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Publications

Journal Article Ahead of print

PubMed: 42386783 DOI: 10.1038/s41531-026-01444-2

CSF turnover dysfunction: a hidden early biomarker in iRBD?

NPJ Parkinsons Dis

Authors: Stephan Grimaldi, Kavita Singh, María Guadalupe García-Gomar, Subhranil Koley, Firdaus Fabrice Hannanu, Ambra Stefani, Berkin Bilgic, Aleksandar Videnovic, Marta Bianciardi

Affiliations

  • Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. APHM, Timone University Hospital, Department of Neurology and Movement Disorders, Marseille, France. CRMBM-CEMEREM, School of Medicine, Aix Marseille University, Marseille, France.
  • Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. Multiscale Imaging and Integrative Biophysics Unit, LBN, National Institute on Aging, NIH, Baltimore, MD, USA.
  • Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. Escuela Nacional de Estudios Superiores Unidad Juriquilla, Universidad Nacional Autónoma de México, Querétaro, Mexico.
  • Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
  • Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Division of Sleep Medicine, Harvard University, Boston, MA, USA.
  • Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Division of Sleep Medicine, Harvard University, Boston, MA, USA.

Abstract

Evidence in Alzheimer's disease and other dementias shows that changes in cerebrospinal fluid (CSF) turnover and perivascular spaces (PVS) volume are associated with disease progression through impairment of waste-clearance glymphatic pathways. Volume of CSF, PVS, and drainage structures such as venous sinus are mostly excluded in current MRI studies of premanifest synucleinopathy. Here, we used 7 Tesla MRI to investigate whether modifications in CSF, PVS, and venous sinus volumes occur in 18 prodromal synucleinopathy patients (namely isolated rapid-eye-movement sleep behavior disorder, iRBD) compared to 20 healthy young and 18 elderly controls. Our results demonstrated increased CSF and PVS volumes in iRBD without a matching increase in drainage venous structures, as observed in elderly controls. This suggests increased CSF and PVS fluid stasis, possibly due to impaired CSF filtration, a mechanism that could reduce glymphatic function and exacerbate the neurodegenerative process in iRBD.

MeSH

Drainage, Biomarkers, Synucleinopathies, Aged