Alzheimer’s disease (AD) and other related dementias are predicted to be the greatest challenge facing healthcare and medical systems across the world. AD is a multifactorial disorder and the most common symptoms include cognitive impairment, progressive memory decline, personality changes, and disorientation (1). Currently, there are no effective treatments or medication to modify the progression of AD. Popular treatments for AD include cholinesterase inhibitors for patients with any stage of AD dementia and memantine for people with moderate-to-severe AD dementia (1,2). Although these drugs help to alter the activity of neurotransmitters and alleviate AD behavioral symptoms, they do not actually alter the progression of the disease (2). Emerging results suggest that food based therapies provide promise for therapeutic interventions and even preventative measures for AD (1). 

Recent evidence suggests that epigenetics can be examined to further understand the complex neurodegenerative patterns seen in AD (3). Epigenetics refers to changes in gene regulation and phenotype of a cell without direct changes to the DNA sequence itself. There are epigenetic marks and changes to DNA structure that can affect how genes are expressed or further silence their expression. Environmental factors such as diet, nutrition, stress, chemical exposure, sleep patterns, brain injury and more can affect mechanisms involved in AD’s neurodegeneration through these epigenetic processes (3, 4). It is widely accepted that diet plays an important role in counteracting biological processes such as oxidative stress and neuroinflammation which are implicated in the pathogenesis of AD (4). 

Unsurprisingly, nutrients derived from our diet have important physiological roles in maintaining the blood-brain barrier and neuroprotective factors (5). Antioxidants from fruits and vegetables suppress AD’s neuroinflammatory processes and neuronal apoptosis, while plant-derived flavonoids can help to down regulate transcription factor activity and inhibit pro-inflammatory cell signaling pathways (5). As a result, many studies suggest limiting intake of trans and saturated fats and dairy products, while increasing consumption of vegetables, fruits, legumes, and whole grains (1). Specific diets such as the ketogenic diet, the Mediterranean diet, and caloric restriction have been shown to reduce the neuropathological hallmarks of AD while also decreasing AD risk factors such as cerebrovascular diseases, diabetes, hypertension, and obesity (1).

The ketogenic diet consists of a high-fat and low-carbohydrate diet, which induces a shift from glucose metabolism to fatty acid metabolism. This diet provides sufficient protein for growth and development, while depending on mainly adipose tissues for energy (1). The ketone bodies produced from this diet ultimately elevate mitochondrial oxidation and result in beneficial downstream metabolic changes such as higher serum fat levels and lower serum glucose levels, protective factors against neuronal loss by apoptosis and necrosis (1,6). Oxidative stress and mitochondrial dysfunction are central features of brain degenerative disease, so the neuroprotective activity of the ketogenic diet stems from improving mitochondrial function, reducing reactive oxygen species production, and decreasing inflammatory and pro-apoptotic activities (6). Additionally, the ketogenic diet may also help to reduce the deposition of amyloid plaques and tau protein dysfunction, both of which are key factors in AD pathogenesis (1).

While various factors such as genetics and environment can contribute to the pathogenesis of AD, simple lifestyle and dietary changes can also help to counteract their effects (7). It is important to understand how diet and food may influence AD pathology so we can better our overall understanding of this disease and work towards the development of therapeutic targets (3).

Sources 

  1. Rusek, M., Pluta, R., Ułamek-Kozioł, M., & Czuczwar, S. J. (2019). Ketogenic Diet in Alzheimer’s Disease. International Journal of Molecular Sciences, 20(16). https://doi.org/10.3390/ijms20163892
  2. Weller, J., & Budson, A. (2018). Current understanding of Alzheimer’s disease diagnosis and treatment. F1000Research, 7. https://doi.org/10.12688/f1000research.14506.1
  3. Shewale, S. J., & Huebinger, R. M. (2012). The Potential Role of Epigenetics in Alzheimer?s Disease Etiology. Biological Systems: Open Access, 02(03). https://doi.org/10.4172/2329-6577.1000114
  4. Cremonini, A. L., Caffa, I., Cea, M., Nencioni, A., Odetti, P., & Monacelli, F. (2019). Nutrients in the Prevention of Alzheimer’s Disease. Oxidative Medicine and Cellular Longevity, 2019. https://doi.org/10.1155/2019/9874159
  5. McGrattan, A. M., McGuinness, B., McKinley, M. C., Kee, F., Passmore, P., Woodside, J. V., & McEvoy, C. T. (2019). Diet and Inflammation in Cognitive Ageing and Alzheimer’s Disease. Current Nutrition Reports, 8(2), 53–65. https://doi.org/10.1007/s13668-019-0271-4
  6. Włodarek, D. (2019). Role of Ketogenic Diets in Neurodegenerative Diseases (Alzheimer’s Disease and Parkinson’s Disease). Nutrients, 11(1). https://doi.org/10.3390/nu11010169
  7. Pacholko, A. G., Wotton, C. A., & Bekar, L. K. (2019). Poor Diet, Stress, and Inactivity Converge to Form a “Perfect Storm” That Drives Alzheimer’s Disease Pathogenesis. Neurodegenerative Diseases, 19(2), 60–77. https://doi.org/10.1159/000503451