The Brain's Stress Response and Dementia

A study published in March 2014 suggests that there is a relationship between the brain's response to stress and dementia. The study suggests that memory and thinking problems may be due to a failure in the brain's stress response system. If the stress response system is working well, it may protect the brain from the abnormal proteins seen in dementia; if it fails, then parts of the brain degenerate.

Researchers at Harvard University studied a protein called REST, which was known to switch off certain genes in the developing brains of fetuses. Although REST becomes inactive in the brain before birth, the researchers found that it becomes active again in old age and plays a role in protecting nerve cells from aging-related stresses. In post-mortem analysis of the brains of older individuals who had been relatively healthy, the level of REST increased with age. However, for those who had had dementia, the level of REST was low in key regions of the brain. This applied to people who had had Alzheimer's disease, mild cognitive impairment, frontotemporal dementia, and Lewy body disease.

An important finding was that some brains had the plaques and tangles associated with abnormal Alzheimer's proteins, but when there were also adequate levels of REST, the people hadn't exhibited the memory and thinking problems of dementia. Those problems had been apparent in those who had had low levels of REST. The lower the level of REST, the worse the dementia had been.

The researchers followed up by genetically engineering mice that would not produce REST. As the mice aged, they lost brain cells.

Much more research will follow to determine whether a low level of REST is a cause or a consequence of dementia. Further research may reveal an avenue for new drug therapies.

You can read the abstract of the study published in Nature. The New York Times has a good article about the research.