Article Text

Download PDFPDF

Original research
Brain iron deposition is linked with cognitive severity in Parkinson’s disease
  1. George Edward Calver Thomas1,
  2. Louise Ann Leyland1,
  3. Anette-Eleonore Schrag2,3,
  4. Andrew John Lees4,
  5. Julio Acosta-Cabronero5,
  6. Rimona Sharon Weil1,6
  1. 1 Dementia Research Centre, UCL Institute of Neurology, London, UK
  2. 2 Department of Clinical Neuroscience, UCL Institute of Neurology, London, UK
  3. 3 Movement Disorders Consortium, University College London, London, UK
  4. 4 Reta Lila Institute for Brain Studies, University College London, London, UK
  5. 5 Tenoke Ltd, Cambridge, UK
  6. 6 Wellcome Centre for Human Neuroimaging, University College London, London, UK
  1. Correspondence to Dr Rimona Sharon Weil, Dementia Research Centre, London WC1N 3BG, UK; r.weil{at}ucl.ac.uk

Abstract

Background Dementia is common in Parkinson’s disease (PD) but measures that track cognitive change in PD are lacking. Brain tissue iron accumulates with age and co-localises with pathological proteins linked to PD dementia such as amyloid. We used quantitative susceptibility mapping (QSM) to detect changes related to cognitive change in PD.

Methods We assessed 100 patients with early-stage to mid-stage PD, and 37 age-matched controls using the Montreal Cognitive Assessment (MoCA), a validated clinical algorithm for risk of cognitive decline in PD, measures of visuoperceptual function and the Movement Disorders Society Unified Parkinson’s Disease Rating Scale part 3 (UPDRS-III). We investigated the association between these measures and QSM, an MRI technique sensitive to brain tissue iron content.

Results We found QSM increases (consistent with higher brain tissue iron content) in PD compared with controls in prefrontal cortex and putamen (p<0.05 corrected for multiple comparisons). Whole brain regression analyses within the PD group identified QSM increases covarying: (1) with lower MoCA scores in the hippocampus and thalamus, (2) with poorer visual function and with higher dementia risk scores in parietal, frontal and medial occipital cortices, (3) with higher UPDRS-III scores in the putamen (all p<0.05 corrected for multiple comparisons). In contrast, atrophy, measured using voxel-based morphometry, showed no differences between groups, or in association with clinical measures.

Conclusions Brain tissue iron, measured using QSM, can track cognitive involvement in PD. This may be useful to detect signs of early cognitive change to stratify groups for clinical trials and monitor disease progression.

https://creativecommons.org/licenses/by/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

View Full Text

Statistics from Altmetric.com

Supplementary materials

Footnotes

  • Twitter @rimonaweil

  • Contributors RSW, LAL and JA-C contributed to the conception and design of the study. GECT, JA-C, RSW and LAL contributed to acquisition, post-processing and analysis of the data. GECT, RSW, JA-C, LAL, AJL and A-ES drafted the text and prepared the figures.

  • Funding RSW is supported by a Clinical Research Career Development Fellowship from the Wellcome Trust and has received funding from UCL, the Academy of Medical Sciences and the National Institute for Health Research University College London Hospitals Biomedical Research Centre. JAC: The Wellcome Centre for Human Neuroimaging is supported by core funding from the Wellcome (203147/Z/16/Z). GECT is supported by a PhD studentship from the Medical Research Council (MR/N013867/1). AES is supported by GE healthcare (PO2580367614), Parkinson’s UK (G-1606K-1213), Movement Disorders Society and ESRC (ES/L009250/1). Recruitment to the study was also supported by Parkinson’s UK, the Cure Parkinson’s Trust. The study was further supported by UCLH Biomedical Research Centre Grant (BRC302/NS/RW/101410) and by grants from the National Institute for Health Research.

  • Competing interests RSW has received personal fees from GE healthcare. A-ES has received personal fees from MedTronic. JA-C has equity and a full-time appointment at Tenoke Limited.

  • Patient consent for publication Not required.

  • Ethics approval The study was approved by the Queen Square Research Ethics Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request. Individual patient data will not be shared to conform with the privacy statement signed by the participants. Pseudononymised data may be shared upon request with the corresponding author.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.