Healthy behaviors are associated with a reduced risk of Alzheimer's disease (AD), but a new study suggests they may also benefit patients who have already been diagnosed with mild cognitive impairment (MCI) or early AD.
After 20 weeks, patients who received the intensive multimodal lifestyle intervention showed greater improvements in three measures of cognition and function and reduced progression in one measure compared with usual care.
Beneficial changes were also observed in several biomarkers, including the plasma amyloid-β (Aβ) 42/40 ratio, which increased by 6.4% in the intervention group and decreased by 8.3% in the control group ( P = .003).
“I'm cautiously optimistic and very encouraged by these findings, which may give new hope and new options for many people,” Dean Ornish, M.D., professor of clinical medicine at the University of California, San Francisco and founder and director of the Preventive Medicine Institute in Sausalito, California, said in an interview.
Ornish and his colleagues have previously reported that lifestyle programs can lead to regression of coronary atherosclerosis, but this is the first randomized controlled trial to show that intensive lifestyle changes can significantly improve cognition and function in the early stages of Alzheimer's disease, he said.
The results of this study were published online in Alzheimer's Research & Therapy on June 7, 2024.
Comprehensive lifestyle interventions
The Phase 2 trial enrolled 51 patients aged 45 to 90 years with MCI or early dementia due to Alzheimer's disease and a Montreal Cognitive Assessment score of 18 or higher between September 2018 and June 2022.
Patients will be randomized to receive either the intervention or usual care for 40 weeks, with the control group able to move onto the lifestyle program after 20 weeks. Results from the 40-week period are expected to be published later this year, Ornish said.
The intervention, conducted via Zoom from March 2020 onwards due to COVID-19, included a minimally processed vegan diet low in harmful fats, sweeteners and refined carbohydrates, as well as eight carefully selected supplements. All meals and snacks were provided free of charge to participants and their spouses or study partners.
An exercise physiologist supervised strength training at least three times a week and encouraged participants to do at least 30 minutes of aerobic exercise such as walking per day. One hour per day was spent in supervised stress management practices such as meditation and yoga.
Participants and their spouses/partners also attended 1-hour group support sessions, 3 days per week, supervised by a licensed mental health professional. Two patients dropped out of the intervention group. All 49 remaining patients had baseline plasma Aβ42/40 ratios <0.0672.
Meaningful Lifestyle Changes
After 20 weeks, Clinical Global Impression testing showed that 10 of the 24 intervention patients had slight improvement, 7 had no change, and 7 had slight deterioration. In the control group, no patients improved, 8 had no change, 14 had slight deterioration, and 3 had moderate deterioration (P = .001).
Clinical Dementia Rating Global (CDR Global) scores improved from 0.69 to 0.65 in the intervention group and worsened from 0.66 to 0.74 in the control group (mean group difference = 0.12, P = .037).
Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores improved from 21.55 to 20.53 in the intervention group and worsened from 21.25 to 22.16 in the control group (mean difference = 1.92 points, P = .053).
CDR sum of boxes (CDR-SB) scores worsened significantly more with usual care (from 3.34 to 3.86) than with lifestyle intervention (from 3.27 to 3.35), with a mean group difference of 0.44 ( P = .032).
“Not everyone gets better, but a lot of people get better. If we can stop the progression or improve cognition, it gives people hope — not false hope, but real hope — as opposed to telling them it's only going to get worse,” Ornish said.
He noted that suicide risk is seven times higher than normal three months after an Alzheimer's diagnosis, and that small improvements don't necessarily represent a clinical reflection of the impact lifestyle changes are having on these patients.
“One patient told us that it used to take him weeks to finish a book, but after participating in the study, he was able to finish it in just three or four days and remembered most of what he read,” Ornish said. “One man couldn't play the bagpipes because he couldn't remember the notes, but now he can and is actually teaching students how to play.”
Larger and more diverse trials are needed
Commenting on the study in Medscape Medical News, Heather M. Snyder, PhD, vice president of medical and scientific affairs at the Alzheimer's Association, said, “This is an exciting paper in an important research area and adds to the growing literature on how behavior and lifestyle relate to cognitive decline.”
“However, this is a small phase 2 study, so it will be important to conduct this and similar studies in larger, more diverse populations and over longer intervention periods,” she added.
The Alzheimer's Association's U.S. Pointer Study is the first large-scale U.S. study to examine the effects of comprehensive lifestyle changes on cognitive health in about 2,000 older adults at risk of cognitive decline, with results expected in the summer of 2025, Snyder said. More than 25% of participants are from groups typically underrepresented in dementia research.
“Right now, healthcare providers have an opportunity to incorporate or expand messaging about habits that patients and families can incorporate into their daily lives,” Snyder said. The Alzheimer's Association offers “10 Healthy Habits for Your Brain,” everyday actions that can make a difference in brain health.
Of note, the current study demonstrated that higher adherence to the multimodal lifestyle intervention was necessary to improve participants' cognition and functioning. In the primary analysis, at 20 weeks, adherence rates were 71.4% for ADAS-Cog, 95.6% for CDR Global, and 120.6% for CDR-SB.
As for whether such drastic lifestyle changes are possible outside of a clinical trial, Ornish said that eating a plant-based diet is easy to implement, and exercising, walking, and spending more time with friends are free. For patients who need more support, he noted that the Centers for Medicare and Medicaid Services already offers Medicare coverage for the exact same lifestyle program for heart disease patients.
“We're hopeful that one day insurance coverage will be extended to people with Alzheimer's so that they too can get support,” Ornish said.
The research was funded by the National Institute of Preventive Medicine and others.
Ornish has served as a consultant to Sharecare, receives book royalties and speaking honoraria, and holds stock in Ornish Lifestyle Medicines. Co-author Miia Kivipelto is one of the Editors-in-Chief of Alzheimer's Disease Research & Therapy and was not involved in the peer review process. Full research funding and other author disclosures are included in the paper. Snyder is a full-time employee of the Alzheimer's Association and, in this role, serves on the US POINTER study leadership team. Her partner works at Abbott Labs in an unrelated field.