The Next Blockbuster Drug for Alzheimer’s Disease is Prevention
Dr. Nancy A. Palermo
Earlier this month the Food and Drug Administration approved the drug Aduhelm (scientific name aducanumab, pronounced add-you-can-you-mab) through its accelerated drug approval program.
This is the first Alzheimer’s drug to pass through the FDA in over 18 years which should be a cause for celebration, but many researchers disagree. The drug, aducanumab, produced by the company Biogen, is an IV-infused antibody developed to reduce amyloid plaques in the brain of Alzheimer’s patients.
Amyloid plaques are collections of the abnormal inflammatory amyloid protein known to be the hallmark of the disease.
While the data from the clinical trials have still not been released, early indications suggest the drug appears to address just the symptoms and not the disease itself … sound familiar?
Additionally, it may only be beneficial to those given the highest doses in the early stages of the disease. There is little data to support that it will reverse or improve the symptoms associated with cognitive decline. Even worse, the drug comes with a huge price tag of $56,000 per patient, per year.
That accounts for a $17 billion dollar boost for Biogen in just one year for treating only those with the disease who are approved to receive it.
That may not be the only price to pay as 40% of those receiving the drug had brain swelling and some even experienced brain bleeding. Biogen has been given until 2029 to show the drug is efficacious to receive full approval. Even if the drug fails approval like many have in the past, with this accelerated approval, they stand to gain $136 billion in the process.
To those of us practicing Functional Medicine, we are reminded of the repeated failures of the disease approach in conventional medicine.
Addressing just the symptoms is not only costly, but it is also not effective. Alzheimer’s disease is unlikely to ever be “cured” through medication, yet there is significant evidence it can be prevented, slowed, or even reversed to some degree through diet and lifestyle interventions. This should be front-page information, but prevention of this deadly disease has hardly received the pomp and fanfare of the new FDA-released drug since there is little money to be made with this approach.
While we wait eight years for the results of the drug trial or hold out for the next blockbuster drug release, we should instead focus on prevention.
In the US, Alzheimer’s disease now affects over 6 million adults over the age of 65. It is the most common cause of dementia and the sixth leading cause of death. More worrisome is that the incidence has increased 146% since 2000. Alzheimer’s disease has been clinically defined by the discovery of amyloid plaques and neurofibrillary tangles (tau protein) which collect in the brain and block the connections and communications between brain cells. These proteins have been the target of drug treatments. The problem is that by the time these deposits have developed in the brain, the damage has already been done which explains why the positive results from the trials are meager to none. The process of protein deposition is believed to occur 15-20 years before the onset of symptoms, so it is likely the process starts in the 4th decade of life. This is when intervention and prevention should take place, especially in those individuals with an increased genetic risk for the development of the disease such as carriers of the APOE4 gene.
Research into the prevention of Alzheimer’s disease has been abundant though rarely discussed.
The work of Dale Bredesen alone is promising for those who are at risk of the disease or show early signs of cognitive changes. His work has shown success in interventions around diet, sleep, exercise, and lifestyle factors. A large focus of prevention is examining the effect these factors have on a protein produced in the brain called Brain-Derived Neurotrophic Factor or BDNF.
BDNF is important for neuronal survival and growth, neurotransmitter modulation, and improvements in neural plasticity. It is called the brain’s growth hormone. All of these are factors important in the prevention of brain damage, cognitive decline, and memory loss. Individuals who notice brain fog, forgetfulness and memory lapses in their 40’s may be showing early signs that BDNF is not being properly produced and may be at risk for further cognitive decline. Lack of proper nutrition and reduced sleep, exercise, and brain stimulation can affect the production of BDNF.
Brain-Derived Neurotrophic Factor or BDNF is a naturally occurring protein that appears to improve brain function through its action on brain cell growth.
In animal studies, BDNF improves neuronal survival and breakage, synaptic plasticity, and long-term memory. BDNF protects and repairs your brain cells, increases the growth of new brain cells, and improves learning, memory, and mood. In fact, many researchers consider it a natural antidepressant. Researchers feel confident that focusing on nutrients, foods, and habits that increase the natural production of BDNF may be the best approach to the prevention of Alzheimer’s disease and possibly other brain diseases including Parkinson’s, Post-concussive syndromes, and even mental diseases like depression.
The foundations of good health – diet, exercise, good sleep, hygiene, and stress reduction – are all beneficial in boosting BDNF levels. A whole-food, plant-rich diet appears to be beneficial for many reasons, but with respect to BDNF, removing processed foods and refined sugars was key. These deleterious components of the Standard American Diet (SAD diet) have been found to lower BDNF levels. How you eat and how much you eat matters too. Those who practiced intermittent fasting and calorie restriction boosted BDNF levels by 400%. Benefits were seen with an intermittent fasting window of 4-16 hours.
Check out Dr. Fletcher's article on Exercise & BDNF
Exercise is one of the most effective ways to increase BDNF levels, and results are seen within 5-6 weeks of implementation in an exercise program.
High-intensity exercise appeared to be most beneficial, though even mild forms of exercise showed results. One study looked at middle age sedentary men who started a high-intensity exercise program for 6 weeks. After the study, BDNF levels and memory were improved. It is not too late to start exercise as similar results were also seen in older individuals.
Sleep is foundational with respect to the prevention of many chronic diseases, but research has shown it can boost BDNF levels significantly. Not surprisingly, sleep deprivation (sleeping less than 6 hours a night) has been shown to reduce BDNF levels. The quantity of sleep is important, but the quality of sleep is key as well. Deep sleep and REM sleep appears to be the most beneficial at increasing BDNF levels.
Stress can wreak havoc on all organ systems and is known to be a contributor to many chronic diseases.
But researchers have shown acute and chronic stress can also reduce BDNF levels and may be a contributor to many brain issues including Alzheimer’s Disease as well as mood and psychiatric disorders like Anxiety and Depression. Stress can also directly affect your sleep, which in turn, can impact all health indices. Adopting a meditation practice while optimizing sleep can be helpful. Biofeedback and modalities like Alpha-Stim and Heart Math may help those who find stress reduction overwhelming. Also, adaptogens like those found in Cortisol Manager (Integrative Therapeutics/Klaire Labs) can be helpful in the short term while stress reduction practices are put into place. This supplement contains Ashwagandha, Rhodiola, Magnolia Officinalis, and L-theanine. All of these are shown to increase BDNF expression in the brain. They are all adaptogens which are compounds that can increase resilience to physical and mental stress, calm you down, and potentially even increase your energy.
While diet and lifestyle interventions are key, there are some nutrients and foods that have a direct impact on levels of Brain-Derived Neurotropic Factor (BDNF) as well. Foods shown to increase BDNF levels are listed below:
(Make sure to incorporate these foods into your diet daily)
- Blueberries Red Grapes
- Organic soy and edamame Dark Chocolate
- Fatty Fish Organic Coffee
- Olive Oil Avocados
- Beets, Nuts, and Seeds
- Prebiotic foods like root vegetables, asparagus, artichokes, prebiotic foods like sauerkraut, miso, tempeh, and resistant starch like potato starch.
Food and diet are key, but some supplements and herbs have been shown to boost BDNF levels significantly and might be a good option while adopting the changes needed. For example, curcumin the active compound found in turmeric has shown significant promise in the reduction of tau the protein associated with the neurofibrillary tangles seen in Alzheimer’s. In fact, the research is so impressive pharmaceutical companies are looking at it for drug interventions. Curcumin is a powerful antioxidant, anti-inflammatory, and detoxifier and can be obtained through just a ¼ tsp a day of grated turmeric root added to shakes or roasted vegetables or through a high-grade supplement at doses of 500 mg a day.
Green Tea has catechins, powerful antioxidants, which have been shown to increase BDNF levels. Drinking green tea is an easy way to improve BDNF levels, but for individuals who do not like green tea, concentrated supplements of EGCG can be taken at 500-1000 mg daily. (Klaire Lab EGCG 500 mg)
Essential Fatty acids and Omega-3s have shown many heart benefits, but research has also shown that EFAs (DHA, EPA) can reduce inflammation and increase BDNF levels. Fatty fish and nuts are a good source, but most individuals do not get the necessary EFAs daily so a high-grade supplement is generally recommended. (Klaire Omegathera or Nordic Naturals Ultimate Omega)
Vitamin D has also received a lot of press lately with respect to its action on the immune system through COVID, but it turns out this multitasker can also increase BDNF levels. The best source of Vitamin D is obtained from sunlight. Exposure to 20-30 minutes of unprotected (no sunscreen) sunlight daily is beneficial and can provide up to 10,000 IUs daily. Optimal levels of D are 50-80 and for those who cannot get sun exposure, a supplement may be necessary to achieve these levels.
There are several brain-building supplement formulations that combine many of these compounds and many more also been shown to boost BDNF levels.
Ultimately addressing diet and lifestyle factors is foundational and taking 20 supplements a day is not recommended for individuals who are working on prevention. A good multivitamin (Pure Encapsulations ONE) and EFA supplement (Klaire Omegathera) along with attention to diet, exercise, sleep optimization, and stress reduction will provide the foundation for optimal brain health today and in the future. Don’t wait on the next blockbuster drug. The time to act is now and the power to prevent is all yours.
