Tantalizing new research suggests intensive diet and lifestyle changes may not only forestall cognitive decline related to Alzheimer’s disease but possibly bring some improvement to those in early stages.

The small, limited study varied from earlier findings, which concluded a healthy lifestyle could lower risk but showed little promise in reversing damage. That result had co-authors on the paper, published in June in the journal Alzheimer’s Research & Therapy, tempering excitement with caution. 

“To get significant results on these cognitive tests in just 20 weeks, in just 50 patients, only altering lifestyle, to be very honest was just shocking to me, but shocking because it says maybe this matters,” said senior author Rudolph Tanzi, Harvard Medical School’s Joseph P. and Rose F. Kennedy Professor of Child Neurology and Mental Retardation, and co-director of the MassGeneral Institute for Neurodegenerative Disease. “But I’m the first to say that it’s a small study. It was only 20 weeks, so let’s not jump to any conclusions. But boy, what a great start.”

Steven Arnold, professor of neurology at HMS, Massachusetts General Hospital’s E. Gerald Corrigan Chair in Alzheimer’s Therapeutic Science, and senior author on the paper, said the findings showed promising results but cautioned against “overinterpreting” them and advised against making wholesale diet and lifestyle changes based on this study alone.

“I think this is a well-done study. It needs to be bigger. It needs to be longer,” Arnold said. “I want people to be intrigued and enthused by its findings, but not overinterpret them because more data is needed.” 

The trial took an everything-but-the-kitchen-sink approach to treating Alzheimer’s disease, pulling together an array of interventions that individually have been seen to lower risk. In addition to their comprehensiveness, researchers said the interventions were also intensive. That is a possible reason, they suggested, their results varied from earlier studies that employed more moderate interventions.

The study’s 51 subjects, whose average age was 73.5, were in the initial stages of Alzheimer’s disease. and all had been diagnosed with mild cognitive impairment or early dementia. Twenty-six were randomly assigned to the intervention group and 25 to the control group.

Over 20 weeks, those in the intervention group were asked to eat a strict vegan diet, with all meals plus snacks for subjects and their spouses delivered to their homes. The regimen, which was not calorie-restricted, was augmented by supplements believed to support cognition, including omega 3 fatty acids, curcumin, a multivitamin, vitamins C and B12, magnesium L-threonate, coenzyme Q, a probiotic, and lion’s mane.

Those interventions were coupled with 30 minutes of aerobic exercise daily and strength training three times a week. For stress reduction, subjects meditated, did yoga poses, stretching, and breathing exercises in a daily hour led by a stress management specialist.

To boost social support, subjects and spouses participated in an hourlong support group three times a week led by a mental health professional. In all, subjects received 12 hours per week of professional support — delivered via Zoom — for the lifestyle interventions.

“In my heart of hearts, I think there is something real here.”

Steven Arnold

“In my heart of hearts, I think there is something real here,” said Arnold, who is also MGH’s head of translational neurology and managing director of its Interdisciplinary Brain Center. “If you do significantly change the metabolic, inflammatory, vascular milieu of the body and the brain, that is good for our brain function. And this diet, exercise, stress reduction/socialization intervention may work as well or better than some of the drugs we use for Alzheimer’s disease.”

To establish a baseline and gauge progress, participants took four standard tests used to measure cognitive performance in FDA drug trials. The results varied by test but generally showed the intervention group improved or stayed the same while the control group stayed the same or worsened. On the Clinical Global Impression of Change, for example, 10 — more than 40 percent — improved after 20 weeks, seven were unchanged, seven worsened slightly, and none worsened moderately. Among the controls, by comparison, none improved, eight were unchanged, and 17 worsened slightly or moderately. Two other tests showed that the intervention group improved on average, while the control group worsened. The fourth test showed both groups doing worse, with the control group worsening significantly more.

Researchers, who hailed from institutions in the U.S., U.K., Finland, and Sweden, also examined participants’ blood and microbiomes. One biomarker, called pTau 181, showed little change between the controls and the intervention group, but researchers found improvements in another marker, which measures the ratio of two forms of the amyloid beta protein, which forms plaques in the brain that are hallmarks of Alzheimer’s disease.

Researchers found improvements in another marker, which measures the ratio of two forms of the amyloid beta protein, which forms plaques in the brain that are hallmarks of Alzheimer’s disease.

Measures associated with cardiac and metabolic health like cholesterol, A1c, hemoglobin, and others also improved. The intervention group’s microbiome shifted, with populations of beneficial bacteria increasing and those thought to be associated with Alzheimer’s disease decreasing. In addition, there was a dose-response effect in both biomarkers and cognitive tests, with the degree of change positively associated with adherence to the lifestyle interventions. 

The work received financial support from more than two dozen private foundations and charitable funds and comes at a moment of optimism about Alzheimer’s disease. After years of failed drug trials that had researchers questioning whether they really understood the disease, a drug called lecanemab gained FDA approval last year after a study of 1,800 people over 18 months showed it to be the first treatment to slow progression in those in early stages of the disease. 

Tanzi and Arnold acknowledged their study’s relatively small sample size was a shortcoming but said the its design as a randomized controlled trial, considered a scientific gold standard, was a strength. The trial was designed to be multimodal, but the fact that so many different lifestyle factors were at play made it difficult to tease out the effect of each, said Tanzi, who is also the director of MGH’s Genetics and Aging Research Unit and its Henry and Allison McCance Center for Brain Health. 

The next step, he and Arnold said, would be a larger study to see whether the results are replicated. Arnold said that among questions such a trial would answer is whether subjects would stick with such an intensive intervention over the long term.

Conduct of the trial was significantly affected by the pandemic. Enrollment, which occurred between 2018 and 2022, was still underway when COVID-19 hit in early 2020, curtailing enrollment, which originally had targeted 100 participants. The need for distancing forced researchers to shift sessions to online, which may have altered the effect of the social support sessions. It did, however, allow expansion of the study population from a single site in San Francisco to others around the country, including Massachusetts General Hospital.

“This should be looked at as a pilot study, but the pilot data are significant and strongly suggest that lifestyle intervention was effective,” Tanzi said.