Delayed clearance of cerebrospinal fluid tracer from entorhinalcortex in idiopathic normal pressure hydrocephalus: A glymphatic magneticresonance imaging study

摘要

The glymphatic system plays a key role for clearance of waste solutes from therodent brain. We recently found evidence of glymphatic circulation in the humanbrain when using magnetic resonance imaging (MRI) contrast agent ascerebrospinal fluid (CSF) tracer in conjunction with multiple MRI acquisitions(gMRI). The present study explored the hypothesis that reduced glymphaticclearance in entorhinal cortex (ERC) may be instrumental in idiopathic normalpressure hydrocephalus (iNPH) dementia. gMRI acquisitions were obtained over a24–48 h time span in cognitively affected iNPH patients and non-cognitivelyaffected patients with suspected CSF leaks. The CSF tracer enrichment wasdetermined as changes in normalized MRI T1 signal units. The study included 30patients with iNPH and 8 individuals with suspected CSF leaks (i.e. referenceindividuals). Compared to reference individuals, iNPH patients presented withhigher medial temporal lobe atrophy score and Evan's index and inferior ERCthickness. We found delayed clearance of the intrathecal CSF tracer gadobutrolfrom CSF, the ERC and adjacent white matter, suggesting impaired glymphaticcirculation. Reduced clearance and accumulation of toxic waste product such asamyloid-β may be a mechanism behind dementia in iNPH. Glymphatic MRI (gMRI) maybecome a tool for assessment of early dementia.