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

Abstract

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.

Abnormal Cerebrovascular Reactivity and Functional Connectivity Caused by White Matter Hyperintensity Contribute to Cognitive Decline

“…Traditionally, the breath holding index of middle cerebral arteries via transcranial doppler ultrasound is useful for measuring global CVR, and previous researchers found that the global CVR decreased as the WMH aggravated (Bakker et al, 1999;Fu et al, 2006). Resting fMRI technique has been used to detect the regional CVR in CSVD (Ni et al, 2021) and hypertensive patients (Ma et al, 2021). Decreased CVR has been shown across different cortical regions, including the frontal cortex, parietal cortex, and occipital cortex in WMH patient (Ni et al, 2021).…”

“…It can be used to calculate the temporal correlations among intrinsic fluctuations of bloodoxygen-level-dependent (BOLD) signals across functionally related areas, also known as functional connectivity (FC) (Damoiseaux et al, 2006). Additionally, rs-fMRI also offers a good option to obtain a quantitative mapping of cerebrovascular reactivity (CVR) (Golestani et al, 2016b;Taneja et al, 2019), which has been applied in several diseases, including carotid artery stenosis/occlusion, Moyamoya disease (De Vis et al, 2018;Ryan et al, 2018;Taneja et al, 2019), cerebral small vessel disease (CSVD) (Ni et al, 2021), and hypertension (Ma et al, 2021). CVR is the change of cerebral blood flow in response to a vasodilatory challenge and reflects underlying vascular dysfunction or pathology (Sobczyk et al, 2014).…”