Published in the journal Nature Neuroscience, the study is the first to unveil a gut-brain connection linking high dietary salt intake to neurovascular and cognitive impairment.
The findings illuminate a potential future target for countering harmful effects to the brain caused by excess salt consumption.
"We discovered that mice fed a high-salt diet developed dementia even when blood pressure did not rise," said Costantino Iadecola, from Weill Cornell Medicine in the US.
"This was surprising since, in humans, the deleterious effects of salt on cognition were attributed to hypertension," said Iadecola.
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The mice were given food containing four per cent or eight per cent salt, representing an 8- to 16-fold increase in salt compared to a normal mouse diet.
The higher level was comparable to the high end of human salt consumption. After eight weeks, the scientists examined the mice using magnetic resonance imaging.
The mice showed marked reductions in resting cerebral blood flow in two areas of the brain involved in learning and memory: 28 per cent decrease in the cortex and 25 per cent in the hippocampus.
To see if the biological effects of a high-salt diet could be reversed, researchers returned some mice to a regular diet for four weeks and found that cerebral blood flow and endothelial function returned to normal.
Rodents that only ate the high-salt diet developed dementia, performing significantly worse on an object recognition test, a maze test and nest building - a typical activity of daily living for mice, spending less time building nests and using much less nesting material than normal mice.
They discovered that the mice developed an adaptive immune response in their guts, with increased activity of a subset of white blood cells that play an important role in the activity of other immune cells.
The increase in those white blood cells, T helper lymphocytes called TH17, boosted the production of a protein called interleukin 17 (IL-17) that regulates immune and inflammatory responses, causing a reduction in the production of nitric oxide in endothelial cells.
In a final experiment, the scientists treated the mice with a drug known to prevent the suppression of nitric oxide activity, called ROCK inhibitor Y27632.