Salt and Impaired Cognition

By Jane Farrell

Here’s another reason to avoid salt besides its connection to hypertension. Scientists who conducted a mouse study have concluded that salt is linked to impaired cognition.

The study was published in Nature Neuroscience.

The researchers discovered that changes in the gut caused by a high-salt diet are linked to impaired blood flow to the brain. According to a news release from the National Institutes of Health (NIH), the reduced blood flow can eventually lead to impaired cognition. But, they said, that could be reversed by changing back to a normal diet.

“For years researchers have wondered how a high-salt diet harms the brain,” said Jim Koenig, Ph.D., program director at the National Institute of Neurological Disorders and Stroke (NINDS), part of the NIH, which supported the study. “This mouse study provides a detailed…diagram for how the problems start in the gut and opens unexpected paths towards new treatments.”

In the study, mice were fed a high-salt diet (HSD) containing 16 times the amount of sodium chloride typically found in their food. After eight weeks, their brains showed a 20 to 30 percent reduction in blood flow compared to mice that ate normal food.

This reduced blood flow was accompanied by the appearance of dementia-like symptoms, including defects in the ability of HSD mice to recognize objects, navigate a maze, and properly build a nest. When the mice were returned to a normal diet, both blood flow and cognition improved.

“The brain is extremely dependent on getting the right amount of blood at the right time. If blood flow isn’t matched to what the brain needs, things go wrong,” said Costantino Iadecola, M.D., director and chair of the Feil Family Brain and Mind Research Institute at Weill Cornell Medicine in New York City and senior author of this study.

To study further how salt affects blood flow in the brain, blood vessels were taken from the brains of mice fed a high-salt diet. Normally, these vessels tighten (constrict) to reduce blood flow or relax (dilate) to increase flow. However, those taken from mice on a high salt diet did not dilate properly when stimulated to do so. An analysis found a reduction in the function of the enzyme eNOS that is responsible for producing nitric oxide (NO), a potent signal for blood vessels to dilate.

When the amino acid L-arginine, which can increase eNOS activity and nitric oxide production, was added to the dishes containing blood vessels from HSD mice, the cells responded normally.

“These findings together show that a high-salt diet affects the activity of the eNOS enzyme, which in turn leads to problems with blood flow and cognition,” said Iadecola, who is on the strategic advisory board and receives a consulting fee from Broadview Ventures Inc. Broadview Ventures Inc. was created by the board of the Foundation Leducq Trust, the supporting trust of the French nonprofit research organization Foundation Leducq. “But the question still remained how the ingestion of salt could lead to these effects in the brain.”

One clue came from evidence showing that eating high levels of salt changes the immune system of the gut, a finding that was first reported by scientists studying salt’s effects in a model of multiple sclerosis. Specifically, a high-salt diet increased the appearance of TH17 immune cells. These cells secrete a molecule, IL-17, that can have toxic effects on blood vessels. Because the researchers did not observe any TH17 cells in the brains of mice on a high-salt diet, they concluded that it must be IL-17, moving throughout the circulatory system, that was acting directly on the brain’s blood vessels.

The combined results of three additional experiments helped to confirm this hypothesis, according to the news release from NIH.

In humans, high levels of salt in the diet have long been associated with high blood pressure, and increasing evidence has linked blood pressure and brain health.

“This study adds to our growing understanding of how the gut can modulate brain function,” said Koenig. “From a public health perspective, the fact that these effects can be reversed by halting the ingestion of salt is very important and could help us improve health in areas where many people eat a high-salt diet.”

In future experiments, Iadecola and his colleagues plan to further investigate how decreased nitric oxide production and reduced blood flow lead to changes in cognition.