Issues with brain’s ‘sewer system’ may spur cognitive problems in Cushing’s
Study finds link between impaired glymphatic function and white matter damage
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In people with Cushing’s disease, high cortisol levels can lead to problems with a key system that clears waste from the brain, and dysfunction of this system may set the stage for damage to the brain that leads to cognitive issues in some Cushing’s patients, according to a study.
The study, “Association Between Glymphatic Function and White Matter Microstructural Injury in Patients With Cushing’s Disease,” published in Brain and Behavior.
Higher cortisol levels associated with worse glymphatic function
Cushing’s disease is a disorder caused by a tumor in the pituitary gland, which leads to excess levels of the stress hormone cortisol. High cortisol levels ultimately drive Cushing’s symptoms such as weight gain, skin changes, and cognitive struggles.
Previous studies have shown that some people with Cushing’s disease experience damage to white matter, which is the part of the brain tissue containing the long nerve fibers that connect different brain regions. This type of brain damage is closely linked with cognitive problems for Cushing’s patients. But the mechanisms by which Cushing’s disease leads to white matter damage are poorly understood.
In this study, scientists in China sought to better understand how Cushing’s disease affects the glymphatic system, which clears waste products from the brain. Normally, the glymphatic system acts like a sewer for the brain, helping flush out toxins and other waste products. There’s growing evidence that dysfunction in this system may play a role in a range of brain disorders, but this is the first study to specifically evaluate the health of this system in people with Cushing’s disease.
The study included 69 people with Cushing’s disease and 64 without the disease for comparison. Brain imaging scans were used to assess both glymphatic function and white matter injury.
This study offers a novel perspective on the mechanisms underlying [white matter] tract damage in patients with [Cushing’s disease]. [These findings] suggest that controlling nighttime cortisol levels may help alleviate glymphatic dysfunction, thereby mitigating damage to certain [white matter] tracts.
Results showed that Cushing’s patients had a significantly lower average diffusion tensor image analysis along the perivascular space (DTI-ALPS) index. A lower score on this index essentially indicates poorer glymphatic function. There was also a correlation between higher nighttime cortisol levels and lower DTI-ALPS index scores— that is, Cushing’s patients with higher levels of the symptom-driving stress hormone tended to have worse glymphatic function.
Cushing’s patients also showed more evidence of white matter damage than people without the disease. Statistical analyses indicated that the relationship between nighttime cortisol levels and white matter damage in certain brain regions was mediated by the DTI-ALPS index. In other words, mathematically, the fact that patients with higher cortisol levels tend to have worse glymphatic flow explained the relationship between nighttime cortisol levels and white matter damage.
Collectively, these data support a model in which high cortisol levels in Cushing’s disease impair glymphatic function, which in turn leads to white matter damage.
“This study offers a novel perspective on the mechanisms underlying [white matter] tract damage in patients with [Cushing’s disease],” the researchers wrote, adding that these findings “suggest that controlling nighttime cortisol levels may help alleviate glymphatic dysfunction, thereby mitigating damage to certain [white matter] tracts.”
The scientists stressed, however, that their study only looked at associations, making it impossible to draw definitive conclusions about cause and effect. They highlighted a need for additional studies to explore the role of glymphatic dysfunction in Cushing’s disease.
