A recent clinical trial has unveiled that intensive lifestyle modifications can significantly enhance cognition and daily functioning in patients with mild cognitive impairment or early dementia due to Alzheimer’s disease. Published in Alzheimer’s Research & Therapy, this multisite study is the first randomized controlled trial to demonstrate that non-drug interventions can offer substantial benefits to those already diagnosed with these conditions.

Alzheimer’s disease is a progressive neurodegenerative disorder that primarily affects older adults, leading to the gradual loss of memory and cognitive functions. It is the most common cause of dementia, a syndrome characterized by a decline in cognitive abilities severe enough to interfere with daily life. Alzheimer’s disease typically progresses through several stages, beginning with mild cognitive impairment (MCI) and advancing to early, moderate, and eventually severe dementia.

Mild cognitive impairment (MCI) is an early stage of memory loss or other cognitive decline that is noticeable but not severe enough to interfere significantly with daily activities. Individuals with MCI may experience memory problems, difficulties with language, and challenges in thinking and judgment that are greater than expected for their age. However, they generally maintain their independence and can carry out most daily tasks. Not everyone with MCI will develop Alzheimer’s disease, but they are at a higher risk compared to those without cognitive impairment.

Early dementia, often resulting from Alzheimer’s disease, involves more pronounced cognitive decline. Symptoms include increasing forgetfulness, confusion, difficulty managing finances, trouble remembering names and events, and impaired reasoning. As the disease progresses, these symptoms worsen, making it increasingly challenging for individuals to perform everyday activities and live independently.

The motivation behind the study stemmed from growing evidence linking lifestyle factors to the onset and progression of Alzheimer’s disease. Unhealthy diets, physical inactivity, emotional stress, and social isolation have all been implicated as contributors to cognitive decline. Previous research indicated that addressing these risk factors through lifestyle changes could potentially prevent or slow down the progression of dementia.

However, no study had conclusively shown whether such changes could benefit individuals already diagnosed with MCI or early dementia due to Alzheimer’s disease. This gap in research inspired the team to investigate whether a comprehensive, intensive lifestyle intervention could improve cognitive function and daily living in these patients.

The study was led by Dean Ornish, the founder of the nonprofit Preventive Medicine Research Institute and clinical professor of medicine at the University of California, San Francisco. Ornish has a deeply personal connection to Alzheimer’s disease. “My mother and all of her siblings died of Alzheimer’s disease, and I have one of the genes for it,” he shared with PsyPost. This personal motivation has driven his commitment to exploring lifestyle interventions as a means to combat this devastating condition.

The study was a randomized controlled trial designed to examine whether an intensive lifestyle intervention could improve cognitive function and daily living activities in patients with mild cognitive impairment (MCI) or early dementia due to Alzheimer’s disease. The trial enrolled 51 participants aged 45 to 90, all diagnosed with MCI or early dementia. These participants were divided into two groups: an intervention group that received the lifestyle modifications and a control group that continued with their usual care.

The lifestyle intervention consisted of four main components: a whole foods, plant-based diet; regular physical exercise; stress management techniques; and participation in social support groups. The diet emphasized minimally processed plant-based foods, low in harmful fats and refined sugars, with meals and snacks provided to ensure adherence. Participants were encouraged to engage in daily aerobic exercise and strength training three times a week, under the guidance of an exercise physiologist. Stress management practices included meditation, yoga-based poses, and relaxation exercises, supervised by a certified stress management specialist. Social support was provided through regular group sessions led by mental health professionals.

The study measured cognitive and functional changes using standard tests such as 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 Global). Additionally, various biomarkers related to Alzheimer’s disease, such as the plasma Aβ42/40 ratio, were monitored to assess biological changes. Participants were evaluated at baseline and after 20 weeks to determine the effects of the intervention.

The study revealed significant improvements in cognitive function and daily living activities among participants in the intervention group compared to those in the control group. The intervention group showed better scores on the CGIC, CDR-SB, and CDR Global tests, with borderline significance in the ADAS-Cog test.

Specifically, the intervention group exhibited improvements in cognitive measures and daily functioning, while the control group experienced declines across these metrics. For example, the CGIC scores improved in the intervention group, indicating better overall cognitive functioning and daily living capabilities.

In terms of biomarkers, the intervention group demonstrated beneficial changes, particularly in the plasma Aβ42/40 ratio, which increased by 6.4% in the intervention group but decreased by 8.3% in the control group. This biomarker is associated with amyloid movement from the brain to the blood, and its improvement suggests a positive impact of the lifestyle intervention on Alzheimer’s disease pathology.

Other biomarkers, such as hemoglobin A1c, insulin, glycoprotein acetyls, LDL-cholesterol, and β-Hydroxybutyrate, also showed significant beneficial changes in the intervention group, providing further evidence of the intervention’s positive effects on biological mechanisms underlying Alzheimer’s disease.

Additionally, there was a significant correlation between the degree of lifestyle change and the improvements in cognitive function and biomarkers. Participants who adhered more closely to the lifestyle intervention experienced greater cognitive and functional benefits. This dose-response relationship underscores the potential of lifestyle modifications in managing Alzheimer’s disease.

“Comprehensive lifestyle changes may increase cognition and function in many people suffering from early-stage Alzheimer’s disease,” Ornish told PsyPost.

“Only three drugs have been approved for treating Alzheimer’s disease in the past 20 years after billions of dollars were spent in drug development costs. When most people are diagnosed with Alzheimer’s disease, they are often told that all three of these drugs only slow down the rate at which they get worse, are very expensive, and often have side effects such as bleeding into the brain or brain swelling.”

“Getting worse more slowly is still getting worse, and this lack of hope often creates despair — when you lose your memories, you lose everything,” Ornish explained. “Because of this, there is a seven-fold increase in suicide during the three months after this diagnosis.”

“These drugs are designed to help remove amyloid from the brain. We found that lifestyle changes also helped remove amyloid from the brain. But amyloid is only one of many mechanisms that causes Alzheimer’s disease — and lifestyle changes also beneficially affect many of these other mechanisms, which is why lifestyle changes may often cause improvement in cognition and function rather than just slowing the rate of worsening. And the only side-effects are good ones.”

The study’s limitations include a relatively small sample size of 51 participants and a short duration of only 20 weeks, which may limit the generalizability and long-term applicability of the findings. Additionally, the lack of racial and ethnic diversity among participants and the inability to blind participants to their group assignments could introduce biases.

“We don’t know how generalizable these findings are to more diverse populations. We don’t know the long-term effects of these lifestyle changes on cognition and function.”

Future research should aim to include larger, more diverse populations and extend the duration of the intervention to better assess long-term effects. Further studies should also explore the underlying mechanisms of lifestyle interventions and their potential synergistic effects with existing drug therapies for Alzheimer’s disease.

“There’s a desperate need for Alzheimer’s treatments,” said study co-author Rudolph E. Tanzi, a 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.”

“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, the president & CEO of the Buck Institute for Research on Aging.

“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,” added Maria Shriver, founder of the Women’s Alzheimer’s Movement (WAM) at The 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.”

Ornish’s latest bestseller, Undo It!, co-authored with Anne Ornish, posits that lifestyle changes positively impact various chronic diseases, including Alzheimer’s, because these diseases share common biological mechanisms influenced by diet, exercise, stress management, and social support, illustrating that “what’s good for your heart is also good for your brain.”

The study, “Effects of intensive lifestyle changes on the progression of mild cognitive impairment or early dementia due to Alzheimer’s disease: a randomized, controlled clinical trial,” was authored by Dean Ornish, Catherine Madison, Miia Kivipelto, Colleen Kemp, Charles E. McCulloch, Douglas Galasko, Jon Artz, Dorene Rentz, Jue Lin, Kim Norman, Anne Ornish, Sarah Tranter, Nancy DeLamarter, Noel Wingers, Carra Richling, Rima Kaddurah-Daouk, Rob Knight, Daniel McDonald, Lucas Patel, Eric Verdin, Rudolph E. Tanzi, and Steven E. Arnold.