Research
Using genetic and imaging techniques to understand the pathogenesis of ischaemic stroke
I use molecular genetic and neuroimaging (MRI and Transcranial Doppler) techniques to investigate the pathogenesis of, and develop treatments for, cerebrovascular disease.
A particular interest is in cerebral small vessel disease, a major cause of stroke and the major cause of vascular cognitive impairment; here we are studying genetic determinants (for both monogenic and polygenic disease), the mechanisms of cognitive decline using advanced multimodal MRI, and evaluating new therapeutic approaches. Our imaging projects involve the application of MRI and PET to look at blood brain barrier leakage and glial activation (neuroinflammation in man, and the use of diffusion tensor MRI to determine how vascular damage leads to white matter damage and cognitive impairment.
I am involved in a number of international studies of stroke genetics including the WTCCC2 ischaemic stroke study which we led, METASTROKE which we established and MEGASTROKE all as part of the the International Stroke Genetics Consortium. I run a National clinical referral service for patients with the monogenic from of stroke CADASIL.
Publications
Most recent publications are listed on PubMed.
1: Lawrence AJ, Zeestraten EA, Benjamin P, Lambert CP, Morris RG, Barrick TR, Markus HS. Longitudinal decline in structural networks predicts dementia in cerebral small vessel disease. Neurology. 2018 May 22;90(21):e1898-e1910. doi: 10.1212/WNL.0000000000005551. Epub 2018 Apr 25. PubMed PMID: 29695593; PubMed Central PMCID: PMC5962914.
2: Croall ID, Tozer DJ, Moynihan B, Khan U, O'Brien JT, Morris RG, Cambridge VC, Barrick TR, Blamire AM, Ford GA, Markus HS; PRESERVE Study Team. Effect of Standard vs Intensive Blood Pressure Control on Cerebral Blood Flow in Small Vessel Disease: The PRESERVE Randomized Clinical Trial. JAMA Neurol. 2018 Jun 1;75(6):720-727. doi: 10.1001/jamaneurol.2017.5153. PubMed PMID: 29507944.
3: Larsson SC, Traylor M, Malik R, Dichgans M, Burgess S, Markus HS; CoSTREAM Consortium, on behalf of the International Genomics of Alzheimer’s Project. Modifiable pathways in Alzheimer's disease: Mendelian randomisation analysis. BMJ. 2017 Dec 6;359:j5375. doi: 10.1136/bmj.j5375. PubMed PMID: 29212772; PubMed Central PMCID: PMC5717765.
4: Larsson SC, Wallin A, Wolk A, Markus HS. Differing association of alcoholconsumption with different stroke types: a systematic review and meta-analysis. BMC Med. 2016 Nov 24;14(1):178. Review. PubMed PMID: 27881167; PubMed Central PMCID: PMC5121939.
5: Lambert C, Benjamin P, Zeestraten E, Lawrence AJ, Barrick TR, Markus HS. Longitudinal patterns of leukoaraiosis and brain atrophy in symptomatic small vessel disease. Brain. 2016 Apr;139(Pt 4):1136-51. doi: 10.1093/brain/aww009. Epub 2016 Mar 1. PubMed PMID: 26936939; PubMed Central PMCID: PMC4806220.
6: Traylor M, Malik R, Nalls MA, Cotlarciuc I, Radmanesh F, Thorleifsson G,Hanscombe KB, Langefeld C, Saleheen D, Rost NS, Yet I, Spector TD, Bell JT,Hannon E, Mill J, Chauhan G, Debette S, Bis JC, Longstreth WT Jr, Ikram MA,Launer LJ, Seshadri S; METASTROKE, UK Young Lacunar DNA Study, NINDS Stroke Genetics Network, Neurology Working Group of the CHARGE Consortium, Hamilton-Bruce MA, Jimenez-Conde J, Cole JW, Schmidt R, Słowik A, Lemmens R, Lindgren A, Melander O, Grewal RP, Sacco RL, Rundek T, Rexrode K, Arnett DK, Johnson JA, Benavente OR, Wasssertheil-Smoller S, Lee JM, Pulit SL, Wong Q, Rich SS, de Bakker PI, McArdle PF, Woo D, Anderson CD, Xu H, Heitsch L, Fornage M, Jern C, Stefansson K, Thorsteinsdottir U, Gretarsdottir S, Lewis CM, Sharma P, Sudlow CL, Rothwell PM, Boncoraglio GB, Thijs V, Levi C, Meschia JF, Rosand J, Kittner SJ, Mitchell BD, Dichgans M, Worrall BB, Markus HS; International Stroke. Genetics Consortium. Genetic variation at 16q24.2 is associated with small vessel stroke. Ann Neurol. 2017 Mar;81(3):383-394. doi: 10.1002/ana.24840. PubMed PMID: 27997041; PubMed Central PMCID: PMC5366092.
