Intensive lifestyle changes improved cognitive outcomes and slowed disease progression in a phase II trial of early Alzheimer’s, with the patients’ scores in cognition and function being significantly better after a 20-week multimodal intervention.
Dean Ornish, MD, of the University of California San Francisco, and co-authors said that 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.
Their findings were published in Alzheimer’s Research & Therapy.
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 told Medpage Today he was “cautiously optimistic” about the 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 said. “I hope our randomised 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 patients 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.”
The study is not the first to show positive cognitive outcomes from multimodal interventions.
One of the largest was the FINGER trial, which showed that a two-year programme 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.
Ornish and colleagues enrolled 51 Alzheimer’s patients with mild cognitive impairment or early-stage dementia in their trial 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 programme 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 one hour a day; and online support groups for participants and spouses or study partners for one-hour sessions three times a week.
The diet had a14% 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 – p-tau181 [phosphorylated-tau181] and GFAP [glial fibrillary acidic protein] – did not change,” noted Suzanne Schindler, MD, PhD, of Washington University, who wasn’t involved with the study.
“Levels of plasma biomarkers can be affected by factors like 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 MedPage Today.
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.
Study details
Effects of intensive lifestyle changes on the progression of mild cognitive impairment or early dementia due to Alzheimer’s disease: a randomised, controlled clinical trial
Dean Ornish, Catherine Madison, Miia Kivipelto et al.
Published in Alzheimer’s Research & Therapy on 7 June 2024
Abstract
Background
Evidence links lifestyle factors with Alzheimer’s disease (AD). We report the first randomised, controlled clinical trial to determine if intensive lifestyle changes may beneficially affect the progression of mild cognitive impairment (MCI) or early dementia due to AD.
Methods
A 1:1 multicentre randomised controlled phase 2 trial, ages 45-90 with MCI or early dementia due to AD and a Montreal Cognitive Assessment (MoCA) score of 18 or higher. The primary outcome measures were changes in cognition and function tests: Clinical Global Impression of Change (CGIC), Alzheimer’s Disease Assessment Scale (ADAS-Cog), Clinical Dementia Rating–Sum of Boxes (CDR-SB), and Clinical Dementia Rating Global (CDR-G) after 20 weeks of an intensive multidomain lifestyle intervention compared to a wait-list usual care control group. ADAS-Cog, CDR-SB, and CDR-Global scales were compared using a Mann-Whitney-Wilcoxon rank-sum test, and CGIC was compared using Fisher’s exact test. Secondary outcomes included plasma Aβ42/40 ratio, other biomarkers, and correlating lifestyle with the degree of change in these measures.
Results
Fifty-one AD patients enrolled, mean age 73.5. No significant differences in any measures at baseline. Only two patients withdrew. All patients had plasma Aβ42/40 ratios <0.0672 at baseline, strongly supporting AD diagnosis. After 20 weeks, significant between-group differences in the CGIC (p= 0.001), CDR-SB (p= 0.032), and CDR Global (p= 0.037) tests and borderline significance in the ADAS-Cog test (p= 0.053). CGIC, CDR Global, and ADAS-Cog showed improvement in cognition and function and CDR-SB showed significantly less progression, compared to the control group which worsened in all four measures. Aβ42/40 ratio increased in the intervention group and decreased in the control group (p = 0.003). There was a significant correlation between lifestyle and both cognitive function and the plasma Aβ42/40 ratio. The microbiome improved only in the intervention group (p <0.0001).
Conclusions
Comprehensive lifestyle changes may significantly improve cognition and function after 20 weeks in many patients with MCI or early dementia due to AD.
Medpage Today article – Alzheimer’s Slowed by Intensive Lifestyle Changes (Open access)
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