The use of continuous brain parenchymal impedance dispersion to measure glymphatic function in humans
Dagum, P.; Giovangrandi, L.; Levendovszky, S. R.; Winebaum, J. J.; Singh, T.; Cho, Y.; Kaplan, R. M.; Jaffe, M. S.; Lim, M. M.; Vandeweerd, C.; Iliff, J. J.
Show abstract
Glymphatic function in animal models supports the clearance of brain proteins whose mis-aggregation is implicated in neurodegenerative conditions including Alzheimers and Parkinsons disease. The measurement of glymphatic function in the human brain has been elusive, limiting its potential in translational research. Here we described a non-invasive multimodal device for the first-in-human continuous measurement of sleep-active glymphatic flow resistance using repeated electrical impedance spectroscopy measurements through two separate clinical validation studies. Device measurements successfully (i) paralleled sleep-associated changes in extracellular volume that regulate glymphatic function, (ii) replicated preclinical findings showing glymphatic function is increased with increasing sleep EEG delta power, and is decreased with increasing sleep EEG beta power and heart rate, and (iii) predicted glymphatic solute exchange measured by contrast-enhanced MRI. The present investigational device permits the continuous and time-resolved assessment of glymphatic flow resistance in naturalistic settings necessary to determine the contribution of glymphatic impairment to risk and progression of Alzheimers disease, and to enable target-engagement studies that modulate glymphatic function in humans.
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