Brain toxins and their disposal by the brain
One of the most exciting discoveries in the past decade is the identification of a “disposal” system in the brain that clears the brain of unwanted compounds (toxins), produced in the course of everyday living. This system is termed the glymphatic system. It shares a large portion of its name with a similar system that resides outside the brain. This outside system is the immune lymphatic system that protects us from viral and bacterial infections.
Characteristics of the glymphatics; importance of sleep
Unlike the immune lymphatic system, the glymphatic system resides solely in the brain and functions to clear proteins or parts of proteins that accumulate as byproducts of normal brain metabolism. The main function of the glymphatics is to clear toxins. Toxins filtered by the glymphatics in the brain are transported in small vessels down the neck and literally dumped into the immune lymphatic system for recycling or elimination elsewhere. Thus the glymphatics contribute significantly to brain health and longevity!
Importantly, the glymphatic system only works at night. It is associated with high frequency brain waves and low levels of norepinephrine, an essential brain regulator, that only occur during sleep. Results of animal studies show that natural sleep produces the essential changes that facilitate the clearance of toxins, in particular beta amyloid protein, implicated in the development and progression of Alzheimer’s Disease. Therefore, sleep appears to serve an extremely important function – enhancing the clearance of metabolic waste products. As summarized by researchers at the Langone Medical Center, New York University “restorative function of sleep may be due to the switching of the brain into a functional state that facilitates the clearance of degradation products of neural activity that accumulate during wakefulness” (Xie, Kang, Xu et al., 2013).
The clearance of toxins by the glymphatic system applies to all neurotoxins. It is postulated that reduced clearance of neurotoxins may contribute not only to the development of Alzheimer’s Disease but may influence the presence of several other diseases e.g. Parkinson’s Disease, Huntingdon’s Disease, amyotrophic lateral sclerosis and frontotemporal dementia.
Age-associated changes in sleep may retard toxin clearance
Unfortunately sleep quality decrease with age. Sleep physiology consists of 4 stages per each sleep cycle and the occurrence of about 8-9 cycles per night. Different brain activities occur in each stage. For example, stages 1 and 2 constitute light sleep while stages 3 and 4 comprise deep sleep and are followed by REM (rapid-eye movement) associated with dreaming. Additionally, there is a period of quiet wakefulness prior to sleep.
With age, the following changes occur:
(1) the period of quiet wakefulness increases such that it takes longer to fall asleep
(2) the time spent in stages 1 and 2 increases – increasing the number of awakenings referred to as sleep fragmentation
(3) the time spent in deep sleep (stages 3 an 4) decreases and may disappear – resulting in the feeling of “not rested”
These changes may lead to daytime “napping” and possibly progress to insomnia. Many factors such as medication use, nocturnal urinary frequency, chronic pain, hormonal changes and age-related co-morbidities, exacerbate age-related changes in sleep patterns.
It is important to know how age-related changes in sleep affect the function of the glymphatics. Regrettably, this has not been critically studied in the elderly. It is known that the extreme condition of no sleep, insomnia, shuts down the glymphatics, allowing build-up of neurological toxins.
How to improve quality of sleep
There is no firm answer on how to improve sleep quality. Clinical trials, generally small with 40-60 participants, point to two interventions that improve sleep quality in the elderly: a program of aerobic exercise and cognitive behavior therapy (CBT). Insight 4 provides sufficient detail for a meaningful program of aerobic exercise.
CBT is a program that provides instruction on the essentials of sleep. This program includes
1) sleep compression (slowly reducing the amount of time spent in bed (not sleeping) to obtain the optimal sleep time)
2) sleep hygiene principles focused on appropriate activities, diet, liquids prior to bed time, daytime physical and social activities, light exposure, sleep environment
3) need to keep a sleep diary and make revisions as necessary
The CBT program (above) was used in a 4-week program for elderly attending a Veteran’s Adult Day Health Care program. The CBT was successful in enhancing sleep quality in elderly individuals compared to controls who received general information but not CBT. This benefit persisted at follow-up 4 months later (Martin et al., 2017).
Reader comments on this discussion are encouraged. Experiences that enhance sleep quality are of special interest.
References
1. Xie, Kang, Xu et al., Sleep Drives Metabolite Clearance from the Adult Brain Science. 18; 342(6156), 2013.
2. Martin, Song, Hughes et al., A four-session sleep intervention program improves sleep for older adult day health care participants: results of a randomized controlled trial. Sleep 40: 1-12, 2017
3. Reviews:
Jessen, Munk, Lundgaard, Nedergaard. The Glymphatic System – A Beginner’s Guide.
Neurochem Res. 40: 2583–2599, 2015.
Sun, Wang, Yang et al., Lymphatic drainage system of the brain: A novel target for intervention of neurological diseases. Progress in Neurobiology 163–164 : 118–143, 2018.