Abstract
Asymptomatic (or “silent”) manifestations of cerebral small vessel disease (CSVD) are widely recognized through incidental findings of white matter hyperintensities (WMHs) as a result of magnetic resonance imaging (MRI). This study aims to examine the potential associations of surrogate markers for the evaluation of white matter integrity in CSVD among asymptomatic individuals through a battery of profiling involving QRISK2 cardiocerebrovascular risk prediction, neuroimaging, neurocognitive evaluation, and microparticles (MPs) titers. Sixty asymptomatic subjects (mean age: 39.83 ± 11.50 years) with low to moderate QRISK2 scores were recruited and underwent neurocognitive evaluation for memory and cognitive performance, peripheral venous blood collection for enumeration of selected MPs subpopulations, and 3T MRI brain scan with specific diffusion MRI (dMRI) sequences inclusive of diffusion tensor imaging (DTI). WMHs were detected in 20 subjects (33%). Older subjects (mean age: 46.00 ± 12.00 years) had higher WMHs prevalence, associated with higher QRISK2 score and reduced processing speed. They also had significantly higher mean percentage of platelet (CD62P)- and leukocyte (CD62L)-derived MPs. No association was found between reduced white matter integrity—especially at the left superior longitudinal fasciculus (LSLF)—with age and neurocognitive function; however, LSLF was associated with higher QRISK2 score, total MPs, and CD62L- and endothelial cell-derived MPs (CD146). Therefore, this study establishes these multimodal associations as potential surrogate markers for “silent” CSVD manifestations in the well-characterized cardiocerebrovascular demographic of relatively young, neurologically asymptomatic adults. Furthermore, to the best of our knowledge, this study is the first to exhibit elevated MP counts in asymptomatic CSVD (i.e., CD62P and CD62L), which warrants further delineation.
Highlights
Cerebral small vessel disease (CSVD) consists of a spectrum of histopathological, clinical, and imaging abnormalities linked to pathology in the microvasculature of small penetrating arteries and arterioles (50–500 μm) in brain irrigating subcortical structures [1,2,3].Generally, it results in brain parenchyma injuries, which are invariably associated with distal leptomeningeal and intracerebral vessel pathology, affecting deep cerebral white matter integrity [4]
We found that white matter hyperintensities (WMHs)− subjects had higher mean scores of perceptual reasoning index (PRI), working memory index (WMI), and processing speed index (PSI) than
It is of interest that we observed that the fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) of left superior longitudinal fasciculus (LSLF) had significant linear relationships with CD62L, CD146, and total MP
Summary
Cerebral small vessel disease (CSVD) consists of a spectrum of histopathological, clinical, and imaging abnormalities linked to pathology in the microvasculature of small penetrating arteries and arterioles (50–500 μm) in brain irrigating subcortical structures [1,2,3]. It results in brain parenchyma injuries, which are invariably associated with distal leptomeningeal and intracerebral vessel pathology, affecting deep cerebral white matter integrity [4]. In magnetic resonance imaging (MRI), the micro-changes in white matter can be seen as WMHs that represent more diffuse areas of white matter lesions [9]. Advancements in diffusion MRI (dMRI) techniques have offered potential new information on disease pathomechanisms as well as surrogate markers for disease onset and progression, and new therapy evaluations using newer magnetic resonance (MR)-based diffusion tensor imaging (DTI) modalities [11,12]
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