A Summary of the article on “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”
Background
The article, authored by Ornish D, Madison C, Kivipelto M et al (2024), was published in the Alzheimer’s Research & Therapy journal in June 2024 and details a significant study on non-pharmacological interventions for Alzheimer’s disease (AD).
The study addresses the growing evidence linking lifestyle factors, such as unhealthy diets, sedentary behaviour, emotional stress, and social isolation, to the onset and progression of dementia, including AD. While previous research, like the FINGER study, has shown that multidomain lifestyle interventions can help prevent cognitive decline in individuals at risk, this trial is notable as the first randomized, controlled clinical trial to determine if intensive lifestyle changes may beneficially affect individuals already diagnosed with mild cognitive impairment (MCI) or early dementia due to AD. The underlying hypothesis was that an intensive multimodal intervention, similar to one previously shown to reverse coronary heart disease, could also positively impact AD progression, given the shared risk factors and biological mechanisms.
Methods
This was a 1:1 multicenter randomized controlled phase 2 trial that enrolled 51 participants, aged 45 to 90, with MCI or early dementia due to AD, confirmed by a Montreal Cognitive Assessment (MoCA) score of 18 or higher and plasma Aβ42/40 ratios <0.0672. Participants were randomly assigned to either a 20-week intensive lifestyle intervention group (26 patients) or a usual-care control group (25 patients). Two patients from the intervention group withdrew during the study.
The intensive multimodal lifestyle intervention comprised four core components:
- Diet: A whole foods, minimally processed plant-based (vegan) diet, low in harmful fats, sweeteners, and refined carbohydrates. To ensure high adherence, 21 meals/week and snacks, plus daily supplements, were provided to participants and their spouses/study partners.
- Exercise: At least 30 minutes per day of aerobic activity (e.g., walking) and mild strength training at least three times per week, with personalized prescriptions.
- Stress Management: One hour per day of practices like meditation, gentle yoga, stretching, progressive relaxation, breathing exercises, and imagery.
- Group Support: Participants and their partners attended one-hour support group sessions three days a week, supervised by a mental health professional, to foster emotional support and adherence strategies. The intervention also included specific nutritional supplements such as Omega-3 fatty acids with Curcumin, a multivitamin and minerals, Coenzyme Q10, Vitamin C, Vitamin B12, Magnesium L-Threonate, Hericium erinaceus (Lion’s Mane), and a probiotic. Primary outcome measures were changes in cognition and function using standard 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). Secondary outcomes included blood-based biomarkers (e.g., plasma Aβ42/40 ratio) and microbiome analysis.
Results
After 20 weeks, the intervention group showed statistically significant beneficial differences in cognition and function compared to the control group:
- Cognition and Function Tests: The CGIC (p = 0.001), CDR Global (p = 0.037), and ADAS-Cog (p = 0.053, borderline significance) tests showed improvement in cognition and function in the intervention group. The CDR-SB test showed significantly less progression in the intervention group (p = 0.032). In contrast, the control group worsened in all four of these measures.
- Biomarkers: The plasma Aβ42/40 ratio increased by 6.4% in the intervention group while decreasing by 8.3% in the control group (p = 0.003), supporting the beneficial impact. Other clinically relevant biomarkers like hemoglobin A1c, insulin, glycoprotein acetyls (GlycA), LDL-cholesterol, and β-Hydroxybutyrate also showed significant beneficial changes.
- Microbiome: There was a significant and beneficial change in the microbiome configuration in the intervention group only (p < 0.0001). This included an increase in taxa associated with reduced AD risk (Blautia, Eubacterium) and a decrease in those linked to increased AD risk (Prevotella, Turicibacter).
- Dose-Response Correlation: A significant dose-response correlation was found between the degree of lifestyle change and the degree of improvement in cognition, function, and many biomarkers. This indicated that greater adherence to the lifestyle intervention led to greater benefits. The study found that extensive lifestyle changes (ranging from 71.4% to 120.6% adherence) were needed to stop or improve the worsening of MCI or early dementia due to AD.
Conclusions
The study concludes that comprehensive lifestyle changes may significantly improve cognition and function in many patients with MCI or early dementia due to AD after just 20 weeks. These findings are strengthened by observed beneficial changes in plasma biomarkers and the microbiome, as well as the clear dose-response relationship. The authors suggest these findings have implications for AD prevention, indicating that intensive lifestyle changes may help prevent the condition and that treating existing AD may require more extensive lifestyle modifications than prevention.
However, the study acknowledges several limitations: the relatively small sample size (51 enrolled, 49 analysed), which limits generalizability and diversity; the short 20-week duration; and the impossibility of blinding participants to their intervention group, which could affect outcomes due to positive expectations. Despite these, the statistically significant differences observed suggest a potent effect of the lifestyle intervention.
References
Ornish, D., Madison, C., Kivipelto, M., Kemp, C., McCulloch, C. E., Galasko, D., Artz, J., Rentz, D., Lin, J., Norman, K., Ornish, A., Tranter, S., DeLamarter, N., Wingers, N., Richling, C., Kaddurah-Daouk, R., Knight, R., McDonald, D., Patel, L., … Arnold, S. E. (2024). 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. Alzheimer’s Research & Therapy, 16(1), 122. https://doi.org/10.1186/s13195-024-01482-z
This post is based on Open Access research and is for informational purposes only.
