Dementia refers to the decline in cognitive abilities, such as thinking, memory, and reasoning. It is a prevalent condition in the US and around the world, posing significant challenges. Unfortunately, the treatment satisfaction for dementia is currently low, and there is no available drug therapy that can cure the disease.

Given the rapidly aging global population, it becomes crucial to prioritize the development of preventive and therapeutic drugs for dementia.

Excessive consumption of table salt, a widely used food seasoning, has been associated with cognitive impairment. Additionally, a high intake of salt can lead to hypertension, a condition characterized by high blood pressure.

The role of angiotensin II (Ang II), a hormone involved in regulating blood pressure and fluid balance, and its receptor known as “AT1,” as well as the physiologically important lipid molecule prostaglandin E2 (PGE2) and its receptor “EP1,” in hypertension and neurotoxicity, is well-recognized. However, their specific involvement in hypertension and emotional/cognitive impairment caused by high salt intake remains unclear.

In pursuit of this objective, a comprehensive examination was conducted by a team of researchers from Japan and published in the esteemed British Journal of Pharmacology. This recent study meticulously investigated the various factors associated with hypertension induced by HS, while also exploring its impact on emotional and cognitive functions. The findings elucidate the intricate interplay between Ang II-AT1 and PGE2-EP1, which contribute to the development of emotional and cognitive impairment in individuals affected by hypertension.

“Excessive salt intake is considered a risk factor for hypertension, cognitive dysfunction, and dementia,” says Author Hisayoshi Kubota.

“However, studies focusing on the interaction between the peripheral and central nervous system have not sufficiently investigated this association.”

Based on the available research data, excessive levels of phosphates have been identified as the primary cause of emotional and cognitive consequences associated with the protein “tau.” This finding is particularly significant as tau is a crucial protein involved in Alzheimer’s disease.

In a study conducted on laboratory mice, the research team administered an HS solution (2% NaCl in drinking water) to the mice for a period of 12 weeks while closely monitoring their blood pressure. To assess the impact of HS intake on emotional and cognitive function, as well as tau phosphorylation, the researchers focused on two critical regions of the mouse brain—the prefrontal cortex and the hippocampus. Professor Mouri further explains that the study also investigated the involvement of the Ang II-AT1 and PGE2-EP1 systems in hypertension induced by HS and the resulting neuronal and behavioral impairment.

The findings of this study are highly promising and provide encouraging results. The experimental mice exhibited remarkable biochemical alterations in their brains, indicating potential avenues for therapeutic intervention. At the molecular level, the researchers observed two significant changes. Firstly, there was an increase in the addition of phosphates to tau, which is a protein associated with neurodegenerative diseases. Secondly, they noted a decrease in the phosphate groups linked to a key enzyme called “CaMKII,” which plays a crucial role in brain signaling.

Furthermore, alterations in the levels of “PSD95,” a protein critical for the organization and function of brain synapses (the connections between brain cells), were also observed. These changes highlight the potential impact of hypertension on cognitive function.

Interestingly, the administration of the antihypertensive drug “losartan” reversed the observed biochemical changes. This suggests that losartan may have a beneficial effect in mitigating the detrimental effects of hypertension on the brain. Additionally, a similar reversal of the biochemical changes was observed when the EP1 gene was knocked out, further supporting the notion that the angiotensin II-AT1 and prostaglandin E2-EP1 systems could serve as promising therapeutic targets for hypertension-induced dementia.

“This study is of particular social and economic importance because the annual social cost of dementia treatment in Japan is surging like never before Therefore, developing preventive and therapeutic drugs for dementia seems critical for Japan’s rapidly aging population,” adds the author.

In order to prevent negative health consequences, the World Health Organization recommends limiting daily salt intake to less than 5 grams.

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