Imperial College London

ProfessorDavidSharp

Faculty of MedicineDepartment of Medicine

Professor of Neurology
 
 
 
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Contact

 

+44 (0)20 7594 7991david.sharp Website

 
 
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Assistant

 

Miss Bruna Cunha +44 (0)20 7594 7992

 
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Location

 

E315B - C3NLBurlington DanesHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

152 results found

Zetterberg H, Winblad B, Bernick C, Yaffe K, Majdan M, Johansson G, Newcombe V, Nyberg L, Sharp D, Tenovuo O, Blennow Ket al., 2018, Head trauma in sports - clinical characteristics, epidemiology and biomarkers., J Intern Med

Traumatic brain injury (TBI) is clinically divided into a spectrum of severities, with mild TBI being the least severe form and a frequent occurrence in contact sports, such as ice hockey, American football, rugby, horse riding and boxing. Mild TBI is caused by blunt non-penetrating head trauma that causes movement of the brain and stretching and tearing of axons, with diffuse axonal injury being a central pathogenic mechanism. Mild TBI is in principle synonymous with concussion; both have similar criteria in which the most important elements are acute alteration or loss of consciousness and/or post-traumatic amnesia following head trauma and no apparent brain changes on standard neuroimaging. Symptoms in mild TBI are highly variable and there are no validated imaging or fluid biomarkers to determine whether or not a patient with a normal computerized tomography scan of the brain has neuronal damage. Mild TBI typically resolves within a few weeks but 10-15% of concussion patients develop post-concussive syndrome. Repetitive mild TBI, which is frequent in contact sports, is a risk factor for a complicated recovery process. This overview paper discusses the relationships between repetitive head impacts in contact sports, mild TBI and chronic neurological symptoms. What are these conditions, how common are they, how are they linked and can they be objectified using imaging or fluid-based biomarkers? It gives an update on the current state of research on these questions with a specific focus on clinical characteristics, epidemiology and biomarkers. This article is protected by copyright. All rights reserved.

JOURNAL ARTICLE

Lally PJ, Montaldo P, Oliveira V, Soe A, Swamy R, Bassett P, Mendoza J, Atreja G, Kariholu U, Pattnayak S, Sashikumar P, Harizaj H, Mitchell M, Ganesh V, Harigopal S, Dixon J, English P, Clarke P, Muthukumar P, Satodia P, Wayte S, Abernethy LJ, Yajamanyam K, Bainbridge A, Price D, Huertas A, Sharp DJ, Kalra V, Chawla S, Shankaran S, Thayyil S, MARBLE consortiumet al., 2018, Magnetic resonance spectroscopy assessment of brain injury after moderate hypothermia in neonatal encephalopathy: a prospective multicentre cohort study., Lancet Neurol

BACKGROUND: In neonatal encephalopathy, the clinical manifestations of injury can only be reliably assessed several years after an intervention, complicating early prognostication and rendering trials of promising neuroprotectants slow and expensive. We aimed to determine the accuracy of thalamic proton magnetic resonance (MR) spectroscopy (MRS) biomarkers as early predictors of the neurodevelopmental abnormalities observed years after neonatal encephalopathy. METHODS: We did a prospective multicentre cohort study across eight neonatal intensive care units in the UK and USA, recruiting term and near-term neonates who received therapeutic hypothermia for neonatal encephalopathy. We excluded infants with life-threatening congenital malformations, syndromic disorders, neurometabolic diseases, or any alternative diagnoses for encephalopathy that were apparent within 6 h of birth. We obtained T1-weighted, T2-weighted, and diffusion-weighted MRI and thalamic proton MRS 4-14 days after birth. Clinical neurodevelopmental tests were done 18-24 months later. The primary outcome was the association between MR biomarkers and an adverse neurodevelopmental outcome, defined as death or moderate or severe disability, measured using a multivariable prognostic model. We used receiver operating characteristic (ROC) curves to examine the prognostic accuracy of the individual biomarkers. This trial is registered with ClinicalTrials.gov, number NCT01309711. FINDINGS: Between Jan 29, 2013, and June 25, 2016, we recruited 223 infants who all underwent MRI and MRS at a median age of 7 days (IQR 5-10), with 190 (85%) followed up for neurological examination at a median age of 23 months (20-25). Of those followed up, 31 (16%) had moderate or severe disability, including one death. Multiple logistic regression analysis could not be done because thalamic N-acetylaspartate (NAA) concentration alone accurately predicted an adverse neurodevelopmental outcome (area under the curve [AUC] of 0·

JOURNAL ARTICLE

Li LM, Violante IR, Leech R, Ross E, Hampshire A, Opitz A, Rothwell JC, Carmichael DW, Sharp DJet al., 2018, Brain state and polarity dependent modulation of brain networks by transcranial direct current stimulation., Hum Brain Mapp

Despite its widespread use in cognitive studies, there is still limited understanding of whether and how transcranial direct current stimulation (tDCS) modulates brain network function. To clarify its physiological effects, we assessed brain network function using functional magnetic resonance imaging (fMRI) simultaneously acquired during tDCS stimulation. Cognitive state was manipulated by having subjects perform a Choice Reaction Task or being at "rest." A novel factorial design was used to assess the effects of brain state and polarity. Anodal and cathodal tDCS were applied to the right inferior frontal gyrus (rIFG), a region involved in controlling activity large-scale intrinsic connectivity networks during switches of cognitive state. tDCS produced widespread modulation of brain activity in a polarity and brain state dependent manner. In the absence of task, the main effect of tDCS was to accentuate default mode network (DMN) activation and salience network (SN) deactivation. In contrast, during task performance, tDCS increased SN activation. In the absence of task, the main effect of anodal tDCS was more pronounced, whereas cathodal tDCS had a greater effect during task performance. Cathodal tDCS also accentuated the within-DMN connectivity associated with task performance. There were minimal main effects of stimulation on network connectivity. These results demonstrate that rIFG tDCS can modulate the activity and functional connectivity of large-scale brain networks involved in cognitive function, in a brain state and polarity dependent manner. This study provides an important insight into mechanisms by which tDCS may modulate cognitive function, and also has implications for the design of future stimulation studies.

JOURNAL ARTICLE

Li LM, Violante IR, Leech R, Hampshire A, Opitz A, McArthur D, Carmichael DW, Sharp DJet al., 2018, Cognitive enhancement with Salience Network electrical stimulation is influenced by network structural connectivity., Neuroimage, Vol: 185, Pages: 425-433

The Salience Network (SN) and its interactions are important for cognitive control. We have previously shown that structural damage to the SN is associated with abnormal functional connectivity between the SN and Default Mode Network (DMN), abnormal DMN deactivation, and impaired response inhibition, which is an important aspect of cognitive control. This suggests that stimulating the SN might enhance cognitive control. Here, we tested whether non-invasive transcranial direct current stimulation (TDCS) could be used to modulate activity within the SN and enhance cognitive control. TDCS was applied to the right inferior frontal gyrus/anterior insula cortex during performance of the Stop Signal Task (SST) and concurrent functional (f)MRI. Anodal TDCS improved response inhibition. Furthermore, stratification of participants based on SN structural connectivity showed that it was an important influence on both behavioural and physiological responses to anodal TDCS. Participants with high fractional anisotropy within the SN showed improved SST performance and increased activation of the SN with anodal TDCS, whilst those with low fractional anisotropy within the SN did not. Cathodal stimulation of the SN produced activation of the right caudate, an effect which was not modulated by SN structural connectivity. Our results show that stimulation targeted to the SN can improve response inhibition, supporting the causal influence of this network on cognitive control and confirming it as a target to produce cognitive enhancement. Our results also highlight the importance of structural connectivity as a modulator of network to TDCS, which should guide the design and interpretation of future stimulation studies.

JOURNAL ARTICLE

Sridharan S, Raffel J, Nandoskar A, Record C, Brooks D, Owen D, Sharp D, Muraro P, Gunn R, Nicholas Ret al., 2018, Confirmation of specific binding of the 18 kDa translocator protein (TSPO) radioligand [F-18]GE-180: a blocking study using XDB173 in multiple sclerosis, 34th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), Publisher: SAGE PUBLICATIONS LTD, Pages: 421-422, ISSN: 1352-4585

CONFERENCE PAPER

Underwood J, Cole JH, Leech R, Sharp DJ, Winston Aet al., 2018, Multivariate Pattern Analysis of Volumetric Neuroimaging Data and Its Relationship With Cognitive Function in Treated HIV Disease, JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, Vol: 78, Pages: 429-436, ISSN: 1525-4135

JOURNAL ARTICLE

Deb S, Leeson V, Aimola L, Bodani M, Li L, Weaver T, Sharp D, Crawford Met al., 2018, Aggression Following Traumatic brain injury: Effectiveness of Risperidone (AFTER): study protocol for a feasibility randomised controlled trial, TRIALS, Vol: 19, ISSN: 1745-6215

JOURNAL ARTICLE

Cole JH, Caan MWA, Underwood J, De Francesco D, van Zoest RA, Wit FWNM, Mutsaerts HJMM, Leech R, Geurtsen GJ, Portegies P, Majoie CBLM, van der Loeff MFS, Sabin CA, Reiss P, Winston A, Sharp DJet al., 2018, No Evidence for Accelerated Aging-Related Brain Pathology in Treated Human Immunodeficiency Virus: Longitudinal Neuroimaging Results From the Comorbidity in Relation to AIDS (COBRA) Project, CLINICAL INFECTIOUS DISEASES, Vol: 66, Pages: 1899-1909, ISSN: 1058-4838

JOURNAL ARTICLE

Whittington A, Sharp DJ, Gunn RN, 2018, Spatiotemporal Distribution of beta-Amyloid in Alzheimer Disease Is the Result of Heterogeneous Regional Carrying Capacities, JOURNAL OF NUCLEAR MEDICINE, Vol: 59, Pages: 822-827, ISSN: 0161-5505

JOURNAL ARTICLE

Cole JH, Ritchie SJ, Bastin ME, Hernandez MCV, Maniega SM, Royle N, Corley J, Pattie A, Harris SE, Zhang Q, Wray NR, Redmond P, Marioni RE, Starr JM, Cox SR, Wardlaw JM, Sharp DJ, Deary IJet al., 2018, Brain age predicts mortality, MOLECULAR PSYCHIATRY, Vol: 23, Pages: 1385-1392, ISSN: 1359-4184

JOURNAL ARTICLE

Jenkins PO, De Simoni S, Bourke NJ, Fleminger J, Scott G, Towey DJ, Svensson W, Khan S, Patel M, Greenwood R, Cole JH, Sharp DJet al., 2018, Dopaminergic abnormalities following traumatic brain injury, BRAIN, Vol: 141, Pages: 797-810, ISSN: 0006-8950

JOURNAL ARTICLE

Cole JH, Jolly A, de Simoni S, Bourke N, Patel MC, Scott G, Sharp DJet al., 2018, Spatial patterns of progressive brain volume loss after moderate-severe traumatic brain injury, BRAIN, Vol: 141, Pages: 822-836, ISSN: 0006-8950

JOURNAL ARTICLE

Scott G, Zetterberg H, Jolly A, Cole JH, De Simoni S, Jenkins PO, Feeney C, Owen DR, Lingford-Hughes A, Howes O, Patel MC, Goldstone AP, Gunn RN, Blennow K, Matthews PM, Sharp DJet al., 2018, Minocycline reduces chronic microglial activation after brain trauma but increases neurodegeneration, BRAIN, Vol: 141, Pages: 459-471, ISSN: 0006-8950

JOURNAL ARTICLE

van Zoest RA, Underwood J, De Francesco D, Sabin CA, Cole JH, Wit FW, Caan MWA, Kootstra NA, Fuchs D, Zetterberg H, Majoie CBLM, Portegies P, Winston A, Sharp DJ, Gisslen M, Reiss Pet al., 2018, Structural Brain Abnormalities in Successfully Treated HIV Infection: Associations With Disease and Cerebrospinal Fluid Biomarkers, JOURNAL OF INFECTIOUS DISEASES, Vol: 217, Pages: 69-81, ISSN: 0022-1899

JOURNAL ARTICLE

De Simoni S, Jenkins PO, Bourke NJ, Fleminger JJ, Hellyer PJ, Jolly AE, Patel MC, Cole JH, Leech R, Sharp DJet al., 2018, Altered caudate connectivity is associated with executive dysfunction after traumatic brain injury, BRAIN, Vol: 141, Pages: 148-164, ISSN: 0006-8950

JOURNAL ARTICLE

Sharp D, 2017, Precision medicine in TBI: Lessons from dopaminergic treatment of cognitive impairment, 23rd World Congress of Neurology (WCN), Publisher: ELSEVIER SCIENCE BV, Pages: 1-2, ISSN: 0022-510X

CONFERENCE PAPER

Sharp D, 2017, Long-term inflammatory and neurodegenerative consequences of traumatic brain injury, 23rd World Congress of Neurology (WCN), Publisher: ELSEVIER SCIENCE BV, Pages: 11-11, ISSN: 0022-510X

CONFERENCE PAPER

Chiou SY, Hellyer PJ, Sharp DJ, Newbould RD, Patel MC, Strutton PHet al., 2017, Relationships between the integrity and function of lumbar nerve roots as assessed by diffusion tensor imaging and neurophysiology, NEURORADIOLOGY, Vol: 59, Pages: 893-903, ISSN: 0028-3940

JOURNAL ARTICLE

Sharp DJ, 2017, BRAIN IMAGING AFTER TBI, 30th Annual General Meeting of the British-Neuropsychiatry-Association (BNPA), Publisher: BMJ PUBLISHING GROUP, Pages: E10-E10, ISSN: 0022-3050

CONFERENCE PAPER

Underwood J, Cole JH, Caan M, De Francesco D, Leech R, van Zoest RA, Su T, Geurtsen GJ, Schmand BA, Portegies P, Prins M, Wit FWNM, Sabin CA, Majoie C, Reiss P, Winston A, Sharp DJet al., 2017, Gray and White Matter Abnormalities in Treated Human Immunodeficiency Virus Disease and Their Relationship to Cognitive Function, CLINICAL INFECTIOUS DISEASES, Vol: 65, Pages: 422-432, ISSN: 1058-4838

JOURNAL ARTICLE

Goverdovsky V, von Rosenberg W, Nakamura T, Looney D, Sharp DJ, Papavassiliou C, Morrell MJ, Mandic DPet al., 2017, Hearables: Multimodal physiological in-ear sensing, SCIENTIFIC REPORTS, Vol: 7, ISSN: 2045-2322

JOURNAL ARTICLE

Roberts RE, Ahmad H, Arshad Q, Patel M, Dima D, Leech R, Seemungal BM, Sharp DJ, Bronstein AMet al., 2017, Functional neuroimaging of visuo-vestibular interaction, BRAIN STRUCTURE & FUNCTION, Vol: 222, Pages: 2329-2343, ISSN: 1863-2653

JOURNAL ARTICLE

Feeney C, Sharp DJ, Hellyer PJ, Jolly AE, Cole JH, Scott G, Baxter D, Jilka S, Ross E, Ham TE, Jenkins PO, Li LM, Gorgoraptis N, Midwinter M, Goldstone APet al., 2017, Serum Insulin-like Growth Factor-I Levels are Associated with Improved White Matter Recovery after Traumatic Brain Injury, ANNALS OF NEUROLOGY, Vol: 82, Pages: 30-43, ISSN: 0364-5134

JOURNAL ARTICLE

Booiman T, Wit FW, Maurer I, De Francesco D, Sabin CA, Harskamp AM, Prins M, Garagnani P, Pirazzini C, Franceschi C, Fuchs D, Gisslen M, Winston A, Reiss P, Kootstra NAet al., 2017, High Cellular Monocyte Activation in People Living With Human Immunodeficiency Virus on Combination Antiretroviral Therapy and Lifestyle-Matched Controls Is Associated With Greater Inflammation in Cerebrospinal Fluid, OPEN FORUM INFECTIOUS DISEASES, Vol: 4, ISSN: 2328-8957

JOURNAL ARTICLE

Martin-Bastida A, Ward RJ, Newbould R, Piccini P, Sharp D, Kabba C, Patel MC, Spino M, Connelly J, Tricta F, Crichton RR, Dexter DTet al., 2017, Brain iron chelation by deferiprone in a phase 2 randomised double-blinded placebo controlled clinical trial in Parkinson's disease, SCIENTIFIC REPORTS, Vol: 7, ISSN: 2045-2322

JOURNAL ARTICLE

Cole JH, Underwood J, Caan MWA, De Francesco D, van Zoest RA, Leech R, Wit FWNM, Portegies P, Geurtsen GJ, Schmand BA, van der Loeff MFS, Franceschi C, Sabin CA, Majoie CBLM, Winston A, Reiss P, Sharp DJet al., 2017, Increased brain-predicted aging in treated HIV disease, NEUROLOGY, Vol: 88, Pages: 1349-1357, ISSN: 0028-3878

JOURNAL ARTICLE

Arshad Q, Roberts RE, Ahmad H, Lobo R, Patel M, Ham T, Sharp DJ, Seemungal BMet al., 2017, Patients with chronic dizziness following traumatic head injury typically have multiple diagnoses involving combined peripheral and central vestibular dysfunction, CLINICAL NEUROLOGY AND NEUROSURGERY, Vol: 155, Pages: 17-19, ISSN: 0303-8467

JOURNAL ARTICLE

Whittington A, Sharp DJ, Gunn RN, 2017, An automated algorithm to quantify brain amyloid load, 28th International Symposium on Cerebral Blood Flow, Metabolism and Function / 13th International Conference on Quantification of Brain Function with PET, Publisher: SAGE PUBLICATIONS INC, Pages: 80-80, ISSN: 0271-678X

CONFERENCE PAPER

Chhabra S, Underwood J, Cole JH, Waldman A, Sharp DJ, Winston A, Sabin Cet al., 2017, Clinical research cerebral MRI findings in HIV positive subjects and appropriate controls, Publisher: WILEY, Pages: 10-10, ISSN: 1464-2662

CONFERENCE PAPER

Su T, Mutsaerts HJMM, Caan MWA, Wit FWNM, Schouten J, Geurtsen GJ, Sharp DJ, Prins M, Richard E, Portegies P, Reiss P, Majoie CBet al., 2017, Cerebral blood flow and cognitive function in HI-infected men with sustained suppressed viremia on combination antiretroviral therapy, AIDS, Vol: 31, Pages: 847-856, ISSN: 0269-9370

JOURNAL ARTICLE

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