Unravelling the role Glymphatic Dysfunction in Vascular Dementia

Summary

The recently discovered glymphatic system plays a key role in drainage of toxic substances from the brain.  It encompasses both perivascular spaces an perivenous channels.

Increasing evidence suggests glymphatic failure plays a crucial role in dementia, particularly dementia caused by vascular disease.  Very recent MRI techniques are allowing us to image glymphatic function in the brain in humans for the first time.

Project aims

This project will involve applying these techniques to investigate the role of glymphatic failure in cerebral small vessel disease (the most common vascular pathology underlying dementia)  and its associated vascular dementia.

The project could involve a number of techniques including advanced MR image analysis and/or statistical analysis and/or correlation of glymphatic function with multiomics data including genomics, metabolomics and proteomics.

The ultimate aim is to identify how glymphatic function contributes to dementia, and then develop treatments which can target impaired glymphatic function to reduce the risk of dementia.

References

Benveniste H, Nedergaard M. Cerebral small vessel disease: A glymphopathy? Curr Opin Neurobiol. 2022 Feb;72:15-21. 

Hong H, Tozer DJ, Markus HS. Relationship of Perivascular Space Markers With Incident Dementia in Cerebral Small Vessel Disease. Stroke. 2024 Apr;55(4):1032-1040. 

Chen Y, Hong H, Nazeri A, Markus HS, Luo X. Cerebrospinal fluid-based spatial statistics: towards quantitative analysis of cerebrospinal fluid pseudodiffusivity. Fluids Barriers CNS. 2024 Jul 18;21(1):59. 

Contact details

Professor Hugh Markus - hsm32@medschl.cam.ac.uk

Opportunities

This project is open to applicants who want to do a:

• PhD