Researchers studying a Scottish cohort tracked from childhood found that people who experienced sharper cognitive decline after age 70 tended to have fewer large nerve fibers and an abnormal buildup of myelin in their brains. The findings, published in Nature Medicine, suggest that myelin—normally essential for fast neural signaling—can become part of the problem when it accumulates excessively around remaining fibers.
Focusing on oligodendrocytes, the cells that make myelin, the team found lower levels of the protective protein NRF2 in people with more severe decline. In mice, reducing NRF2 in these cells produced the same pattern of excess myelin and loss of large nerve fibers, along with weaker cognitive improvement as the animals aged. This indicates that declining NRF2 activity directly disrupts oligodendrocyte function.
Because drugs that activate NRF2 are already used for multiple sclerosis, and previous studies have shown they can improve cognition in MS patients, the authors suggest these medications might be repurposed to protect the aging brain. Further research is needed to test whether such treatments would work in older adults with cognitive decline.