Brain Cells Once Thought Protective May Drive Cognitive Decline With Age

A new study finds that brain cells once thought to be purely protective may actually drive cognitive decline with age. The cells, called oligodendrocytes, produce myelin, the fatty coating that insulates nerve fibers so electrical signals travel quickly between brain regions. The findings, from researchers at the University of Edinburgh and the UK Dementia Research Institute, were published in Nature Medicine on August 25.

The team studied brain tissue and cognitive test results from the Lothian Birth Cohort 1936, a group of 1,091 people whose cognition has been tracked from childhood into old age; 866 of them returned for testing after age 70. Post-mortem tissue from a subset of participants showed that people whose cognition declined faster had fewer large nerve fibers and abnormal, excess myelin around the fibers that remained.

The researchers then found that people with more severe cognitive decline had lower levels of a protein called NRF2 in their oligodendrocytes; NRF2 normally helps protect cells from damage. When the researchers lowered NRF2 in oligodendrocytes in mice, the animals developed excess myelin, lost large nerve fibers, and their expected age-related improvements in cognitive performance were impaired too.

NRF2 is already targeted by an existing multiple sclerosis drug, and earlier research has shown that activating NRF2 can improve cognitive function in people with multiple sclerosis. Study leader Veronique Miron of the University of Edinburgh and the UK Dementia Research Institute said the findings point to a possible strategy for new treatments to preserve cognitive ability in aging, since no such treatments currently exist.