Glymphatic function maintains sleep‐sensitive cognitive performance and predicts overnight changes in plasma amyloid β in humans

Abstract

AbstractBackgroundDuring sleep, the glymphatic system facilitates rapid exchange of fluid through brain tissues, clearing solutes, including amyloid β (Aβ), tau, and α synuclein that accumulate through the course of waking activity. Glymphatic clearance is widely believed to underlie the restorative effects of sleep on cognition, and its impairment is proposed to reflect the biological basis for the corrosive effects of sleep disruption. We sought to determine if glymphatic function or sleep EEG predicted changes in cognitive performance and overnight differences in Aβ biomarker levels using a new non‐invasive investigational medical device (IMD) to measure glymphatic function by dynamic impedance spectro‐tomography.MethodEighteen healthy 50‐65 y/o participants were enrolled in a cross‐over randomized control clinical trial encompassing one night of sleep and one night of sleep deprivation. Participants were instrumented with the IMD and overnight change in brain parenchymal resistance to flow, R, was measured. Sleep EEG powerbands, slow (0.4‐1Hz), delta (1‐4Hz), beta (15‐30Hz), and time spent in N2, N3 and REM sleep were derived from the device EEG. In both sleep and sleep deprivation interventions, cognitive tests (symbol digit modality test, SDMT; psychomotor vigilance test, PVT) were administered at 7am and blood Aβ biomarkers (Aβ40; Aβ42) were taken at 10pm and 7am.ResultOvernight parenchymal resistance R predicted intraindividual paired differences (sleep – sleep deprivation) in cognitive test scores (A SDMT ρ = ‐0.65, p = 0.003; B PVT STD RT, ρ = 0.41, p = 0.095) and Aβ42 blood amyloid biomarker changes (C Aβ42 ρ = ‐0.53, p = 0.03; D Aβ40 ρ = ‐0.33, p = 0.21). Sleep EEG powerbands and time spent in N2, N3, and REM sleep were not predictive of sleep‐related changes in cognition or plasma Aβ biomarker levels.ConclusionGlymphatic function, measured continuously by dynamic impedance spectro‐tomography, predicted changes in the restorative effect of sleep on cognition and plasma Ab biomarker levels as hypothesized, but not previously demonstrated. In contrast, sleep EEG powerbands and time spent in N2, N3 and REM were not predictive. Detection of glymphatic impairment in real‐world settings may permit (i) early identification of individuals at‐risk for developing sleep‐related Alzheimer’s disease pathology, and (ii) enable precision targeted enhancement of glymphatic function to enhance glymphatic function and pathological protein clearance.