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Abstract

Objective:

To measure changes in psychometric state, neural activation, brain volume (BV), and cerebral metabolite concentrations during treatment of minimal hepatic encephalopathy.

Methods:

As proof of principle, 22 patients with well-compensated, biopsy-proven cirrhosis of differing etiology and previous minimal hepatic encephalopathy were treated with oral l-ornithine l-aspartate for 4 weeks. Baseline and 4-week clinical review, blood chemistry, and psychometric evaluation (Psychometric Hepatic Encephalopathy Score and Cognitive Drug Research Score) were performed. Whole-brain volumetric and functional MRI was conducted using a highly simplistic visuomotor task, together with proton magnetic resonance spectroscopy of the basal ganglia. Treatment-related changes in regional BV and neural activation change (blood oxygenation level dependent) were assessed.

Results:

Although there was no change in clinical, biochemical state, basal ganglia magnetic resonance spectroscopy, or in regional BV, there were significant improvements in Cognitive Drug Research Score (+1.2, p = 0.003) and Psychometric Hepatic Encephalopathy Score (+1.5, p = 0.003) with treatment. This cognitive amelioration was accompanied by changes in blood oxygenation level–dependent activation in the posterior cingulate and ventral medial prefrontal cortex, 2 regions that form part of the brain's structural and metabolic core. In addition, there was evidence of greater visual cortex activation.

Conclusions:

These structurally interconnected regions all showed increased function after successful encephalopathy treatment. Because no regional change in BV was observed, this implies that mechanisms unrelated to astrocyte volume regulation were involved in the significant improvement in cognitive performance.

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Supplementary Material

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Information & Authors

Information

Published In

Neurology®
Volume 80Number 11March 12, 2013
Pages: 1041-1047
PubMed: 23427320

Publication History

Received: July 23, 2012
Accepted: November 26, 2012
Published online: February 20, 2013
Published in print: March 12, 2013

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Disclosure

M.J.W. McPhail is supported by the Wellcome Trust, UK. R. Leech is supported by a fellowship from the Research Councils, UK. V.P.B. Grover was supported by grants from the Royal College of Physicians of London, the University of London, and the Trustees of St. Mary's Hospital, Paddington. J.A. Fitzpatrick reports no disclosures. N.S. Dhanjal is supported by the Medical Research Council UK. M.M.E. Crossey and H. Pflugrad report no disclosures. B.K. Saxby was previously employed by Cognitive Drug Research Ltd., provider of the CDRS to the pharmaceutical industry, now owned by United Biosource Corporation. The CDR system and analysis was provided unrestricted and free of charge. K. Wesnes was previously employed by Cognitive Drug Research Ltd., provider of the CDRS to the pharmaceutical industry, now owned by United Biosource Corporation. The CDR system and analysis was provided unrestricted and free of charge. M.A. Dresner, A.D. Waldman, and H.C. Thomas report no disclosures. S.D. Taylor-Robinson holds grants from the United Kingdom Medical Research Council, which provided running costs and some infrastructure support for the study. Go to Neurology.org for full disclosures.

Study Funding

All authors acknowledge the infrastructure support of the National Institute for Health Research Biomedical Research Centre at Imperial College London.

Authors

Affiliations & Disclosures

Mark J.W. McPhail, PhD*
From the Hepatology & Gastroenterology Section (M.J.W.M., V.P.B.G., J.A.F., M.M.E.C., H.P., H.C.T.), Division of Diabetes, Endocrinology & Metabolism, Department of Medicine, St. Mary's Hospital Campus, Imperial College London; Division of Brain Sciences (R.L., N.S.D.), Department of Medicine, Hammersmith Hospital Campus, Imperial College London; Robert Steiner Magnetic Resonance Imaging Unit (J.A.F., M.A.D., A.D.W.), MRC Clinical Sciences Centre, Imperial College London; Institute for Ageing and Health (B.K.S.), Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne; and United Biosource Corporation (K.W.), Goring-on-Thames, UK.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
Academic position as postdoctoral research in liver failure. Funded by the Wellcome Trust but not specifically for this study
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
1) Wellcome Trust, UK. Salary and consumables support for study into biomarkers in liver failure (Oct 2010 to Oct 2012) (2) National Institute for Health Research, UK - Biomedical Research Facility, Imperial College London - infrastructure support during academic clinical fellow tenureship (Oct 2008 to Oct 2010)
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Robert Leech, PhD*
From the Hepatology & Gastroenterology Section (M.J.W.M., V.P.B.G., J.A.F., M.M.E.C., H.P., H.C.T.), Division of Diabetes, Endocrinology & Metabolism, Department of Medicine, St. Mary's Hospital Campus, Imperial College London; Division of Brain Sciences (R.L., N.S.D.), Department of Medicine, Hammersmith Hospital Campus, Imperial College London; Robert Steiner Magnetic Resonance Imaging Unit (J.A.F., M.A.D., A.D.W.), MRC Clinical Sciences Centre, Imperial College London; Institute for Ageing and Health (B.K.S.), Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne; and United Biosource Corporation (K.W.), Goring-on-Thames, UK.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Vijay P.B. Grover, PhD
From the Hepatology & Gastroenterology Section (M.J.W.M., V.P.B.G., J.A.F., M.M.E.C., H.P., H.C.T.), Division of Diabetes, Endocrinology & Metabolism, Department of Medicine, St. Mary's Hospital Campus, Imperial College London; Division of Brain Sciences (R.L., N.S.D.), Department of Medicine, Hammersmith Hospital Campus, Imperial College London; Robert Steiner Magnetic Resonance Imaging Unit (J.A.F., M.A.D., A.D.W.), MRC Clinical Sciences Centre, Imperial College London; Institute for Ageing and Health (B.K.S.), Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne; and United Biosource Corporation (K.W.), Goring-on-Thames, UK.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Julie A. Fitzpatrick, BSc
From the Hepatology & Gastroenterology Section (M.J.W.M., V.P.B.G., J.A.F., M.M.E.C., H.P., H.C.T.), Division of Diabetes, Endocrinology & Metabolism, Department of Medicine, St. Mary's Hospital Campus, Imperial College London; Division of Brain Sciences (R.L., N.S.D.), Department of Medicine, Hammersmith Hospital Campus, Imperial College London; Robert Steiner Magnetic Resonance Imaging Unit (J.A.F., M.A.D., A.D.W.), MRC Clinical Sciences Centre, Imperial College London; Institute for Ageing and Health (B.K.S.), Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne; and United Biosource Corporation (K.W.), Goring-on-Thames, UK.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Novraj S. Dhanjal, PhD
From the Hepatology & Gastroenterology Section (M.J.W.M., V.P.B.G., J.A.F., M.M.E.C., H.P., H.C.T.), Division of Diabetes, Endocrinology & Metabolism, Department of Medicine, St. Mary's Hospital Campus, Imperial College London; Division of Brain Sciences (R.L., N.S.D.), Department of Medicine, Hammersmith Hospital Campus, Imperial College London; Robert Steiner Magnetic Resonance Imaging Unit (J.A.F., M.A.D., A.D.W.), MRC Clinical Sciences Centre, Imperial College London; Institute for Ageing and Health (B.K.S.), Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne; and United Biosource Corporation (K.W.), Goring-on-Thames, UK.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Mary M.E. Crossey, RN
From the Hepatology & Gastroenterology Section (M.J.W.M., V.P.B.G., J.A.F., M.M.E.C., H.P., H.C.T.), Division of Diabetes, Endocrinology & Metabolism, Department of Medicine, St. Mary's Hospital Campus, Imperial College London; Division of Brain Sciences (R.L., N.S.D.), Department of Medicine, Hammersmith Hospital Campus, Imperial College London; Robert Steiner Magnetic Resonance Imaging Unit (J.A.F., M.A.D., A.D.W.), MRC Clinical Sciences Centre, Imperial College London; Institute for Ageing and Health (B.K.S.), Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne; and United Biosource Corporation (K.W.), Goring-on-Thames, UK.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Henning Pflugrad, MD
From the Hepatology & Gastroenterology Section (M.J.W.M., V.P.B.G., J.A.F., M.M.E.C., H.P., H.C.T.), Division of Diabetes, Endocrinology & Metabolism, Department of Medicine, St. Mary's Hospital Campus, Imperial College London; Division of Brain Sciences (R.L., N.S.D.), Department of Medicine, Hammersmith Hospital Campus, Imperial College London; Robert Steiner Magnetic Resonance Imaging Unit (J.A.F., M.A.D., A.D.W.), MRC Clinical Sciences Centre, Imperial College London; Institute for Ageing and Health (B.K.S.), Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne; and United Biosource Corporation (K.W.), Goring-on-Thames, UK.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
German Association for Neurology, bursary for travel (2011)
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
German Federal Ministry of Education and Research, 01EO0802, assistant physician, 2011, 2012
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Brian K. Saxby, PhD
From the Hepatology & Gastroenterology Section (M.J.W.M., V.P.B.G., J.A.F., M.M.E.C., H.P., H.C.T.), Division of Diabetes, Endocrinology & Metabolism, Department of Medicine, St. Mary's Hospital Campus, Imperial College London; Division of Brain Sciences (R.L., N.S.D.), Department of Medicine, Hammersmith Hospital Campus, Imperial College London; Robert Steiner Magnetic Resonance Imaging Unit (J.A.F., M.A.D., A.D.W.), MRC Clinical Sciences Centre, Imperial College London; Institute for Ageing and Health (B.K.S.), Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne; and United Biosource Corporation (K.W.), Goring-on-Thames, UK.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
Cognitive Drug Research Ltd., Principal Scientist
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Keith Wesnes, PhD
From the Hepatology & Gastroenterology Section (M.J.W.M., V.P.B.G., J.A.F., M.M.E.C., H.P., H.C.T.), Division of Diabetes, Endocrinology & Metabolism, Department of Medicine, St. Mary's Hospital Campus, Imperial College London; Division of Brain Sciences (R.L., N.S.D.), Department of Medicine, Hammersmith Hospital Campus, Imperial College London; Robert Steiner Magnetic Resonance Imaging Unit (J.A.F., M.A.D., A.D.W.), MRC Clinical Sciences Centre, Imperial College London; Institute for Ageing and Health (B.K.S.), Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne; and United Biosource Corporation (K.W.), Goring-on-Thames, UK.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
I am an employee and stockholder in Bracket which provides services to the clinical trial industry
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
M. Alex Dresner, PhD
From the Hepatology & Gastroenterology Section (M.J.W.M., V.P.B.G., J.A.F., M.M.E.C., H.P., H.C.T.), Division of Diabetes, Endocrinology & Metabolism, Department of Medicine, St. Mary's Hospital Campus, Imperial College London; Division of Brain Sciences (R.L., N.S.D.), Department of Medicine, Hammersmith Hospital Campus, Imperial College London; Robert Steiner Magnetic Resonance Imaging Unit (J.A.F., M.A.D., A.D.W.), MRC Clinical Sciences Centre, Imperial College London; Institute for Ageing and Health (B.K.S.), Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne; and United Biosource Corporation (K.W.), Goring-on-Thames, UK.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Adam D. Waldman, PhD
From the Hepatology & Gastroenterology Section (M.J.W.M., V.P.B.G., J.A.F., M.M.E.C., H.P., H.C.T.), Division of Diabetes, Endocrinology & Metabolism, Department of Medicine, St. Mary's Hospital Campus, Imperial College London; Division of Brain Sciences (R.L., N.S.D.), Department of Medicine, Hammersmith Hospital Campus, Imperial College London; Robert Steiner Magnetic Resonance Imaging Unit (J.A.F., M.A.D., A.D.W.), MRC Clinical Sciences Centre, Imperial College London; Institute for Ageing and Health (B.K.S.), Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne; and United Biosource Corporation (K.W.), Goring-on-Thames, UK.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
Bayer Schering, speaker honoraria
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
Clinical MR Neuroimaging; Physiological and Functional Techniques, Cambridge University Press, 2004 (1st ed), 2009 (2nd ed).
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
GlaxoSmithKline; general consultancy on imaging.
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Howard C. Thomas, MD
From the Hepatology & Gastroenterology Section (M.J.W.M., V.P.B.G., J.A.F., M.M.E.C., H.P., H.C.T.), Division of Diabetes, Endocrinology & Metabolism, Department of Medicine, St. Mary's Hospital Campus, Imperial College London; Division of Brain Sciences (R.L., N.S.D.), Department of Medicine, Hammersmith Hospital Campus, Imperial College London; Robert Steiner Magnetic Resonance Imaging Unit (J.A.F., M.A.D., A.D.W.), MRC Clinical Sciences Centre, Imperial College London; Institute for Ageing and Health (B.K.S.), Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne; and United Biosource Corporation (K.W.), Goring-on-Thames, UK.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
(1) Journal of viral hepatitis, editorial board, c 1990 to present
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Simon D. Taylor-Robinson, MD
From the Hepatology & Gastroenterology Section (M.J.W.M., V.P.B.G., J.A.F., M.M.E.C., H.P., H.C.T.), Division of Diabetes, Endocrinology & Metabolism, Department of Medicine, St. Mary's Hospital Campus, Imperial College London; Division of Brain Sciences (R.L., N.S.D.), Department of Medicine, Hammersmith Hospital Campus, Imperial College London; Robert Steiner Magnetic Resonance Imaging Unit (J.A.F., M.A.D., A.D.W.), MRC Clinical Sciences Centre, Imperial College London; Institute for Ageing and Health (B.K.S.), Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne; and United Biosource Corporation (K.W.), Goring-on-Thames, UK.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE

Notes

Correspondence to Prof. Simon D. Taylor-Robinson: [email protected]
*
These authors contributed equally to the manuscript.
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

Author Contributions

Dr. M.J.W.M. analyzed and interpreted the data and wrote the manuscript. Dr. R.L. analyzed and interpreted the data and wrote the manuscript. Dr. V.P.B.G. designed the study, recruited patients, acquired data, and assisted in manuscript revision. Ms. J.A.F. acquired the imaging data. Dr. N.S.D. assisted in data analysis and manuscript revision. Ms. M.M.E.C. recruited patients and assisted in psychometric evaluation. Dr. H.P. analyzed data. Dr. B.K.S. designed psychometric examinations and analyzed data. Prof. K.W. designed psychometric examinations and analyzed data. Dr. M.A.D. designed the imaging protocols. Dr. A.D.W. analyzed imaging data. Prof. H.C.T. assisted in study design. Prof. S.D.T.-R. supervised and designed the study, recruited patients, and wrote the manuscript. Prof. S.D.T.-R. is the guarantor.

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