Lowering salt intake could stave off dementia

A high-salt diet may negatively affect cognitive function.

A high-salt diet may negatively affect cognitive function by causing a deficiency of nitric oxide, which is vital for maintaining vascular health in the brain, according to a new study in mice from Weill Cornell Medicine researchers.

When nitric oxide levels are too low, chemical changes to the protein tau occur in the brain, contributing to dementia.

The investigators concluded that lowering salt intake and maintaining healthy blood vessels in the brain may “stave off” dementia. Accumulation of tau deposits has been implicated in the development of Alzheimer’s disease in humans.

“Our study proposes a new mechanism by which salt mediates cognitive impairment and also provides further evidence of a link between dietary habits and cognitive function,” said lead author Giuseppe Faraco, an assistant professor of research in neuroscience in the Feil Family Brain and Mind Research Institute at Weill Cornell Medicine.

The study builds upon research published in 2018 that found that a high-salt diet caused dementia in mice. The rodents became unable to complete daily living tasks such as building their nests and had problems passing memory tests. The research team determined that the high-salt diet was causing cells in the small intestine to release the molecule interleukin-17 (IL-17), which promotes inflammation as part of the body’s immune response.

IL-17 enters the bloodstream and prevents the cells in the walls of blood vessels feeding the brain from producing the compound nitric oxide. This compound works by relaxing and widening the blood vessels, allowing blood to flow. Conversely, a shortage of nitric oxide can restrict blood flow.

In their new study, the investigators found that decreased nitric oxide production in blood vessels also affects the stability of tau proteins in neurons. “Tau becoming unstable and coming off the cytoskeleton causes trouble,” said Costantino Iadecola, senior author of the study. He added that tau is not supposed to be free in the cell. Once tau detaches from the cytoskeleton, the protein can accumulate in the brain, causing cognitive problems. The researchers determined that healthy levels of nitric oxide keep tau in check. “It puts the brakes on activity caused by a series of enzymes that leads to tau disease pathology,” he said.

Overall, the study highlights how vascular health is important to the brain. “As we demonstrated, there’s more than one way that the blood vessels keep the brain healthy,” Iadecola said.