Disrupted brain blood flow tied to poorer cognitive function in MS

Altered neurovascular coupling (NVC), the process that matches brain activity with the blood flow needed to support it, is associated with poorer cognitive function and greater disability in people with multiple sclerosis (MS), a study found.

The most consistent finding was an abnormal balance between blood flow and spontaneous brain activity in the left medial prefrontal cortex (mPFC), a brain region involved in advanced cognitive skills.

“These findings suggest altered NVC in MS, with regional prefrontal abnormalities representing the most robust and clinically relevant finding,” the researchers wrote. “Regional prefrontal NVC abnormalities may provide a potential imaging correlate of cognitive performance in MS.”

The study, “Prefrontal Neurovascular Coupling Abnormalities Associated With Cognitive Performance in Multiple Sclerosis,” was published in CNS Neuroscience & Therapeutics.

Cognitive problems are common in people with MS and can develop early in the disease course, affecting daily activities and quality of life. However, the biological mechanisms underlying cognitive impairment in MS are not fully understood.

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NVC disrupted in MS

Normal brain function depends on a constant match between the activity of nerve cells and the blood flow that supplies them with oxygen and nutrients. This process — NVC — relies on coordinated communication between nerve cells and nearby blood vessels. In MS, inflammation and damage to the brain may disrupt NVC, potentially affecting cognitive function.

To learn more, researchers in China examined available data from 97 MS patients and 83 healthy controls matched for age, sex, and education to assess whether impaired NVC may be related to cognitive performance in MS.

Participants with MS had a median disease duration of about three years, and the majority (89.7%) had relapsing-remitting MS (RRMS), the most common form of MS. Almost 80% were receiving disease-modifying therapies (DMTs).

MS patients had significantly impaired cognitive function compared with healthy controls, as seen by significantly lower scores in three standard cognitive tests: the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE), which screen for problems in memory, language, attention, and thinking; and the Symbol Digit Modalities Test (SDMT), which evaluates how quickly a person can process and respond to information.

In imaging analysis, participants with MS also had significantly lower NVC than healthy controls, as well as higher blood flow to brain activity ratio in the mPFC. A higher ratio means blood supply is disproportionately high relative to neuronal activity.

Further analysis demonstrated that the blood flow-to-brain activity ratio in the mPFC was associated with clinical and cognitive measures in people with MS. Specifically, higher ratios in the left mPFC were associated with poorer performance on the MoCA and SDMT tests, as well as greater disability measured by the Expanded Disability Status Scale. A higher ratio in the right mPFC was also associated with lower SDMT scores.

“The clinical relevance of the mPFC finding is supported by its associations with both cognition and disability,” the researchers wrote. “This is particularly important because the mPFC is a key hub for higher-order cognitive processing and large-scale network integration.”

The main findings remained unchanged after additional analyses that accounted for other measures of neuronal activity, MS lesion volume, gray matter volume, disability levels, and DMT status. They also did not change when only patients with RRMS were included in the analyses.

While the findings suggest “multilevel NVC alterations in MS,” further studies are needed to clarify its prognostic relevance and determine whether improving NVC leads to better cognitive outcomes in MS, the researchers concluded.