Oligodendrocyte NRF2 changes linked to cognitive decline in aging

Researchers studied cognitive trajectories in the Lothian Birth Cohort 1936, where 866 of 1,091 participants completed additional testing after age 70. Assessments between ages 70 and 82 measured memory, processing speed and spatial reasoning. In postmortem brain tissue from a subset, faster decline was associated with fewer large nerve fibers and abnormal myelin accumulation. The tissue findings tracked the rate of decline, rather than cognitive performance at a single age.

The team found lower levels of NRF2 in oligodendrocytes among people with greater decline. In mice, reducing NRF2 specifically in these cells led to excess myelin, loss of large nerve fibers and less improvement in cognitive performance with age. The experiments support a role for oligodendrocyte NRF2 in the observed brain changes, but do not establish that the same mechanism causes cognitive decline in humans.

The results suggest a potential therapeutic target, as the NRF2 pathway is targeted by drugs used for other neurological conditions. No treatment for age-related cognitive decline was tested in this study, and the source does not identify a specific drug or provide clinical trial evidence in older adults. Further research is needed before the findings can inform clinical care.