UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Combining biomarkers for prognostic modelling of Parkinson's disease

Vijiaratnam, Nirosen; Lawton, Michael; Heslegrave, Amanda J; Guo, Tong; Tan, Manuela; Jabbari, Edwin; Real, Raquel; ... PRoBaND clinical consortium; + view all (2022) Combining biomarkers for prognostic modelling of Parkinson's disease. Journal of Neurology, Neurosurgery and Psychiatry (JNNP) 10.1136/jnnp-2021-328365. (In press). Green open access

[thumbnail of jnnp-2021-328365.full.pdf]
Preview
Text
jnnp-2021-328365.full.pdf - Published Version

Download (1MB) | Preview

Abstract

BACKGROUND: Patients with Parkinson's disease (PD) have variable rates of progression. More accurate prediction of progression could improve selection for clinical trials. Although some variance in clinical progression can be predicted by age at onset and phenotype, we hypothesise that this can be further improved by blood biomarkers. OBJECTIVE: To determine if blood biomarkers (serum neurofilament light (NfL) and genetic status (glucocerebrosidase, GBA and apolipoprotein E (APOE))) are useful in addition to clinical measures for prognostic modelling in PD. METHODS: We evaluated the relationship between serum NfL and baseline and longitudinal clinical measures as well as patients' genetic (GBA and APOE) status. We classified patients as having a favourable or an unfavourable outcome based on a previously validated model, and explored how blood biomarkers compared with clinical variables in distinguishing prognostic phenotypes . RESULTS: 291 patients were assessed in this study. Baseline serum NfL was associated with baseline cognitive status. Nfl predicted a shorter time to dementia, postural instability and death (dementia-HR 2.64; postural instability-HR 1.32; mortality-HR 1.89) whereas APOEe4 status was associated with progression to dementia (dementia-HR 3.12, 95% CI 1.63 to 6.00). NfL levels and genetic variables predicted unfavourable progression to a similar extent as clinical predictors. The combination of clinical, NfL and genetic data produced a stronger prediction of unfavourable outcomes compared with age and gender (area under the curve: 0.74-age/gender vs 0.84-ALL p=0.0103). CONCLUSIONS: Clinical trials of disease-modifying therapies might usefully stratify patients using clinical, genetic and NfL status at the time of recruitment.

Type: Article
Title: Combining biomarkers for prognostic modelling of Parkinson's disease
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1136/jnnp-2021-328365
Publisher version: http://dx.doi.org/10.1136/jnnp-2021-328365
Language: English
Additional information: © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.
Keywords: parkinson's disease
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > UK Dementia Research Institute
URI: https://discovery.ucl.ac.uk/id/eprint/10148857
Downloads since deposit
38Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item