Circulating metabolomics profiling reveals novel pathways associated with cognitive decline in patients with hypertension

Abstract

Background: Hypertension is a significant risk factor for cardiovascular disease, and it is associated with dementia, including Alzheimer’s disease (AD). Although it may be correlated with AD in terms of symptoms, the link between hypertension and AD pathological biomarkers, and the potential underlying mechanism of hypertension with cognitive decline, are still not well understood. Methods: The Mini-Mental State Examination (MMSE) scores were used to evaluate cognitive function. Enzyme-linked immunosorbent assays were used to examine plasma amyloid-beta (Aβ) 40 , Aβ 42 , and tau concentration in hypertensive patients. Metabolomics and metagenomics were performed to identify the significantly changed circulating metabolites and microbiota between healthy individuals and hypertensive patients. Pearson’s correlation was used to examine the association between cognitive indicators and differential metabolites. Results: We found significantly decreased MMSE scores, elevated plasma Aβ 40 , and decreased Aβ 42 /Aβ 40 ratio in hypertensive patients, which are critically associated with AD pathology. Based on metabolomics, we found that significantly altered metabolites in the plasma of hypertensive patients were enriched in the benzoate degradation and phenylpropanoid biosynthesis pathways, and they were also correlated with changes in MMSE scores and Aβ 42 /Aβ 40 ratio. In addition, metabolomics signaling pathway analysis suggested that microbial metabolism was altered in hypertensive patients. We also identified altered blood microbiota in hypertensive patients compared with the controls. Conclusions: Our study provides a novel metabolic and microbial mechanism, which may underlie the cognitive impairment in hypertensive patients.