Article Text

Original research
Late onset depression: dopaminergic deficit and clinical features of prodromal Parkinson’s disease: a cross-sectional study
  1. Hiba Kazmi1,
  2. Zuzana Walker2,3,
  3. Jan Booij4,
  4. Faraan Khan5,
  5. Sachit Shah6,
  6. Carole H Sudre7,8,
  7. Joshua E.J. Buckman9,10,
  8. Anette-Eleonore Schrag1
  1. 1 Department of Clinical and Movement Neuroscience, UCL Institute of Neurology, London, UK
  2. 2 Division of Psychiatry, University College London, London, UK
  3. 3 St Margaret's Hospital, Essex Partnership University NHS Foundation Trust, Essex, UK
  4. 4 Department of Radiology and Nuclear Medicine, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
  5. 5 Atkinson Morley Regional Neuroscience Centre, St George's University Hospitals NHS Foundation Trust, London, UK
  6. 6 Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, London, UK
  7. 7 School of Biomedical Engineering and Imaging Sciences, King’s College London, London, UK
  8. 8 Dementia Research Centre, Department of Neurodegenerative Disease, University College London Institute of Neurology, London, UK
  9. 9 Centre for Outcomes Research and Effectiveness, Research Department of Clinical, Educational & Health Psychology, University College London, London, UK
  10. 10 iCope, Camden and Islington Psychological Therapies Services, Camden & Islington NHS Foundation Trust, Camden & Islington NHS Foundation Trust, London, UK
  1. Correspondence to Professor Anette-Eleonore Schrag, Department of Clinical and Movement Neuroscience, UCL Institute of Neurology, London NW3 2PF, UK; a.schrag{at}


Background Late onset depression (LOD) may precede the diagnosis of Parkinson’s disease (PD) or dementia with Lewy bodies (DLB). We aimed to determine the rate of clinical and imaging features associated with prodromal PD/DLB in patients with LOD.

Methods In a cross-sectional design, 36 patients with first onset of a depressive disorder (Diagnostic and Statistical Manual of Mental Disorders IV criteria) diagnosed after the age of 55 (LOD group) and 30 healthy controls (HC) underwent a detailed clinical assessment. In addition, 28/36 patients with LOD and 20/30 HC underwent a head MRI and 29/36 and 25/30, respectively, had dopamine transporter imaging by 123I-ioflupane single-photon emission computed tomography (SPECT) imaging. Image analysis of both scans was performed by a rater blind to the participant group. Results of clinical assessments and imaging results were compared between the two groups.

Results Patients with LOD (n=36) had significantly worse scores than HC (n=30) on the PD screening questionnaire (mean (SD) 1.8 (1.9) vs 0.8 (1.2); p=0.01), Movement Disorder Society Unified Parkinson’s Disease Rating Scale total (mean (SD) 19.2 (12.7) vs 6.1 (5.7); p<0.001), REM-sleep behaviour disorder screening questionnaire (mean (SD) 4.3 (3.2) vs 2.1 (2.1); p=0.001), Lille Apathy Rating Scale (mean (SD) −23.3 (9.6) vs −27.0 (4.7); p=0.04) and the Scales for Outcomes in PD-Autonomic (mean (SD) 14.9 (8.7) vs 7.7 (4.9); p<0.001). Twenty-four per cent of patients with LOD versus 4% HC had an abnormal 123I-ioflupane SPECT scan (p=0.04).

Conclusions LOD is associated with increased rates of motor and non-motor features of PD/DLB and of abnormal 123I-ioflupane SPECTs. These results suggest that patients with LOD should be considered at increased risk of PD/DLB.

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:

Statistics from

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.

Supplementary materials

  • Supplementary Data

    This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.


  • Contributors Design and conceptualisation of the study: A-ES, ZW and JB. Acquisition and analysis of the data: HK and A-ES. Recruitment of the IAPT sample: JEJB. Interpretation of the data:HK, A-ES and ZW. Drafting and revising the manuscript for intellectual content: HK, A-ES, ZW, JB, JEJB. Visual analysis of the MR scans: FK and SS. Processing the MR images, providing the volumetric data and advice on the analysis of the volumetric data: CHS.

  • Funding University College London (no grant code), GE Healthcare (DAT-12-02 LOD (Late Onset Depression Study), AS was funded by the UCL/H Biomedical Research Centre (no grant code), JEJB was funded through a Clinical Research Fellowship by the Wellcome Trust (grant reference code: 201292/Z/16/Z).

  • Competing interests ZW has received consultancy fees, travel expenses and research support from GE Healthcare and research support from Life molecular imaging. A-ES has received research support from GE Healthcare. JB has received research support from GE Healthcare (paid to the institution)

  • Patient consent for publication Not required.

  • Ethics approval All participants gave informed consent to participate in the study, which was approved by the Health Research Authority National Research Ethics Committee London-Hampstead (13/LO/0634).

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

  • Data availability statement Data are available upon reasonable request. Anette Schrag ORCID 0000-0002-9872-6680.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.