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Evaluating the Link Between Dopaminergic Treatment, Gait Impairment, and Anxiety in Parkinson's Disease.

ABSTRACT: Background:Anxiety is the most under-recognized nonmotor symptom of Parkinson's disease (PD), yet it is unclear whether motor impairment exacerbates anxiety observed in PD, or vice versa. The current study examined: (1) whether movement (i.e., walking vs. standing) elevates distress in PD; (2) how dopaminergic treatment influences anxiety specifically while walking; and (3) whether these responses are worse in PD patients with gait impairments (compared to those without). Methods:Twenty healthy control participants (HC), 17 PD participants without gait impairments (PD-GI), and 14 PD participants with gait impairments (PD+GI) performed two tasks (stand vs. walk) in two virtual environments: (1) LOW threat; (2) HIGH threat. This protocol was completed in on and off dopaminergic states (to evaluate the effect of exacerbating motor symptoms). Results:PD+GI reported greater levels of anxiety compared to PD-GI and HC overall. All participants reported greater levels of anxiety and had higher skin conductance levels (SCLs) when walking compared to standing. The HIGH threat condition also generated greater levels of anxiety in all participants, compared to LOW threat, especially when required to walk. Notably, only PD+GI reported greater levels of anxiety when walking compared to standing in the LOW threat environment. Dopaminergic medication reduced self-reported levels of anxiety, but did not significantly change SCL. Conclusion:This study provides evidence that movement exacerbates anxiety in all older adults, but is particularly influential in those with gait impairments, which emphasizes the importance of optimally treating movement impairments as a method of reducing movement driven anxiety.

SUBMITTER: Ehgoetz Martens KA

PROVIDER: S-EPMC6178607 | biostudies-literature | 2016 Jul-Aug

REPOSITORIES: biostudies-literature

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Evaluating the Link Between Dopaminergic Treatment, Gait Impairment, and Anxiety in Parkinson's Disease.

Ehgoetz Martens Kaylena A KA Ellard Colin G CG Almeida Quincy J QJ

Movement disorders clinical practice 20160109 4

<h4>Background</h4>Anxiety is the most under-recognized nonmotor symptom of Parkinson's disease (PD), yet it is unclear whether motor impairment exacerbates anxiety observed in PD, or vice versa. The current study examined: (1) whether movement (i.e., walking vs. standing) elevates distress in PD; (2) how dopaminergic treatment influences anxiety specifically while walking; and (3) whether these responses are worse in PD patients with gait impairments (compared to those without).<h4>Methods</h4> ...[more]

PMID: 30363509

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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:Cognitive and gait deficits are common symptoms in Parkinson's disease (PD). Motor-cognitive dual tasks (DTs) are used to explore the interplay between gait and cognition. However, it is unclear if DT gait performance is indicative for cognitive impairment. Therefore, the aim of this study was to investigate if cognitive deficits are reflected by DT costs of spatiotemporal gait parameters. Methods:Cognitive function, single task (ST) and DT gait performance were investigated in 67 PD patients. Cognition was assessed by the Montreal Cognitive Assessment (MoCA) followed by a standardized, sensor-based gait test and the identical gait test while subtracting serial 3's. Cognitive impairment was defined by a MoCA score <26. DT costs in gait parameters [(DT?-?ST)/ST?×?100] were calculated as a measure of DT effect on gait. Correlation analysis was used to evaluate the association between MoCA performance and gait parameters. In a linear regression model, DT gait costs and clinical confounders (age, gender, disease duration, motor impairment, medication, and depression) were correlated to cognitive performance. In a subgroup analysis, we compared matched groups of cognitively impaired and unimpaired PD patients regarding differences in ST, DT, and DT gait costs. Results:Correlation analysis revealed weak correlations between MoCA score and DT costs of gait parameters (r/rSp???0.3). DT costs of stride length, swing time variability, and maximum toe clearance (|r/rSp|?>?0.2) were included in a regression analysis. The parameters only explain 8% of the cognitive variance. In combination with clinical confounders, regression analysis showed that these gait parameters explained 30% of MoCA performance. Group comparison revealed strong DT effects within both groups (large effect sizes), but significant between-group effects in DT gait costs were not observed. Conclusion:These findings suggest that DT gait performance is not indicative for cognitive impairment in PD. DT effects on gait parameters were substantial in cognitively impaired and unimpaired patients, thereby potentially overlaying the effect of cognitive impairment on DT gait costs. Limits of the MoCA in detecting motor-function specific cognitive performance or variable individual response to the DT as influencing factors cannot be excluded. Therefore, DT gait parameters as marker for cognitive performance should be carefully interpreted in the clinical context.

Dataset Information

Evaluating the Link Between Dopaminergic Treatment, Gait Impairment, and Anxiety in Parkinson's Disease.

Publications

Evaluating the Link Between Dopaminergic Treatment, Gait Impairment, and Anxiety in Parkinson's Disease.

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