)
• Buck Institute for Research on Aging (Eric Verdin, M.D.)

"I'm cautiously optimistic and very encouraged by these findings, which may empower many people with new hope and new choices," said Dr. Ornish. "We do not yet have a cure for Alzheimer's, but as the scientific community continues to pursue all avenues to identify potential treatments, we are now able to offer an improved quality of life to many people suffering from this terrible disease."

The research team recruited 51 participants with a diagnosis of mild cognitive impairment or early dementia due to Alzheimer's disease and randomly assigned them to either an intensive lifestyle intervention group (no drugs added) or a usual-care control (comparison) group. Members of the control group were instructed not to make any lifestyle changes during the 20-week trial.

The intervention group participated in an intensive lifestyle program with four components: (1) a whole-foods, minimally processed plant-based diet low in harmful fats, refined carbohydrates, alcohol and sweeteners — predominantly fruits, vegetables, whole grains and legumes, plus selected supplements — with all meals sent to each patient's home to maximize adherence; (2) moderate aerobic exercise and strength training for at least 30 minutes per day; (3) stress management, including meditation, stretching, breathing and imagery, for one hour per day; and (4) support groups for patients and their spouses or study partners, for one hour three times per week.

Improvements in patients with early Alzheimer's disease
To measure pre- and post-trial cognitive function, the researchers utilized four standard tests used in Food and Drug Administration drug trials: the Alzheimer's Disease Assessment Scale–Cognitive Subscale (ADAS-Cog), Clinical Global Impression of Change (CGIC), Clinical Dementia Rating–Sum of Boxes (CDR-SB) and Clinical Dementia Rating Global (CDR-G).

Results after 20 weeks showed overall statistically significant differences between the intervention group and the randomized control group in cognition and function in three of these measures (CGIC, p = 0.001; CDR-SB, p = 0.032; CDR-G, p = 0.037), and differences of borderline significance in the fourth test (ADAS-Cog, p = 0.053). When a mathematical outlier was excluded, all four measures showed significant differences in cognition and function in the experimental group. Three of these measures showed improvement in cognition and function in the intervention group and one test showed significantly less disease progression. In contrast, the randomized control group worsened in all four of these measures.

Not all patients in the intervention group improved; in the CGIC test, 71% improved or were unchanged. In contrast, none of the patients in the control group improved, eight were unchanged and 17 (68%) worsened.

Many patients who experienced improvement reported regaining lost cognition and function. For example, several patients in the intervention group reported that they had been unable to read a book or watch a movie because they kept forgetting what they had just read or viewed and had to keep starting over, but now they were able to do so and retain most of this information. One individual reported that it used to take him weeks to finish reading a book, but after participating in the study he was able to do so in only three or four days and was able to remember most of what he read.

A former business executive reported regaining the ability to manage his own finances and investments. "It was so much a part of my life — who I am, and who I was — it was hard saying that part of me was just gone," he said. "I'm back to reconciling our finances monthly; I keep up to date on our investments. A lot of self-worth comes back."

A woman said that for five years she had been unable to prepare their family business financial reports, but now she is able to do so accurately. "A deep sense of identity is returning. It's given me a new lease on life, and yet it's a familiarity and something I've always prided myself on. I'm coming back like I was prior to the disease being diagnosed. I feel like I'm me again — an older but better version of me."

There was a statistically significant dose-response correlation between the degree of lifestyle changes in both groups and the degree of change in most measures of cognition and function testing. In short, the more these patients changed their lifestyle in the prescribed ways, the greater was the beneficial impact on their cognition and function.

This dose-response correlation adds to the biological plausibility of these findings and may help to explain, in part, why some patients in the intervention group improved and others did not (although other mechanisms may also play a role). Other studies have shown that more moderate lifestyle changes such as adopting the Mediterranean diet may slow the rate of progression (worsening) of Alzheimer's disease but may not go far enough to improve cognition and function.

In addition to improvements in cognition and function, the intervention group also demonstrated significant improvements in several key blood-based biomarkers. One of the most clinically relevant biomarkers is called the Aβ42/40 ratio, which is a measure of amyloid, thought to be an important mechanism in Alzheimer's disease. This measure improved in the lifestyle intervention group (with the presumption that this improvement reflected amyloid moving out of the brain and into the blood), but it worsened in the randomized control group, and these differences were statistically significant (p = 0.003).

There was also a statistically significant dose-response correlation between the degree of lifestyle change and the degree of improvement in this amyloid ratio (p = 0.035). This direction of change in amyloid was also a major finding with lecanemab, a drug approved for treating Alzheimer's disease last year.

Also, the gut microbiome in the intervention group showed a significant decrease in organisms that raise the risk of Alzheimer's disease and an increase in organisms that are protective against Alzheimer's disease. These biomarker and gut microbiome results also add to the biological plausibility of the overall findings.

According to renowned Alzheimer's scientist Miia Kivipelto, M.D., Ph.D., "These findings add to the growing body of evidence that moderate multimodal lifestyle changes may help prevent Alzheimer's disease or slow its progression, and also suggest that more intensive multimodal lifestyle changes may have additional benefits for improving cognition in patients with early Alzheimer's disease."

New hope in tackling a devastating and costly disease
Alzheimer's disease, the fifth-leading cause of death among Americans aged 65 and older, is not only physically and emotionally devastating; it's also extremely costly. The disease currently affects more than six million people in the U.S., at an annual cost of more than $345 billion. By 2050, the number affected is expected to reach 13 million, with costs projected to skyrocket to $1.1 trillion annually.

"There's a desperate need for Alzheimer's treatments," said study co-author Rudolph E. Tanzi, Ph.D., an acclaimed professor of neurology at Harvard Medical School and director of the McCance Center for Brain Health at Massachusetts General Hospital, one of the study's clinical sites. "Biopharma companies have invested billions of dollars in the effort to find medications to treat the disease, but only two Alzheimer's drugs have been approved in the past 20 years — one of which was recently taken off the market, and the other is minimally effective and extremely expensive and often has serious side effects such as brain swelling or bleeding into the brain. In contrast, the intensive lifestyle changes implemented in this study have been shown here to improve cognition and function, at a fraction of the cost — and the only side effects are positive ones."

"I am delighted and honored to be a part of this groundbreaking study showing for the first time in a controlled clinical trial what the epidemiology has told us all along: Lifestyle factors are critically important in our efforts to address Alzheimer's. While efforts to develop drugs to treat this disease will continue, this study provides a blueprint for practical, easily implemented steps that can significantly alter the progression to full Alzheimer's disease," said study co-author Eric Verdin, M.D., president and CEO of the Buck Institute for Research on Aging.

This study has implications for preventing Alzheimer's disease as well. New technologies such as artificial intelligence now make it possible to predict an individual's likelihood of developing this disease years before it becomes clinically apparent, but many people ask, "Why would I want to know if I'm likely to get Alzheimer's disease if I can't do anything about it? It will just make me worry." Although further research is needed, it is reasonable to believe that the same intensive lifestyle changes that often improve cognition and function in those with mild cognitive impairment or early dementia due to Alzheimer's may help prevent the disease as well.

"This study finally gives us scientific data to support what many of us in this field have believed instinctively for years, that lifestyle interventions may determine the trajectory of people's Alzheimer's journeys," said Maria Shriver, founder of the Women's Alzheimer's Movement (WAM) at Cleveland Clinic, which provided early seed funding for this study. "We opened the WAM Prevention and Research Clinic at Lou Ruvo Center for Brain Health in Las Vegas for women 30 to 60 years of age who are at higher risk than average for developing Alzheimer's. The protocols we use involve adopting many of the lifestyle interventions employed in this study. So, showing success in improving the health trajectories of those already diagnosed with Alzheimer's clearly offers hope to those who want to delay or prevent developing the disease altogether. This is a study to give us hope."

A growing body of lifestyle medicine research
Dr. Ornish has directed peer-reviewed research at the nonprofit Preventive Medicine Research Institute for over four decades. He is often referred to as "the father of lifestyle medicine."

The Institute's studies, published in leading peer-reviewed medical and scientific journals, focus on the power of lifestyle medicine to help prevent and often reverse the progression of many of the most common and costly chronic diseases. These include coronary heart disease, Type 2 diabetes, early-stage prostate cancer, hypertension, hypercholesterolemia, and now, early-stage Alzheimer's disease.

Dr. Ornish's most recent bestselling book, "Undo It!," co-authored with Anne Ornish, puts forth his unifying theory: the reason that the same lifestyle changes may beneficially affect so many different chronic diseases is that these share common biological mechanisms that are directly affected by what people eat, how much they exercise, how they respond to stress, and how much love and support they enjoy. Alzheimer's is the latest example of why "what's good for your heart is also good for your brain."

In 2010, the Centers for Medicare & Medicaid Services (CMS) began providing nationwide Medicare coverage for Dr. Ornish's program, which has been shown to often reverse the progression of coronary heart disease, as "intensive cardiac rehabilitation." This nine-week program is offered online, so individuals can join classes from the comfort of their own homes, enabling participation by those who cannot afford to take time off work, who live far from a hospital or who cannot afford childcare, thereby reducing health disparities and inequities. "I'm very grateful to CMS for providing Medicare coverage. Having seen what a powerful difference this program of lifestyle changes can make, I appreciate very much that it is now available to all eligible Medicare beneficiaries with heart disease who can benefit from it," Dr. Ornish said.

About the Preventive Medicine Research Institute 
The Preventive Medicine Research Institute (PMRI), a 501(c)(3) nonprofit organization, was founded in 1984 by Dean Ornish, M.D., to conduct pioneering research evaluating the power of lifestyle medicine and to make healthy lifestyle changes more widely available to those who can benefit from them. PMRI's research uses the latest in high-tech medical and scientific technologies to assess the benefits of these low-tech and low-cost lifestyle changes. For more information about PMRI's four decades of peer-reviewed lifestyle medicine research, please visit https://pmri.org.

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SOURCE Preventative Medicine Research Institute