The relationship of genetics with cognitive and behavioral impairments in idiopathic Parkinson’s disease patients

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dc.contributor.advisorMonchi, Oury
dc.contributor.advisorPfeffer, Gerald
dc.contributor.authorRamezani, Mehrafarin
dc.contributor.committeememberPike, Bruce
dc.contributor.committeememberMartino, Davide
dc.contributor.committeememberArnold, Paul
dc.date2021-11
dc.date.accessioned2021-06-14T17:55:38Z
dc.date.available2021-06-14T17:55:38Z
dc.date.issued2021-06-10
dc.description.abstractParkinson’s disease (PD) is currently characterized by cardinal motor symptoms of rigidity, tremor and bradykinesia. However, this disease is far from a mere movement disorder, and non-motor symptoms have a substantial adverse effect on the quality of life for PD patients. PD patients suffer from a broad range of non-motor symptoms but two of them are the focus of this thesis, neuropsychiatric and cognitive impairments. The true cause of these symptoms’ manifestation is still unknown, but it is speculated that they might originate from the extensive neuronal damage due to PD. The investigation of genetic variants associated with these non-motor symptoms can provide valuable information on the possible causes of non-motor symptoms, their prevention, and even their treatment. In this thesis, the association of some specified genetic variants were investigated with neuropsychiatric symptoms and cognitive impairments in idiopathic PD patients (iPD). In the 1st part, mild behavioral impairment (MBI) in iPD patients was investigated using the mild behavioral impairment checklist (MBI-C). In chapter 3, the association of MBI and rs6265 in the Brain-Derived-Neurotrophic-Factor (BDNF) was studied and it was shown that the Met allele for this variant was linked to higher risk of MBI. It was observed that the Met allele was associated with specific neuropsychiatric symptoms related to emotional dysregulation and distorted thoughts. In chapter 4, the relationship between rs4680 in Catechol-O-methyltransferase (COMT) and rs28363170 in Solute carrier family 3 member 6 (SLC6A3) with MBI was explored in iPD patients. These two variants are both pertinent in the regulation of dopamine availability in the frontal lobe. No association was found for either of these variants with MBI in iPD patients. In the second part, the association of a specific variant rs894280 in Synuclein-alpha (SNCA) and mild cognitive impairment (MCI) in iPD patients was explored. In chapter 5, a machine learning analysis was used to predict cognition in iPD patients. rs894280 was ranked as the second most important feature for prediction of cognition in PD patients. The post-hoc analysis demonstrated a connection between this variant and overall cognition, attention and visual-spatial abilities in iPD patients. This variant was further investigated in chapter 6 using longitudinal data from the Parkinson’s Progression Marker Initiative (PPMI) dataset. It was shown that rs894280 was linked to the cognitive status of drug-naïve iPD patients at baseline. This variant was associated with the rate of MCI conversion in iPD patients longitudinally, but no association was found between the variant and neuropsychiatric symptoms. In conclusion, this thesis presents genetic association with two prominent non-motor symptoms in iPD patients. These findings can be used to assist identification of PD patients at risk of cognitive decline or neuropsychiatric impairments. Nonetheless, further studies should be conducted to elucidate and validate the results of this thesis further. Limitations of the present projects and a framework for future studies are discussed in the last chapter.en_US
dc.identifier.citationRamezani, M. (2021). The relationship of genetics with cognitive and behavioral impairments in idiopathic Parkinson’s disease patients (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/38921
dc.identifier.urihttp://hdl.handle.net/1880/113493
dc.language.isoengen_US
dc.publisher.facultyCumming School of Medicineen_US
dc.publisher.institutionUniversity of Calgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.en_US
dc.subjectparkinson's diseaseen_US
dc.subjectmild cognitive impairment (MCI)en_US
dc.subjectmild behavioural impairment (MBI)en_US
dc.subjectidiopathic Parkinson's diseaseen_US
dc.subjectgeneticsen_US
dc.subjectsynuclein alpha (SNCA)en_US
dc.subjectBrain-derived-neurotrophic-factor-derived-neurotrophic-factor (BDNF)en_US
dc.subjectcatechol-O-methyltransferase (COMT)en_US
dc.subjectSolute Carrier Family 6 member 3 (SLC6A3)en_US
dc.subjectnon-motor symptomsen_US
dc.subjectcandidate gene approachen_US
dc.subject.classificationGeneticsen_US
dc.subject.classificationNeuroscienceen_US
dc.subject.classificationPsychology--Cognitiveen_US
dc.titleThe relationship of genetics with cognitive and behavioral impairments in idiopathic Parkinson’s disease patientsen_US
dc.typedoctoral thesisen_US
thesis.degree.disciplineMedicine – Neuroscienceen_US
thesis.degree.grantorUniversity of Calgaryen_US
thesis.degree.nameDoctor of Philosophy (PhD)en_US
ucalgary.item.requestcopytrueen_US
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