Age-related decline in cerebral oxygen consumption in multiple sclerosis

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

  • Maria H. Knudsen
  • Mark B. Vestergaard
  • Ulrich Lindberg
  • Helle J. Simonsen
  • Jette L. Frederiksen
  • Stig P. Cramer
  • Larsson, Henrik Bo Wiberg
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.
OriginalsprogEngelsk
TidsskriftJournal of Cerebral Blood Flow and Metabolism
Antal sider14
ISSN0271-678X
DOI
StatusAccepteret/In press - 2024

Bibliografisk note

Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by Sanofi Genzyme [Grant number GZ-2016-11629] and The Danish Multiple Sclerosis Society [Grant numbers A37989, A40212, A41682]. The funding bodies had no influence on the study design, inclusion of patients, data analysis, interpretation or writing of the final manuscript. Acknowledgements

Funding Information:
The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The authors declare the following potential conflicts of interest with respect to the research, authorship and/or publication of this article. M.H. Knudsen received funding from Sanofi Genzyme and The Danish Multiple Sclerosis Society and non-financial support from Merck. H.B.W. Larsson & S.P. Cramer received funding from Sanofi Genzyme and The Danish Multiple Sclerosis Society. Sanofi Genzyme had no influence on the study design, inclusion of patients, data analysis or interpretation. U. Lindberg, M.B. Vestergaard and H.J. Simonsen have nothing to disclose. J.L. Frederiksen received no funding to support this study. She has served on scientific advisory boards for and received funding for travel related to these activities and honoraria from Biogen Idec, Merck Serono, Sanofi-Aventis, Teva, Novartis and Almirall. She has also received speaker honoraria from Biogen Idec, Teva and Novartis. She has served as an advisor on preclinical development for Takeda. J. L Frederiksen participated in advisory board meetings with Alexion and Chiesi.

Publisher Copyright:
© The Author(s) 2024.

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