Researchers Identify Potential Cause of Hypertension-Induced Dementia

Yesterday, the National Institutes of Health (NIH) issued a press release identifying a potential pathway for hypertension-induced dementia. The announcement cites a study published in Nature Neuroscience and funded by the National Institute of Neurological Disorders and Stroke (NINDS), a subset of the NIH, which used mouse models to simulate the effects of hypertension on cognitive function.

Led by Costantino Iadecola, MD, director and chair of the Feil Family Brain and Mind Research Institute, New York City, researchers used a mouse model that closely mimics human hypertension. Iadecola maintains that this mouse model, called the deoxycorticosterone acetate (DOCA) salt model, is the most accurate model of hypertension in humans.

Researchers found that DOCA models had elevated interleukin-17 (IL-17) levels in the brain’s cerebrospinal fluid. IL-17 is a chemical compound that the body releases to activate the immune system, causing immune cells to trigger inflammation and fight infections.

According to the NIH press release, the activation of the macrophages initiated by IL-17 production is linked to changes in cognition. Investigators validated this claim by showing that when mouse models were manipulated to delete IL-17 receptors in the brain, both healthy and DOCA mice did not experience cognitive impairment.

“The role of immune signaling in cognitive decline is critically important to understand,” said Roderick Corriveau, PhD, program director, NINDS, in the press release. “These findings offer insight into how signaling from the immune system could contribute to symptoms of cognitive decline that ultimately result in dementia diagnoses.”

A previous study conducted by Iadecola demonstrated that a high salt diet triggered IL-17 production in the gut, which eventually led to cognitive impairment.

Based on that, the team initially hypothesized that IL-17 is produced in the gut and travels to the brain through the bloodstream, triggering the cascade of events that cause cognitive impairment. However, further analysis revealed that another source of IL-17 must be acting on the brain, as blocking the brain blood vessels’ IL-17 responses only moderately improved cognition.

“Together, our data suggest two different effects are caused by hypertension,” added Iadecola. “One is IL-17 acting on blood vessels, but this appears to be relatively minor. A more prominent central effect is caused by cells in the meninges releasing IL-17, that directly affects immune cells in the brain. It is these immune cells, activated by signaling from the meninges, that ultimately affect the brain in a way that causes cognitive impairment.”