In Vivo Imaging of Molecular Clearance From Human Entorhinal Cortex: A Possible Method for Preclinical Testing of Dementia

Accumulation in the brain of metabolic waste products such as amyloid-β and hyperphosporylated tau (tau) is a hallmark of dementia (e.g., Alzheimer's disease). One possible underlying mechanism is impaired cerebral paravascular (glymphatic) clearance of toxic solutes. Recently, we have provided evidence of glymphatic circulation being present in the human brain, utilizing repeated magnetic resonance imaging (MRI) acquisitions before/after intrathecal injection of an MRI contrast agent, serving as a cerebrospinal fluid (CSF) tracer (glymphatic MRI [gMRI]). In a recent study, we utilized the same methodology to assess glymphatic clearance function within an anatomical region that has a key role in cognitive function-the entorhinal cortex (ERC). gMRI was compared in individuals with the dementia subtype idiopathic normal pressure hydrocephalus (iNPH; n = 30) and reference (REF; n = 8) subjects. We found delayed clearance of CSF tracer from CSF nearby ERC, the ERC itself, and the white matter adjacent to ERC, which was most evident after 24 hr. The observations were interpreted as indicative of impaired glymphatic circulation and further suggested this being a possible mechanism behind accumulation of amyloid-β and tau in ERC and instrumental for dementia in iNPH. We suggest that gMRI may serve as a tool for assessment of early dementia, or even in the preclinical stage.