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Mechanisms underlying cognitive impairment (CI) in hypertensive patients remain relatively unclear. The present study aimed to explore the relationship among serum exosomal microRNAs (miRNAs), cerebrovascular reactivity (CVR), and cognitive function in hypertensive patients. Seventy-three hypertensive patients with CI (HT-CI), 67 hypertensive patients with normal cognition (HT-NC), and 37 healthy controls underwent identification of exosomal miRNA, multimodal magnetic resonance imaging (MRI) scans, and neuropsychological tests. CVR mapping was investigated based on resting-state functional MRI data. Compared with healthy subjects and HT-NC subjects, HT-CI subjects displayed decreased serum exosomal miRNA-330-3p. The group difference of CVR was mainly found in the left frontal lobe and demonstrated that HT-CI group had a lower CVR than both HT-NC group and control group. Furthermore, both the CVR in the left medial superior frontal gyrus and the miRNA-330-3p level were significantly correlated with executive function ( r  = −0.275,  P  = 0.021, and  r  = −0.246,  P  = 0.04, respectively) in HT-CI subjects, and the CVR was significantly correlated with the miRNA-330-3p level ( r  = 0.246,  P  = 0.040). Notably, path analysis showed that the CVR mediated the association between miRNA-330-3p and executive function. In conclusion, decreased miRNA-330-3p might contribute to CI in hypertensive patients by decreasing frontal CVR and could be a biomarker of early diagnosis.

Exosomal MicroRNAs Contribute to Cognitive Impairment in Hypertensive Patients by Decreasing Frontal Cerebrovascular Reactivity