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

 

Mrs Margaret Collett +44 (0)20 7594 7992

 
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Location

 

E315B - C3NLBurlington DanesHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

144 results found

Cole JH, Caan MWA, Underwood J, De Francesco D, van Zoest RA, Wit FWNM, Mutsaerts HJMM, Leech R, Geurtsen GJ, Portegies P, Majoie CBLM, Schim van der Loeff MF, Sabin CA, Reiss P, Winston A, Sharp DJ, COBRA collaborationet al., 2018, No evidence for accelerated ageing-related brain pathology in treated HIV: longitudinal neuroimaging results from the Comorbidity in Relation to AIDS (COBRA) project., Clin Infect Dis

Background: Despite successful antiretroviral therapy people living with HIV (PLWH) experience higher rates of age-related morbidity, including abnormal brain structure, brain function and cognitive impairment. This has raised concerns that PLWH may experience accelerated ageing-related brain pathology. Methods: We performed a multi-centre longitudinal study of 134 virologically-suppressed PLWH (median age = 56.0 years) and 79 demographically-similar HIV-negative controls (median age = 57.2 years). To measure cognitive performance and brain pathology, we conducted detailed neuropsychological assessments and multi-modality neuroimaging (T1-weighted, T2-weighted, diffusion-MRI, resting-state functional-MRI, spectroscopy, arterial spin labelling) at baseline and after two-year follow-up. Group differences in rates of change were assessed using linear mixed effects models. Results: 123 PLWH and 78 HIV-negative controls completed longitudinal assessments (median interval = 1.97 years). There were no differences between PLWH and HIV-negative controls in age, sex, years of education, smoking, alcohol use, recreational drug use, blood pressure, body-mass index or cholesterol levels. At baseline, PLWH had poorer global cognitive performance (P<0.01), lower grey matter volume (P=0.04), higher white matter hyperintensity load (P=0.02), abnormal white-matter microstructure (P<0.005) and greater 'brain-predicted age difference' (P=0.01). Longitudinally, there were no significant differences in rates of change in any neuroimaging measure between PLWH and HIV-negative controls (P>0.1). Cognitive performance was stable across the study period in both groups. Conclusions: Our finding indicate that when receiving successful treatment, middle-aged PLWH are not at increased risk of accelerated ageing-related brain changes or cognitive decline over two years, when compared to closely-matched HIV-negative controls.

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

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

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

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

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., J Acquir Immune Defic Syndr

BACKGROUND: Accurate prediction of longitudinal changes in cognitive function would potentially allow targeted intervention in those at greatest risk of cognitive decline. We sought to build a multivariate model using volumetric neuroimaging data alone to accurately predict cognitive function. METHODS: Volumetric T1-weighted neuroimaging data from virally suppressed HIV-positive individuals from the CHARTER cohort (n=139) were segmented into grey and white matter and spatially normalised before were entering into machine learning models. Prediction of cognitive function at baseline and longitudinally was determined using leave-one-out cross validation. Additionally, a multivariate model of brain ageing was used to measure the deviation of apparent brain age from chronological age and assess its relationship with cognitive function. RESULTS: Cognitive impairment, defined using the global deficit score, was present in 37.4%. However, it was generally mild and occurred more commonly in those with confounding comorbidities (p<0.001). Although multivariate prediction of cognitive impairment as a dichotomous variable at baseline was poor (AUC 0.59), prediction of the global T-score was better than a comparable linear model (adjusted R=0.08, p<0.01 vs. adjusted R=0.01, p=0.14). Accurate prediction of longitudinal changes in cognitive function was not possible (p=0.82).Brain-predicted age exceeded chronological age by mean (95% confidence interval) 1.17 (-0.14-2.53) years, but was greatest in those with confounding comorbidities (5.87 [1.74-9.99] years) and prior AIDS (3.03 [0.00-6.06] years). CONCLUSION: Accurate prediction of cognitive impairment using multivariate models using only T1-weighted data was not achievable, which may reflect the small sample size, heterogeneity of the data or that impairment was usually mild.

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

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

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

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

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

Cole JH, Ritchie SJ, Bastin ME, Valdés Hernández MC, Muñoz Maniega S, 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., 2017, Brain age predicts mortality., Mol Psychiatry

Age-associated disease and disability are placing a growing burden on society. However, ageing does not affect people uniformly. Hence, markers of the underlying biological ageing process are needed to help identify people at increased risk of age-associated physical and cognitive impairments and ultimately, death. Here, we present such a biomarker, 'brain-predicted age', derived using structural neuroimaging. Brain-predicted age was calculated using machine-learning analysis, trained on neuroimaging data from a large healthy reference sample (N=2001), then tested in the Lothian Birth Cohort 1936 (N=669), to determine relationships with age-associated functional measures and mortality. Having a brain-predicted age indicative of an older-appearing brain was associated with: weaker grip strength, poorer lung function, slower walking speed, lower fluid intelligence, higher allostatic load and increased mortality risk. Furthermore, while combining brain-predicted age with grey matter and cerebrospinal fluid volumes (themselves strong predictors) not did improve mortality risk prediction, the combination of brain-predicted age and DNA-methylation-predicted age did. This indicates that neuroimaging and epigenetics measures of ageing can provide complementary data regarding health outcomes. Our study introduces a clinically-relevant neuroimaging ageing biomarker and demonstrates that combining distinct measurements of biological ageing further helps to determine risk of age-related deterioration and death.Molecular Psychiatry advance online publication, 25 April 2017; doi:10.1038/mp.2017.62.

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

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

Ghajari M, Hellyer PJ, Sharp DJ, 2017, Computational modelling of traumatic brain injury predicts the location of chronic traumatic encephalopathy pathology, BRAIN, Vol: 140, Pages: 333-343, ISSN: 0006-8950

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

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

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

Shamshiri EA, Tierney TM, Centeno M, St Pier K, Pressler RM, Sharp DJ, Perani S, Cross JH, Carmichael DWet al., 2017, Interictal activity is an important contributor to abnormal intrinsic network connectivity in paediatric focal epilepsy, HUMAN BRAIN MAPPING, Vol: 38, Pages: 221-236, ISSN: 1065-9471

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

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

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

Violante IR, Li LM, Carmichael DW, Lorenz R, Leech R, Hampshire A, Rothwell JC, Sharp DJet al., 2017, Externally induced frontoparietal synchronization modulates network dynamics and enhances working memory performance., Elife, Vol: 6

Cognitive functions such as working memory (WM) are emergent properties of large-scale network interactions. Synchronisation of oscillatory activity might contribute to WM by enabling the coordination of long-range processes. However, causal evidence for the way oscillatory activity shapes network dynamics and behavior in humans is limited. Here we applied transcranial alternating current stimulation (tACS) to exogenously modulate oscillatory activity in a right frontoparietal network that supports WM. Externally induced synchronization improved performance when cognitive demands were high. Simultaneously collected fMRI data reveals tACS effects dependent on the relative phase of the stimulation and the internal cognitive processing state. Specifically, synchronous tACS during the verbal WM task increased parietal activity, which correlated with behavioral performance. Furthermore, functional connectivity results indicate that the relative phase of frontoparietal stimulation influences information flow within the WM network. Overall, our findings demonstrate a link between behavioral performance in a demanding WM task and large-scale brain synchronization.

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

Whittington A, Sharp DJ, Gunn RN, 2017, Spatiotemporal distribution of β-amyloid in Alzheimer's disease results from heterogeneous regional carrying capacities., J Nucl Med

β-amyloid (Aβ) accumulation in the brain is one of two pathological hallmarks of Alzheimer's Disease (AD) and its spatial distribution has been studied extensively ex vivo. We apply mathematical modelling to Aβ in vivo PET imaging data in order to investigate competing theories of Aβ spread in AD. Our results provide evidence that Aβ accumulation starts in all brain regions simultaneously and that its spatiotemporal distribution is a result of heterogeneous regional carrying capacities (regional maximum possible concentration of Aβ) for the aggregated protein rather than longer term spreading from seed regions.

JOURNAL ARTICLE

Ahmad H, Arshad Q, Roberts R, Patel M, Ham T, Sharp D, Seemungal Bet al., 2016, CHRONIC DIZZINESS POST TRAUMATIC BRAIN INJURY: A CROSS-SECTIONAL STUDY, Annual Meeting of the Association-of-British-Neurologists (ABN), Publisher: BMJ PUBLISHING GROUP, ISSN: 0022-3050

CONFERENCE PAPER

De Simoni S, Grover PJ, Jenkins PO, Honeyfield L, Quest RA, Ross E, Scott G, Wilson MH, Majewska P, Waldman AD, Patel MC, Sharp DJet al., 2016, Disconnection between the default mode network and medial temporal lobes in post-traumatic amnesia, BRAIN, Vol: 139, Pages: 3137-3150, ISSN: 0006-8950

JOURNAL ARTICLE

De Simoni S, Kochaj R, Jenkins P, Cole J, Sharp Det al., 2016, Changes in cerebral blood flow and their relationship to cognition following traumatic brain injury, Publisher: TAYLOR & FRANCIS INC, Pages: 605-605, ISSN: 0269-9052

CONFERENCE PAPER

Dinov M, Lorenz R, Scott G, Sharp DJ, Fagerholmand ED, Leech Ret al., 2016, Novel Modeling of Task vs. Rest Brain State Predictability Using a Dynamic Time Warping Spectrum: Comparisons and Contrasts with Other Standard Measures of Brain Dynamics, FRONTIERS IN COMPUTATIONAL NEUROSCIENCE, Vol: 10, ISSN: 1662-5188

JOURNAL ARTICLE

Fagerholm ED, Scott G, Shew WL, Song C, Leech R, Knopfel T, Sharp DJet al., 2016, Cortical Entropy, Mutual Information and Scale-Free Dynamics in Waking Mice, CEREBRAL CORTEX, Vol: 26, Pages: 3945-3952, ISSN: 1047-3211

JOURNAL ARTICLE

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