Abstract Background and aims Excess dietary sodium intake is a major contributor to hypertension and vascular disease and has recently been implicated in cerebral small vessel disease and vascular cognitive impairment through mechanisms beyond blood pressure, including endothelial dysfunction and tau pathology. Despite clear recommendations, sodium consumption remains excessively high due to poor long-term adherence. Substitution of regular salt with plant-based alternatives derived from Salicornia, naturally lower in sodium and enriched in potassium, fiber, and polyphenols, may offer a feasible and sustainable strategy to improve cerebrovascular health and delay cognitive decline. Methods To determine whether reducing dietary sodium by substituting Salicornia-derived vegetable salt (50% less sodium) improves neurovascular function and cognitive outcomes. Secondary aims include identifying vascular and molecular biomarkers and estimating potential population-level effects. Results The project combines preclinical and clinical approaches. In spontaneously hypertensive rats, vegetable salt will be compared with regular salt, assessing cognition, vascular stiffness, neuroimaging, histopathology, and proteomic biomarkers. A prospective, randomized, open-label pilot trial in individuals ≥60 years with transient ischemic attack, small vessel cerebrovascular disease, or cognitive impairment will compare Salicornia salt versus conventional salt over six months. Outcomes include 24-hour urinary sodium, blood pressure, pulse wave velocity, and cognitive performance (MoCA). The project also includes discovery of proteomic biomarkers and population-level analyses using electronic health records to investigate hypertension, treatments, stroke, and cognitive outcomes. Conclusions Primary outcomes include cognitive performance and vascular aging markers. Secondary outcomes include blood pressure control, sodium reduction, molecular signatures, and sex-specific effects. Conflict of interest
Ramírez et al. (Fri,) studied this question.