scholarly journals Dopamine-Induced Nonmotor Symptoms of Parkinson's Disease

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Ariane Park ◽  
Mark Stacy

Nonmotor symptoms of Parkinson's disease (PD) may emerge secondary to the underlying pathogenesis of the disease, while others are recognized side effects of treatment. Inevitably, there is an overlap as the disease advances and patients require higher dosages and more complex medical regimens. The non-motor symptoms that emerge secondary to dopaminergic therapy encompass several domains, including neuropsychiatric, autonomic, and sleep. These are detailed in the paper. Neuropsychiatric complications include hallucinations and psychosis. In addition, compulsive behaviors, such as pathological gambling, hypersexuality, shopping, binge eating, and punding, have been shown to have a clear association with dopaminergic medications. Dopamine dysregulation syndrome (DDS) is a compulsive behavior that is typically viewed through the lens of addiction, with patients needing escalating dosages of dopamine replacement therapy. Treatment side effects on the autonomic system include nausea, orthostatic hypotension, and constipation. Sleep disturbances include fragmented sleep, nighttime sleep problems, daytime sleepiness, and sleep attacks. Recognizing the non-motor symptoms that can arise specifically from dopamine therapy is useful to help optimize treatment regimens for this complex disease.

2009 ◽  
Vol 4 (2) ◽  
pp. 29 ◽  
Author(s):  
Claire Hinnell ◽  
K Ray Chaudhuri ◽  
◽  

Non-motor symptoms (NMS) are common in Parkinson’s disease (PD), affecting up to 90% of patients during their illness, and include neuropsychiatric complications, autonomic disorders, sleep disturbances and sensory symptoms. Although NMS correlate strongly with advancing disease, they may precede the onset of motor symptoms by a number of years. It is increasingly recognised that NMS result in a significant burden for people with PD and affect quality of life (QoL) to a greater extent than motor features. However, NMS often remain undiagnosed and untreated. Herein we review the impact of common NMS on QoL for patients with PD.


2020 ◽  
Author(s):  
Monica R. Langley ◽  
Shivani Ghaisas ◽  
Bharathi N. Palanisamy ◽  
Muhammet Ay ◽  
Huajun Jin ◽  
...  

AbstractMitochondrial dysfunction has been implicated as a key player in the pathogenesis of Parkinson’s disease (PD). The MitoPark mouse, a transgenic mitochondrial impairment model developed by specific inactivation of TFAM in dopaminergic neurons, spontaneously exhibits progressive motor deficits and neurodegeneration, recapitulating several features of PD. Since non-motor symptoms are now recognized as important features of the prodromal stage of PD, we monitored the clinically relevant motor and nonmotor symptoms from ages 8-24 wks in MitoPark mice and their littermate controls. As expected, motor deficits in MitoPark mice began around 12-14 wks and became severe by 16-24 wks. Interestingly, male MitoPark mice showed spatial memory deficits before female mice, beginning at 8 wks and becoming most severe at 16 wks, as determined by Morris water maze. When compared to age-matched control mice, MitoPark mice exhibited olfactory deficits in novel and social scent tests as early as 10-12 wks. MitoPark mice between 16-24 wks spent more time immobile in forced swim and tail suspension tests, and made fewer entries into open arms of the elevated plus maze, indicating a depressive and anxiety-like phenotype, respectively. Importantly, depressive behavior as determined by immobility in forced swim test was reversible by antidepressant treatment with desipramine. Collectively, our results indicate that MitoPark mice progressively exhibit deficits in cognitive learning and memory, olfactory discrimination, and anxiety-and depression-like behaviors. Thus, MitoPark mice can serve as an invaluable model for studying motor and non-motor symptoms in addition to studying pathology in PD.


2019 ◽  
Vol 126 (11) ◽  
pp. 1471-1478 ◽  
Author(s):  
Dareia S. Roos ◽  
Jos W. R. Twisk ◽  
Pieter G. H. M. Raijmakers ◽  
Richard L. Doty ◽  
Henk W. Berendse

Abstract The aim of this study was to evaluate the relationship of hyposmia in Parkinson’s disease (PD) with other motor and non-motor symptoms and with the degree of nigrostriatal dopaminergic cell loss. A total of 295 patients with a diagnosis of PD were included. Olfactory function was measured using the University of Pennsylvania Smell Identification Test (UPSIT). Motor symptoms were rated using the Unified Parkinson’s Disease Rating Scale motor subscale (UPDRS III). To evaluate other non-motor symptoms, we used the Mini-Mental State Examination (MMSE) as a measure of global cognitive function and validated questionnaires to assess sleep disturbances, psychiatric symptoms, and autonomic dysfunction. A linear regression model was used to calculate correlation coefficients between UPSIT score and motor and non-motor variables [for psychiatric symptoms a Poisson regression was performed]. In a subgroup of patients (n = 155) with a dopamine transporter (DaT) SPECT scan, a similar statistical analysis was performed, now including striatal DaT binding. In the regression models with correction for age, sex, disease duration, and multiple testing, all motor and non-motor symptoms were associated with UPSIT scores. In the subgroup of patients with a DaT-SPECT scan, there was a strong association between olfactory test scores and DaT binding in both putamen and caudate nucleus. Hyposmia in PD is associated with various motor and non-motor symptoms, like cognition, depression, anxiety, autonomic dysfunction and sleep disturbances, and with the degree of nigrostriatal dopaminergic cell loss. This finding adds further confirmation that hyposmia holds significant promise as a marker of disease progression.


2020 ◽  
pp. 089198872096425
Author(s):  
Diego Santos-García ◽  
E. Suárez Castro ◽  
T. de Deus Fonticoba ◽  
M. J. Feal Panceiras ◽  
J. G. Muñoz Enriquez ◽  
...  

Introduction: The aim of the present study was to examine the frequency of self-reported sleep problems and their associated factors in a large cohort of PD patients. Methods: PD patients and controls, recruited from 35 centers of Spain from the COPPADIS cohort were included in this cross-sectional study. Sleep problems were assessed by the Spanish version of the Parkinson’s disease Sleep Scale version 1 (PDSS-1). An overall score below 82 or a score below 5 on at least 1 item was defined as sleep problems. Results: The frequency of sleep problems was nearly double in PD patients compared to controls: 65.8% (448/681) vs 33.5% (65/206) (p < 0.0001). Mean total PDSS score was lower in PD patients than controls: 114.9 ± 28.8 vs 132.8 ± 16.3 (p < 0.0001). Quality of life (QoL) was worse in PD patients with sleep problems compared to those without: PDQ-39SI, 19.3 ± 14 vs 13 ± 11.6 (p < 0.0001); EUROHIS-QoL8, 3.7 ± 0.5 vs 3.9 ± 0.5 (p < 0.0001). Non-motor symptoms burden (NMSS; OR = 1.029; 95%CI 1.015–1.043; p < 0.0001) and impulse control behaviors (QUIP-RS; OR = 1.054; 95%CI 1.009–1.101; p = 0.018) were associated with sleep problems after adjustment for age, gender, disease duration, daily equivalent levodopa dose, H&Y, UPDRS-III, UPDRS-IV, PD-CRS, BDI-II, NPI, VAS-Pain, VAFS, FOGQ, and total number of non-antiparkinsonian treatments. Conclusion: Sleep problems were frequent in PD patients and were related to both a worse QoL and a greater non-motor symptoms burden in PD. These findings call for increased awareness of sleep problems in PD patients.


Author(s):  
Beatrice Orso ◽  
Francesco Famà ◽  
Laura Giorgetti ◽  
Pietro Mattioli ◽  
Andrea Donniaquio ◽  
...  

Abstract Background Sleep disturbances are common non-motor symptoms of Parkinson’s Disease (PD). Methods The aim of this study was to investigate the polysomnographic correlates of sleep changes, as investigated by the Parkinson’s Disease Sleep Scale-2 (PDSS-2), in a cohort of sixty-two consecutive de novo, drug naïve PD patients (71.40 ± 7.84 y/o). Results PDSS-2 total score showed a direct correlation with stage shifts (p = 0.008). Fragmented sleep showed an inverse correlation with sleep efficiency (p = 0.012). Insomnia symptoms showed an inverse correlation with wake after sleep onset (p = 0.005) and direct correlation with periodic leg movements (p = 0.006) and stage shift indices (p = 0.003). Motor Symptoms showed a direct correlation with Apnoea-Hypopnoea (AHI; p = 0.02) and awakenings indices (p = 0.003). Dream distressing showed a direct correlation with REM without atonia (RWA, p = 0.042) and an inverse correlation with AHI (p = 0.012). Sleep quality showed an inverse correlation with RWA (p = 0.008). Conclusion PDSS-2 features are significantly correlated with polysomnography objective findings, thus further supporting its reliability to investigate sleep disturbances in PD patients.


2021 ◽  
Author(s):  
Keisuke Suzuki ◽  
Kei Funakoshi ◽  
Hiroaki Fujita ◽  
Koichi Hirata

Abstract Background: We hypothesized that rotigotine may have a positive effect on cognitive function in patients with Parkinson’s disease (PD) by improving daytime motor function and nighttime sleep status due to its 24-hour sustained properties.Methods: We evaluated the effect of rotigotine on motor symptoms, cognitive function, daytime sleepiness, sleep disturbances, and motor symptoms in 10 PD patients with sleep disturbances, defined as a PD Sleep Scale (PDSS)-2 score of ≥ 15, in a single-center, 3-month open-label study. Participants received 24 mg/24 h (patch content: 4.5-9 mg) rotigotine for a 3-month period. At baseline and 3 months, patients were evaluated on the Movement Disorder Society Revision of the Unified PD Rating Scale (MDS-UPDRS) parts III and IV and cognitive assessments, such as the Mini-Mental State Examination (MMSE), frontal assessment battery (FAB) and Montreal Cognitive Assessment (MoCA). The Epworth Sleepiness Scale (ESS) and PDSS-2 were administered at baseline and at 1 month, 2 months and 3 months.Results: At 3 months, MDS-UPDRS part III (-10.7, p<0.001) and MDS-UPDRS part IV (-1.0, p=0.023) scores significantly decreased, MoCA scores (1.7, p=0.0095) significantly increased, and off time significantly decreased (-43.0 min; p=0.029) from baseline. PDSS-2 scores significantly decreased from baseline at 2 months (-14.5, p<0.05) and 3 months (-20.0, p<0.001). ESS, MMSE or FAB scores did not significantly change after rotigotine treatment.Conclusion: Our preliminary findings suggest that low-dose rotigotine could improve motor symptoms, sleep disturbance, and cognitive function without worsening daytime sleepiness in patients with PD.


Author(s):  
Shakthi C. ◽  
Sritharan B. ◽  
Muthuveeran M. ◽  
Manivannan M. R. ◽  
Justin C. ◽  
...  

Background: Parkinson’s disease is a common neurodegenerative movement disorder characterised by motor symptoms of rest tremor, bradykinesia, rigidity and postural instability and non-motor symptoms (NMS) which include neuropsychiatric symptoms, sleep disturbances, autonomic symptoms, sensory symptoms and symptoms of mixed aetiology. Parkinson’s Disease Non Motor Group (PD-NMG) devised a comprehensive clinic-based self-completed NMS questionnaire that allows easy identification of NMS by the physician. Most NMS have a poor response to dopaminergic therapy as it is due to dysfunction of the serotonergic and noradrenergic pathways. Treatment of these nonmotor symptoms help in improving the quality of life in patients with Parkinson’s disease.Methods: There were 100 patients with Parkinson’s disease who had presented to our neuromedicine movement clinic were included in the study. Patients were diagnosed as PD based on UK Parkinson’s disease brain bank criteria. The inclusion criteria were diagnosis as PD, age >18 yrs, inclusion of both males and females and consent for the study. Patients with atypical parkinsonism and secondary parkinsonism, stroke, intake of antipsychotics were excluded from the study. Non motor symptom questionnaire was given to the study group and frequency of occurrence of each non motor symptoms and their predominance in both males and females were studied. The frequency of each NMS was calculated by computing the number of yes response and calculating the percentage related to the number of patients in the sample. Analysis was done to calculate the frequency of all NMS among the enrolled patient.Results: Nocturnal sleep disturbances (43%) were most common followed by constipation (29%).The most common non motor symptoms in males were constipation (20%), urinary urgency (18%) and nocturia (11%).The most common non motor symptoms in females were nocturnal sleep disturbance (25%), feeling sad (19%), unexplained pains (17%) and being anxious (13%).Conclusions: Non motor symptom questionnaire helps in screening patients with Parkinson’s disease of non-motor symptoms and aims at providing holistic treatment improving the quality of life.


2015 ◽  
Vol 10 (01) ◽  
pp. 23 ◽  
Author(s):  
Amos D Korczyn ◽  
K Ray Chaudhuri ◽  
Teus van Laar ◽  
◽  
◽  
...  

Parkinson’s disease (PD) is primarily considered as a motor disorder but there is increasing recognition of the wide range of non-motor symptoms (NMS), such as low mood, pain, apathy, fatigue and sleep problems, which may be experienced by PD patients across the spectrum of the disease. Notably, NMS often occur before motor symptoms develop and are known to place a significant burden on health-related quality of life (HRQoL) of the person with PD. Commonly, NMS go undiagnosed by the clinician and are therefore undertreated; however, to optimise patient outcomes, both motor and non-motor aspects of PD need to be recognised and managed effectively. The 10th International Congress on Non-Motor Dysfunctions in Parkinson’s Disease and Related Disorders held in Nice, France, in December 2014, offered the opportunity to look further into the dopaminergic basis of NMS and how this may affect clinical management. Britannia arranged an international faculty, chaired by Professor Amos Korczyn (Tel Aviv, Israel), to review the latest developments in our understanding of the underlying aetiology and clinical burden of non-motor features in PD that will ultimately help inform clinical practice. Surveys indicate that NMS have an extremely high prevalence among PD patients and evidence now suggests that it is the total ‘burden’ of NMS, combining frequency and severity, and not just the occurrence of individual NMS such as depression, which is the major determinant of a patient’s HRQoL. Recognising the significant contribution of NMS to the total clinical picture in PD, in order to provide a more comprehensive grading of PD severity, it is now proposed that the clinical assessment of PD patients needs a combined approach using for example the validated Non-motor Symptoms Scale (NMSS) to assess total NMS burden in addition to classic motor symptom scoring. Recent data from newly diagnosed PD patients also suggests there are different subtypes of PD that may have implications for both clinical trial design and the selection of therapy. Cognitive impairment often occurs in patients with PD, even in early disease, progressing to PD dementia in a substantial proportion of patients, which can limit therapeutic options. Posterior cortical dysfunction is a negative predictor of the progression of PD with mild cognitive impairment to PD dementia. Pronounced nigrostriatal denervation is characteristic of PD; however, cholinergic changes are also observed. Cholinergic depletion starts early in the disease process and by the time PD dementia develops patients will have a significant cholinergic deficit in various cortical regions. Current research is focused on the potential to reduce cognitive decline by decreasing beta-amyloid plaques.


2021 ◽  
pp. 1-10
Author(s):  
Norbert Kovács ◽  
Lars Bergmann ◽  
Marieta Anca-Herschkovitsch ◽  
Esther Cubo ◽  
Thomas L. Davis ◽  
...  

Background: It is believed that motor symptoms, including dyskinesia, and non-motor symptoms impact health-related quality of life (HRQoL) in patients with Parkinson’s disease (PD), and that improvements in these metrics are correlated. Objective: Investigate the relationship between HRQoL and measures of PD severity and treatment efficacy, including motor and nonmotor symptoms. Methods: This was a planned investigation of an international, prospective, single-arm, post-marketing observational study of the long-term effectiveness of levodopa-carbidopa intestinal gel (LCIG) in patients with advanced PD. Pearson correlation coefficients (PCC) were calculated for baseline and change from baseline at 12 months between HRQoL, and motor and nonmotor symptoms. Results: A total of 195 patients were included. At baseline, HRQoL was moderately positively correlated with Activities of Daily Living (UPDRS II, PCC = 0.44), non-motor symptoms (0.48), and measures of sleep (0.50 and 0.40); all p <  0.001. After 12 months of treatment with LCIG, improvements in HRQoL were moderately positively correlated with improvement from baseline in non-motor symptoms (PCC = 0.42), sleep (0.54), and daytime sleepiness (0.40; all p <  0.001), and weakly correlated with improvement in dyskinesia signs and symptoms (PCC = 0.23; p = 0.011). Improvement in HRQoL was not correlated with improvements in OFF time or dyskinesia time. Conclusion: Both at baseline and for change from baseline at 12 months, HRQoL was correlated with baseline and change from baseline in dyskinesia, Activities of Daily Living, and non-motor symptoms, including sleep; but not with baseline or change in OFF time.


2018 ◽  
Vol 80 (3-4) ◽  
pp. 193-199 ◽  
Author(s):  
Takeo Matsubara ◽  
Keisuke Suzuki ◽  
Hiroaki Fujita ◽  
Yuji Watanabe ◽  
Hirotaka Sakuramoto ◽  
...  

Objective: The objective of this study was to clarify the relationship between autonomic and non-autonomic non-motor symptoms in patients with Parkinson’s disease (PD). Methods: Sixty-five PD patients were included in this study (27 men and 38 women; aged 68.5 ± 10.0; Hoehn and Yahr (HY) stage 2.6 ± 1.1). The autonomic symptoms were evaluated by the Japanese version of the Scales for outcomes in PD autonomic (SCOPA-AUT) questionnaire. The patients were assessed with the mini-mental state examination (MMSE), PD sleep evaluation scale-2 (PDSS-2), Epworth sleepiness scale (ESS) and Beck’s depression inventory II (BDI-II). The Non-Motor Symptom Scale (NMSS) total scores and subscores of non-autonomic non-motor symptom domains (sleep/fatigue, mood/cognition, perceptual problems/hallucination, and attention/memory) were evaluated. A dopamine transporter (DAT) scan, metaiodobenzylguanidine (MIBG) myocardial scintigraphy, and card type olfactory identification test (open essence [OE, Wako]) were performed. Results: The SCOPA-AUT total score was positively correlated with the disease duration, HY stage, levodopa equivalent dose, PDSS-2, ESS, BDI-II and non-autonomic NMSS and inversely correlated with the MMSE. The high-SCOPA-AUT group (≥9) had lower MMSE scores and higher PDSS-2, ESS, BDI-II and non-motor NMSS scores than the low-SCOPA-AUT group (< 9). The DAT scan, MIBG uptake and OE score did not differ between the groups. In a stepwise linear regression analysis, which excluded possibly overlapping items among the scales, the subtotals of PDSS-2 items, except for item 8 (nocturia), (p < 0.0001) and non-autonomic NMSS domains (p = 0.00040) were significant predictors of the total SCOPA-AUT score. Conclusion: Our study shows significant correlations among autonomic symptoms, PD-related sleep problems and non-autonomic non-motor symptoms in PD patients.


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