Delayed clearance of cerebrospinal fluid tracer from entorhinal cortex in idiopathic normal pressure hydrocephalus: A glymphatic magnetic resonance imaging study.
The glymphatic system plays a key role for clearance of waste solutes from the rodent brain. We recently found evidence of glymphatic circulation in the human brain when using magnetic resonance imaging (MRI) contrast agent as cerebrospinal fluid (CSF) tracer in conjunction with multiple MRI acquisitions (gMRI). The present study explored the hypothesis that reduced glymphatic clearance in entorhinal cortex (ERC) may be instrumental in idiopathic normal pressure hydrocephalus (iNPH) dementia. gMRI acquisitions were obtained over a 24-48 h time span in cognitively affected iNPH patients and non-cognitively affected patients with suspected CSF leaks. The CSF tracer enrichment was determined as changes in normalized MRI T1 signal units. The study included 30 patients with iNPH and 8 individuals with suspected CSF leaks (i.e. reference individuals). Compared to reference individuals, iNPH patients presented with higher medial temporal lobe atrophy score and Evan's index and inferior ERC thickness. We found delayed clearance of the intrathecal CSF tracer gadobutrol from CSF, the ERC and adjacent white matter, suggesting impaired glymphatic circulation. Reduced clearance and accumulation of toxic waste product such as amyloid-β may be a mechanism behind dementia in iNPH. Glymphatic MRI (gMRI) may become a tool for assessment of early dementia.
['Eide|Per K|PK|0000-0001-6881-9280', 'Ringstad|Geir|G|']
D000328:Adult D000368:Aged D000369:Aged, 80 and over D002555:Cerebrospinal Fluid D003287:Contrast Media D003704:Dementia D018728:Entorhinal Cortex D005260:Female D000077502:Glymphatic System D006801:Humans D006850:Hydrocephalus, Normal Pressure D008279:Magnetic Resonance Imaging D008297:Male D008657:Metabolic Clearance Rate D008875:Middle Aged D009664:Norway D009942:Organometallic Compounds D066127:White Matter
cerebrospinal fluid tracer entorhinal cortex Idiopathic normal pressure hydrocephalus glymphatic circulation dementia