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Research Theme Neurons, Circuits and Networks Lifelong Brain Development and Brain Ageing
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Professor Hugh Markus

University Position
Professor

Interests

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. I am involved in a number of international studies of stroke genetics including the WTCCC2 ischaemic stroke study and the International Stroke Genetics Consortium. I run a National clinical referral service for patients with the monogenic from of stroke CADASIL. My research is currently funded by the Wellcome Trust, NIHR, British Heart Foundation, Stroke Association, Alzheimers Research UK and the EU FP7.

Associated News Items

Key Publications

Association of Baseline Metabolomic Profiles With Incident Stroke and Dementia and With Imaging Markers of Cerebral Small Vessel Disease.

DOI: http://doi.org/10.1212/WNL.0000000000207458
Journal: Neurology
E-pub date: 1 Aug 2023
Authors: EL Harshfield, HS Markus

Metabolomic profiling in small vessel disease identifies multiple associations with disease severity.

DOI: http://doi.org/10.1093/brain/awac041
Journal: Brain
E-pub date: 29 Jul 2022
Authors: EL Harshfield, CJ Sands, AM Tuladhar, FE de Leeuw, MR Lewis, HS Markus

In vivo neuroinflammation and cerebral small vessel disease in mild cognitive impairment and Alzheimer’s disease.

DOI: http://doi.org/10.1136/jnnp-2020-323894
Journal: J Neurol Neurosurg Psychiatry
E-pub date: 11 Sep 2020
Authors: A Low, E Mak, M Malpetti, L Passamonti, N Nicastro, JD Stefaniak, G Savulich, L Chouliaras, L Su, JB Rowe, HS Markus, JT O'Brien

Inflammation and cerebral small vessel disease: A systematic review.

DOI: http://doi.org/10.1016/j.arr.2019.100916
Journal: Ageing Res Rev
E-pub date: 31 Aug 2019
Authors: A Low, E Mak, JB Rowe, HS Markus, JT O'Brien

PET imaging of the neurovascular interface in cerebrovascular disease.

DOI: http://doi.org/10.1038/nrneurol.2017.129
Journal: Nat Rev Neurol
E-pub date: 1 Nov 2017
Authors: NR Evans, JM Tarkin, JR Buscombe, HS Markus, JHF Rudd, EA Warburton

Publications

Are Central and Systemic Inflammation associated with Fatigue in Cerebral Small Vessel Disease?

DOI: http://doi.org/10.1177/17474930241245613
Journal: Int J Stroke
E-pub date: 1 Jul 2024
Authors: AA Jolly, RB Brown, DJ Tozer, YT Hong, TD Fryer, F Aigbirhio, J O'brien, HS Markus

Sleep Characteristics and Risk of Stroke and Dementia: An Observational and Mendelian Randomization Study.

DOI: http://doi.org/10.1212/WNL.0000000000209141
Journal: Neurology
E-pub date: 12 Mar 2024
Authors: C Guo, EL Harshfield, HS Markus

Immune regulation and blood-brain barrier permeability in cerebral small vessel disease: study protocol of the INflammation and Small Vessel Disease (INSVD) study – a multicentre prospective cohort study.

DOI: http://doi.org/10.1136/bmjopen-2024-084303
Journal: BMJ Open
E-pub date: 26 Feb 2024
Authors: A Low, S van Winden, L Cai, RPC Kessels, MC Maas, RG Morris, M Nus, DJ Tozer, A Tuladhar, A van der Kolk, R Wolters, Z Mallat, NP Riksen, H Markus, F-E de Leeuw

Contribution of Conventional Cardiovascular Risk Factors to Brain White Matter Hyperintensities.

DOI: http://doi.org/10.1161/JAHA.123.030676
Journal: J Am Heart Assoc
E-pub date: 18 Jul 2023
Authors: F Koohi, EL Harshfield, HS Markus

Do Regions of Increased Inflammation Progress to New White Matter Hyperintensities?: A Longitudinal Positron Emission Tomography-Magnetic Resonance Imaging Study.

DOI: http://doi.org/10.1161/STROKEAHA.122.039517
Journal: Stroke
E-pub date: 1 Feb 2023
Authors: DJ Tozer, RB Brown, J Walsh, YT Hong, GB Williams, JT O'Brien, FI Aigbirhio, TD Fryer, HS Markus

MINocyclinE to Reduce inflammation and blood brain barrier leakage in small Vessel diseAse (MINERVA) trial study protocol.

DOI: http://doi.org/10.1177/23969873221100338
Journal: Eur Stroke J
E-pub date: 1 Sep 2022
Authors: RB Brown, DJ Tozer, L Loubière, YT Hong, TD Fryer, GB Williams, MJ Graves, FI Aigbirhio, JT O'Brien, HS Markus

Fluid-attenuated inversion recovery magnetic resonance imaging textural features as sensitive markers of white matter damage in midlife adults.

DOI: http://doi.org/10.1093/braincomms/fcac116
Journal: Brain Commun
E-pub date: 1 Aug 2022
Authors: M-E Dounavi, A Low, G Muniz-Terrera, K Ritchie, CW Ritchie, L Su, HS Markus, JT O'Brien

Metabolic associations with stroke, dementia, and imaging markers of cerebral small vessel disease: a comprehensive metabolomics study

DOI: http://doi.org/10.1101/2022.03.24.22272911
Journal:
E-pub date: 1 Aug 2022
Authors: E Harshfield, H Markus

Both vascular risk factors and common genetic variants influence penetrance of variants causing monogenic stroke

DOI: http://doi.org/10.1101/2022.05.24.22275509
Journal:
E-pub date: 1 Aug 2022
Authors: BPH Cho, E Harshfield, M Al-Thani, D Tozer, S Bell, H Markus

CAIDE dementia risk score relates to severity and progression of cerebral small vessel disease in healthy midlife adults: the PREVENT-Dementia study.

DOI: http://doi.org/10.1136/jnnp-2021-327462
Journal: J Neurol Neurosurg Psychiatry
E-pub date: 1 May 2022
Authors: A Low, MA Prats-Sedano, JD Stefaniak, EF McKiernan, SF Carter, M-E Douvani, E Mak, L Su, O Stupart, G Muniz, K Ritchie, CW Ritchie, HS Markus, JT O'Brien

Central obesity is selectively associated with cerebral gray matter atrophy in 15,634 subjects in the UK Biobank.

DOI: http://doi.org/10.1038/s41366-021-00992-2
Journal: Int J Obes (Lond)
E-pub date: 1 May 2022
Authors: C-P Pflanz, DJ Tozer, EL Harshfield, J Tay, S Farooqi, HS Markus

Rate of, and risk factors for, white matter hyperintensity growth: a systematic review and meta-analysis with implications for clinical trial design.

DOI: http://doi.org/10.1136/jnnp-2021-326569
Journal: J Neurol Neurosurg Psychiatry
E-pub date: 1 Dec 2021
Authors: R Brown, A Low, HS Markus

White Matter Hyperintensities and Cerebral Microbleeds in Ataxia-Telangiectasia.

DOI: http://doi.org/10.1212/NXG.0000000000000640
Journal: Neurol Genet
E-pub date: 1 Dec 2021
Authors: MY Tiet, S Nannoni, D Scoffings, K Schon, R Horvath, HS Markus, AE Hensiek

NOTCH3 variants are more common than expected in the general population and associated with stroke and vascular dementia: an analysis of 200 000 participants.

DOI: http://doi.org/10.1136/jnnp-2020-325838
Journal: J Neurol Neurosurg Psychiatry
E-pub date: 1 Jul 2021
Authors: BPH Cho, S Nannoni, EL Harshfield, D Tozer, S Gräf, S Bell, HS Markus

Microglial activation and blood-brain barrier permeability in cerebral small vessel disease.

DOI: http://doi.org/10.1093/brain/awab003
Journal: Brain
E-pub date: 22 Jun 2021
Authors: J Walsh, DJ Tozer, H Sari, YT Hong, A Drazyk, G Williams, NJ Shah, JT O'Brien, FI Aigbirhio, G Rosenberg, TD Fryer, HS Markus

Metabolomic profiling in small vessel disease identifies multiple associations with disease severity

DOI: http://doi.org/10.1101/2021.05.13.21257190
Journal:
E-pub date: 14 May 2021
Authors: EL Harshfield, CJ Sands, AM Tuladhar, F-E de Leeuw, MR Lewis, HS Markus

Diabetes Mellitus, Glycemic Traits, and Cerebrovascular Disease: A Mendelian Randomization Study.

DOI: http://doi.org/10.1212/WNL.0000000000011555
Journal: Neurology
E-pub date: 30 Mar 2021
Authors: MK Georgakis, EL Harshfield, R Malik, N Franceschini, C Langenberg, NJ Wareham, HS Markus, M Dichgans

Modifiable Lifestyle Factors and Risk of Stroke: A Mendelian Randomization Analysis.

DOI: http://doi.org/10.1161/STROKEAHA.120.031710
Journal: Stroke
E-pub date: 1 Mar 2021
Authors: EL Harshfield, MK Georgakis, R Malik, M Dichgans, HS Markus

Inherited risk of dementia and the progression of cerebral small vessel disease and inflammatory markers in cognitively healthy midlife adults: the PREVENT-Dementia study.

DOI: http://doi.org/10.1016/j.neurobiolaging.2020.10.029
Journal: Neurobiol Aging
E-pub date: 1 Feb 2021
Authors: A Low, L Su, JD Stefaniak, E Mak, M-E Dounavi, G Muniz-Terrera, K Ritchie, CW Ritchie, HS Markus, JT O'Brien

Is periodontitis a risk factor for ischaemic stroke, coronary artery disease and subclinical atherosclerosis? A Mendelian randomization study.

DOI: http://doi.org/10.1016/j.atherosclerosis.2020.09.029
Journal: Atherosclerosis
E-pub date: 1 Nov 2020
Authors: S Bell, JT Gibson, EL Harshfield, HS Markus

Peak Width of Skeletonized Mean Diffusivity as a Marker of Diffuse Cerebrovascular Damage.

DOI: http://doi.org/10.3389/fnins.2020.00238
Journal: Front Neurosci
E-pub date: 1 Aug 2020
Authors: A Low, E Mak, JD Stefaniak, M Malpetti, N Nicastro, G Savulich, L Chouliaras, HS Markus, JB Rowe, JT O'Brien

Modifiable lifestyle factors and risk of stroke: a Mendelian randomization analysis

DOI: http://doi.org/10.1101/2020.03.17.20037549
Journal:
E-pub date: 1 Aug 2020
Authors: EL Harshfield, MK Georgakis, R Malik, M Dichgans, HS Markus

NOTCH3 variants are common in the general population and associated with stroke and vascular dementia: an analysis of 200,000 participants

DOI: http://doi.org/10.1101/2020.12.14.20248151
Journal:
E-pub date: 1 Aug 2020
Authors: BPH Cho, S Nannoni, E Harshfield, D Tozer, S Gräf, S Bell, H Markus

The role of haematological traits in risk of ischaemic stroke and its subtypes.

DOI: http://doi.org/10.1093/brain/awz362
Journal: Brain
E-pub date: 1 Jan 2020
Authors: EL Harshfield, MC Sims, M Traylor, WH Ouwehand, HS Markus

Diabetes mellitus, glycemic traits, and cerebrovascular disease: a Mendelian randomization study

DOI: http://doi.org/10.1101/2019.12.27.19015834
Journal:
E-pub date: 1 Aug 2019
Authors: M Georgakis, E Harshfield, R Malik, N Franceschini, C Langenberg, N Wareham, H Markus, M Dichgans

Stenting for symptomatic vertebral artery stenosis: a preplanned pooled individual patient data analysis.

DOI: http://doi.org/10.1016/S1474-4422(19)30149-8
Journal: Lancet Neurol
E-pub date: 1 Jul 2019
Authors: HS Markus, EL Harshfield, A Compter, W Kuker, LJ Kappelle, A Clifton, HB van der Worp, P Rothwell, A Algra, Vertebral Stenosis Trialists' Collaboration

The role of haematological traits in stroke and its subtypes

DOI: http://doi.org/10.1177/2396987319845560
Journal: European Stroke Journal
E-pub date: 1 May 2019
Authors: E Harshfield, M Sims, M Traylor, W Astle, W Ouwehand, H Markus

Investigating the causal role of haematological traits on stroke and its subtypes

DOI: http://doi.org/10.1212/nxg.0000000000000325
Journal: Neurology Genetics
E-pub date: 1 Apr 2019
Authors: EL Harshfield, MC Sims, WJ Astle, M Traylor, WH Ouwehand, HS Markus

Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting.

DOI: http://doi.org/10.1212/WNL.0000000000006851
Journal: Neurology
E-pub date: 28 Jan 2019
Authors: G Chauhan, HHH Adams, CL Satizabal, JC Bis, A Teumer, M Sargurupremraj, E Hofer, S Trompet, S Hilal, AV Smith, X Jian, R Malik, M Traylor, SL Pulit, P Amouyel, B Mazoyer, Y-C Zhu, S Kaffashian, S Schilling, GW Beecham, TJ Montine, GD Schellenberg, O Kjartansson, V Guðnason, DS Knopman, ME Griswold, BG Windham, RF Gottesman, TH Mosley, R Schmidt, Y Saba, H Schmidt, F Takeuchi, S Yamaguchi, T Nabika, N Kato, KB Rajan, NT Aggarwal, PL De Jager, DA Evans, BM Psaty, JI Rotter, K Rice, OL Lopez, J Liao, C Chen, C-Y Cheng, TY Wong, MK Ikram, SJ van der Lee, N Amin, V Chouraki, AL DeStefano, HJ Aparicio, JR Romero, P Maillard, C DeCarli, JM Wardlaw, MDCV Hernández, M Luciano, D Liewald, IJ Deary, JM Starr, ME Bastin, S Muñoz Maniega, PE Slagboom, M Beekman, J Deelen, H-W Uh, R Lemmens, H Brodaty, MJ Wright, D Ames, GB Boncoraglio, JC Hopewell, AH Beecham, SH Blanton, CB Wright, RL Sacco, W Wen, A Thalamuthu, NJ Armstrong, E Chong, PR Schofield, JB Kwok, J van der Grond, DJ Stott, I Ford, JW Jukema, MW Vernooij, A Hofman, AG Uitterlinden, A van der Lugt, K Wittfeld, HJ Grabe, N Hosten, B von Sarnowski, U Völker, C Levi, J Jimenez-Conde, P Sharma, CLM Sudlow, J Rosand, D Woo, JW Cole, JF Meschia, A Slowik, V Thijs, A Lindgren, O Melander, RP Grewal, T Rundek, K Rexrode, PM Rothwell, DK Arnett, C Jern, JA Johnson, OR Benavente, S Wasssertheil-Smoller, J-M Lee, Q Wong, BD Mitchell, SS Rich, PF McArdle, MI Geerlings, Y van der Graaf, PIW de Bakker, FW Asselbergs, V Srikanth, R Thomson, R McWhirter, C Moran, M Callisaya, T Phan, LCA Rutten-Jacobs, S Bevan, C Tzourio, KA Mather, PS Sachdev, CM van Duijn, BB Worrall, M Dichgans, SJ Kittner, HS Markus, MA Ikram, M Fornage, LJ Launer, S Seshadri, WT Longstreth, S Debette, Stroke Genetics Network (SiGN), the International Stroke Genetics Consortium (ISGC), METASTROKE, Alzheimer's Disease Genetics Consortium (ADGC), and the Neurology Working Group of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium

A comparison of functional and tractography based networks in cerebral small vessel disease.

DOI: http://doi.org/10.1016/j.nicl.2018.02.013
Journal: Neuroimage Clin
E-pub date: 1 Aug 2018
Authors: AJ Lawrence, DJ Tozer, EA Stamatakis, HS Markus

Cardiometabolic effects of genetic upregulation of the interleukin 1 receptor antagonist: a Mendelian randomisation analysis.

DOI: http://doi.org/10.1016/S2213-8587(15)00034-0
Journal: Lancet Diabetes Endocrinol
E-pub date: 1 Apr 2015
Authors: Interleukin 1 Genetics Consortium

Using genome-wide complex trait analysis to quantify ‘missing heritability’ in Parkinson’s disease.

DOI: http://doi.org/10.1093/hmg/dds335
Journal: Hum Mol Genet
E-pub date: 15 Nov 2012
Authors: MF Keller, M Saad, J Bras, F Bettella, N Nicolaou, J Simón-Sánchez, F Mittag, F Büchel, M Sharma, JR Gibbs, C Schulte, V Moskvina, A Durr, P Holmans, LL Kilarski, R Guerreiro, DG Hernandez, A Brice, P Ylikotila, H Stefánsson, K Majamaa, HR Morris, N Williams, T Gasser, P Heutink, NW Wood, J Hardy, M Martinez, AB Singleton, MA Nalls, International Parkinson's Disease Genomics Consortium (IPDGC), Wellcome Trust Case Control Consortium 2 (WTCCC2)