CEEVs, Neurovascular Coupling, and Functional Connectivity Are Potential Markers For Mild Cognitive Impairment

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Several measurements of the brain, such as blood flow and the brain’s ability to compensate for the lack of it, are better at predicting mild cognitive impairment (MCI) in individuals than risk factors like hypertension and high cholesterol, reports study findings published in the Alzheimer’s Association’s journal, Alzheimer’s & Dementia. The findings, according to the investigators, help further the understanding and prospects of the early prevention or treatment of memory problems before dementia progression.^1,2

According to the investigators, approximately 18% of the world’s population has MCI, and 10% to 15% will eventually develop dementia. A projected 152 million individuals are predicted to be affected by dementia by the year 2050.¹

“People with MCI are at highest risk for the next step, which is dementia,” Calin Prodan, MD, professor of neurology in the OU College of Medicine, said in a news release. “We’re trying to decipher the ‘fingerprints’ of MCI—what happens to the brain when a person moves from healthy aging to MCI, and is there something we can do to intervene and prevent the decline to dementia?”¹

For this study, the investigators focused on the brain’s vasculature, which is its network of blood vessels, to assess how it acts differently in older adults who have MCI. Participants with MCI and age-matched controls (CN) were enrolled. Participants were screened and placed in the MCI if they were older than 50 years of age, had a Clinical Dementia Rating (CDR) of 0.5 and/or Montreal Cognitive Assessment (MoCA) of 19 to 25. Patients were placed in the CN group if they presented no clinical diagnosis of MCI or any cognitive impairment, as well as a MoCA score of 26 or higher. All patients were administered cognitive tasks during functional near-infrared spectroscopy (fNIRS) recording, and changes in plasma levels of extracellular vesicles (EVs) were assessed using small-particle flow cytometry.²

The study found that neurovascular coupling (NVC) dysfunction and functional connectivity (FC) were decreased in participants with MCI compared with the CN group. These findings were localized to the left-dorsolateral prefrontal cortex (LDLPFC), and an exploratory study also showed an elevated ratio and concentration of cerebrovascular endothelial EVs (CEEVs) to total endothelial EVs in patients with MCI compared with CN.²

Existing research demonstrates that if the inner lining of blood vessels were damaged, it secretes CEEVs. Those who have MCI have more CEEVs in their brains compared with those who have “healthy” aging brains. Further, magnetic resonance imaging images have confirmed that those with higher levels of CEEVs also presented more ischemic damaging, resulting in the small vessels in the brain not receiving an adequate supply of blood. According to the researchers, this is the first time that CEEVs have been measured within a cognitive condition.^1,2

“People with MCI have lost that compensation mechanism. There is a drastic change in brain activity in those with mild cognitive impairment,” Cameron Owens, PhD, OU College of Medicine’s MD/PhD degree program student, said in the news release.¹

NVC, CEEVs, and FC show their potential as markers for MCI cerebrovascular pathology and ability to predict MCI diagnosis over demographic or comorbidity factors. With this finding, the investigators note that they will continue research to better understand the impact of CEEV on MCI and its contribution to dementia diagnoses. Further, the authors note that because the study commenced during the COVID-19 pandemic, there may be potential impacts of the virus on the acceleration of dementia progression in those with MCI. Future research will address this.^1,2

“Every brain is different, and there may be differing reasons for cognitive impairment, but having these predictors—measuring NVC, FC, 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,” Andriy Yabluchanskiy, PhD, associate professor of neurosurgery, OU College of Medicine, said in the news release.¹

REFERENCES

1. University of Oklahoma. Brain vasculature changes important for predicting cognitive impairment. News release. September 16, 2024. Accessed September 17, 2024. https://www.eurekalert.org/news-releases/1058143

2. Owens CD, Pinto CB, Mukli P, et al. Neurovascular coupling, functional connectivity, and cerebrovascular endothelial extracellular vesicles as biomarkers of mild cognitive impairment. Alzheimer's Dement. 2024; 20: 5590–5606. doi:10.1002/alz.14072