Research Paper Volume 13, Issue 18 pp 22030—22039

Cerebral small vessel disease, systemic vascular characteristics and potential therapeutic targets

Salim Elyas1,2, , Damilola Adingupu1, , Kunihiko Aizawa1, , Francesco Casanova1, , Kim Gooding1, , Jonathan Fulford1, , Dave Mawson1, , Phillip E. Gates1, , Angela C. Shore1, , David Strain1,2, ,

  • 1 Institute of Biomedical and Clinical Science and NIHR Exeter Clinical Research Facility, University of Exeter Medical School, Exeter EX2 5AX, UK
  • 2 Academic Department of Healthcare for Older People, Royal Devon and Exeter NHS Foundation Trust, Exeter EX2 5DW, UK

Received: April 6, 2021       Accepted: August 31, 2021       Published: September 22, 2021
How to Cite

Copyright: © 2021 Elyas et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Introduction: Cerebral small vessel disease (SVD) is prevalent in the elderly population and is associated with increased risk of dementia, stroke and disability. Currently there are no clear targets or strategies for the treatment of cerebral SVD. We set out to identify modifiable vascular treatment targets.

Patients and Methods: 112 participants with and without a history of CVD underwent macrovascular, microvascular and endothelial function tests and an MRI head scan.

Results: Increased carotid intima media thickness and carotid-femoral pulse wave velocity were associated with cerebral WMH (β=1·1 p=0·001 and β=1·66, p<0·0001 respectively). Adjusted cerebral resistance index (p=0·03) and brachial flow mediated dilation time to peak (p=0·001) were associated with the severity of cerebral WMH independent of age and sex. Post occlusive reactive hyperaemia time as a measure of microvascular reactivity was associated with WMH after adjustment for age and sex (p=0·03). Ankle Brachial Pressure Index and urinary albumin excretion rate predicted the severity of cerebral WMH (p=0·02 and 0·01 respectively). Age and hypertension were the most important risk factors for WMH severity (p< 0·0001).

Discussion: In addition to hypertension, microalbuminuria, arterial stiffness, vascular reactivity and cerebrovascular resistance could be potential treatment targets to halt the development or progression of cerebral SVD.


Ach: Acetylecholine; ABPI: Ankle Brachial Pressure Index; BP: Blood Pressure; CVD: Cerebrovascular diseases; EDV: End Diastolic Velocity; FMD: Flow Mediated Dilation; IMT: Intima Media Thickness; MAP: Mean Arterial Pressure; cMAP: Central Mean Arterial Pressure; MFV: Mean Flow Velocity; MRI: Magnetic Resonance Imaging; PORH: Post Occlusive Reactive Hyperaemia; PSV: Peak Systolic Velocity; PWV: Pulse Wave Velocity; SNP: Sodium Nitroprusside; SVD: Small vessel disease; TCD: Transcranial Doppler; TIA: Transient Ischaemic Attack; WMH: White Matter Hyperintensities.