Brain Vasculature Changes Important for Predicting Cognitive Impairment

University of Oklahoma researchers recently published a study showing that several measurements of the brain, including blood flow and the brain’s ability to compensate for the lack of it, are better predictors of mild cognitive impairment than risk factors like hypertension and high cholesterol.

The findings further the prospects of preventing or treating memory problems early before they progress to dementia. The need is only becoming greater: Approximately 18% of the world’s population has mild cognitive impairment, and 10-15% will go on to develop dementia. By 2050, dementia is projected to affect 152 million people.

The research was led by a multidisciplinary group of researchers in the OU College of Medicine and published in Alzheimer’s & Dementia, a journal of the Alzheimer’s Association. Their studies centered on the brain’s vasculature – its network of blood vessels – and how this acts differently in older adults with mild cognitive impairment.

“People with mild cognitive impairment are at highest risk for the next step, which is dementia,” said Calin Prodan, M.D., a professor of neurology in the OU College of Medicine and a co-author of the paper. “We’re trying to decipher the ‘fingerprints’ of mild cognitive impairment – what happens to the brain when a person moves from healthy aging to mild cognitive impairment, and is there something we can do to intervene and prevent the decline to dementia?”

The research team took several types of brain measurements in people at three stages of life: young adults, older adults with aging but healthy brains, and older adults with mild cognitive impairment. Each group played a short memory challenge game on a computer while wearing what looked like a swim cap with light sensors; the technology, called functional near-infrared spectroscopy, measured blood flow in the brain as participants were challenged to memorize increasingly larger sequences of letters.

In the brains of young adults, blood flow increased, giving their brains the energy they needed to meet the demands of the game, a process called neurovascular coupling. In people with healthy aging brains, the blood flow did not increase as much, but to compensate, their brains engaged other regions of the brain to help with the challenge, a process known as functional connectivity. In the brains of older adults with mild cognitive impairment, the blood flow was greatly reduced, and they lost the ability to compensate by recruiting other parts of the brain to help.

“People with mild cognitive impairment have lost that compensation mechanism. There is a drastic change in brain activity in those with mild cognitive impairment,” said Cameron Owens, Ph.D., lead author of the study. After earning his doctorate, Owens is now in his third year of medical school as part of the OU College of Medicine’s M.D./Ph.D. degree program.

Another type of assessment – a liquid biopsy – gave researchers an additional window into the brains of people with cognitive impairment. This blood analysis measured the amount of cerebrovascular endothelial extracellular vesicles, or CEEVs, which are tiny particles released from the cells lining the brain’s blood vessels. Existing research shows that when the inner lining of blood vessels is damaged, it secretes CEEVS. People with mild cognitive impairment had more CEEVs in their brains than those with healthy aging brains. Furthermore, MRI images confirmed that people with higher levels of CEEVs also had more ischemic damage, meaning the small vessels in their brains did not receive adequate blood supply. The researchers believe this is the first time that CEEVs have been measured in a cognitive condition.

“Every brain is different, and there may be differing reasons for cognitive impairment, but having these predictors – measuring neurovascular coupling, functional connectivity, and CEEVs – potentially opens opportunities to develop individualized interventions, whether it’s a pharmacological therapy or non-invasive brain stimulation, or something as simple as cognitive behavioral therapy,” said Andriy Yabluchanskiy, Ph.D., OU College of Medicine associate professor of neurosurgery and co-author of the study.

The research will continue with several additional angles. The team plans to further analyze CEEVs, which are like bubbles carrying a variety of materials, to see if that cargo also contributes to mild cognitive impairment. In addition, because the study began during the COVID-19 pandemic, researchers are evaluating whether infection with the virus accelerated the progression to dementia in people with mild cognitive impairment

“We are in year two of a four-year study,” Yabluchanskiy said. “This is a prospective study in which all of our participants are living right here in Oklahoma.”

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About the project

Read the full study, “Neurovascular coupling, functional connectivity, and cerebrovascular endothelial extracellular vesicles as biomarkers of mild cognitive impairment,” at https://doi.org/10.1002/alz.14072. Funding for this research is from the American Heart Association and the National Institutes of Health. Support from the Oklahoma City-based Presbyterian Health Foundation has also been instrumental.