Intensive lifestyle changes can mitigate early-stage Alzheimer’s Disease

Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder that primarily affects memory, cognition, and behavior, and is the most common cause of dementia (~80%) worldwide. As a leading cause of morbidity in older adults, AD has significant personal, societal, and economic impacts. The risk factors for developing Alzheimer’s are multifactorial, with age being the strongest known predictor, particularly affecting those aged 65 and older. Additional risk factors include genetics (such as the presence of the APOE ε4 allele), cardiovascular health, lifestyle factors (e.g., diet, physical activity), and the presence of certain comorbid conditions like diabetes and hypertension.

Lifestyle interventions can play a crucial role in reducing the risk and slowing the progression of Alzheimer’s Disease. Regular physical activity has been shown to improve brain health, as well as a balanced diet (e.g. Mediterranean or DASH diet), rich in vegetables, whole grains, lean proteins, and healthy fats. Cognitive engagement, such as reading, puzzles, and learning new skills, stimulates the brain, potentially delaying the onset of Alzheimer’s symptoms. Social engagement also has protective benefits, as it fosters emotional well-being and reduces isolation, which can accelerate cognitive decline. Additionally, managing stress through mindfulness practices and ensuring adequate, high-quality sleep is vital, as chronic stress and poor sleep contribute to Alzheimer’s. 

A committee of medical experts (Lancet commission) identified 12 modifiable risk factors that may account for ~40% of the global dementia burden. Rather than performing interventions one by one, in a new paper, researchers adopted a throw everything but the kitchen sink approach, and investigated the impact of employing numerous interventions at the same time.

In a small randomized study, 51 participants aged 45 to 90 with mild cognitive impairment (MCI) or early-stage dementia due to AD, but not moderate or severe dementia, were split 50-50 into a treatment group (26) and a control group (25). The intervention group received intensive lifestyle intervention described below for 20 weeks, whereas the 25 control participants were asked not to make any lifestyle changes for 20 weeks. Before and after the 20 week trial, each subject was assessed by several tests including a Clinical Global Impression of Change (CGIC), Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), and two Clinical Dementia Ratings (CDR). 

The intervention involved dramatic lifestyle changes to the following:

• Diet: Whole-food, plant-based (vegan) diet, high in complex carbs (fruits, vegetables, grains, legumes, soy, seeds, nuts). Low in harmful fats, sweeteners, and refined carbs. Provided 21 meals/week, including snacks and supplements to participants.
• Exercise: Daily 30 minutes of aerobic exercise and mild strength training three times/week. Supervised by exercise physiologist and personalized based on age/fitness.
• Stress Management: Daily one-hour practices including meditation, yoga-based poses, stretching, relaxation techniques, breathing exercises, and imagery. Supervised by certified stress management specialists.
• Group Support: Group support sessions three days/week for one hour each, supervised by mental health professionals. Included memory exercises and provided social and emotional support.
• Supplements: Omega-3 with Curcumin, Multivitamin and Minerals, Coenzyme Q10, Vitamin C, Vitamin B12, Magnesium L-Threonate, Lion’s Mane mushroom, and a probiotic.

Reading through the list underscores the stringency of the intervention with a vegan diet (21 meals provided per week), memory exercises and group (social) support 3 hours per week, and 30 minutes of aerobic exercise each day. Basically all aspects of daily life were affected in what can be termed an onerous regimen.

After 20 weeks, the results were equally dramatic with the intervention group showing significant improvements in cognitive and functional outcomes compared to the control group. The intervention treatment produced cognitive improvements on three of the four tests, whereas the control group worsened in all four. The p-values of the treatment effect were as follows: CGIC (p=0.001), CDR-SB (p=0.032), CDR Global (p=0.037), and ADAS-Cog (p=0.053, borderline significance).

The investigators also examined the Aβ42/40 ratio, a key blood biomarker of AD. It is derived from the ratio of two specific amyloid-beta (Aβ) peptides: Aβ42 and Aβ40 which are produced from the amyloid precursor protein (APP) and accumulate to form damaging plaques in the brain. Aβ42 is more prone to aggregation and plaque formation than Aβ40 so that the Aβ42/40 ratio in the blood often decreases during AD progression as Aβ42 is deposited in the brain, i.e. a lower ratio correlates with deteriorating AD. Interestingly, the the Aβ42/40 ratio increased in the intervention group but decreased in the control group (p=0.003), which is consistent with the improvements on the cognitive tests.

The authors conclude: "Comprehensive lifestyle changes may significantly improve cognition and function after 20 weeks in many patients with MCI or early dementia due to AD." Indeed, it is striking that there was a significant effect in a relatively short time period (20 weeks) with improvements and statistically significant differences from control on 3 out 4 tests as well as a blood biomarker. The benefits were achieved through lifestyle changes, and not a drug treatment. A next step would be disentangling the multiple interventions to figure out which ones had the biggest positive impact.

Figure 1. Lifestyle intervention resulted in a decreased (improvement) ADAS-Cog score after 20 weeks. The control group showed a higher (declining condition) score. The ADAS-Cog test includes various tasks, such as word recall, following commands, naming objects, and recognizing word meanings. The test is scored on a scale from 0 to 70, with higher scores indicating greater cognitive impairment (Ornish et al. Alzheimer's Research and Therapy, 2024).