13 Jun

New Approaches to Fighting Alzheimer’s

The following article was inspired by the Institute for Function Medicine’s 2017 Annual Conference “The Dynamic Brain”.  The aim is to help family, friends, and caregivers of those with cognitive decline – who are just starting out – to understand the process and to provide links to useful resources for treatment and prevention. 

Fighting Alzheimer’s with the kitchen sink

Thomas M. Arnold, Department of Biology, Dickinson College, Carlisle, PA 17007

June 12, 2017
If you are in the fight against Alzheimer’s disease – as a caregiver, health care professional, or one of the 45 million Americans who will develop the disease in their lifetimes – here’s something you must know: your brain is not a computer.  Unlike your mobile device or laptop, it won’t become obsolete.  Healthy brains upgrade themselves continuously.  They adapt, grow, learn, and repair themselves.  This process, is called “neuroplasticity” and it may be our best hope for treating neurodegenerative disorders.

Some hope is sorely needed.  An estimated 15% of U.S. citizens will develop Alzheimer’s, which is set to become our nation’s third leading cause of death.  The staggering cost of Alzheimer’s care is already straining our healthcare systems.  It is estimated that by 2050, when more than 13 million Americans will be affected, the price of Alzheimer’s disease will bankrupt the Medicare system.  One by one, promising new therapies have failed to cure or slow the disease.  As a result, those with cognitive decline hesitate to seek medical help, knowing that their physician is unlikely to offer up any effective treatment. Clearly, we need new approaches.

These new approaches were the topic of the 2017 Dynamic Brain conference in Los Angeles, hosted by the Institute for Functional Medicine.  Here experts described surprising successes in treating Alzheimer’s disease by taking a more holistic, multifaceted approach.  Some of these researchers had become so frustrated by the lack of progress on a miracle pill they opted to try, well, everything.  All at once.  They combined the best of traditional medicine, nutritional science, exercise science, and brain training into comprehensive programs.  One such program, termed reCODE, was created and tested by Dr. Dale Bredesen, a researcher at the Buck Institute for Aging and UCLA.  The results were promising.  In small studies most patients on the program stopped getting worse, then got better and, amazingly, returned to work.  Elsewhere, other researchers were trying other “everything and the kitchen sink” programs.  Their goal: get the brain healthy, however you can, so that they can repair themselves through the power of neuroplasticity.

It helps, of course, that we know more about the brain than ever before.  We know that a healthy brain is fast and flexible, and can mend itself.  We also know that when infected, injured, or denied necessary hormones and growth factors the brain assumes a protective stance: neuroplasticity ceases and the brain deploys defensive countermeasures.

Normally, the brain is protected by the blood-brain barrier but sometimes, when this lining is unhealthy, the brain is more easily breached by pathogens and toxins.  Then neurons must defend themselves.  As it turns out, they have a clever security system.  Each neuron is coated with surface proteins that, when cut into fragments and released, surround and trap pathogens in the brain.  This molecular sticky trap is part of the innate immune response that is required for our survival.

One of these sticky surface protein fragments is amyloid beta – the molecule that forms the plaques and tangles that are the hallmark of Alzheimer’s disease.  These masses may accumulate slowly in the brain as we age or they may form with surprising quickness in response to pathogen attack.  Inside the plaques and tangles researchers find the proof – invading viruses and microbes safely entombed in amyloid.  Luckily, at least some of these plaques and tangles are cleared away in healthy brains.

However, some things interfere with this self-cleaning.  Genetics are important.  Some of us have brains that are just less enthusiastic housekeepers, and more vulnerable to cognitive decline.  But even brains that are normally squeaky-clean can become overrun by amyloid when they are infected, stressed, or exposed to environmental toxins.  So the root cause of Alzheimer’s disease is usually some combination of insults to the brain – anything that causes amyloid beta peptides to pile up.

Unfortunately, there is more trouble ahead for brains accumulating plaques and tangles: a state of persistent inflammation.  This part of the brain’s defense system is controlled primarily by a gene switch called CD33.  Activation of this gene is associated with higher amyloid beta loads and a worsening of cognitive decline.  In addition, CD33 activates brain inflammation and gets the attention of migrating cells called microglia.  These cells normally nurture and care for neurons, but when reprogrammed by CD33 they go rogue, attacking the brain’s neurons and consuming them.  Amazingly, it is possible to observe this in real time thanks to Dr. Rudy Tanzi, Professor of Neurology at Harvard University and Director of the Genetics and Aging Research Unit at Massachusetts General Hospital.  His team cultures neurons in a dish so that they form simple networks, exposes them to “angry” microglial cells, , and watches one type of brain cell consume the other!  Over time this state of affairs causes the brain to become slower, noisier, and disorganized.  Regions of the brain, especially the hippocampus, shrink.  And decades later, after the brain can no longer find ways to compensate, the cognitive symptoms of Alzheimer’s emerge.

What is it then, exactly, that puts us on this road to Alzheimer’s?  Age is the obvious risk factor.  Family history plays a role, especially the inheritance of genetic risk factors, such as the APOE4 gene.  This version of the APOE gene significantly increases the risk of Alzheimer’s by raising background levels of inflammation and slowing the clearance of amyloid beta[1].  Gender matters for Alzheimer’s too.  For reasons not completely understood, women are more likely to suffer from the disease (and to suffer indirectly as caregivers).  The other known and suspected causes of Alzheimer’s are at least partly within our control: exposure to viruses, bacteria, and other pathogens; our pre-packaged fast-food diets; excess sugars and diabetes; obesity and a sedentary lifestyle; head injury, stress, and emotional trauma; air pollution; heavy metal pollution; toxins from mold; pesticides and herbicides; and industrial chemicals and solvents.  All can cause inflammation in the brain and trigger the innate immune response.  Lucky for us, it usually takes a combination of these factors, over time, to start us down the road to Alzheimer’s.

With so many possible triggers working in combination you might expect that not every case of Alzheimer’s is exactly the same.  Indeed, Bredesen suggests that there are some identifiable types.  Some arise mostly from infection, others from deficiencies in hormones, vitamins, and growth factors.  Alzheimer’s associated with diabetes is a bit different.  And cognitive decline caused by exposure to metals or toxic mold prevents special challenges.  All result in inflammation and the build-up of plaques and tangles in the brain, but each requires a slightly different treatment program.

As a result, the reCODE programs are personalized for each patient.  A battery of tests pinpoint the potential problems, which are then addressed one-by-one to promote brain health.  Inflammation is reduced, toxins are eliminated, and sugar levels are normalized.  Levels of nutrients, hormones, and other factors are optimized.  Patients are urged to get eight or more hours of sleep, fast overnight for at least twelve hours, reduce stress, and do some online brain training.  (If you don’t have a device suitable for brain training, you might try Scrabble or the 1980’s-era game Simon. You get the idea.)  And patients should be ready to move.  One of the program’s key goals is to get your brain to produce lots of brain-derived neurotropic growth factor (BDNF), which promotes brain growth and maintenance, including the clearing of amyloid beta.  As it turns out, exercise is the best way to increase BDNF levels.  And the higher the calorie burn, the better the result.  Another way to increase brain BDNF, is to consume green coffee fruit.  Yes, there was a fruit around that wonderful bean – and something in it seems to raise BDNF quite dramatically.  To limit inflammation and stimulate neuroplasticity, patients on these programs take fish oils, curcumin, and vitamins and they consume certain mushrooms.  Most of these aren’t too exotic and are available on the shelves of your local health store, but don’t go try this yourself without good medical advice.  You want to be safe!  Besides, the brands, dosages, and schedules matter, and may depend upon your initial test results.

For those starting out, two aspects of these “kitchen sink” programs deserve special mention.

First, for optimal brain health one must adopt a low-carb, anti-inflammatory diet.  Patients shun processed foods, reduce or eliminate grains and dairy, and limit excess sugar.  Most experts agree it is also important to avoid artificial sweeteners; so say farewell to diet sodas.  Those following the programs nom on fresh organic vegetables and leafy greens, pigments foods rich in polyphenols, and healthy organic meats.  Dr. David Perlmutter, a strong advocate for adopting a healthy diet to fight Alzheimer’s, has published a series of best-selling books on this subject.  Perlmutter is a neurologist and Fellow of the American College of Nutrition.  His books are worth a read, and here’s why.  Your digestive system is alive, teaming with cultures of gut bacteria.  And you really want to keep them happy.  As Permutter advises “You are eating for three trillion” gut bacteria and they have a real impact on your brain.

The story of the gut-brain axis goes something like this.  Your gut microbiome is an ecosystem with a community of helpful and not-so-helpful bacteria.  Yours is unique and has been shaped since birth by where you live and what you eat.  (You also a similar microbial ecosystem in your mouth.  Good oral hygiene helps them, and you, stay healthy.)

Hopefully, you’ve cultivated a healthy gut microbiome through diet and exercise.  Cardiovascular fitness improves the diversity and health of your microbiome about as much as a healthy diet.  If you haven’t, the ecosystem may malfunction, damaging the lining of the gut, allowing bacteria and their products to leak into the blood.  Eventually, they reach the brain and, once again, the brain must defend itself – with inflammation of the accumulation of plaques and tangles.  This explains why studies show a link between the health of the gut microbiome and the size of specific regions of the brain.  There are other ways the gut can impact the brain.  The two organs are connected by a large nerve bundle, and the fibers innervate the entire digestive system.  In fact, there are more nerve cells around your gut than there are in your brain.  These nerves can be a conduit for exchanging information, but some toxic molecules and perhaps even viruses can use this as a direct route to the brain as well.  It is now pretty clear.  To prevent cognitive decline we should cultivate a healthy gut microbiome.

Unfortunately, the modern world is full of threats to a healthy microbiome.  Antibiotics are devastating.  They were designed to kill microbes.  And the microbiome can be harmed by certain water treatments and stress, and chemicals commonly applied to fields of GMO crops.  For most of us, however, the main threat to a healthy gut microbiome is a poor, inflammatory diet.  So you might want to pick up one of Dr. Perlmutter’s books. Your gut bacteria would be grateful.  And if they need new microbial friends, consider a probiotic.

The other part of these programs that is worth special mention is what you can do to help your mitochondria.  Those powerhouses of the cell supply energy, and your brain and gut need a lot.  Early in the evolution of life mitochondria were free-living bacteria but now they are our supportive endosymbionts, along for the ride.  When healthy they act as organic batteries and energy convertors.  You really want to help them flourish.  Because when they are injured they discharge damaging oxygen radicals, and then they self-destruct.  Worse, when they go they tend to take the host cells – including neurons – down with them in a process called apoptosis (“programmed cell death”).  What can endanger your mitochondria?  Environmental toxins are the primary culprit.  These include chemicals designed to kill pests on our crops, weeds on farms, and infections in our bodies.  There’s plenty of evidence that some of the most popular antibiotics and herbicides are essentially mitochondrial toxins.

At this point it may come as no great surprise that toxins from our environment are the primary driver of disease in industrialized world.  And that living in a chemical soup, as Bredesen explained, is bound to be bad for our brains.  So it’s worth becoming informed and eliminating environmental toxins from our diets and homes whenever we can.  While we are at it, we might want to be more careful about spreading them around in the first place; it’s awfully hard to have good personal health in an unhealthy world.

So that, in a nutshell, is the current state-of-knowledge for preventing and treating Alzheimer’s disease.  If these programs seem like combinations of modern medicine and the stuff-we-knew-we-should-have-been-doing all along, that’s about right.  Many aspects of these programs are good for your overall health and may help prevent a range of other diseases, from heart disease to cancer to depression.  Other aspects of the treatment programs require a knowledgeable and dedicated healthcare team, something well beyond the scope of most family physicians.  It can be a challenge to find a well-informed team leader, but it is critical.  It is also helpful if the team includes a “coach” (or family member).  After all, sticking with these programs could be a challenge even for those not suffering from cognitive decline.

If all this feels a bit overwhelming and seems like a lot of change to make late in life, remember this: the goal is simply to make enough positive changes to re-establish a healthy balance between inflammation and neurogenesis.  Your neuroplastic brain will do the rest.

[1] You may be wondering why evolution would allow a gene like APOE4, which increases the risk of cognitive declines and cardiovascular disease, to become so common.  As it turns out the APOE4 gene does confer some advantages.  By putting the body in a low-level inflammatory state APOE4 version of this gene confers superior protections against parasites.  This would have been a real advantage for early humans – who ate raw meat, drank from streams, and walked through a messy world on tender soles.  It was a good trade-off then.  In the era of microwaves, Reeboks, and bottled water, well, not so much.

Resources and acknowledgements:

Audio and video recording of the lectures from the 2017 IFM Dynamic Brain conference are available for purchase through their website.  Or go to YouTube; a few older lectures are there for free.

For those with the APOE4 gene, who are at a greater risk of developing the disease (or anyone interested in prevent in general) the APOE4info website and forum (https://www.apoe4.info/wp/) is an interactive source of useful information and support.  You can find out your APOE status using online genetic sequencing services, if you want to.  Some people want to know, and it motivates them to adopt some preventative measures.  Just remember, being APOE4 does not automatically mean you will develop Alzheimer’s disease.  Also, be aware that knowing your APOE status will tell you something about the status of your parents and children.  They may or may not want their APOE4 status revealed to family, friends, or their employer.  They might not want to know themselves.  Discussing your APOE status could reveal theirs, at least in part.

Dr. David Perlmutter maintains a website of up-to-date information and has published four NY Times best-selling books, including “Grain Brain” and “Brain Maker”.  His lectures at the IFM conference were inspiring.  I laughed more than I thought I would at a conference dedicated to cognitive decline.

Dr. Dale Bredesen has the website of a prolific academic researcher (which he is).  His peer-reviewed scientific articles are listed there.  His reCODE treatment program seems to work for many patients.  You can read about it here: http://www.aging-us.com/article/100690.  And here: http://www.aging-us.com/article/100981.  You can see his interview with Maria Shriver (June 2017) here: http://mariashriver.com/blog/2016/09/alzheimers-prevention-dale-bredesen-maria-shriver/.  He also has a new book “The End of Alzheimer’s” coming out in August 2017.  You can pre-order it on Amazon now.

Dr. Bredesen works with MPI Cognition, an organization that puts people in touch with physicians trained to use reCODE program.  As you may have found, many physicians aren’t up-to-date on these new programs.  So this organization might be helpful. https://www.drbredesen.com/

Dr. Rudolph Tanzi has published 500 scientific scientific papers and several best-selling books, including “Decoding Darkness: The Search the Genetic Causes of Alzheimer’s Disease”, “Super Brain: Unleashing the Explosive Power of Your Mind to Maximize Health, Happiness, and Spiritual Well-Being” and “Super Genes: Unlock the Astonishing Power of Your DNA for Optimum Health and Well-Being” (with Deepak Chopra). His team developed “Alzheimer’s in a dish” as a research tool and created Spark Memories Radio. http://sparkmemoriesradio.com/

Michael Merzenich, PhD, has authored over 150 scientific articles and a book “How the New Science of Brain Plasticity Can Change Your Life”.  He is the co-founder and chief scientific officer of Posit Science and developed the BRAIN HQ training programs that are a part of most treatment programs.  (He is also the reason I can no longer just automatically tell me kids to “get off your phones!”).

I would also acknowledge the influence of Dr. Joe Pizzorno, who spoke about environmental toxins in a way that made it all too clear that we did much of this to ourselves, and Dr. Terry Wahls, who uses a similar program she designed – and large doses of inspiration and humor – to treat patients with multiple sclerosis.

Thanks to Carla Maranto-Arnold, Julie Gregory, and Kris Willing Moore who made helpful suggestions to improve early drafts.