Thursday, June 13, 2019

The Current State of Alzheimer’s Disease Treatment


The Current State of Alzheimer’s Disease Treatment

Is a bona fide cure for Alzheimer’s disease (AD) truly right around the corner? Despite the glowing reports we read about from experiments conducted in test tubes and animals, the short answer is No.

I have spent decades in the Pharmaceutical and Biotech industries looking for the elusive small molecule or biologic to halt the production of the plaques and tangles that are a hallmark feature of this neurologically destructive disease. These compounds work just fine in animals but do not improve cognitive health in humans. 

The current pharmaceutical agents to treat AD patients focus on acetylcholine which is a neurotransmitter that supports memory. For mild to moderate cases of AD, doctors prescribe Aricept® or Exelon® which are cholinesterase inhibitors that prevent the breakdown of acetylcholine. For moderate to severe AD doctors recommend Namenda® which is a N-methy-D-aspartate (NMDA) antagonist that blocks the toxic effects associated with another neurotransmitter, glutamate. The newest drug, Namzaric®, is simply a combination of Aricept® and Namenda® to treat symptoms of moderate to severe AD.

Other classes of drug treatment merely help with the depression, aggression, restlessness and anxiety seen in AD but none of these drugs, including the cholinesterase inhibitors, reverse neurodegeneration and also come with numerous side effects.  

Novel treatments in clinical development focus on reducing plaques and tangles, and while several compounds have proven to be effective in this manner they do not reverse or delay disease progression.  The current theory for this lack of efficacy is that treatment must start long before obvious symptoms of AD appear.  In most cases this could be a matter of decades, not years. As a result  the founders and active members of the AD foundation and physicians from the Weill Cornell Medical Center  are strong supporters of disease prevention using dietary and lifestyle intervention to reduce cognitive decline in AD. Although statistical significance is much harder to quantify for these remedies, since there are so many variables, the results cannot be ignored. 

Since I am a fitness enthusiast I am happy to report that there is a wealth of data to show that exercise, weight lifting in particular, improves cognitive health in a variety of ways. These studies have shown that exercise increases brain size and function with measurable improvement in memory.  These changes may be related to increased blood flow and subsequent oxygenation of the brain along with increased delivery of glucose. Decreased glucose utilization is a hallmark feature of Alzheimer’s disease which is why it is sometimes referred to as Type 3 Diabetes.  Also, yoga and meditation are shown to reduce the stress hormone cortisol to improve overall well-being.  These studies mirror the utility of physical therapy used to restore neuronal function in brain injury.

Numerous studies have been undertaken to assess the importance of nutrients that are critical for brain health, including vitamins B1, B6, B12 and D3 along with Omega-3 fatty acids.  Huperzine is a moss extract that has properties similar to those of colinesterase inhibitors. Other nutrients under investigation include coconut oil, phosphatidylserine, and a Medical food called Tramiprosate.  Coconut oil is high in medium chain triglycerides thought to be an exceptional energy source for the brain.  Phosphatidylserine is a primary component of the membranes that surround nerve cells and Tramiprosate is rich in taurine, an amino acid that plays an important role in creating new brain cells and is often used to boost cardiac function.

A more practical solution to ensure consumption of all of these nutrients would be to follow The Mind Diet which is basically a combination of a Mediterranean diet that is rich in healthy fats from fish, olives, olive oil, nuts and seeds, and avocados, and the DASH diet which helps to reduce sodium levels and increase fiber from fruits, vegetables and whole grains. These foods increase the growth of beneficial bacteria in the gut, leading to greater production of acetylcholine.  Improved gut health will also increase levels of serotonin and dopamine to obviate the need for anti-depressant and anti-anxiety meds.  One piece of The Mind Diet that I probably would not support is the inclusion of red wine. Alcohol is a solvent that inhibits nutrient absorption and may interfere with digestion. It is also a stimulant that will interfere with a good night’s sleep. Despite it’s reputation for being heart healthy I do not believe that red wine is beneficial in AD.


Treatment of Alzheimer’s disease is not nearly where it needs to be, given the acceleration in aging of the World’s population (Fig. 1). In their quest to chase down that next billion-dollar drug pharmaceutical researchers are wasting valuable time and resources. A greater emphasis on holistic treatments that increase memory will lead to improved outcomes with less pain and suffering by both patients and families.



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