Sleeping (on One's Side) to Avoid Alzheimer's Disease?

[Dean Pomerleau]

All,

 

As we've discussed elsewhere, the formation of amyloid-beta plaques are known to be an important step in the progression of Alzheimer's disease. Exercise is known to help reduce amyloid plaque buildup, as discussed here. I think the fermented food natto may be beneficial for amyloid clearance as well, but that is more controversial. Sleep is known to be a time when the brain "cleans house", psychologically in terms of memory consolidation and synapse decay, but also literally, through the glymphatic transport system, which flushes toxins from the brain, including beta-amyloid plaques [2]:

 

Clearance [of toxic proteins including beta-amyloid] during sleep is as much as two-fold faster than during waking hours.

 

This new study [1] (popular press article), found that at least in rats, sleep posture influences the rate of glymphatic transport and toxin clearance. In particular, rats that were made to sleep on their (right) side while sleeping had better flow of their glymphatic fluid than rats who were either sitting up or lying on the back although beta-amyloid clearance wasn't much different between the two prone positions. And of course, rat brain morphology and circulatory system is quite a bit different from people, but the authors nevertheless speculate that sleeping on your side may be advantageous for brain health relative to sleeping on your back (or stomach).  

 

They didn't compare sleeping on the left vs right side in these rats, but in people it looks like sleeping on one's left side appears to be better for digestion / acid reflux than sleeping on one's right side.

 

--Dean

 

-----

[1] J Neurosci. 2015 Aug 5;35(31):11034-44. doi: 10.1523/JNEUROSCI.1625-15.2015.

 

The Effect of Body Posture on Brain Glymphatic Transport.

 

Lee H(1), Xie L(2), Yu M(3), Kang H(2), Feng T(4), Deane R(2), Logan J(5),

Nedergaard M(2), Benveniste H(6).

 

full text: http://www.jneurosci.org.sci-hub.io/content/35/31/11034.long

 

The glymphatic pathway expedites clearance of waste, including soluble amyloid β 

(Aβ) from the brain. Transport through this pathway is controlled by the brain's 

arousal level because, during sleep or anesthesia, the brain's interstitial space

volume expands (compared with wakefulness), resulting in faster waste removal.

Humans, as well as animals, exhibit different body postures during sleep, which

may also affect waste removal. Therefore, not only the level of consciousness,

but also body posture, might affect CSF-interstitial fluid (ISF) exchange

efficiency. We used dynamic-contrast-enhanced MRI and kinetic modeling to

quantify CSF-ISF exchange rates in anesthetized rodents' brains in supine, prone,

or lateral positions. To validate the MRI data and to assess specifically the

influence of body posture on clearance of Aβ, we used fluorescence microscopy and

radioactive tracers, respectively. The analysis showed that glymphatic transport 

was most efficient in the lateral position compared with the supine or prone

positions. In the prone position, in which the rat's head was in the most upright

position (mimicking posture during the awake state), transport was characterized 

by "retention" of the tracer, slower clearance, and more CSF efflux along larger 

caliber cervical vessels. The optical imaging and radiotracer studies confirmed

that glymphatic transport and Aβ clearance were superior in the lateral and

supine positions. We propose that the most popular sleep posture (lateral) has

evolved to optimize waste removal during sleep and that posture must be

considered in diagnostic imaging procedures developed in the future to assess

CSF-ISF transport in humans.

 

SIGNIFICANCE STATEMENT: The rodent brain removes

waste better during sleep or anesthesia compared with the awake state. Animals

exhibit different body posture during the awake and sleep states, which might

affect the brain's waste removal efficiency. We investigated the influence of

body posture on brainwide transport of inert tracers of anesthetized rodents. The

major finding of our study was that waste, including Aβ, removal was most

efficient in the lateral position (compared with the prone position), which

mimics the natural resting/sleeping position of rodents. Although our finding

awaits testing in humans, we speculate that the lateral position during sleep has

advantage with regard to the removal of waste products including Aβ, because

clinical studies have shown that sleep drives Aβ clearance from the brain.

 

Copyright © 2015 the authors 0270-6474/15/3511034-11$15.00/0.

 

PMCID: PMC4524974 [Available on 2016-02-05]

PMID: 26245965

 

-------

[2]  Rejuvenation Res. 2013 Dec;16(6):518-23. doi: 10.1089/rej.2013.1530.

 

Sleep facilitates clearance of metabolites from the brain: glymphatic function in

aging and neurodegenerative diseases.

 

Mendelsohn AR(1), Larrick JW.

 

Author information: 

(1)Panorama Research Institute and Regenerative Sciences Institute , Sunnyvale,

California.

 

Decline of cognition and increasing risk of neurodegenerative diseases are major 

problems associated with aging in humans. Of particular importance is how the

brain removes potentially toxic biomolecules that accumulate with normal neuronal

function. Recently, a biomolecule clearance system using convective flow between 

the cerebrospinal fluid (CSF) and interstitial fluid (ISF) to remove toxic

metabolites in the brain was described. Xie and colleagues now report that in

mice the clearance activity of this so-called "glymphatic system" is strongly

stimulated by sleep and is associated with an increase in interstitial volume,

possibly by shrinkage of astroglial cells. Moreover, anesthesia and attenuation

of adrenergic signaling can activate the glymphatic system to clear potentially

toxic proteins known to contribute to the pathology of Alzheimer disease (AD)

such as beta-amyloid (Abeta). Clearance during sleep is as much as two-fold

faster than during waking hours. These results support a new hypothesis to answer

the age-old question of why sleep is necessary. Glymphatic dysfunction may pay a 

hitherto unsuspected role in the pathogenesis of neurodegenerative diseases as

well as maintenance of cognition. Furthermore, clinical studies suggest that

quality and duration of sleep may be predictive of the onset of AD, and that

quality sleep may significantly reduce the risk of AD for apolipoprotein E (ApoE)

ɛ4 carriers, who have significantly greater chances of developing AD. Further

characterization of the glymphatic system in humans may lead to new therapies and

methods of prevention of neurodegenerative diseases. A public health initiative

to ensure adequate sleep among middle-aged and older people may prove useful in

preventing AD, especially in apolipoprotein E (ApoE) ɛ4 carriers.

 

PMID: 24199995

 

[Zeta]

I started sleeping on my side many years ago, partly because I ended up snoring less. STarting a year or so ago, I also decided to try sleeping with my bed inclined. I highly recommend that everyone at least try it, under the following conditions:

 

Do a few-day trial of "sleeping level", put your smartphone by your pillow (flight mode, to avoid melatonin-supression), record the whole night. Call up the recording in a program like Audacity to see how much you're snoring (it's obvious from the visual representation of the sound wave forms).

 

Then do a few-day trial with an inclined bed. Google around a bit for different ideas about how much to incline. (I have a 2-meter long bed raised 25 cm at the head.)

 

I was astonished that I went from snoring a LOT to almost not at all.

 

Now, back to amyloid: I'd be willing to guess I'm also getting better amyloid clearance. But the micro-wakings (even if it's not apnea per se) are also potentially causative in dementia, so I'm being helped on two fronts. (Though, note: there are plenty of Alz. researchers who think amyloid is an innocent bystander.)

 

Zeta

[Sthira]

I think the above study tells us more about stupid people who force rats to sleep in uncomfortable positions than anything at all about "glymphatic transport" or whatever the hell. One day when 60-foot rats rule this troubled world -- watch your own backs now, cruel humans.

[Dean Pomerleau]

Sthira, You are quite the poet and the visionary. I appreciate your humor and your perspective. Thanks for brightening my day!

 

Zeta, regarding inclined sleeping. Glymphatic transport is improved in a lying down position relative to an upright position in rodents and humans. Do you worry that having your head elevated while sleeping might reduce the flushing of toxins from the brain since it is (albeit modestly) closer to upright than sleeping flat?

 

--Dean

[Zeta]

Zeta, regarding inclined sleeping. Glymphatic transport is improved in a lying down position relative to an upright position in rodents and humans. Do you worry that having your head elevated while sleeping might reduce the flushing of toxins from the brain since it is (albeit modestly) closer to upright than sleeping flat?

 

I am now that I've read your post more closely! I can't get the full paper (the download keeps hanging), but I would want to think carefully about how the different rodent positions map onto my side-sleeping inclined position.

 

Zeta

[Dean Pomerleau]

The paper really has a lot of fascinating information about the glymphatic system and its operation in the brain. If you can't get the paper let me know and I'll send it to you off-forum.

 

--Dean