Aberrant Changes in Cortical Complexity in Right-Onset Versus Left-Onset Parkinson’s Disease in Early-Stage

There is increasing evidence to show that motor symptom lateralization in Parkinson’s disease (PD) is linked to non-motor features, progression, and prognosis of the disease. However, few studies have reported the difference in cortical complexity between patients with left-onset of PD (LPD) and right-onset of PD (RPD). This study aimed to investigate the differences in the cortical complexity between early-stage LPD and RPD. High-resolution T1-weighted magnetic resonance images of the brain were acquired in 24 patients with LPD, 34 patients with RPD, and 37 age- and sex-matched healthy controls (HCs). Cortical complexity including gyrification index, fractal dimension (FD), and sulcal depth was analyzed using surface-based morphometry via CAT12/SPM12. Familywise error (FWE) peak-level correction at p < 0.05 was performed for significance testing. In patients with RPD, we found decreased mean FD and mean sulcal depth in the banks of the left superior temporal sulcus (STS) compared with LPD and HCs. The mean FD in the left superior temporal gyrus (STG) was decreased in RPD compared with HCs. However, in patients with LPD, we did not identify significantly abnormal cortical complex change compared with HCs. Moreover, we observed that the mean FD in STG was negatively correlated with the 17-item Hamilton Depression Scale (HAMD) among the three groups. Our findings support the specific influence of asymmetrical motor symptoms in cortical complexity in early-stage PD and reveal that the banks of left STS and left STG might play a crucial role in RPD.

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

Frontiers in Neurology ◽

10.3389/fneur.2021.663232 ◽

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.

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Discriminative Pattern of Reduced Cerebral Blood Flow in Parkinson's Disease and Parkinsonism-Plus Syndrome: an ASL-MRI study

10.21203/rs.2.21208/v2 ◽

2020 ◽

Author(s):

Lina Cheng ◽

Xiaoyan Wu ◽

Ruomi Guo ◽

Yuzhou Wang ◽

Wensheng Wang ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Blood Flow ◽

Cerebral Blood Flow ◽

Early Stage ◽

Inferior Frontal Gyrus ◽

Surrogate Marker ◽

Depression Scale ◽

Hamilton Depression Scale ◽

The Right

Abstract Background: Accurate identification of Parkinson's disease (PD) and Parkinsonism-Plus syndrome (PPS), especially in the early stage of the disease, is very important. The purpose of this study was to investigate the discriminative spatial pattern of cerebral blood flow (CBF) between patients with PD and PPS. Methods: Arterial spin labeling (ASL) perfusion-weighted imaging was performed in 20 patients with PD (mean age 56.35±7.56 years), 16 patients with PPS (mean age 59.62±6.89 years), and 17 healthy controls (HCs, mean age 54.17±6.58 years). Voxel-wise comparison of the CBF was performed among PD, PPS, and HC groups. The receiver operating characteristic (ROC) curve was used to evaluate the performance of CBF in discriminating between PD and PPS. The relationship between CBF and non-motor neuropsychological scores was assessed by correlation analysis. Results: PD group showed a significantly decreased CBF in the right cerebelum_crus2, the left middle frontal gyrus (MFG), the triangle inferior frontal gyrus (IFG_Tri), the left frontal medial orbital gyrus (FG_Med_Orb) and the left caudate nucleus (CN) compared with the HC group (P < 0.05). Besides the above regions, the left supplementary motor area (SMA), the right thalamus had decreased CBF in the PPS group compared with the HC group (P < 0.05). PPS group had lower CBF value in the left MFG, the left IFG_Tri, the left CN, the left SMA, and the right thalamus compared with the PD group (P < 0.05). CBFs in left IFG_Tri, the left CN, the left SMA, and the right thalamus had moderate to high capacity in discriminating between PD and PPS patients (AUC 0.719-0.831). The CBF was positively correlated with MMSE and Montreal cognitive assessment (MoCA) scores in PD patients, while positively correlated with the Mini-mental State Examination (MMSE), Hamilton anxiety scale (HAMA), Hamilton depression scale (HAMD) scores in PPS patients (P < 0.05). Conclusion: PD and PPS patients have certain discriminative patterns of reduced CBFs, which can be used as a surrogate marker for differential diagnosis.

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Depression in Parkinson's disease: study of 60 cases

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x2005000500009 ◽

2005 ◽

Vol 63 (3b) ◽

pp. 766-771 ◽

Cited By ~ 14

Author(s):

Roberto César Pereira do Prado ◽

Egberto Reis Barbosa

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Psychiatric Symptoms ◽

Depression Scale ◽

Hamilton Depression Scale ◽

Structured Interviews ◽

Clinical Criteria ◽

Disease Study ◽

Age Range ◽

Relationship Of

Depression is very frequent in Parkinson’s disease (PD) and largely unrecognized by neurologists, emphasizing the need of an approach to psychiatric symptoms by non psychiatrists in order to ensure an early diagnosis of depression in PD; clinical characteristics and the prevalence rate of depression in PD were evaluated and the relationship of depression in PD with other variables were determined. Sixty PD subjects, who fulfilled the clinical criteria for primary PD, 56,6% males, age range from 44 to 85 years old, in different stages of the disease were investigated. All subjects were submitted to the UPDRS-III, V and VI, Clinical Interview Schedule and the Hamilton depression scale. A significant correlation was found between depression and UPDRS-III, V and VI, anxiety and irritability. The frequency of depression in PD in this study was nearly 40% possessing specific features. Structured interviews and evaluation scales are essential for an accurate diagnosis and proper treatment of depression in PD.

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The Clinical Non-Motor Connectome in Early Parkinson’s Disease

Journal of Parkinson s Disease ◽

10.3233/jpd-202102 ◽

2020 ◽

Vol 10 (4) ◽

pp. 1797-1806

Author(s):

Nico J. Diederich ◽

Nicolas Sauvageot ◽

Vannina Pieri ◽

Géraldine Hipp ◽

Michel Vaillant

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Early Stage ◽

Correlation Coefficients ◽

P Value ◽

The Mean ◽

Disease Initiation ◽

Non Motor Symptoms ◽

Early Parkinson’S Disease

Background: Non-motor symptoms (NMS) of various anatomical origins are seen in early stage idiopathic Parkinson’s disease (IPD). Objective: To analyse when and how NMS are linked together at this stage of the disease. Methods: Prospective study recruiting 64 IPD patients with ≤3 years of disease duration and 71 age-matched healthy controls (HC). NMS were clustered in 7 non-motor domains (NMD): general cognition, executive function, visuospatial function, autonomic function, olfaction, mood, and sleep. Correlation coefficients ≥|0.3| were considered as significant. Bootstrapped correlation coefficients between the scores were generated in both groups. Fourteen IPD patients and 19 HC were available for a follow-up study two years later. Results: The mean age of both groups was similar. 58% of IPD patients and 37% of HC were male (p = 0.01). At baseline IPD patients performed less well than HC on all NMD (p value between 0.0001 and 0.02). Out of 91 possible correlations between NMD, 21 were significant in IPD patients and 14 in HC at the level of ≥|0.3|. The mean correlation level was higher in IPD patients than in HC, as evidenced by the higher box plot of correlation coefficients. Visuospatial scores at baseline were predictive of the motor deterioration at the follow-up exam. Conclusion: At early IPD stage various NMS are linked together, although not connected by anatomical networks. Such a clinical NMD connectome suggests almost synchronous disease initiation at different sites as also supported by fMRI findings. Alternatively, there may be compensation-driven interconnectivity of NMD.

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Analysis of serum levels of organochlorine pesticides and related factors in Parkinson’s disease

10.21203/rs.3.rs-64368/v2 ◽

2020 ◽

Author(s):

Shaoqing Xu ◽

Xiaodong Yang ◽

Yiwei Qian ◽

Dayong Wan ◽

Fenghua Sun ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Organochlorine Pesticides ◽

Genetic Variants ◽

Cell Model ◽

Elevated Serum ◽

Depression Scale ◽

Serum Levels ◽

Hamilton Depression Scale ◽

Increased Risk

Abstract Background: There is evidence that genetic and environmental factors contribute to the onset and progression of Parkinson’s disease (PD). Pesticides are a class of environmental toxins that are linked to increased risk of PD. However, few studies have investigated the interaction between specific pesticides and genetic variants related to PD in the Chinese population.Methods: In this cross-sectional study, 19 serum levels of pesticides were measured. In addition, we also analyzed the interaction between specific pesticides and candidate genetic variants for PD. Finally, we investigated the mechanistic basis for the association between pesticides and increased risk of PD.Results: Serum levels of organochlorine pesticides including α-hexachlorocyclohexane (α-HCH), β-HCH, γ-HCH, δ-HCH, propanil, heptachlor, dieldrin, hexachlorobenzene, p,p’-dichlorodiphenyltrichloroethane (p,p’-DDE) and o,p’-dichloro-diphenyl-trichloroethane (o,p’-DDT) were higher in PD patients than in controls. α-HCH and propanil levels were associated with increased PD risk. Serum levels of dieldrin were associated with Hamilton Depression Scale and Montreal Cognitive Assessment scores in PD patients. Interactions between high pesticide levels and polymorphisms in rs11931074 and rs16940758 (α-HCH or β-HCH interacted with TT genotype in rs11931074 and δ-HCH interacted with TT genotype in rs16940758) were associated with the risk of PD. In cell model, α-HCH and propanil increased the level of reactive oxygen species and decreased the mitochondrial membrane potential. Propanil but not α-HCH induced the aggregation of α-synuclein.Conclusions: Elevated serum levels of α-HCH and propanil are associated with increased risk of PD. Serum levels of dieldrin were associated with depression and cognitive function in PD patients. The interaction between genetic variants and pesticides also increased the risk of PD. Effects of genetic variants and pesticides on the risk of PD should be studied in more detail with a larger sample size to further understand the mechanisms involved.

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The efficacy of cognitive-cycling dual-task training in patients with early-stage Parkinson’s disease: A pilot study

Neurorehabilitation ◽

10.3233/nre-203090 ◽

2020 ◽

Vol 47 (4) ◽

pp. 415-426

Author(s):

Hsiu-Chen Chang ◽

Chiung-Chu Chen ◽

Yi-Hsin Weng ◽

Wei-Da Chiou ◽

Ya-Ju Chang ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Performance ◽

Dual Task ◽

Rating Scale ◽

Early Stage ◽

Freezing Of Gait ◽

Timed Up And Go ◽

Gait Performance ◽

The Mean

BACKGROUND: Recent studies have suggested that cognitive-motor dual-task (DT) training might improve gait performance, locomotion automaticity, balance, and cognition in patients with Parkinson’s disease (PD). OBJECTIVE: We aimed to investigate the efficacy of cognitive-cycling DT training in patients with early-stage PD. METHODS: Participants were scheduled to perform cognitive tasks simultaneously with the cycling training twice per week for eight weeks for a total of 16 sessions during their on-states. Clinical assessments were conducted using the unified Parkinson’s disease rating scale (UPDRS), modified Hoehn and Yahr stage, Timed Up and Go (TUG) test, gait and cognitive performances under dual-task paradigm, the new freezing of gait questionnaire, Schwab and England Activities of Daily Living scale, 39-item Parkinson’s disease questionnaire, and cognitive performance. RESULTS: Thirteen eligible patients were enrolled in the study. The mean age was 60.64±5.32 years, and the mean disease duration was 7.02±3.23 years. Twelve PD patients completed 16 serial cognitive-cycling sessions for two months. After 16 sessions of training (T2), the UPDRS III scores improved significantly in both the off- and on-states, and TUG were significantly less than those at pretraining (T0). During both the single-task and the DT situations, gait performance and spatial memory cognitive performance significantly improved from T0 to T2. CONCLUSION: The present study demonstrated that cognitive-cycling DT training improves the motor functions, gait and cognitive performances of PD patients.

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An Open-Label, 8-Week Study of Safety and Efficacy of Pimavanserin Treatment in Adults with Parkinson’s Disease and Depression

Journal of Parkinson s Disease ◽

10.3233/jpd-202058 ◽

2020 ◽

Vol 10 (4) ◽

pp. 1751-1761

Author(s):

Daryl DeKarske ◽

Gustavo Alva ◽

Jason L. Aldred ◽

Bruce Coate ◽

Marc Cantillon ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Adverse Events ◽

Reuptake Inhibitor ◽

Adjunctive Therapy ◽

Rating Scale ◽

Depression Scale ◽

System Organ Class ◽

Hamilton Depression Scale ◽

Open Label

Background: Many patients with Parkinson’s disease (PD) experience depression. Objective: Evaluate pimavanserin treatment for depression in patients with PD. Methods: Pimavanserin was administered as monotherapy or adjunctive therapy to a selective serotonin reuptake inhibitor or serotonin/noradrenaline reuptake inhibitor in this 8-week, single-arm, open-label phase 2 study (NCT03482882). The primary endpoint was change from baseline to week 8 in Hamilton Depression Scale–17-item version (HAMD-17) score. Safety, including collection of adverse events and the Mini-Mental State Examination (MMSE) and Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale Part III (MDS-UPDRS III) scores, was assessed in patients who received ≥1 pimavanserin dose. Results: Efficacy was evaluated in 45 patients (21 monotherapy, 24 adjunctive therapy). Mean (SE) baseline HAMD-17 was 19.2 (3.1). Change from baseline to week 8 (least squares [LS] mean [SE]) in the HAMD-17 was –10.8 (0.63) (95% CI, –12.0 to –9.5; p < 0.0001) with significant improvement seen at week 2 (p < 0.0001) and for both monotherapy (week 8, –11.2 [0.99]) and adjunctive therapy (week 8,–10.2 [0.78]). Most patients (60.0%) had ≥50% improvement at week 8, and 44.4% of patients reached remission (HAMD-17 score ≤7). Twenty-one of 47 patients experienced 42 treatment-emergent adverse events; the most common by system organ class were gastrointestinal (n = 7; 14.9%) and psychiatric (n = 7; 14.9%). No negative effects were observed on MMSE or MDS-UPDRS Part III. Conclusion: In this 8-week, single-arm, open-label study, pimavanserin as monotherapy or adjunctive therapy was well tolerated and associated with early and sustained improvement of depressive symptoms in patients with PD.

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Depression in Parkinson's disease: clinical-epidemiological correlates and comparison with a controlled group of non-parkinsonian geriatric patients

Brazilian Journal of Psychiatry ◽

10.1590/s1516-44462009000100010 ◽

2009 ◽

Vol 31 (1) ◽

pp. 39-42 ◽

Cited By ~ 12

Author(s):

Beatriz Azevedo dos Anjos Godke Veiga ◽

Vanderci Borges ◽

Sonia Maria César de Azevedo Silva ◽

Fabrício de Oliveira Goulart ◽

Maysa Seabra Cendoroglo ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Major Depression ◽

Beck Depression Inventory ◽

Geriatric Patients ◽

Rating Scale ◽

Depression Scale ◽

Hamilton Depression Scale ◽

Yahr Scale ◽

Disease Rating

OBJECTIVE: To evaluate and compare the frequency and severity of major depression in patients with Parkinson's disease and in individuals older than 60 years without neurological, rheumatological and/or oncological comorbidities. METHOD: We studied 50 patients with Parkinson's disease older than 60 years and 50 geriatric patients. Subjects with scores of Mini Mental State Examination indicating cognitive impairment were excluded. We used Diagnostic Statistical Manual of Mental Diseases-IV criteria to diagnose major depression and the Hamilton Depression Scale and the Beck Depression Inventory to rate it. The Unified Parkinson's Disease Rating Scale part 3 and the Hoehn and Yahr Scale were used to evaluate the motor severity of Parkinson's disease. RESULTS: Major depression was found in 42% of Parkinson's disease patients and in 10% of the geriatric patients (p < 0.001). The scores of the Hamilton Depression Scale and the Beck Depression Inventory were higher in Parkinson's disease patients (p < 0.001). Depressed Parkinson's disease patients had longer duration of Parkinson's disease (p = 0.020) and higher scores on the Unified Parkinson's Disease Rating Scale part 3 (p = 0.029) and the Yahr Scale (p = 0.027). CONCLUSIONS: The frequency (42%) and severity of major depression were higher in Parkinson's disease patients. Longer duration of Parkinson's disease, higher scores on the Unified Parkinson's Disease Rating Scale part 3 and the Hoehn and Yahr Scale were significantly associated with major depression.

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The role of brain perivascular space burden in early-stage Parkinson’s disease

npj Parkinson s Disease ◽

10.1038/s41531-021-00155-0 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Ting Shen ◽

Yumei Yue ◽

Shuai Zhao ◽

Juanjuan Xie ◽

Yanxing Chen ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

White Matter ◽

Early Stage ◽

Mean Diffusivity ◽

Perivascular Space ◽

Motor Symptom ◽

Imaging Features ◽

Subcortical Nuclei ◽

The Difference

AbstractPerivascular space (PVS) is associated with neurodegenerative diseases, while its effect on Parkinson’s disease (PD) remains unclear. We aimed to investigate the clinical and neuroimaging significance of PVS in basal ganglia (BG) and midbrain in early-stage PD. We recruited 40 early-stage PD patients and 41 healthy controls (HCs). Both PVS number and volume were calculated to evaluate PVS burden on 7 T magnetic resonance imaging images. We compared PVS burden between PD and HC, and conducted partial correlation analysis between PVS burden and clinical and imaging features. PD patients had a significantly more serious PVS burden in BG and midbrain, and the PVS number in BG was significantly correlated to the PD disease severity and L-dopa equivalent dosage. The fractional anisotropy and mean diffusivity values of certain subcortical nuclei and white matter fibers within or nearby the BG and midbrain were significantly correlated with the ipsilateral PVS burden indexes. Regarding to the midbrain, the difference between bilateral PVS burden was, respectively, correlated to the difference between fiber counts of white fiber tract passing through bilateral substantia nigra in PD. Our study suggests that PVS burden indexes in BG are candidate biomarkers to evaluate PD motor symptom severity and aid in predicting medication dosage. And our findings also highlight the potential correlations between PVS burden and both grey and white matter microstructures.

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The relationship between specific cognitive defects and burden of care in Parkinson's disease

International Psychogeriatrics ◽

10.1017/s1041610215001593 ◽

2015 ◽

Vol 28 (2) ◽

pp. 275-281 ◽

Cited By ~ 14

Author(s):

Michael Zhong ◽

Richard Peppard ◽

Dennis Velakoulis ◽

Andrew H. Evans

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Caregiver Burden ◽

Assessment Tool ◽

Linear Regression Analysis ◽

Depression Scale ◽

Multiple Linear Regression Analysis ◽

Motor Symptom ◽

Depression And Anxiety ◽

Psychosocial Effects

ABSTRACTBackground:In spite of the recognized physical and psychosocial effects of caring for patients with Parkinson's disease (PD), caregiver burden (CB) in this setting is poorly understood. The objective of this research was to identify factors that were associated with CB in an Australian population of PD caregivers using a novel instrument – the Parkinson's Disease Caregiver Burden (PDCB) questionnaire.Methods:Fifty patient–caregiver couples were recruited from three movement disorders clinics in Melbourne, Australia. Burden on caregivers was rated using the PDCB questionnaire. Burden scores were correlated with patient factors, including motor symptom severity (Unified Parkinson's Disease Ratings Scale and Hoehn & Yahr (H&Y) scale), patient cognition (Neuropsychiatry Unit Cognitive Assessment Tool; NUCOG), presence of impulsive and compulsive behaviors (Questionnaire for Impulsive–Compulsive Disorders in Parkinson's disease), and patient olfaction. Caregiver and patient demographics, as well as results for depression and anxiety (Hospital Anxiety and Depression Scale; HADS), were also examined for their relationship with CB.Results:H&Y stage, depression or anxiety in either caregiver or patient, and decreased patient NUCOG score were significantly associated with higher PDCB score. Multiple linear regression analysis identified caregiver and patient depression score and patient score for the visuoconstructional subscale of NUCOG to predict burden score. In addition, disease duration, duration of caregiving, and increased hours per day spent in giving care were significantly associated with increased burden.Conclusions:We found psychiatric and cognitive factors to be the most relevant factors in the perception of burden in PD caregivers. On top of this, we found deficits in the domain of visuoconstruction predicted burden – a relationship not yet described in literature. Targeting depression and anxiety in this setting as well as identifying caregivers at high risk of burden may give clinicians the chance to optimize care of patients with PD through the caregiver.

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