Elevated Circulating Microparticle Subpopulations in Incidental Cerebral White Matter Hyperintensities: A Multimodal Study

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.

Reduced cerebral vascular fractal dimension among asymptomatic individuals as a potential biomarker for cerebral small vessel disease

“…The data for this study were derived from a well-characterized cohort established from a recent study on CSVD based at a single centre, Hospital Universiti Sains Malaysia (HUSM), Kubang Kerian, Kelantan 32 . Approximately 96% of this region is predominated by Malay.…”

“…MRI acquisition was performed at 3.0 Tesla using a 32-channel head coil MRI scanner (Philips Achieva) with the b -value of 1000 s/mm 2 . The MRI acquisition parameters are as the followings; 3D-T1: echo time (TE) = 10 ms, repetition time (TR) = 678 ms, reconstruction matrix = 512 × 512 × 40, field of view (FOV) = 230 mm, voxel size = 0.45 mm × 0.45 mm, slice spacing = 0 mm, slice thickness = 2.5 mm, flip angle = 70°, and 180 contiguous sagittal slices orientation; T2: TE = 80 ms, TR = 3000 ms, reconstruction matrix = 512 × 512 × 24, FOV = 230 mm, voxel size = 0.45 × 0.45, slice spacing = 1.0 mm, slice thickness = 2.5 mm, and flip angle = 90°; 3D-fluid attenuated inversion recovery (FLAIR): TE = 125 ms, TR = 11,000 ms, TI = 2800 ms, reconstruction matrix = 512 × 512 × 24, FOV = 230 mm, voxel size = 0.45 mm × 0.45 mm, slice spacing = 0 mm, slice thickness = 2.5 mm, flip angle = 90°, and 170 contiguous sagittal slices orientation 32 . The image of the circle of Willis and its tributaries were captured using 3D-TOF MRA with the following parameters: TE = 3.5 ms, TR = 20 ms, reconstruction matrix = 720 × 720 × 200, FOV 200 mm, voxel size = 0.28 mm × 0.28 mm, slice spacing = 1.0 mm, slice thickness = 0.6 mm, flip angle = 20°.…”

Neuroprotective Potentials of Honey for Cerebral Small Vessel Disease

“…(1) the occlusion of small cerebral penetrating arteries and (2) arteriosclerosis or lipohyalinosis (i.e., thickening and/or damage of the arteriolar wall) [42]. Nevertheless, it is now accepted that the majority of macrostructural changes observed from neuroimaging manifestations of CSVD are plausibly due to underlying meso-structural responses, such as obstruction of cerebral microcirculation flow [43]. In this case, the arteriolar narrowing and/or occlusion may result in a symptomatic ischemic event, as seen in small lacunar infarcts in the traditional CSVD spectrum, or simply occult.…”

“…Besides modulating hypertension, a previous in vitro study showed the inhibitory effect of natural honey on platelet aggregation and blood coagulation [151]. Whereby, increased platelet aggregation and hypercoagulation have been proposed as an emerging molecular mechanism of CSVD [43,114]. Interestingly, in a recent in vivo study, honey has been found to exhibit an antiplatelet effect by increasing bleeding time when a group of mice was given commercial honey for 12 days as compared to that aspirin [164].…”

Linear brain measurement: a new screening method for cognitive impairment in elderly patients with cerebral small vessel disease

“…Greater multimodal and advanced magnetic resonance imaging (MRI) technologies including brain volume, diffusion tensor imaging (DTI), functional magnetic resonance imaging (fMRI) have been applied in the evaluation of cognitive function of CSVD patients ( 7 ). Screening test for cognitive impairment in elderly CSVD patients by means of imaging techniques is a promising approach.…”