Causes of Cognitive Deficits in Multiple Sclerosis Patients

Platelet activator factor receptors are to blame for the cognitive issues that multiple sclerosis (MS) patients develop as their disease progresses, according to a study published in the Journal of Neuroscience.

Researchers from the University of Rochester Medical Center used mice models of MS in order to demonstrate that neurons undergo injury which leaves them susceptible to aggravation from platelet activating factors. It is widely understood that gray matter degeneration contributes to white matter disease, the researchers noted, but they speculated that the neurons could undergo direct injury independent of the original demyelination.

The researchers learned that the cognitive problems such as difficulty processing information, concentrating, finding the right word when speaking, and memory loss, could be contributed to the microglia when activated to help fight infection or other functions. The microglia release platelet activating factor — and high levels of the factor can cause the destruction of the nerve synapse. More microglia rush in, and the cycle continues.

“This study identifies for the first time a new disease mechanism in MS which causes damage to neurons independent of the loss of white matter and demyelination that is the hallmark of the disease,” lead author, neurologist Matthew Bellizzi, MD, PhD, said in a press release. “This damage represents another component of the disease and one that is not prevented by the current immunosuppressive drugs employed to treat MS.”

The researchers liken this effect to like trying to put a fire out with gasoline, and added that this cycle is likely behind the cognitive impairment and progressive cognitive decline that MS patients experience as their disease continues.

The findings may lead to therapeutic treatments, the investigators said, because the current therapies don’t target the activation of microglia and the resulting brain damage. The researchers added in the statement that they are now focused on finding potential drug candidates which are known to target the signaling pathways which cause the nerve cells and microglia to overcompensate. One of those drugs is currently being investigated to treat neurological disorders linked to HIV.

“For too long, MS has been characterized as a disease that impairs people’s mobility, speech, or vision,” senior author Harris Gelbard, MD, PhD added in the statement. “However, the aspect of the disease that many patients complain has the greatest impact on their quality of life is the loss of cognitive independence.”