Age-Related Decline in Brain Myelination: Quantitative Macromolecular Proton Fraction Mapping, T2-FLAIR Hyperintensity Volume, and Anti-Myelin Antibodies Seven Years Apart

Biomedicines. 2023 Dec 27;12(1):61. doi: 10.3390/biomedicines12010061.

Abstract

Age-related myelination decrease is considered one of the likely mechanisms of cognitive decline. The present preliminary study is based on the longitudinal assessment of global and regional myelination of the normal adult human brain using fast macromolecular fraction (MPF) mapping. Additional markers were age-related changes in white matter (WM) hyperintensities on FLAIR-MRI and the levels of anti-myelin autoantibodies in serum. Eleven healthy subjects (33-60 years in the first study) were scanned twice, seven years apart. An age-related decrease in MPF was found in global WM, grey matter (GM), and mixed WM-GM, as well as in 48 out of 82 examined WM and GM regions. The greatest decrease in MPF was observed for the frontal WM (2-5%), genu of the corpus callosum (CC) (4.0%), and caudate nucleus (5.9%). The age-related decrease in MPF significantly correlated with an increase in the level of antibodies against myelin basic protein (MBP) in serum (r = 0.69 and r = 0.63 for global WM and mixed WM-GM, correspondingly). The volume of FLAIR hyperintensities increased with age but did not correlate with MPF changes and the levels of anti-myelin antibodies. MPF mapping showed high sensitivity to age-related changes in brain myelination, providing the feasibility of this method in clinics.

Keywords: FLAIR hyperintensities; MPF; demyelination; macromolecular fraction mapping; myelin; myelin-specific autoantibodies; neuroimaging; normal aging; quantitative MRI; white matter.