The News: A high-salt diet may negatively affect cognitive function by causing a deficiency of the compound 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.
In the study, recently published in Nature, the investigators sought to understand the series of events that occur between salt consumption and poor cognition and 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, says ScienceDaily.
“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 study author Dr. Giuseppe Faraco, an assistant professor of research in neuroscience in the Feil Family Brain and Mind Research Institute at Weill Cornell Medicine.
The new study builds upon research published last year in Nature Neuroscience by Dr. Faraco and senior author Dr. Costantino Iadecola, director of the Feil Family Brain and Mind Research Institute and the Anne Parrish Titzell Professor of Neurology at Weill Cornell Medicine.
The 2018 study 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 then entered the bloodstream and prevented the cells in the walls of blood vessels feeding the brain from producing 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.
Based on these findings, Dr. Iadecola, Dr. Faraco and their colleagues theorized that salt likely caused dementia in mice because it contributed to restricted blood flow to the brain, essentially starving it. However, as they continued their research, they realized that the restricted blood flow in mice was not severe enough to prevent the brain from functioning properly.
“We thought maybe there was something else going on here,” Dr. Iadecola said.
In their new Nature study, the investigators found that decreased nitric oxide production in blood vessels affects the stability of tau proteins in neurons. Tau provides structure for the scaffolding of neurons. This scaffolding, also called the cytoskeleton, helps to transport materials and nutrients across neurons to support their function and health.
“Tau becoming unstable and coming off the cytoskeleton causes trouble,” Dr. Iadecola said, adding 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.
To further explore the importance of tau in dementia, the researchers gave mice with a high-salt diet and restricted blood flow to the brain an antibody to promote tau stability. Despite restricted blood flow, researchers observed normal cognition in these mice.
“This demonstrated that’s what’s really causing the dementia was tau and not lack of blood flow,” Dr. Iadecola said.
Overall, this 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,” Dr. Iadecola said.
Although research on salt intake and cognition in humans is needed, the current mouse study is a reminder for people to regulate salt consumption, Dr. Iadecola said.
“And the stuff that is bad for us doesn’t [just] come from a saltshaker, it comes from processed food and restaurant food,” he said. “We’ve got to keep salt in check. It can alter the blood vessels of the brain and do so in vicious way.”
Ironically, I was jogging on my favorite route yesterday when I was suddenly overcome by the extremely rare urge to visit the grocery store and pick up a bag of potato chips and the ingredients for clam dip. Or maybe onion dip. Turns out I was too lazy to shower after the run and drive down to the store, so instead I feasted on some cheese and crackers as an appetizer before dinner.
Then I read the news (above) about the connection between salt, dementia and Alzheimer’s disease. Frankly, I hadn’t heard about this connection and was taken aback by the certainty of the researchers’ findings. What’s the key take away? Simple. Significantly reducing salt intake could have a preventative effect when it comes to AD.
Translating the study’s findings into English, a team led by Dr. Constantino Iadecola at Cornell University used both a mouse model and human cells to examine the impact of a high-salt diet over time. In the study report published in the journal Nature Neuroscience, they said a diet that regularly exceeded the daily recommended salt intake resulted in an increase in the number of immune cells called TH17 in the blood following a trigger response from the intestines.
This then boosted a chemical these cells produce called IL-17, which has an inflammatory effect and also suppresses the production of nitric oxide in the blood vessels. Nitric oxide is known to assist in the relaxation of blood vessels and also contributes to the formation of new memories in the hippocampus.
After just a few days on the high-salt diet, it was found that the mice had experienced a reduction in blood flow to the brain. They had also altered behaviorally, forgetting how to build a nest, struggling to recall objects and becoming unable to find their way out of a simple maze.
Importantly though, the findings of damage were also true for human cerebral endothelial cells, suggesting diet can play an important function in keeping the brain healthy. When the diet was reversed and the mice were given normal food, their blood flow and endothelial function returned to healthy levels again within four weeks.
Dr. Iadecola said the study indicates a “gut-brain axis” that links dietary habits to long-term health and suggested a change in lifestyle could protect the brain in the long term.
Bottom Line: It has long been known that the presence of toxic plaques called beta-amyloids is a marker of Alzheimer’s in the brain tissue, but this study came about because Dr. Iadecola wanted to investigate why the blood vessels in the brains of patients also frequently do not look “normal.” New drugs that block IL-17 may therefore be able to reverse some symptoms of Alzheimer’s in the future before they even show up, Iadecola believes.
Dr. Sara Imarisio of Alzheimer’s Research UK said: “The findings highlight the importance of cutting out excess salt in our diets, as well as identifying possible new avenues in the search for treatments to help those with memory problems or dementia.”
Despite accounting for only 2% of the body’s weight, the brain requires around 15% of its total blood supply in order to remain healthy.
Changes in the brain can occur up to ten years before a person starts to display symptoms of Alzheimer’s or other degenerative brain conditions. Currently around 60% of people diagnosed with dementia will progress to Alzheimer’s–the most common form of the condition among people over 65.
Figures recently released for 2016 showed that dementia is the biggest threat to human life in rich nations, often beating out even heart disease. So, throw away that super-size bag of potato chips and switch to celery stalks, don’t reach for the saltshaker before eating that buttery ear of corn and, forget about covering the rim of that scrumptious margarita with rock salt. Oh, and any food ingredient containing the word “sodium” probably has a salt component.
It’s not too late to reduce your salt intake. Considering the stakes, why not start now.