Reevaluating Alzheimer's treatments

Alzheimer's disease is the most common neurodegenerative disorder, which presents with impaired cognition, and diminished quality of life for the patient but ultimately even more so for the caregivers. Prominent Alzheimer’s researcher Alexandra Oxford writes in the Journal of Alzheimer’s Disease:

“For the last 25 years, clinical trials involving Alzheimer’s disease have centered on beta-amyloid (Aβ) and the Aβ hypothesis of Alzheimer’s progression and pathology. According to this hypothesis, the progression of Alzheimer’s disease begins following an accumulation of Aβ peptide, leading to eventual synapse loss and neuronal cell death: the true overriding pathological feature of Azheimer’s disease. Clinical trials arising from the Aβ hypothesis target causal steps in the pathway in order to reduce the formation of Aβ or enhance clearance, and though agents have been successful in this aim, they remain unsuccessful in rescuing cognitive function or slowing cognitive decline. As such, further use of resources in the development of treatment options for Alzheimer’s disease that target Aβ, its precursors, or its products should be reevaluated.”

The cost of dementia care is unsustainable. In 2016, the estimated per patient cost of formal care was $28,078, and informal care cost valued in terms of replacement cost and forgone wages was $36,667 and $15,792, respectively, according to the journal Aging-US. Aggregate formal care cost and formal plus informal care cost using replacement cost and forgone wage methods were $196 billion, $450 billion, and $305 billion, respectively, in 2020. These are projected to increase to $1.4 trillion, $3.3 trillion, and $2.2 trillion, respectively, by 2060.

The gut-brain connection

The scientific exploration of a microbial gut-brain axis, now solidly established for over two decades, confirms that microbiota inhabiting the intestines dynamically affects its host’s central nervous system activity (including vegetative and cognitive functions), and vice versa in that brain activity impacts microbiota development and composition. Clinical and experimental evidence indicates that this is true for humans as well as the early and ongoing research subjects such as germ-free mice.

Gut microbes play a pivotal role in the development of metabolic and mental diseases. According to the World Health Organization, metabolic and mental disorders lead the global burden of disease, and the WHO has urged researchers, clinicians, governments, public agencies and private funders to focus on how to reduce the burden of metabolic and cognitive diseases. Understanding the bidirectional signaling between the gut microbiome and the brain provides potential for significant positive impacts on global health by elucidating new preventive and therapeutic opportunities.

Building a better diet

Despite relatively few trials studying dietary patterns in Alzheimer’s disease, we have seen that diets characterized by higher intake of low-fat plant foods and specific plant-derived compounds lower the risk of T2DM, metabolic syndrome and Alzheimer’s disease, all diseases of systemic inflammation. Thus, future randomized clinically controlled dietary interventions targeting the gut microbiota studies in humans to determine the underlying mechanisms of diet-induced gut dysbiosis and the development of Alzheimer’s disease will prove fruitful. In the short term, policies which promote more fresh, plant-based food and disincentivize buying and eating processed foods, will open up inquiry as to the precise mechanisms of dietary-based intervention strategies in Alzheimer’s disease.

Bi-directional communication between the gut and central nervous systems occurs largely via the vagus nerve. Gut microbiota can activate the vagus nerve and vagal signals from the gut can induce anti-inflammatory responses. Vagus nerve stimulation has been used successfully in the treatment of epilepsy and depression, and is under investigation as a therapy for Alzheimer’s disease. Epilepsy, depression, and Alzheimer’s disease are all closely connected with neuroinflammation.

The renowned and ancient Mediterranean diet, rich in vegetables, fruit, whole grains, nuts, olive oil, moderate consumption of fish and poultry and limited consumption of red meat and sweets, has been extensively described for its protective role against a variety of non- communicable diseases.

The DASH diet (Dietary Approaches to Stop Hypertension), designed for hypertension treatment, overlaps the Mediterranean diet in composition, with more attention on salt restriction (less than 2.4 grams per day).

Similarly, the MIND diet (Mediterranean-DASH Intervention for Neurodegenerative Delay) is a combination of both DASH and Mediterranean diets, specifically developed to delay neurodegeneration. Besides being rich in fruits, vegetables and legumes, MIND includes the consumption of single dietary components such green leafy vegetables and berries, which have displayed a superior effect against cognitive impairment and decline compared to other vegetables and fruits. Most healthy centenarians in Blue Zones are eating a Mediterranean style diet. Let’s join them.

Emily Kane is a naturopathic doctor based in Juneau. Contact her online at

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