Age-related decline in cerebral oxygen consumption in multiple sclerosis

Maria H Knudsen, Mark B Vestergaard, Ulrich Lindberg, Helle J Simonsen, Jette L Frederiksen, Stig P Cramer*, Henrik Bw Larsson

*Corresponding author for this work


Cerebral oxygen metabolism is altered in relapsing-remitting multiple sclerosis (RRMS), possibly a result of disease related cerebral atrophy with subsequent decreased oxygen demand. However, MS inflammation can also inhibit brain metabolism. Therefore, we measured cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) using MRI phase contrast mapping and susceptibility-based oximetry in 44 patients with early RRMS and 36 healthy controls. Cerebral atrophy and white matter lesion load were assessed from high-resolution structural MRI. Expanded Disability Status Scale (EDSS) scores were collected from medical records. The CMRO2 was significantly lower in patients (-15%, p = 0.002) and decreased significantly with age in patients relative to the controls (-1.35 µmol/100 g/min/year, p = 0.036). The lower CMRO2 in RRMS was primarily driven by a higher venous oxygen saturation in the sagittal sinus (p = 0.007) and not a reduction in CBF (p = 0.69). There was no difference in cerebral atrophy between the groups, and no correlation between CMRO2 and MS lesion volume or EDSS score. Therefore, the progressive CMRO2 decline observed before the occurrence of significant cerebral atrophy and despite adequate CBF supports emerging evidence of dysfunctional cellular respiration as a potential pathogenic mechanism and therapeutic target in RRMS.

Original languageEnglish
JournalJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
Issue number6
Pages (from-to)1039-1052
Number of pages14
Publication statusPublished - 2024


  • Adult
  • Aging/metabolism
  • Atrophy
  • Brain/metabolism
  • Cerebrovascular Circulation/physiology
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting/metabolism
  • Multiple Sclerosis/metabolism
  • Oxygen Consumption/physiology
  • Oxygen/metabolism
  • Young Adult
  • magnetic resonance imaging
  • oxygen extraction fraction (OEF)
  • multiple sclerosis
  • Aging
  • cerebral metabolism


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