乌鸦传媒

Intensive lifestyle changes improved cognitive outcomes in a phase II trial of early Alzheimer's disease.

In Alzheimer's patients with mild cognitive impairment or early dementia, scores on three measures of cognition and function were significantly better after a 20-week multimodal intervention compared with usual care, reported Dean Ornish, MD, of the University of California San Francisco, and co-authors.

The intervention led to improvements on the Clinical Global Impression of Change (CGIC; P=0.001) and the Clinical Dementia Rating (CDR) global assessment (P=0.037), while the usual-care control group worsened on both measures, the researchers wrote in .

On the CDR-Sum of Boxes (CDR-SB), the intervention group showed slower cognitive decline compared with controls (P=0.032). Scores on the Alzheimer's Disease Assessment Scale (ADAS-Cog) improved with treatment and worsened in the control group, but the difference was not significant (P=0.053).

Ornish said he was "cautiously optimistic" about the study results. "While our findings are valid and biologically plausible for all the reasons outlined in our research manuscript, all studies need to be replicated," he told 乌鸦传媒. "I hope our randomized controlled trial will motivate other researchers to conduct larger-scale studies with more diverse populations over longer periods of time."

"In the meantime, physicians should encourage their patients with Alzheimer's disease to make these lifestyle changes, as there is a good chance they may improve their cognition and function, as opposed to just slowing down the rate of getting worse," Ornish added. "They don't cost anything, and the only side effects are good ones."

The study is not the first to show positive cognitive outcomes from multimodal interventions. One of the largest was the FINGERS trial, which showed that a 2-year program targeting exercise, diet, cognitive stimulation, and self-monitoring of cardiac and metabolic risk factors had a protective effect on cognition. More recently, the SMARRT trial demonstrated that personal coaching focused on multiple risk factors led to modest cognitive improvements compared with a control group. Unlike the Ornish trial, these studies focused on adults at risk for dementia, not people who had been diagnosed with Alzheimer's disease.

Ornish and colleagues enrolled 51 Alzheimer's patients with mild cognitive impairment or early-stage dementia in their from September 2018 to June 2022. All participants had plasma amyloid-beta (Aβ)42/40 ratios that strongly suggested Alzheimer's disease at baseline. The mean age of the group was 73.5 years.

The researchers randomly assigned 26 participants to an intervention group for 20 weeks, and 25 participants to a control group that was asked to not make any lifestyle changes during the trial, after which they would be offered the intervention.

The intervention program had four components: a whole-food, minimally processed, plant-based diet of predominantly fruits, vegetables, whole grains, legumes, and selected supplements; moderate aerobic exercise (such as walking) and strength training for at least 30 minutes a day; stress management including meditation, stretching, breathing, and imagery for 1 hour a day; and online support groups for participants and spouses or study partners for 1-hour sessions three times a week.

The diet had approximately 14% to 18% of its calories as total fat, 16% to 18% as protein, and 63% to 68% as mostly complex carbohydrates. Calories were unrestricted. All meals were sent to each participant's home twice a week.

At 20 weeks, blood levels of Aβ42/40 improved in the intervention group and worsened in the control group (P=0.003). Microbiome biomarkers improved in the intervention group only (P<0.0001).

"Plasma Aβ42/40 became less abnormal over 20 weeks in participants undergoing intensive lifestyle changes, but two other plasma biomarkers associated with Alzheimer's disease -- p-tau181 [phosphorylated-tau181] and GFAP [glial fibrillary acidic protein] -- did not change," noted Suzanne Schindler, MD, PhD, of Washington University in St. Louis, who wasn't involved with the study.

"Levels of plasma biomarkers can be affected by factors such as body mass index and kidney function, and it is unclear whether the plasma Aβ42/40 change in this study is related to Alzheimer's disease pathology or is a non-specific effect related to the intervention," Schindler told 乌鸦传媒.

A dose-response correlation between the degree of lifestyle change and most measures of cognition and function testing emerged over 20 weeks, but not everyone in the intervention group improved. On the CGIC test, for example, 10 of 24 people in the intervention group improved, seven were unchanged, and seven worsened. In the control group, none improved, eight were unchanged, and 17 worsened.

The study had several limitations: the sample size was small and the study duration was short. While raters were blinded, participants were not.

Comment