While the biochemistry of the brain is segregated from the biochemistry of the rest of the body by the blood-brain barrier, a lining of specialized cells wrapping blood vessels that pass through the brain, large amounts of cerebrospinal fluid flow through the brain and exit into the body, carrying away metabolic waste. The major known pathways include (a) channels in the bone of the cribriform plate that drain the olfactory bulb region of the brain, and (b) the glymphatic system that is made up of fluid filled channels that parallel blood vessels where they enter and exit the brain. Both of these pathways decline in efficiency with age: the cribriform plate channels ossify and close, while the glymphatic system loses its ability to drive fluid flow by pulsation. Researchers hypothesize that impaired drainage of cerebrospinal fluid contributes to neurodegeneration by causing a harmful buildup of metabolic waste in the brain.
The ability to measure flow of cerebrospinal fluid through the glymphatic system is a fairly recent innovation, indeed the structure and function of the glymphatic system itself is a relatively recent discovery. Now, however, researchers can use features of magnetic resonance imaging (MRI) in some portions of the glymphatic system to create a measure of the fluid flow exiting the brain. This works because MRI can measure the scatter of water molecules, and if that scatter is heavily biased in one direction, that can be taken as a flow - a technique given the unwieldy name of diffusion tensor image analysis along the perivascular space (DTI-ALPS). All that is needed is a good straight stretch of glymphatic vessel, and there is a location in human physiology that suffices for this purpose. Thus the research community can produce studies such as the one noted here, in which reduced cerebrospinal fluid drainage through the glymphatic system is correlated to dementia risk.
Impaired cerebrospinal fluid (CSF) dynamics may contribute to dementia, but human evidence is limited. Recently, a number of magnetic resonance imaging (MRI)-based proxies have been proposed allowing different aspects of CSF dynamics to be non-invasively studied in humans. These include perivascular space (PVS) volume, diffusion tensor image analysis along the PVS (DTI-ALPS), blood oxygen level-dependent CSF (BOLD-CSF) coupling, and choroid plexus volume. Using the UK Biobank, we measured CSF dynamics: PVS volume, DTI-ALPS), BOLD-CSF coupling, and choroid plexus volume. We assessed cardiovascular risk factors and their associations with CSF dynamics and dementia based on general practitioner, mortality, and hospital records. Mediation analysis evaluated CSF dysfunction in cardiovascular risk-dementia relationships.
Lower DTI-ALPS, lower BOLD-CSF coupling, and higher choroid plexus volume predicted dementia, but PVS volume did not. DTI-ALPS and choroid plexus volume mediated the effect of white matter hyperintensities and diabetes duration on dementia. In conclusion, we demonstrated three MRI proxies of CSF dynamics markers predict future dementia risk. Strategies to improve CSF dynamics may reduce dementia risk, although this needs testing in intervention studies.
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