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Department
  • Clinical Neurosciences
    • Institute
  • Cambridge Heart and Lung Institute | Cambridge Cardiovascular
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    Research Theme Neurons, Circuits and Networks Lifelong Brain Development and Brain Ageing
    Research Focus

    Keywords

  • Stroke
  • Cerebral Small Vessel Disease
  • Genetics
  • MRI
  • Vascular Cognitive Impairment

    • Clinical Conditions

  • Stroke

    • Equipment & Techniques

  • Magnetic resonance imaging (MRI)
  • Positron Emission Tomography (PET)
  • Microscopy

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    Professor Hugh Markus

    University Position
    Professor
    Professor Hugh Markus is pleased to consider applications from prospective PhD students.

    Interests

    I use molecular genetic and neuroimaging (MRI and PET) techniques to investigate the pathogenesis of, and develop treatments for, cerebrovascular disease. A particular interest is in cerebral small vessel disease, an importantcause 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 many via 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 WNIHR, British Heart Foundation, MRC, Stroke Association, and Alzheimers Research UK.

    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

    How often does white matter hyperintensity volume regress in cerebral small vessel disease?

    DOI: http://doi.org/10.1177/17474930231169132
    Journal: Int J Stroke
    E-pub date: 1 Oct 2023
    Authors: RB Brown, DJ Tozer, M Egle, AM Tuladhar, F-E de Leeuw, HS Markus

    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

    Prevalence of, and risk factors for, cognitive impairment in lacunar stroke.

    DOI: http://doi.org/10.1177/17474930211064965
    Journal: Int J Stroke
    E-pub date: 1 Jan 2023
    Authors: L Ohlmeier, S Nannoni, C Pallucca, RB Brown, L Loubiere, HS Markus, DNA Lacunar 2 Investigators

    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

    Cognitive impact of cerebral microbleeds in patients with symptomatic small vessel disease.

    DOI: http://doi.org/10.1177/17474930211012837
    Journal: Int J Stroke
    E-pub date: 1 Apr 2022
    Authors: S Nannoni, L Ohlmeier, RB Brown, RG Morris, AD MacKinnon, HS Markus, DNA Lacunar 2 investigators

    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

    Individual markers of cerebral small vessel disease and domain-specific quality of life deficits.

    DOI: http://doi.org/10.1002/brb3.2106
    Journal: Brain Behav
    E-pub date: 1 May 2021
    Authors: J Fernando, RB Brown, H Edwards, M Egle, HS Markus, J Tay

    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

    Do Cerebral Small Vessel Disease and Multiple Sclerosis Share Common Mechanisms of White Matter Injury?

    DOI: http://doi.org/10.1161/STROKEAHA.118.023649
    Journal: Stroke
    E-pub date: 31 Aug 2019
    Authors: RB Brown, M Traylor, S Burgess, S Sawcer, 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)