Reduced Glymphatic Flow of Cerebrospinal Fluid Correlates with Risk of Cognitive Impairment – Fight Aging! Leave a comment
About a decade ago, researchers developed a way to use magnetic resonance imaging (MRI) to measure the passage of fluid through channels leading from the brain into the body. One can use MRI to assess the diffusion of water molecules in many small volumes of scanned tissue. If there is a flow, then it appears as though the “diffusion” is biased in a specific direction. There is one small section of the glymphatic system that drains cerebrospinal fluid from the brain in which the vessels run in parallel, and this allows researchers to measure the flow of cerebrospinal fluid from the brain.
This ability to measure glymphatic fluid flow is important because the drainage of cerebrospinal fluid from the brain into the body carries away metabolic waste with it. This process of drainage occurs through a few different important channels, but the flow rate declines with age in all of them. Researchers hypothesize, and with a growing body of experimental and epidemiological data to support these hypotheses, that impaired drainage allows a buildup of waste in the brain that contributes to inflammation and neurodegeneration. You might recall a recent study linking reduced glymphatic flow with progression of Alzheimer’s disease. In today’s open access paper, researchers perform much the same study for the earlier progression of mild cognitive impairment leading into the initial onset of Alzheimer’s disease. Again, an impaired drainage of cerebrospinal fluid correlates with worse loss of cognitive function and progression towards disease.
One can be done about this? Well, there are some promising initial signs. Loss of glymphatic flow may be largely a problem of dysfunctional lymphatic vessels, unable to contract efficiently enough to sustain a pulsatile flow of fluid. Classes of drug that affect the smooth muscle that surrounds these vessels were recently shown restore the ability of aged glymphatic vessels to drive fluid flow. Further, since a great deal of work has gone into ways to manipulate blood vessel behavior, and blood and lymphatic vessels share many similarities, there may be more existing options beyond this that will also work to restore cerebrospinal fluid drainage.
The glymphatic and meningeal lymphatic systems are crucial for clearing metabolic waste from cerebrospinal fluid (CSF) in the brain, and their dysfunction, particularly regarding the accumulation of amyloid-β and extracellular tau, may contribute to Alzheimer’s disease (AD). Recently, researchers developed a method to measure diffusivity along the perivascular space (ALPS) based on diffusion tensor images, which allows for noninvasive and efficient assessment of glymphatic function. This approach quantifies the diffusion of water within the perivascular space along deep medullary veins and has been correlated with glymphatic clearance by dynamic contrast-enhanced imaging. Recent studies have shown that the ALPS index is associated with cognitive decline, AD, and multiple neurological disorders, and might serve as a biomarker for neurodegenerative diseases. However, no studies have been conducted on the association of ALPS index with mild cognitive impairment (MCI) and its progression to AD.
This study included 519 adults including 253 cognitively normal (CN) and 266 MCI participants from Alzheimer’s Disease Neuroimaging Initiative. Glymphatic function (assessed by along the perivascular space [ALPS] index) was measured by diffusion tensor image at baseline. During follow-up (median 3.6 years), 30 (11.86%) participants developed MCI in the CN cohort and 73 (27.4%) participants progressed to AD in the MCI cohort. The hazard ratios of the higher ALPS index, indicating greater glymphatic flow, was 0.605 for MCI and 0.501 for AD. In addition, participants with high ALPS index had 3.837 and 3.466 years prolonged onset of MCI and AD, separately.
In conclusion, high ALPS index decreases MCI risk and delays MCI progression to AD by approximately 3.5 years. Amyloid-β in choroid plexus, tau in cortex, and executive function may partially mediate the MCI-AD progression in relation to ALPS index.
