The Glymphatic System: The Link Between Sleep Deprivation, Alzheimer’s and Dementia

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Science has known for a long time there is a link between abnormal sleep and disease states including heart disease, obesity and neurodegenerative disorders like Alzheimer's.

But what, exactly, that  link was remained elusive until 2012.  That year Danish neuroscientist Dr. Maiken Nedergaard, and her team, discovered the glymphatic system.

The discovery would forever change how the importance of sleep was viewed, yet sleep deprivation remains a chronic issue for millions of people world-wide despite the fact there is a plethora of research that confirms adequate sleep is vital to overall health, optimal aging and disease prevention.

As a functional healthcare practitioner and a recovering “voluntary insomniac,” I’ve seen the damage it can do first hand which I talk about in my podcast ReInvent Healthcare, Why Sleep is the Key Ingredient for Healing.

It’s also the reason I’ve put together a free video and guide, “Optimizing Sleep with Herbs & Hormone Balance.” Even if you believe you get enough sleep, I think you will find my guide to be a valuable resource.

But if you need more convincing or just another reason that will motivate you to get your needed zzzz’s, read on. It might just scare you to sleep. (In a good way of course!)

What is the Glymphatic System?

For a long-time science was puzzled by a biological question. Even though the brain and spinal cord had a high metabolic rate, it was unknown how the body managed to get rid of the waste it produced. The central nervous system (CNS) didn’t have a lymphatic system, so how did it take out the garbage?

It was known that a build-up of waste, including the toxic proteins beta amyloid and tau, were linked to Alzheimer’s, dementia, and other neurodegenerative disorders. What wasn’t known was why some people were able to clear this molecular waste from the brain while others weren’t.

In 2012 a research team at the University of Rochester, headed up by Dr. Maiken Nedergaard, published a research paper that helped to answer that question. They had discovered what would eventually be named the glymphatic system which stands for “glial-dependent lymphatic transport,” paying tribute to the primary influence glial cells have on the process.

The glymphatic system is a system of tubes that act as a waste management system for the CNS. When asleep, fresh cerebrospinal fluid (CSF), the clear fluid that surrounds the brain and spinal cord, is pumped into the brain in waves. It mixes with interstitial fluid (ISF), the fluid that fills the space between the brain cells, where most toxic compounds produced by metabolic activity accumulate. The mix is then flushed out into the bloodstream which carries the waste away to be disposed of.

The inflow of CSF also serves to oxygenate the brain, a function critical to cellular repair and regeneration.

How does the Glymphatic System Work?

What Nedergaard and her team unexpectedly found in mice studies, was that sleep seemed to change the cellular structure of the brain. They found that CSF flowed rapidly when the mice were unconscious. In contrast, it barely flowed at all when the same mice were awake.

It was eventually determined the space inside the brain increased by 60% when the mice were either asleep or anesthetized. How could the state of consciousness be changing the structure of the brain?

One of the more fascinating studies to look at this was led by Laura Lewis of Boston University. Her team found a direct connection between three things that functioned in “lockstep”: blood flow, the slow delta-wave pattern associated with deep, non-REM sleep (N-3), and CSF flow in the brain.

It happens consistently in the same order. Once asleep, neurons quiet. This is followed by an outflow of blood from the brain and an inflow of CSF.

Lewis had speculated that the outflow of blood may be a result of lowered brain activity resulting in less oxygen being needed. However, later research suggests it may be connected to the hormone noradrenaline.

Noradrenaline – is an arousal hormone known to control cell volume. As the hormone increases, so does cell size and if the hormone is blocked it induces an unconscious state.

At night when falling asleep, noradrenaline levels decrease which reduces the size of brain cells and induces unconsciousness. This may account for the 60% increase in space within the brain which then triggers the inflow of CSF to fill that space, allowing toxins to be collected and removed.

Although it was known that neurons produced electrical waves, it was not known that CSF flowed in pulsing waves that coincided with those slow, delta wave patterns of deep sleep.

If the proper flow of CSF is dependent on delta waves, this has profound implications for the importance of deep sleep and brain health. Slow delta waves produced during deep sleep diminish with age which may contribute to age-related neurodegenerative disease. An under functioning glymphatic system may also play a role in the neurodegeneration that follows brain injury as well as other disorders associated with oxygenation of the brain.

Understanding the function of the glymphatic system may one day explain why so much disease is linked to sleep deprivation.

How Can Lifestyle Influence the Glymphatic System?

Science is still debating the casual roles of sleep and disease. Is disease onset the cause of poor sleep or does poor sleep cause the onset of disease? It may be a long time before there are any definitive answers, if ever, but what is known without a doubt is that quality, restful sleep is vital to optimal health and disease prevention.

It’s also known that the better the glymphatic system is working, the greater its ability to clear the metabolic waste that accumulates in the CNS. So besides quality sleep, are there any other lifestyle choices that can support this newly discovered waste management system? Research says yes!

  • Omega-3 fatty acids

Omega-3’s are known to modulate the glymphatic system by their anti-inflammatory effect on the CNS. This promotes higher CSF influx as well as clearance.  They are also known to reduce both the production and formation of the waste proteins beta amyloid and tau.

  • Intermittent Fasting

Specifically, alternate day fasting consisting of a day of eating followed by a fasting day, was shown to lower the amount of beta amyloid deposited in the ISF.  It’s also shown to indirectly prevent histone acetylation which positively impacts gene expression.  This all leads to boosting glymphatic clearance.

  • Sleeping Position

Glymphatic transport is most efficient in a right lateral sleeping position compared to sleeping on the back or stomach.  It’s all about gravity.

  • Exercise

A voluntary study looked at how running impacted the glymphatic system. After six weeks there was a reduction of neuroinflammation and an acceleration of glymphatic flow. It also showed a reduction in the accumulation of beta amyloid plaque in the ISF.

  • Chronic Stress

In a study with mice, chronic stress was shown to accelerate the accumulation and deposit of beta amyloid.  It was also shown to decrease glymphatic influx and clearance.

The discovery of the glymphatic system and the resulting research is exciting, especially as it allows further insight into the link between sleep and disease.

But what often strikes me the most when science reveals these amazing things about the human body is that there is little, if anything, I would change about how I practice healthcare, or how I teach others. Yes, tweaking here and there is a constant and necessary to stay current and on the cutting edge, but when it comes to the fundamentals of optimal health; sleep, nutrition, exercise, stress management, etc., functional healthcare is well ahead of the game.

The broken healthcare system isn’t, and the only way to change that is through education and action.

If you are a practitioner who wants to bring the kind of meaningful change so desperately needed to the broken healthcare system, my hope is that you will consider joining my Nutritional Endocrinology Practitioner Training (NEPT) program.  The expansive curriculum takes both you and your practice to the next level as it focuses on root cause healthcare and how to bring it successfully and dynamically to a waiting clientele who need it desperately.

If you are not a practitioner, but are looking for the kind of answers and support that can finally bring resolution to health challenges you’ve had to deal with for far too long, consider my Empowered Self-Care Lab.  You will find a community of people who, like you, know there is a way to live their best life through optimal health.

Regardless of where you find yourself on this journey, you are not alone.  There is help, there are answers, and there are people who care.

Join us!

Resources:

  1. Brain may flush out toxins during sleep | National Institutes of Health (NIH)
  2. The Glymphatic System – A Beginner's Guide – PMC
  3. Frontiers | Glymphatic System as a Gateway to Connect Neurodegeneration From Periphery to CNS
  4. Noradrenaline as a key neurotransmitter in modulating microglial activation in stress response – ScienceDirect
  5. Are toxins flushed out of the brain during sleep? – Harvard Health

 

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