Halloween’s here! Folks make wiggly desserts that look like brains; even real post-mortem brains can be mushy. With that ghoulish intro, there is a hypothesis about dementia pathogenesis that seems to be apropos [click for link], with complex ideas about sleep, the accumulation of abnormal protein aggregates found in dementia brains, and the “glymphatic system” (defined below), invoking a microscopic image of the brain being like a “marsh.” More on that later.
Ever wake up groggy from a poor night’s sleep, or an interrupted nap? Why is that? And why do so many folks naturally shake their heads to “clear out the cobwebs” from the old brain jello? Sleep researchers tend to call grogginess “sleep inertia.” How similar or different is that effect from what a person gets from anti-histamines, or “chemo brain”, or just being plain drunk and high?
Sleep inertia has been studied with cognitive performance tests and EEGs, [click for nice review] in dastardly sleep lab experiments where they have volunteers become sleep deprived, or investigators allow some subjects to sleep but keep waking them up, etc. (Seems like one easy way to make a Halloween zombie.) One might expect that after a “recovery” sleep that the brain should just snap right back to it, but that’s not the case. So our college all-nighters can get replicated in someone’s lab, but exactly how and why does grogginess happen? No easy answers in the review.
Oh, if you read the paper, you’ll see that the most effective “countermeasure” is apparently caffeine taken before going to sleep. Seems better than music, light, temperature or exercise, good to know if you have to fly your own airplane first thing in the AM.
Loss of sleep can make a person groggy (slowed cognition) and crabby (moody), too. How does that mood change happen? Well normal sleep is sometimes called “sleep homeostasis;” not only are there apps for that, but there’s a recent molecular review paper for it too! The review paper delves into what might be happening in sleeping mammals, and in the fruit fly model, at both the cellular and molecular level. But as the abstract says, it’s still a “mystery.”
This brings us back to the mechanistic hypothesis in the Science review linked above. “Glymphatic” is a fairly new word combining “glial” and “lymphatic,” implying a regulatory role of glial cells in the brain’s fluid handling and immune system.
These neuroscience investigators describe how sleep seems to facilitate cleansing the brain using this system. A previous idea that the brain “recycled” old proteins now seems to be giving way to a waste fluid disposal system featuring glymphatic transport. This idea is that the proteins eventually make their way through the cervical lymphatic and venous systems to the liver. How’s that for outsourcing, out of sight and out of mind? (sorry, couldn’t resist…)
Along the way, they describe the brain’s anatomy in metaphorical terms, being made up of a: “…disorientingly crowded and compact architecture…, the neuropil, through which interstitial fluid flow is necessarily slow and restricted —akin to a marsh, flowing to the glymphatic system’s creeks and then rivers.” Just like that marsh frog in the picture above, taking its time.
It may or not having anything to do with the temporary and acute daily cognitive impairment after awakening, but is purported to be involved in the long term and progressive cognitive impairment seen in dementia.
Although the image below is from another paper (copyright issues), it shows some of the putative components of fluid flows through and around the brain that that paper says might be failing in dementia.
from Shen MD, J Neurodev Disord. 2018;10(1)/39. CCA 4.0
From schoolwork done in the last century, AlzGadfly thinks those perivascular spaces might be called Virchow-Robin spaces, but the authors might be discussing something else. One wonders if cranial radiation or intrathecal chemotherapy (as used in AlzGadfly’s former career) would accelerate or delay this circumstance.
AlzGadfly enjoys learning of new ideas about cognitive physiology, especially if they lend themselves to disease-modifying therapies. The authors state that some therapy might come from these ideas, or maybe we should all just sleep better. While we wait for this and other hypotheses to come to fruition, just hand me another scoop of that gummy worm and brain salad (fruition is on the bottom, I guess), while we try to enjoy life in 2020 with what we have!
