Raphael Thys
Elderly people eating healthy food
In a randomized, controlled trial in humans, scientists have demonstrated that a multimodal lifestyle intervention consisting of a vegan diet, exercise, supplements, and stress management can improve the symptoms of Alzheimer’s [1].
Can we roll it back?
Despite billions of dollars invested in finding a cure for Alzheimer’s disease (AD), progress has been frustratingly slow. The current standard of pharmaceutical care can only slightly slow the progression of the disease while also causing harsh side effects.
Lifestyle modifications can have a profound impact on health, including decreasing the risk of getting Alzheimer’s. For example, the Lancet commission on dementia prevention, intervention, and care estimates that 12 potentially modifiable risk factors together account for about 40% of the world dementia burden [2].
However, it has been unclear if lifestyle interventions can help people who already have the disease. The research into this has been scant, which makes this new randomized controlled Phase 2 trial done by scientists from the UCSF, UCSD, Harvard Medical School, and Duke University all the more important.
The trial was of a moderate size, with 51 AD patients divided between the treatment group and the control group. The treatment group received a 20-week multimodal lifestyle intervention that included diet, exercise, stress management, and several supplements.
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In two earlier trials, the same program led to regression of coronary atherosclerosis [3], which the authors tout as an unprecedented result: “Until then,” they write, “it was believed that coronary heart disease progression could only be slowed, not stopped or reversed, similar to how MCI (mild cognitive impairment) or early dementia due to AD are viewed today.”
This study’s length was on the shorter side, but the researchers offer an interesting explanation for that. In these studies, participants in the control group are aware that they are not receiving the intervention and the accompanying health benefits; it is impossible to have a placebo control. However, it is highly important that the control group does not change their lifestyle for the whole duration of the experiment.
In the researchers’ previous experience, 20 weeks was the longest a control group could reliably go on without starting to spontaneously improve their own lifestyle. In compensation, the control group was offered the same intervention course after the experiment free of charge. Both groups continued to receive their usual AD-related care.
Diet, exercise, yoga
The intervention program was built upon several pillars, starting with a wholesome, minimally processed vegan diet that is high in complex carbohydrates (predominantly fruits, vegetables, whole grains, legumes, soy products, seeds, and nuts) and low in harmful fats, sweeteners, and refined carbohydrates. 14-18% of calories came from fat, 16-18% from protein, and 63-68% from mostly complex carbohydrates. Caloric intake was unrestricted.
The exercise routine included aerobic physical activity such as walking for at least 30 minutes a day as well as mild strength training at least three times a week. The program was personalized based on age and fitness level. The third major element was stress management, which included meditation, gentle yoga, stretching, relaxation, and breathing exercises for a total of one hour per day.
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The supplement stack included omega-3, curcumin, a multivitamin, coenzyme Q10, vitamin C, vitamin B12, magnesium, probiotics, and lion’s mane mushroom.
The researchers say that while using many interventions simultaneously makes it impossible to detect each one’s effect, it is also becoming increasingly clear that such multimodal programs may have a cumulative effect and hence should be tested.
Improvements for many study group participants
The researchers report significant correlations between the degree of lifestyle change (from baseline to 20 weeks) and the degree of change in three of four measures of cognition and function. The ratio of the two types of amyloid-β peptides (Aβ42 and Aβ40), an important Alzheimer’s metric, also showed a statistically significant response to the intervention. While it increased by 6.4% in the intervention group, it declined by 8.3% in the control group. Two more biomarkers were robustly improved: the concentration of harmful LDL cholesterol and microbiome composition.
Of the 24 patients in the study group, 10 showed improvement as measured by the cognitive test CGIC. In another 7, the symptoms were unchanged, and in 7 patients, they worsened. Not a single patient in the control group improved: 8 were unchanged, and 17 worsened. These results are impressive compared to our current best anti-AD drugs, but the duration of the study was relatively short, and it is possible that the gains would have maxed out over a longer term.
Literature
[1] Ornish, D., Madison, C., Kivipelto, M., Kemp, C., McCulloch, C. E., Galasko, D., … & 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.
[2] Livingston, G., Huntley, J., Sommerlad, A., Ames, D., Ballard, C., Banerjee, S., … & Mukadam, N. (2020). Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. The Lancet, 396(10248), 413-446.
[3] Ornish, D., Scherwitz, L. W., Billings, J. H., Gould, K. L., Merritt, T. A., Sparler, S., … & Brand, R. J. (1998). Intensive lifestyle changes for reversal of coronary heart disease. Jama, 280(23), 2001-2007.