Dataset Information

Earlier Dopaminergic Treatment in Parkinson's Disease Is Not Associated With Improved Outcomes.

ABSTRACT:

Background

The appropriate timing of dopaminergic treatment initiation in Parkinson's disease (PD) remains a matter of debate. The primary objective of this study was to determine whether earlier initiation of treatment was associated with less worsening of total UPDRS scores over 48 months.

Methods

We performed a secondary analysis of data from the CALM-PD (Comparison of the Agonist Pramipexole With Levodopa on Motor Complications of Parkinson's Disease) trial to examine the associations between years since diagnosis and 48-month changes in total and component UPDRS scores, Parkinson's Disease Quality of Life Scale (PDQUALIF) score, and the EuroQol-5D visual analogue scale (VAS) score.

Results

There were no associations between years since PD diagnosis and 48-month changes in total UPDRS, component UPDRS scores, PDQUALIF score, or EuroQol-5D VAS score.

Conclusion

Earlier treatment was not associated with improved long-term outcomes in this secondary analysis. Prospective studies are required to determine the appropriate timing of initiation of dopaminergic treatment to inform clinical practice.

SUBMITTER: Schneider RB

PROVIDER: S-EPMC6417760 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Publications

Earlier Dopaminergic Treatment in Parkinson's Disease Is Not Associated With Improved Outcomes.

Schneider Ruth B RB Lu Xiang X Biglan Kevin K McDermott Michael P MP

Movement disorders clinical practice 20190128 3

<h4>Background</h4>The appropriate timing of dopaminergic treatment initiation in Parkinson's disease (PD) remains a matter of debate. The primary objective of this study was to determine whether earlier initiation of treatment was associated with less worsening of total UPDRS scores over 48 months.<h4>Methods</h4>We performed a secondary analysis of data from the CALM-PD (Comparison of the Agonist Pramipexole With Levodopa on Motor Complications of Parkinson's Disease) trial to examine the asso ...[more]

PMID: 30949553

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Project description:Dopaminergic pathway is the most disrupted pathway in the pathogenesis of Parkinson's disease. Several studies reported associations of dopaminergic genes with the occurrence of adverse events of dopaminergic treatment. However, none of these studies adopted a pathway based approach. The aim of this study was to comprehensively evaluate the influence of selected single nucleotide polymorphisms of key dopaminergic pathway genes on the occurrence of motor and non-motor adverse events of dopaminergic treatment in Parkinson's disease. In total, 231 Parkinson's disease patients were enrolled. Demographic and clinical data were collected. Genotyping was performed for 16 single nucleotide polymorphisms from key dopaminergic pathway genes. Logistic and Cox regression analyses were used for evaluation. Results were adjusted for significant clinical data. We observed that carriers of at least one COMT rs165815 C allele had lower odds for developing visual hallucinations (OR = 0.34; 95% CI = 0.16-0.72; p = 0.004), while carriers of at least one DRD3 rs6280 C allele and CC homozygotes had higher odds for this adverse event (OR = 1.88; 95% CI = 1.00-3.54; p = 0.049 and OR = 3.31; 95% CI = 1.37-8.03; p = 0.008, respectively). Carriers of at least one DDC rs921451 C allele and CT heterozygotes had higher odds for orthostatic hypotension (OR = 1.86; 95% CI = 1.07-3.23; p = 0.028 and OR = 2.30; 95% CI = 1.26-4.20; p = 0.007, respectively). Heterozygotes for DDC rs3837091 and SLC22A1 rs628031 AA carriers also had higher odds for orthostatic hypotension (OR = 1.94; 95% CI = 1.07-3.51; p = 0.028 and OR = 2.57; 95% CI = 1.11-5.95; p = 0.028, respectively). Carriers of the SLC22A1 rs628031 AA genotype had higher odds for peripheral edema and impulse control disorders (OR = 4.00; 95% CI = 1.62-9.88; p = 0.003 and OR = 3.16; 95% CI = 1.03-9.72; p = 0.045, respectively). Finally, heterozygotes for SLC22A1 rs628031 and carriers of at least one SLC22A1 rs628031 A allele had lower odds for dyskinesia (OR = 0.48; 95% CI = 0.24-0.98, p = 0.043 and OR = 0.48; 95% CI = 0.25-0.92; p = 0.027, respectively). Gene-gene interactions, more specifically DDC-COMT, SLC18A2-SV2C, and SLC18A2-SLC6A3, also significantly influenced the occurrence of some adverse events. Additionally, haplotypes of COMT and SLC6A3 were associated with the occurrence of visual hallucinations (AT vs. GC: OR = 0.34; 95% CI = 0.16-0.72; p = 0.005) and orthostatic hypotension (ATG vs. ACG: OR = 2.48; 95% CI: 1.01-6.07; p = 0.047), respectively. Pathway based approach allowed us to identify new potential candidates for predictive biomarkers of adverse events of dopaminergic treatment in Parkinson's disease, which could contribute to treatment personalization.

Project description:Introduction:Impulse control disorders (ICDs) are frequent non-motor symptoms in Parkinson's disease (PD), with potential negative effects on the quality of life and social functioning. ICDs are closely associated with dopaminergic therapy, and genetic polymorphisms in several neurotransmitter pathways may increase the risk of addictive behaviors in PD. However, clinical differentiation between patients at risk and patients without risk of ICDs is still troublesome. The aim of this study was to investigate if genetic polymorphisms across several neurotransmitter pathways were associated with ICD status in patients with PD. Methods:Whole-exome sequencing data were available for 119 eligible PD patients from the Norwegian ParkWest study. All participants underwent comprehensive neurological, neuropsychiatric, and neuropsychological assessments. ICDs were assessed using the self-report short form version of the Questionnaire for Impulsive-Compulsive Disorders in PD. Single-nucleotide polymorphisms (SNPs) from 17 genes were subjected to regression with elastic net penalization to identify candidate variants associated with ICDs. The area under the curve of receiver-operating characteristic curves was used to evaluate the level of ICD prediction. Results:Among the 119 patients with PD included in the analysis, 29% met the criteria for ICD and 63% were using dopamine agonists (DAs). Eleven SNPs were associated with ICDs, and the four SNPs with the most robust performance significantly increased ICD predictability (AUC?=?0.81, 95% CI 0.73-0.90) compared to clinical data alone (DA use and age; AUC?=?0.65, 95% CI 0.59-0.78). The strongest predictive factors were rs5326 in DRD1, which was associated with increased odds of ICDs, and rs702764 in OPRK1, which was associated with decreased odds of ICDs. Conclusion:Using an advanced statistical approach, we identified SNPs in nine genes, including a novel polymorphism in DRD1, with potential application for the identification of PD patients at risk for ICDs.

Dataset Information

Earlier Dopaminergic Treatment in Parkinson's Disease Is Not Associated With Improved Outcomes.

Background

Methods

Results

Conclusion

Publications

Earlier Dopaminergic Treatment in Parkinson's Disease Is Not Associated With Improved Outcomes.

Similar Datasets

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