Association of Blood Pressure Lowering Intensity With White Matter Network Integrity in Patients With Cerebral Small Vessel Disease

Abstract

Background and Objectives:Diffusion tensor imaging (DTI) networks integrate damage from a variety of pathological processes in cerebral small vessel disease (SVD) and may be a sensitive marker to detect treatment effects. We determined whether brain network analysis could detect treatment effects in the PRESERVE trial dataset, in which intensive versus standard blood pressure (BP) lowering was compared. The primary endpoint of DTI had not shown treatment differences.Methods:Subjects with lacunar stroke were randomised to standard (systolic 130-140 mmHg), or intensive (systolic </= 125 mmHg) BP lowering and followed for 2-years with MRI at baseline and at 2 years. Graph-theory based metrics were derived from DTI data to produce a measure of network integrity weighted global efficiency, and compared to individual MRI markers of DTI, brain volume and white matter hyperintensities.Results:Data were available in 82 subjects; standard n=40 (mean age 66.3±1.5), intensive n=42 (69.6±1.0). Mean (SD) systolic blood pressure was reduced by 13(14) and 23(23) mmHg in the standard and intensive groups respectively (P<0.001 between groups). Significant differences in diffusion network metrics were found, with improved network integrity (weighted global efficiency, P=0.002) seen with intensive BP lowering. In contrast there were no significant differences in individual MRI markers including DTI histogram metrics, brain volume or white matter hyperintensities.Discussion:Brain network analysis may be a sensitive surrogate marker in trials in small vessel disease. This work suggests that measures of brain network efficiency may be more sensitive to the effects of blood pressure control treatment than conventional DTI metrics.Trial Registration Information:The trial is registered with the ISRCTN Registry (ISRCTN37694103; //doi.org/10.1186/ISRCTN37694103) and the NIHR Clinical Research Network (CRN 10962; //public-odp.nihr.ac.uk/QvAJAXZfc/opendoc.htm?document=crncc_users%5Cfind%20a%20clinical%20research%20study.qvw&lang=en-US&host=QVS%40crn-prod-odp-pu&anonymous=true)Classification of Evidence:This study provides Class II evidence that intensive BP lowering in patients with small vessel disease results in improved brain network function when assessed by DTI based brain network metrics.

Burden of cerebral small vessel disease and changes of diastolic blood pressure affect clinical outcome after acute ischemic stroke

“…Assessment of CMB was performed on T2*-weighted gradient-recalled echo (T2*-GRE) scans or on susceptibility-weighted images (SWI). Lacunes were defined as CSF-filled cavities with a diameter of at least 3 mm 29 . cSVD burden was visually rated on MR scans and divided in absent/mild cSVD (Fazekas 0–1, no CMB) and moderate/severe cSVD (Fazekas 2–3 and/or ≥ 1 CMB).…”

Burden of cerebral small vessel disease and changes of diastolic blood pressure affect clinical outcome after acute ischemic stroke

“…Assessment of CMB was performed on T2*-weighted gradient-recalled echo (T2*-GRE) scans or on susceptibilityweighted images (SWI). Lacunes were de ned as CSF-lled cavities with a diameter of at least 3mm 30 . cSVD burden was visually rated on MR scans and divided in absent/ mild cSVD (Fazekas 0-1, no CMB) and moderate/severe cSVD (Fazekas 2-3 and/or ≥ 1 CMB).…”

Cerebrovascular health mediates processing speed change through anterior white matter alterations: A UK Biobank Study

“…However, WMHs reflect an advanced stage of white matter injury and it's unlikely that intervention at this stage would have a beneficial impact on brain health or cognitive function 5 . Diffusion imaging allows for microscale white matter changes to be mapped, which reflect a much earlier stage of injury that may be more receptive to intervention, relative to their macroscale counterparts 6 . These microscale measures of white matter integrity (WMI) may be particularly valuable when applied to studying middle-age populations in the early stages of cerebrovascular burden, where damage is likely subtle and difficult to detect.…”