Modifiable Physiological Factors Associated With Human Glymphatic and Interstitial Fluid Dynamics-Related Measures: A...

Human glymphatic and interstitial fluid (ISF) dynamics are increasingly studied using direct, fluid-dynamic, and surrogate measures, but modifiable physiological correlates have not been comprehensively mapped. To map human evidence on non-pharmacological modifiable physiological factors associated with glymphatic- and ISF dynamics-related measures and characterize the methods used. PubMed and Web of Science Core Collection were searched through July 31, 2026. Eligible human studies evaluated at least one modifiable physiological factor and a glymphatic- or ISF-related outcome. Measures were classified as direct/near-direct transport or clearance (Level I), functional or diffusion-based imaging (Level II), CSF/ISF fluid dynamics (Level III), or indirect structural/tissue surrogates (Level IV). Of 4134 records, 105 studies were included. Sleep quality, efficiency, architecture, or insomnia was the largest domain (n = 45), followed by blood pressure/hypertension (n = 25). Other domains included sleep deprivation, sleep duration, circadian timing, obstructive sleep apnea, hemodynamics/vasomotion, metabolic factors, physical activity, respiration, and nutrition. Measurement memberships were Level I (n = 5), Level II (n = 41), Level III (n = 14), and Level IV (n = 59), with some studies spanning multiple levels. Human evidence supports associations between modifiable physiological states and glymphatic/ISF-related measures, especially for sleep and vascular physiology, but is dominated by observational studies and surrogate outcomes. Standardized multimodal and interventional studies using more direct measures are needed.