Despite recent novel advancement in pharmacotherapies for dementia, particularly Alzheimer’s disease (AD), there is renewed focus on modifiable risk factors for both disease prevention and progression. Here we review the data relevant to the key areas in this regard, namely nutrition, sleep and exercise. In our experience there is a great community and patient interest in the benefit of dietary supplementation, which will be discussed as well.
Nutrition
Recommendations for nutrition and diet in AD emphasize adherence to the Mediterranean and DASH diets. These diets are rich in fruits, vegetables, whole grains, nuts, legumes, fish and healthy fats like olive oil, while limiting red meat, processed foods and saturated fats. These dietary patterns are associated with reduced cognitive decline and lower risk of developing AD.
One systematic review reported that higher adherence to the Mediterranean diet was associated with a lower risk of AD, with an odds ratio (OR) of 0.73 (95% CI 0.62-0.85).1 The Mediterranean diet, in particular, has been linked to decreased Aß accumulation and improved cognitive function. Omega-3 fatty acids, polyphenols and antioxidants found in these diets have neuroprotective effects, reducing inflammation and oxidative stress, which are key factors in AD pathology. Evidence shows that adherence to these diets can improve memory, cognition and overall brain health, potentially slowing the progression of AD.
Sleep
Improving sleep quality is essential because it facilitates the clearance of Aß and tau from the brain, reducing their accumulation and potentially slowing the progression of AD. Additionally, better sleep is associated with improved cognitive performance and reduced neurodegeneration. One study showed persistent short sleep duration (<5 hours) at age 50-70 compared to persistent normal sleep duration was also associated with a 30% increased dementia risk independent of other risk factors.2
General recommendations include Cognitive Behavioral Therapy for Insomnia (CBT-I), structured exercise programs, sleep apnea intervention and bright light therapy. Healthy sleep habits, such as prioritizing getting 6-8 hours a night and reducing nighttime distractions, are also recommended.
Exercise
Recommendations for exercise in AD include aerobic, resistance and multimodal exercises. Aerobic exercise – such as walking or cycling – for 30-50 minutes per session, three times a week for at least 16 weeks, has shown significant benefits in cognitive function and quality of life.
A recent meta-analysis reported that aerobic exercise following these guidelines resulted in standardized mean differences (SMD) of 0.95 for the Mini-Mental State Examination (MMSE) and -0.67 for the Alzheimer’s Disease Assessment Scale-Cognitive Section (ADAS-cog), indicating substantial cognitive benefits and significant improved quality of life.3 Resistance training has also been shown to improve cognitive function and memory when performed 2-3 times a week with sessions lasting 30-60 minutes.
Both aerobic exercise and resistance training can increase the expression of brain-derived neurotrophic factor (BDNF), which promotes the survival of hippocampal neurons, synaptic plasticity, and learning and memory abilities. Further exercise-induced protective benefits include irisin, a myokine that enhances synaptic plasticity and memory by reducing Aß pathology and promoting BDNF, and GDF-15, which aids in Aß clearance by increasing insulin-degrading enzyme expression, offering neuroprotective effects in AD.
Exercise reduces neuroinflammation, enhances neurogenesis and improves cardiovascular fitness, which collectively slow cognitive decline and improve physical performance and ADLs in AD patients.
Non-prescriptive Supplements
Evidence shows that omega-3 fatty acids, with a focus on EPA and DHA, can lead to reduced neuroinflammation by supporting cell integrity and reducing cognitive decline. While vitamins B6, B9 and B12 have also shown cognitive benefits, especially in individuals with high baseline omega-3 fatty acids.
B vitamins lower homocysteine levels, which are associated with brain atrophy. When combined with high baseline omega-3 fatty acid levels, B vitamins have shown enhanced cognitive benefits. Specifically, participants with high omega-3 levels experienced a 40% reduction in brain atrophy rates and improved cognitive outcomes, including better verbal delayed recall and global cognition scores.4 This synergistic effect is likely due to the combined anti-inflammatory and neuroprotective properties of omega-3 fatty acids and the homocysteine-lowering effect of B vitamins, which together help to preserve brain structure and function.
Vitamin D supplementation in AD has shown potential cognitive benefits in certain populations, although the evidence is inconclusive. Vitamin D is thought to benefit AD by reducing neuroinflammation, enhancing amyloid clearance and supporting overall brain health. However, some studies have shown conflicting results, with one indicating that prolonged vitamin D supplementation might worsen AD progression.
Other common supplements include magnesium, curcumin, resveratrol and CoQ10. Magnesium is thought to support neuron function and may reduce Aß plaque formation, as shown in preclinical studies. Yet human studies have not conclusively demonstrated that magnesium supplementation can slow disease progression, despite evidence that AD patients often have lower circulating magnesium levels compared to healthy controls.
Curcumin, resveratrol and CoQ10 are all thought to have anti-inflammatory and antioxidant benefits, though clinical still evidence is insufficient to show direct benefit in slowing the progression of AD.
Finally, evidence showed no difference between vitamin E and placebo in brief cognitive test performance, neuropsychological performance or memory. Additional supplements with inconclusive evidence include Ginkgo biloba and MCT oil. While some may offer short-term benefits, none are proven to stop AD progression. The best approach is combining supplements with a healthy diet, regular exercise, quality sleep and cognitive engagement.
Ms. Wells is a medical student at the AU/UGA Medical Partnership with Medical College of Georgia. She has a background in chemical and biomolecular engineering from Georgia Tech and is currently focused on pursuing emergency medicine with a special interest in population health and health equity.
Dr. Lazarus is a board-certified movement disorder specialist neurologist and the director of clinical research at Atlanta Neuroscience. He is also an assistant clinical professor at the University of Augusta/University of Georgia Medical Partnership. Dr. Lazarus completed his neurology residency training as well as a clinical fellowship in movement disorders at Emory University. His work, along with collaborators at GSU, has been recognized with the 2021 College of Education and Human Development Partnership Award.
References
1. Association Between Mediterranean Diet and Dementia and Alzheimer Disease: A Systematic Review With Meta-Analysis. Nucci D, Sommariva A, Degoni LM, et al. Aging Clinical and Experimental Research. 2024;36(1):77. doi:10.1007/s40520-024-02718-6.
2. Sabia, S., Fayosse, A., Dumurgier, J. et al. Association of sleep duration in middle and old age with incidence of dementia. Nat Commun 12, 2289 (2021). https://doi.org/10.1038/s41467-021-22354-2
3. Effects of Aerobic Exercise on Cognitive Function and Quality of Life in Patients With Alzheimer’s Disease: A Systematic Review and Meta-Analysis. Yang L, Yuan Z, Peng C. BMJ Open. 2025;15(1):e090623. doi:10.1136/bmjopen-2024-090623.
4. Brain Atrophy in Cognitively Impaired Elderly: The Importance of Long-Chain Ω-3 Fatty Acids and B Vitamin Status in a Randomized Controlled Trial. Jernerén F, Elshorbagy AK, Oulhaj A, et al. The American Journal of Clinical Nutrition. 2015;102(1):215-21. doi:10.3945/ajcn.114.103283.
1. Pharmacological and Non-Pharmacological Interventions to Enhance Sleep in Mild Cognitive Impairment and Mild Alzheimer’s Disease: A Systematic Review. Blackman J, Swirski M, Clynes J, et al. Journal of Sleep Research. 2021;30(4):e13229. doi:10.1111/jsr.13229.
2. Effect of Nutrition in Alzheimer’s Disease: A Systematic Review. Xu Lou I, Ali K, Chen Q. Frontiers in Neuroscience. 2023;17:1147177. doi:10.3389/fnins.2023.1147177.
3. Physical Activity for Executive Function and Activities of Daily Living in AD Patients: A Systematic Review and Meta-Analysis. Zhu L, Li L, Wang L, Jin X, Zhang H. Frontiers in Psychology. 2020;11:560461. doi:10.3389/fpsyg.2020.560461.
4. A Meta-Analysis of the Efficacy of Physical Exercise Interventions on Activities of Daily Living in Patients With Alzheimer’s Disease. Xiao Y, Fan Y, Feng Z. Frontiers in Public Health. 2024;12:1485807. doi:10.3389/fpubh.2024.1485807.
