Cognitive impairment and levodopa induced dyskinesia in Parkinson’s disease: a longitudinal study from the PACOS cohort

Luca, Antonina; Monastero, Roberto; Baschi, Roberta; Cicero, Calogero Edoardo; Mostile, Giovanni; Davi, Maria; Restivo, Vincenzo; Zappia, Mario

doi:10.1038/s41598-020-79110-7

Cited by 11 publications

(10 citation statements)

References 31 publications

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“…We conducted additional analyses for motor complications using daily levodopa dose as a variable instead of LEDD ( Supplementary Table 4 and 6 in the online-only Data Supplement) based on these previous studies that reported a higher levodopa dose as a risk factor for motor complications [ 38 , 39 ]. The association of visuospatial dysfunction with levodopa-induced dyskinesia in our study lacks evidence, which is inconsistent with the result of one previous study that reported impairment of attention and executive function as a risk factor for levodopa-induced dyskinesia [ 40 ]. Additional research is needed with a longer observation period, including sufficient cases of the occurrence of motor complications.…”

Section: Discussioncontrasting

confidence: 99%

Association of Depression With Early Occurrence of Postural Instability in Parkinson’s Disease

Hwang

Park

et al. 2023

JMD

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ObjectiveaaDepression in Parkinson's disease (PD) affects the quality of life of patients. Postural instability and gait disturbance are associated with the severity and prognosis of PD. We investigated the association of depression with axial involvement in early-stage PD patients.MethodsaaThis study involved 95 PD patients unexposed to antiparkinsonian drugs. After a baseline assessment for depression, the subjects were divided into a depressed PD group and a nondepressed PD group. Analyses were conducted to identify an association of depression at baseline with the following outcome variables: the progression to Hoehn and Yahr scale (H-Y) stage 3, the occurrence of freezing of gait (FOG), levodopa-induced dyskinesia, and wearing-off. The follow-up period was 53.40 ± 16.79 months from baseline.ResultsaaKaplan-Meier survival curves for H-Y stage 3 and FOG showed more prominent progression to H-Y stage 3 and occurrences of FOG in the depressed PD group than in the nondepressed PD group (log-rank p = 0.025 and 0.003, respectively). Depression in drug-naïve, early-stage PD patients showed a significant association with the progression to H-Y stage 3 (hazard ratio = 2.55; 95% confidence interval = 1.32-4.93; p = 0.005), as analyzed by Cox regression analyses. In contrast, the occurrence of levodopa-induced dyskinesia and wearing-off did not differ between the two groups (log-rank p = 0.903 and 0.351, respectively).ConclusionaaDepression in drug-naïve, early-stage PD patients is associated with an earlier occurrence of postural instability. This suggests shared nondopaminergic pathogenic mechanisms and potentially enables the prediction of early development of postural instability. KeywordsaaDepression; Freezing of gait; Parkinson's disease; Postural instability.

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Section: Discussioncontrasting

confidence: 99%

Association of Depression With Early Occurrence of Postural Instability in Parkinson’s Disease

Hwang

Park

et al. 2023

JMD

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“…In our present investigation, we corroborated these findings, reaffirming the significant association between dyskinesia and disease duration, LEDD, UPDRS II and MoCA scores. This conveys that dyskinesia arises not solely from medication usage but is intricately intertwined with disease severity and cognitive functioning [ 28 ]. In addition to these well-established insights, our study unearthed a compelling revelation—a notable surge in the incidence of moderate to severe OAB symptoms, encompassing urinary frequency, urgency, and nocturia, among PD patients grappling with dyskinesia.…”

Section: Discussionmentioning

confidence: 99%

Unraveling the interplay between dyskinesia and overactive bladder symptoms in Parkinson’s disease: a comprehensive cohort study based on the long-term follow-up database of Parkinson’s disease

Jin,

Du,

Yan

et al. 2024

BMC Neurol

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Objectives Overactive bladder (OAB) and dyskinesia are frequent complications in patients with Parkinson’s disease (PD). However, the correlation between OAB and dyskinesia has been insufficiently explored. The purpose of this study was to examine the relationship between dyskinesia, OAB, and clinical characteristics among individuals with PD. Methods 1338 PD patients were included in the present study. Demographic features were compared between patients with or without dyskinesia and OAB symptoms. Logistic regression was conducted on dyskinesia to screen clinically relevant factors. Overactive Bladder Symptom Score (OABSS) was further used to stratify the association between the severity of OAB and the occurrence of dyskinesia. Results This study indicates that both dyskinesia and OAB are significantly related to disease severity and cognitive status. PD patients with dyskinesia and OAB having higher UPDRS scores (p < 0.001), H-Y scores (p < 0.001), NMSQ (p < 0.001) and MoCA scores (p < 0.001), and lower MMSE scores (p < 0.001) are identified. The multivariate logistic regression confirms that disease duration (p = 0.041), LEDD (p < 0.001), UPDRSII (p < 0.001), MoCA (p = 0.024), urgency (p < 0.001), frequency (p < 0.001), and nocturia (p = 0.002) are independent risk factors for dyskinesia. Trend analysis indicates that the risk of dyskinesia significantly increases when patients exhibit moderate to severe OAB symptoms (OABSS > 5) (p < 0.001). No significant interactions were found between OABSS and age, gender, disease duration, LEDD, and NMSQ scores in different subgroups, indicating that dyskinesia is more pronounced in patients with OABSS > 5. Discussion This study provides compelling evidence supporting the strong correlation between OAB and dyskinesia in PD patients, emphasizing the presence of shared pathogenic mechanisms between these two conditions. Our findings underscore the importance of considering both OAB and dyskinesia in the clinical management of PD, investigating the intricate connections between OAB and dyskinesia could unveil valuable insights into the complex pathophysiology of PD and potentially identify novel therapeutic targets for more effective PD treatment strategies.

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“…Tremor, bradykinesia, dyskinesia, and cognitive deficits are among the motor and non-motor symptoms seen in patients with disorders of dopaminergic neurotransmission such as Parkinson’s disease and neurotoxicant-induced parkinsonism ( Zhu et al, 2011 ; Luca et al, 2021 ). In vivo electrophysiology can be used to elucidate the effects of altered dopaminergic neurotransmission on neural network activity.…”

Section: Current State Of the Art: Changes In Neural Network Activity...mentioning

confidence: 99%

Probing the Neural Circuitry Targets of Neurotoxicants In Vivo Through High Density Silicon Probe Brain Implants

Ratner

Farb

2022

Front. Toxicol.

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Adverse effects of drugs on the human nervous system are rarely possible to anticipate based on preclinical neurotoxicity data, thus propagating the centuries long single most important obstacle to drug discovery and development for disorders of the nervous system. An emerging body of evidence indicates that in vivo electrophysiology using chronically implanted high-density electrodes (ciHDE) in freely moving animals is a rigorous method with enhanced potential for use in translational research. In particular, the structure and function of the hippocampal trisynaptic circuit (HTC) is conserved from rodents to primates, including Homo sapiens, suggesting that the effects of therapeutic agents and other potential neurologically active agents, whether beneficial or adverse, are likely to translate across species when interrogated using a conserved neural circuitry platform. This review explores science advances in the rapidly moving field of in vivo ciHDE in animal models of learning and memory. For this reason we focus on the HTC, where substantial research has investigated neural circuitry level responses and specific behaviors that reflect memory permitting a test of the ground truth validity of the findings. Examples of changes in neural network activity induced by endogenous neurotoxicants associated with neurodegenerative diseases, as well as exogenous therapeutics, drugs, and neurotoxicants are presented. Several illustrative examples of relevant findings that involve longer range neural circuitry outside of the HTC are discussed. Lastly, the limitations of in vivo ciHDE as applied to preclinical neurotoxicology are discussed with a view toward leveraging circuitry level actions to enhance our ability to project the specificity of in vitro target engagement with the desired psychopharmacological or neurological outcome. At the same time, the goal of reducing or eliminating significant neurotoxic adverse events in human is the desired endpoint. We believe that this approach will lead to enhanced discovery of high value neuroactive therapeutics that target neural circuitry domains as their primary mechanism of action, thus enhancing their ultimate contribution toward discovery of precision therapeutics.

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Cognitive impairment and levodopa induced dyskinesia in Parkinson’s disease: a longitudinal study from the PACOS cohort

Cited by 11 publications

References 31 publications

Association of Depression With Early Occurrence of Postural Instability in Parkinson’s Disease

Association of Depression With Early Occurrence of Postural Instability in Parkinson’s Disease

Unraveling the interplay between dyskinesia and overactive bladder symptoms in Parkinson’s disease: a comprehensive cohort study based on the long-term follow-up database of Parkinson’s disease

Probing the Neural Circuitry Targets of Neurotoxicants In Vivo Through High Density Silicon Probe Brain Implants

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