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Blood biomarkers with Parkinson's disease clusters and prognosis: The oxford discovery cohort.

ABSTRACT: BACKGROUND:Predicting prognosis in Parkinson's disease (PD) has important implications for individual prognostication and clinical trials design and targeting novel treatments. Blood biomarkers could help in this endeavor. METHODS:We identified 4 blood biomarkers that might predict prognosis: apolipoprotein A1, C-reactive protein, uric acid and vitamin D. These biomarkers were measured in baseline serum from 624 Parkinson's disease subjects (median disease duration, 1.0?years; interquartile range, 0.5-2.0) from the Oxford Discovery prospective cohort. We compared these biomarkers against PD subtypes derived from clinical features in the baseline cohort using data-driven approaches. We used multilevel models with MDS-UPDRS parts I, II, and III and Montreal Cognitive Assessment as outcomes to test whether the biomarkers predicted subsequent progression in motor and nonmotor domains. We compared the biomarkers against age of PD onset and age at diagnosis. The q value, a false-discovery rate alternative to P values, was calculated as an adjustment for multiple comparisons. RESULTS:Apolipoprotein A1 and C-reactive protein levels differed across our PD subtypes, with severe motor disease phenotype, poor psychological well-being, and poor sleep subtype having reduced apolipoprotein A1 and higher C-reactive protein levels. Reduced apolipoprotein A1, higher C-reactive protein, and reduced vitamin D were associated with worse baseline activities of daily living (MDS-UPDRS II). CONCLUSION:Baseline clinical subtyping identified a pro-inflammatory biomarker profile significantly associated with a severe motor/nonmotor disease phenotype, lending biological validity to subtyping approaches. No blood biomarker predicted motor or nonmotor prognosis. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

SUBMITTER: Lawton M

PROVIDER: S-EPMC7028059 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Blood biomarkers with Parkinson's disease clusters and prognosis: The oxford discovery cohort.

Lawton Michael M Baig Fahd F Toulson Greg G Morovat Alireza A Evetts Samuel G SG Ben-Shlomo Yoav Y Hu Michele T MT

Movement disorders : official journal of the Movement Disorder Society 20191106 2

<h4>Background</h4>Predicting prognosis in Parkinson's disease (PD) has important implications for individual prognostication and clinical trials design and targeting novel treatments. Blood biomarkers could help in this endeavor.<h4>Methods</h4>We identified 4 blood biomarkers that might predict prognosis: apolipoprotein A1, C-reactive protein, uric acid and vitamin D. These biomarkers were measured in baseline serum from 624 Parkinson's disease subjects (median disease duration, 1.0 years; int ...[more]

PMID: 31693246

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Project description:PurposeThe Oxford Parkinson's Disease Centre (OPDC) Discovery Cohort MRI substudy (OPDC-MRI) collects high-quality multimodal brain MRI together with deep longitudinal clinical phenotyping in patients with Parkinson's, at-risk individuals and healthy elderly participants. The primary aim is to detect pathological changes in brain structure and function, and develop, together with the clinical data, biomarkers to stratify, predict and chart progression in early-stage Parkinson's and at-risk individuals.ParticipantsParticipants are recruited from the OPDC Discovery Cohort, a prospective, longitudinal study. Baseline MRI data are currently available for 290 participants: 119 patients with early idiopathic Parkinson's, 15 Parkinson's patients with pathogenic mutations of the leucine-rich repeat kinase 2 or glucocerebrosidase (GBA) genes, 68 healthy controls and 87 individuals at risk of Parkinson's (asymptomatic carriers of GBA mutation and patients with idiopathic rapid eye movement sleep behaviour disorder-RBD).Findings to dateDifferences in brain structure in early Parkinson's were found to be subtle, with small changes in the shape of the globus pallidus and evidence of alterations in microstructural integrity in the prefrontal cortex that correlated with performance on executive function tests. Brain function, as assayed with resting fMRI yielded more substantial differences, with basal ganglia connectivity reduced in early Parkinson'sand RBD. Imaging of the substantia nigra with the more recent adoption of sequences sensitive to iron and neuromelanin content shows promising results in identifying early signs of Parkinsonian disease.Future plansOngoing studies include the integration of multimodal MRI measures to improve discrimination power. Follow-up clinical data are now accumulating and will allow us to correlate baseline imaging measures to clinical disease progression. Follow-up MRI scanning started in 2015 and is currently ongoing, providing the opportunity for future longitudinal imaging analyses with parallel clinical phenotyping.

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Blood biomarkers with Parkinson's disease clusters and prognosis: The oxford discovery cohort.

Publications

Blood biomarkers with Parkinson's disease clusters and prognosis: The oxford discovery cohort.

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