The Sleeping Brain: Harnessing the Power of the Glymphatic System through Lifestyle Choices

Abstract

The glymphatic system is a "pseudo-lymphatic" perivascular network distributed throughout the brain, responsible for replenishing as well as cleansing the brain. Glymphatic clearance is the macroscopic process of convective fluid transport in which harmful interstitial metabolic waste products are removed from the brain intima. This paper addresses the glymphatic system, its dysfunction and the major consequences of impaired clearance in order to link neurodegeneration and glymphatic activity with lifestyle choices. Glymphatic clearance can be manipulated by sleep deprivation, cisterna magna puncture, acetazolamide or genetic deletion of AQP4 channels, but how lifestyle choices affect this brain-wide clearance system remains to be resolved. This paper will synthesize existing literature on glymphatic clearance, sleep, Alzheimer's disease and lifestyle choices, in order to harness the power of this mass transport system, promote healthy brain ageing and possibly prevent neurodegenerative processes. This paper concludes that 1. glymphatic clearance plays a major role in Alzheimer's pathology; 2. the vast majority of waste clearance occurs during sleep; 3. dementias are associated with sleep disruption, alongside an age-related decline in AQP4 polarization; and 4. lifestyle choices such as sleep position, alcohol intake, exercise, omega-3 consumption, intermittent fasting and chronic stress all modulate glymphatic clearance. Lifestyle choices could therefore alter Alzheimer's disease risk through improved glymphatic clearance, and could be used as a preventative lifestyle intervention for both healthy brain ageing and Alzheimer's disease.

Keywords: Alzheimer’s disease; amyloid-beta; disease prevention; glymphatic system; protein aggregates; sleep.

Figure 1

(Figure 1. was created according to the guidelines [9] p. 3). Of the 389 papers obtained, ultimately only 19 were included in the final literature review.

Figure 2

(Figure illustrated by Jessamyn Camille Reddy, adapted from; [1] p. 22, permission obtained) The four fluid compartments of the brain, separated by the blood–brain barrier or the blood–CSF barrier. The blood–brain barrier is situated wherever the vasculature reaches; the blood–CSF barrier is situated only in the choroid plexus and allows the passage of macromolecules.

Figure 3

(Figure illustrated by Jessamyn Camille Reddy, adapted from; [2] p. 16) This figure depicts the circulation of cerebrospinal fluid (CSF) and its interchange with interstitial fluid (ISF), CSF entering the perivascular space of penetrating arteries, then through convective flow clearing waste products into the perivenous spaces, ultimately leaving the brain through paravenous efflux routes.

Figure 4

(Figure illustrated by Jessamyn Camille Reddy, adapted from; [1] p. 26, permission obtained) Model of glymphatic function in Young, Old and Alzheimer’s disease. In young people, CSF travels along periarterial routes, entering the brain parenchyma, and washes solutes and waste products into the veins. In older people, the loss of AQP4 water channels will result in reduced glymphatic clearance. In those with Alzheimer’s disease, the accumulation of amyloid-beta impairs fluid movement within the interstitial space, decreasing glymphatic clearance.