Nutritional considerations in Alzheimer’s prevention and treatment

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By Kellie Blake, RDN, LD, IFNCP

I remember being devastated when my grandmother was diagnosed with Alzheimer’s dementia (AD) in her late sixties. She had always maintained a healthy weight, didn’t smoke, exercised daily, was an avid reader, and could complete even the toughest crossword puzzle (in pen). If someone like her could develop AD, then the rest of us were surely doomed.

A diagnosis of AD may seem like a death sentence. After all, this disease is the sixth leading cause of death in the United States and the third leading cause of death for older Americans and conventional therapy offers no measurable benefit. Patients are often given prescriptions for ineffective medications and sent home with instructions to get their affairs in order. But groundbreaking research is finally offering the hope that has been lacking for patients and families alike.

For years, AD was thought to be the result of the accumulation of amyloid-β (Aβ) in the brain. This Aβ was presumed to initiate the inflammatory cascade leading to the production of tau protein tangles that eventually caused neuronal cell death and brain atrophy. Most AD research and medications have been based on this premise. The most recent research, as reported in the Journal of Alzheimer’s Disease & Parkinsonism, indicates AD results from myriad treatable factors including chronic inflammation, pathogen and toxin exposure, trophic withdrawal, hormonal imbalance, insulin resistance, vascular compromise, and trauma.

When each contributing factor is identified and addressed in a specific patient, cognitive decline can absolutely be reversed. Nutrition is certainly one important factor and research in the areas of the gut microbiome and the endocannabinoid system (ECS) is providing new nutrition treatment targets for AD patients.

The gut microbiome is a prime topic of conversation for every integrative provider. We now know a balanced gut microbiome is vital for overall health and gut microbiome alterations underly all chronic inflammatory diseases, including AD. Since the gut and brain are connected by the vagus nerve with bi-directional communication, the gut may be an important culprit in the development of neurodegenerative diseases and thus a target of therapy.

As described in Molecular Neurobiology, there are myriad lifestyle and environmental factors leading to dysbiosis in the gut. This microbiome imbalance allows pathogenic and opportunistic bacteria and their byproducts like lipopolysaccharides (LPS) to influence intestinal permeability. Increased intestinal permeability triggers the innate immune system to intervene with the production of proinflammatory cytokines. These inflammatory mediators enter the circulatory and central nervous system and can  increase the permeability of the blood brain barrier, upregulate inflammation, and induce Aβ accumulation in the brain. This cascade of events leads to neurodegenerative changes and neuronal cell death.

While targeting the gut microbiome will require a personalized approach, identifying patients with gut microbiome dysfunction and treating that dysfunction is one option for preventing and reversing cognitive decline. I like to target the gut with a full elimination diet and systematic reintroduction to uncover potential adverse food reactions that could be negatively affecting the gut lining. I typically remove the top known food allergens, including eggs, fish, shellfish, soy, dairy, peanuts, tree nuts, wheat, and sesame, but also remove foods and substances known to be harmful to the gut lining and gut microbiome. Examples include sugar, caffeine, inflammatory oils and additives, pork, conventionally raised beef, chocolate, corn, alcohol, soda, and processed meats. I implement the elimination diet for a minimum of eight weeks and then systematically reintroduce foods to determine tolerance.

During the elimination period, I provide the necessary digestive enzymes, nutrients, and probiotics to allow the gut lining to heal and to begin to rebalance the microbiome. I also address any potential infections that may be present. In addition, I educate patients on the need for lifestyle modification to address stress, toxin exposure, and potential nutritional deficiencies that could be contributing to dysbiosis and increased intestinal permeability.

Once gut microbiome balance has been restored, the long-term meal plan is tailored but is always rich in plant-based foods and healthy fats and free of known inflammatory foods and additives, such as fast or fried foods, highly processed foods, conventional red meat, conventional dairy, margarine and inflammatory oils, pastries, and sweets.

Another exciting area of research in AD involves the ECS. The ECS is the endogenous system responsible for restoring and maintaining homeostasis in the body. It includes lipid neurotransmitters called endocannabinoids, their receptors, and degrading enzymes. The CB1 and CB2 receptors are located throughout the brain and body and CB2 receptors are important neurobiological regulators. The body produces endocannabinoids to act on the CB1 and CB2 receptors, but phytocannabinoids from a variety of plants can also interact with these receptors.

When a healthy brain is under attack, the immune cells of the brain, called microglia, upregulate inflammation to protect delicate brain tissues. Once the insult is neutralized, inflammation is then downregulated, and homeostasis is restored. However, in the brains of AD patients, the microglial response is altered, and inflammation continues unchecked ultimately leading to neuronal cell death. Interestingly, when there is an insult to the brain, the microglia also upregulate the CB2 receptor and targeting this receptor with phytocannabinoids is one novel approach for those with neurodegenerative disorders.

According to a study published in the journal Antioxidants, beta-caryophyllene (BCP) is one CB2 receptor agonist with anti-inflammatory, antioxidant, and neuroprotective effects. BCP is a bicyclic sesquiterpene found in the Cannabis sativa plant, but also in the essential oils of various other plants. It is the first dietary cannabinoid to receive approval by the Food and Drug Administration and is used as a flavoring agent in food. Additionally, as reported in Pharmacology, in a murine model of AD, treatment with oral BCP prevented cognitive impairment and reduced Aβ in the hippocampus and cerebral cortex, led to less microglial activation, and reduced the levels of proinflammatory cytokines in the brain. The researchers determined the effects were likely related to BCP activation of the CB2 receptors and the upregulation of PPARγ. When a CB2 receptor antagonist was provided, the positive effects were reversed.   

While more human trials are needed and there are certainly other nutrition-related factors to address, targeting the gut microbiome and the ECS as part of a personalized, comprehensive plan offers the hope that has been absent for AD patients and their families. Since no two patients are alike, the treatment plan must be specifically tailored and based on a single patients’ risk factors and exposure for maximum benefit.

References

Bredesen DE (2018) Reversal of Cognitive Decline: 100 Patients. Journal of Alzheimer’s Disease & Parkinsonism. Retrieved from: https://www.omicsonline.org/open-access/reversal-of-cognitive-decline-100-patients-2161-0460-1000450-105387.html

Cheng, Y., Dong, Z., & Liu, S. (2014) β-Caryophyllene ameliorates the Alzheimer-like phenotype in APP/PS1 Mice through CB2 receptor activation and the PPARγ pathway. Pharmacology. Retrieved from: https://pubmed.ncbi.nlm.nih.gov/25171128/

Sochocka, M. (2019) The Gut Microbiome Alterations and Inflammation-Driven Pathogenesis of Alzheimer’s Disease-a Critical Review. Molecular neurobiology. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394610/

Ullah, H. (2021) Improvement of Oxidative Stress and Mitochondrial Dysfunction by β-Caryophyllene: A Focus on the Nervous System. Antioxidants (Basel, Switzerland). Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066981/