Biomarkers in Parkinson disease: studies on clinical, radiological and biological biomarkers

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dc.contributor.advisor Sullivan, Aideen M. en
dc.contributor.advisor O'Keeffe, Gerard W. en
dc.contributor.advisor O'Sullivan, Sean en
dc.contributor.author Crotty, Grace F.
dc.date.accessioned 2019-01-30T14:35:13Z
dc.date.issued 2018
dc.date.submitted 2018
dc.identifier.citation Crotty, G. F. 2018. Biomarkers in Parkinson disease: studies on clinical, radiological and biological biomarkers. MD Thesis, University College Cork. en
dc.identifier.endpage 133 en
dc.identifier.uri http://hdl.handle.net/10468/7381
dc.description.abstract Parkinson disease is the second most common neurodegenerative disorder after Alzheimer disease. It affects 2 to 3 percent of those over 65 years with an age-dependent prevalence. Currently, the diagnosis of PD is hampered by the limited sensitivity and specificity of the available investigations. The diagnosis is usually made based on the clinical presentation which has a number of significant limitations. First of all, the disease has been present for decades before motor symptoms develop. Secondly, using clinical exam alone, the misdiagnosis rate remains high with both over-and under-diagnosis common. It is important to make an expeditious and correct diagnosis of PD, especially in this era of increasing interest in neuroprotective strategies for PD and other neurodegenerative conditions. Delaying the diagnosis until motor symptoms develop is suboptimal as more than 40% of dopaminergic neurons have been destroyed at this stage. We also need to ensure that true cases of PD are being enrolled in PD trials and that these trials are not being confounded by the inclusion of individuals with other causes of parkinsonism. To accomplish these goals, there is a need for PD biomarkers that are both sensitive and specific. The objective of this thesis was to investigate, using a case-control study design, a number of potential biomarkers for PD. These biomarkers included clinical, biological and radiological markers. In the first study, we investigated the role of autonomic neuropathy as a clinical biomarker for PD. Using thermal threshold testing, nerve conduction testing and questionnaires, the PD group demonstrated a higher prevalence of autonomic neuropathy. Other outcome measures, including the presence of non-motor symptoms, pain, depressive symptoms and electrophysiological evidence of large fiber neuropathy were also found to be more prevalent in the PD group. In the second and third studies, we explored the potential role of CSF biological biomarkers in PD. In the second study, we evaluated CSF cytokine levels with the aim of identifying a unique cytokine pattern in the CSF of PD subjects. We failed to detect a cytokine pattern and found no difference in cytokine levels between PD and control groups. However, within a cohort of the PD group, we identified an association between IL-2 levels and disease severity, with higher concentrations of IL-2 seen in those with more severe disease. In the third study, we measured GDF5 protein levels in the CSF and found lower concentrations of GDF5 in the PD group compared to controls. GDF5 levels were lower in the female PD subjects compared to males. There was no association between GDF5 concentrations and PD characteristics, age or cognition. In the final study, we assessed the utility of SPECT imaging of dopamine transporters in the striatal region of the brain (DaTSCAN) as a radiological biomarker for PD in our healthcare system. Following a review of scans over a five-year period, 69% of scans showed evidence of dopaminergic deficit, supporting a diagnosis of PD. Review of request forms for DaTSCAN, demonstrated inappropriate referrals in 13% of cases. Chart review in a subgroup of scans documented a change in patient management in 65% of cases, based on the result of the scan. In this thesis, we sought to identify potential biomarkers for PD. We found significant differences between the subjects with PD and controls using clinical and biological tests. We also demonstrated findings that support the utility of a radiological biomarker in clinical practice. Our studies showed promising results and require further research. In the future, we envision studies investigating a multimodal biomarker approach in large cohorts of PD subjects. en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher University College Cork en
dc.rights © 2018, Grace F. Crotty. en
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/3.0/ en
dc.subject Biomarkers en
dc.subject Parkinson disease en
dc.title Biomarkers in Parkinson disease: studies on clinical, radiological and biological biomarkers en
dc.type Doctoral thesis en
dc.type.qualificationlevel Doctoral en
dc.type.qualificationname MD en
dc.internal.availability Full text not available en
dc.check.info Restricted to everyone for one year en
dc.check.date 2020-01-30T14:35:13Z
dc.description.version Accepted Version
dc.contributor.funder University College Cork- Denis O'Sullivan Fellowship en
dc.contributor.funder University College Cork- UCC Translational Research Access Programme (TRAP) grant en
dc.description.status Not peer reviewed en
dc.internal.school Medicine en
dc.check.reason This thesis is due for publication or the author is actively seeking to publish this material en
dc.check.opt-out Not applicable en
dc.thesis.opt-out false
dc.check.chapterOfThesis Chapters of thesis- 1,2,3,4
dc.check.embargoformat Apply the embargo to both hard bound copy and e-thesis (If you have submitted an e-thesis and a hard bound thesis and want to embargo both) en
ucc.workflow.supervisor seansosullivan@ucc.ie
dc.internal.conferring Summer 2019 en
dc.internal.ricu Parkinson's Disease Research Cluster en


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© 2018, Grace F. Crotty. Except where otherwise noted, this item's license is described as © 2018, Grace F. Crotty.
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