scholarly journals Swallowing and chewing difficulties are associated with presynaptic dopaminergic dysfunction and greater non-motor symptom burden in early drug-naïve Parkinson’s patients

2019 ◽  
Author(s):  
Sotirios Polychronis ◽  
Georgios Dervenoulas ◽  
Tayyabah Yousaf ◽  
Flavia Niccolini ◽  
Gennaro Pagano ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Experimental Design ◽  
Motor Symptom ◽  
Motor Symptoms ◽  
Swallowing Difficulties ◽  
Progression Markers ◽  
Drug Naïve ◽  
Non Motor Symptoms ◽  
Early Drug

ABSTRACTBackgroundThe underlying pathophysiology of swallowing and chewing difficulties is multifactorial and evidence clarifying the precise mechanisms are scarce. Dysfunction in dopamine-related and non-dopamine-related pathways, changes in cortical networks related with swallowing and peripheral mechanisms have been implicated in the pathogenesis of swallowing difficulties. We aimed at investigating whether swallowing and chewing difficulties are associated with presynaptic dopaminergic deficits, faster motor symptom progression and cognitive decline in a population of early drug-naïve patients with Parkinson’s disease.MethodsBy exploring the database of Parkinson’s Progression Markers Initiative we identified forty-nine early drug-naïve Parkinson’s disease patients with swallowing difficulties. Swallowing and chewing impairment was identified with SCOPA-AUT question 1 (answer regularly) and was assessed with MDS-UPDRS Part-II, Item 2.3 (Chewing and Swallowing). We compared Parkinson’s disease patients with swallowing and chewing difficulties to Parkinson’s disease patients without difficulties, and investigated differences in striatal [123I]FP-CIT single photon emission computed tomography levels. Using Cox proportional hazards analyses, we also evaluated whether swallowing impairment can predict motor deterioration and cognitive dysfunction.ResultsPatients with Parkinson’s disease, harbored a greater deterioration regarding motor and non-motor symptoms and decreased [123I]FP-CIT binding when compared with patients without swallowing and chewing impairment. Higher burden of swallowing and chewing dysfunction (MDS-UPDRS-II, item 2.3) was correlated with lower [123I]FP-CIT uptakes within the striatum (rs=−0.157; P=0.002) and the caudate (rs=−0.156; P=0.002). The presence of swallowing and chewing difficulties was not a predictor of motor progression (Hazard ratio [HR]: 1.143, 95% confidence interval [CI]: 0.848–1.541; P=0.379) or cognitive decline (HR: 1.294, 95% CI: 0.616–2.719; P=0.496).ConclusionsSwallowing and chewing impairment is associated with decreased presynaptic dopaminergic integrity within caudate and greater motor and non-motor symptoms burden in early drug-naïve PD.Author contributionsS.P. and M.P. conceived the study, conceptualized the experimental design. M.P., S.P., G.D. and G.P. gave input to experimental design. S.P. wrote the first draft and prepared the manuscript. G.P. and S.P. performed the statistical analysis. G.P., G.D., T.Y. and S.P. generated the figures. F.N., M.P., S.P., G.P., G.D. interpreted the data. All authors revised and gave input to the manuscript.Financial Disclosure StatementData used in the preparation of this article were obtained from the Parkinson’s Progression Markers Initiative (PPMI) database (www.ppmi-info.org/data). For up-to-date information on the study, visit www.ppmi-info.org. PPMI – a public-private partnership - is sponsored by the Michael J. Fox Foundation for Parkinson’s Research (MJFF) and is co-funded by MJFF, Abbvie, Avid Radiopharmaceuticals, Biogen Idec, Bristol-Myers Squibb, Covance, Eli Lilly & Co., F. Hoffman-La Roche, Ltd., GE Healthcare, Genentech, GlaxoSmithKline, Lundbeck, Merck, MesoScale, Piramal, Pfizer and UCB.PPMI. Industry partners are contributing to PPMI through financial and in-kind donations and are playing a lead role in providing feedback on study parameters through the Industry Scientific Advisory Board (ISAB). Through close interaction with the study, the ISAB is positioned to inform the selection and review of potential progression markers that could be used in clinical testing.Mr. Polychronis, Dr. Dervenoulas, Ms Yousaf, Dr. Niccolini, Dr. Pagano and Prof. Politis report no disclosures.Potential Conflicts of InterestNo potential conflict of interest relevant to this article was reported.

Gender differences in non-motor symptoms in early, drug naïve Parkinson’s disease

2013 ◽  
Vol 260 (11) ◽  
pp. 2849-2855 ◽  
Author(s):  
Marina Picillo ◽  
Marianna Amboni ◽  
Roberto Erro ◽  
Katia Longo ◽  
Carmine Vitale ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Gender Differences ◽  
Parkinson's Disease ◽  
Motor Symptoms ◽  
Drug Naïve ◽  
Non Motor Symptoms ◽  
Early Drug

scholarly journals Progression of Nonmotor Symptoms in Parkinson’s Disease by Sex and Motor Laterality

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Zimple Kurlawala ◽  
Paul H. Shadowen ◽  
Joseph D. McMillan ◽  
Levi J Beverly ◽  
Robert P. Friedland
Keyword(s):  
Quality Of Life ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Motor Symptom ◽  
Motor Symptoms ◽  
Healthy Controls ◽  
Nonmotor Symptoms ◽  
Start Up ◽  
Progression Markers

Nonmotor symptoms (NMS) in Parkinson’s disease (PD) can start up to a decade before motor manifestations and strongly correlate with the quality of life. Understanding patterns of NMS can provide clues to the incipient site of PD pathology. Our goal was to systematically characterize the progression of NMS in PD (n = 489), compared to healthy controls, HC (n = 241), based on the sex of the subjects and laterality of motor symptom onset. Additionally, NMS experienced at the onset of PD were also compared to subjects with scans without dopaminergic deficit, SWEDD (n = 81). The Parkinson’s Progression Markers Initiative (PPMI) database was utilized to analyze several NMS scales. NMS experienced by PD and SWEDD cohorts were significantly higher than HC and both sex and laterality influenced several NMS scales at the onset of motor symptoms. Sex Differences. PD males experienced significant worsening of sexual, urinary, sleep, and cognitive functions compared to PD females. PD females reported significantly increased thermoregulatory dysfunction and anxious mood over 7 years and significantly more constipation during the first 4 years after PD onset. Laterality Differences. At onset, PD subjects with right-sided motor predominance reported significantly higher autonomic dysfunction. Subjects with left-sided motor predominance experienced significantly more anxious mood at onset which continued as Parkinson’s progressed. In conclusion, males experienced increased NMS burden in Parkinson’s disease. Laterality of motor symptoms did not significantly influence NMS progression, except anxious mood. We analyzed NMS in a large cohort of PD patients, and these data are valuable to improve PD patients’ quality of life by therapeutically alleviating nonmotor symptoms.

scholarly journals Polysomnographic correlates of sleep disturbances in de novo, drug naïve Parkinson’s Disease

2021 ◽  
Author(s):  
Beatrice Orso ◽  
Francesco Famà ◽  
Laura Giorgetti ◽  
Pietro Mattioli ◽  
Andrea Donniaquio ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Sleep Disturbances ◽  
De Novo ◽  
Sleep Onset ◽  
Inverse Correlation ◽  
Motor Symptoms ◽  
Periodic Leg Movements ◽  
Drug Naïve ◽  
Non Motor Symptoms

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.

scholarly journals Prevalence of non-motor symptoms in Parkinson’s disease

2019 ◽  
Vol 7 (5) ◽  
pp. 1459
Author(s):  
Shakthi C. ◽  
Sritharan B. ◽  
Muthuveeran M. ◽  
Manivannan M. R. ◽  
Justin C. ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Sleep Disturbances ◽  
Motor Symptom ◽  
Motor Symptoms ◽  
Nocturnal Sleep ◽  
Males And Females ◽  
Non Motor Symptoms

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.

scholarly journals Motor and Non-motor Symptoms Associated With Exercise Behavior in Parkinson's Disease Patients: Factors Differ Between Patients With and Without Postural Instability

2021 ◽  
Vol 12 ◽  
Author(s):  
Joomee Song ◽  
Jinyoung Youn ◽  
Young Eun Huh ◽  
Jun Kyu Mun ◽  
Jong Hyeon Ahn ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Postural Instability ◽  
Exercise Behavior ◽  
Motor Symptom ◽  
Disease Stage ◽  
Motor Symptoms ◽  
Non Motor Symptoms ◽  
Positive Determinant ◽  
Updrs Part

Background: Exercise is an important treatment for Parkinson's disease (PD). Therefore, recognizing determinants of exercise behavior for PD based on disease stage is essential. We sought to find whether the determinants differ based on presence of postural instability (PI), which is indicative of disease stage in PD.Methods: We enrolled patients at Samsung Medical Center from September 2019 to November 2020, who had the ability to perform exercise [modified Hoehn and Yahr (HY) stage ≤ 3]. All the motor and non-motor symptoms were investigated. The exercise of the PD patients was evaluated using the Physical Activity Scale of the Elderly (PASE)-leisure score. We classified patients into PD without PI (HY stage 1 – 2) and PD with PI (HY stage 2.5 – 3) groups. Multivariate linear regression was performed using backward elimination in each group to determine factors associated with PASE-leisure score.Results: A total of 233 patients were enrolled. In the PD without PI group (n = 177), the positive determinant of exercise was Activities-Specific Balance Confidence (ABC) score (β = 0.142, p = 0.032), and the negative determinants were fatigue score (β = −0.228, p = 0.018), female (β = −6.900, p = 0.016) and currently employed status (β = −6.072, p = 0.046). In the PD with PI group (n = 56), the positive determinant was non-motor symptom scale (NMSS) score (β = 0.221, p = 0.017) and disease duration (β = 1.001, p = 0.036), while the negative determinants were UPDRS part 3 score (β = −0.974, p < 0.001), UPDRS part 4 score (β = −2.192, p = 0.002), and age (β = −1.052, p < 0.001).Conclusion: Different motor and non-motor symptoms were associated with the exercise in PD patients with and without PI. When encouraging PD patients to exercise, personalized and different strategies should be applied based on the presence of PI.

scholarly journals The Association Between Clinical Characteristics and Motor Symptom Laterality in Patients With Parkinson's Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Sha Zhu ◽  
Min Zhong ◽  
Yu Bai ◽  
Zhuang Wu ◽  
Ruxin Gu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Sleep Quality ◽  
Rating Scale ◽  
Depression Scale ◽  
Motor Symptom ◽  
Motor Symptoms ◽  
Hamilton Depression Scale ◽  
Gait Performance ◽  
Non Motor Symptoms

Background and Purpose: The unilateral onset and persistent asymmetry of motor symptoms are important characteristics of Parkinson's disease (PD). By using scales and wearable sensors, this study explored whether motor symptom laterality could affect non-motor symptom and gait performance.Methods: A total of 130 right-handed patients with PD were enrolled in our study and were divided into two groups according to the side of predominant motor symptom presentation by using the Unified Parkinson's Disease Rating Scale part III. We measured the non-motor symptoms with the Non-motor symptoms Scale, sleep quality with the Parkinson's Disease Sleep Scale and Pittsburgh sleep quality index, cognitive function with the Mini-mental State Examination and Montreal Cognitive Assessment, quality of life with the Parkinson's Disease Questionnaire-39, and the severity of anxiety and depression with the Hamilton Anxiety Scale and Hamilton Depression Scale, respectively. All participants underwent the instrumented stand and walk test, and gait data were collected using a set of JiBuEn gait analysis system.Results: We observed that left-dominant symptom PD patients (LPD) were associated with a greater impairment of sleep quality than right-dominant symptom PD patients (RPD). We found no difference between LPD and RPD in terms of gait performance. However, compared with the severe asymmetry RPD patients (RPD-S), severe asymmetry LPD patients (LPD-S) showed a shorter stride length and decreased range of motion of hip joints.Conclusions: In this study, LPD was associated with a more severe sleep-related dysfunction than RPD. In addition, LPD-S exhibited more gait impairments than RPD-S. Considering that motor symptom laterality may affect the non-motor symptom and gait performance, it should be taken into account when evaluating and treating PD patients.

scholarly journals Extending our Understanding of the Dopaminergic Basis of Non-motor Symptoms in Parkinson’s Disease

2015 ◽  
Vol 10 (01) ◽  
pp. 23 ◽  
Author(s):  
Amos D Korczyn ◽  
K Ray Chaudhuri ◽  
Teus van Laar ◽  
◽  
◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Sleep Problems ◽  
Disease Process ◽  
Motor Symptom ◽  
Motor Disorder ◽  
Motor Symptoms ◽  
Wide Range ◽  
Non Motor Symptoms

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.

scholarly journals Depression Is Associated With Constipation in Patients With Parkinson's Disease

2020 ◽  
Vol 11 ◽  
Author(s):  
Qin Xiao-ling ◽  
Chen Gang ◽  
Lu Bo ◽  
Li Zai-li ◽  
Liu Xue-kui ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rating Scales ◽  
Clinical Stage ◽  
Motor Symptom ◽  
Motor Symptoms ◽  
Depression And Anxiety ◽  
Non Motor Symptoms

Objective: Constipation is one of the most frequent non-motor symptoms (NMS) in Parkinson's disease (PD), causing great disturbance to patients. The present study investigated the prevalence and the clinical features of constipation in patients with PD and explored the difference between prodromal and clinical constipation of PD.Methods: A total of 186 patients with PD were recruited into this study. Subjective constipation was defined by ROME III criteria. Demographic and PD-related clinical information of the participants were collected. The PD patients were objectively assessed by a spectrum of rating scales of motor symptoms, non-motor symptoms, and quality of life.Results: In total, 51.61% (96/186) of PD patients suffer from constipation. Compared with patients without constipation, the patients with constipation were prone to have restless leg syndrome, depression, and anxiety and have higher scores of the non-motor symptoms scale. Among patients with constipation, 21.88% (21/96) patients had constipation in prodromal stage. Compared with patients with constipation in clinical stage, patients with prodromal constipation had a lower age of constipation onset (56.48 ± 9.63 and 65.26 ± 8.42, χ2 = 4.091, P < 0.001), longer timespan from constipation onset to motor symptom onset (6.62 ± 3.91 and 3.18 ± 2.13, χ2 = −3.877, P = 0.001). Patients with prodromal constipation were predominantly tremor onset (χ2 = 4.405, P = 0.044) and usually had a better quality of life [28 (14.50–37.5) and 40 (25.0–55.0), χ2 = 2.011, P = 0.046]. Depression was the only risk factor of constipation in PD patients. Body mass index, depression, and anxiety were factors that affected the life quality in patients with constipation.Conclusions: Our results supported the high incidence of constipation in patients with PD and that, in some patients, constipation occurred before the onset of motor symptoms. The specific clinical characteristics of patients with constipation and with prodromal constipation help to make early diagnosis, to discover the relationship between constipation and PD, and to further explore the pathogenesis of this degenerative disease.

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