Journal of Parkinson's Disease - Volume 13, issue 2

Authors: McFarthing, Kevin | Bloem, Bastiaan R. | Kalia, Lorraine V.

Article Type: Editorial

Keywords: Parkinson’s disease, editorial, patient advocate, patient participation, participatory care

DOI: 10.3233/JPD-239000

Citation: Journal of Parkinson's Disease, vol. 13, no. 2, pp. 125-126, 2023

Authors: Pirker, Walter | Katzenschlager, Regina | Hallett, Mark | Poewe, Werner

Article Type: Review Article

Abstract: The pathophysiology of Parkinson’s disease (PD) tremor remains incompletely understood and there is a lack of clinical trials specifically addressing its pharmacological treatment. Levodopa is the most efficacious drug for most patients and should be used as primary approach to control troublesome tremor. While the efficacy of oral dopamine agonists on PD tremor has been demonstrated in controlled trials, there is no evidence of greater antitremor efficacy compared to levodopa. The magnitude of the antitremor effect of anticholinergics is generally lower than that of levodopa. Due to their adverse effects, anticholinergics have a limited role in selected young and cognitively …intact patients. Propranolol may improve resting and action tremor and may be considered as an adjunct in patients with insufficient tremor response to levodopa and this also applies to clozapine, despite its unfavorable adverse effect profile. Treating motor fluctuations with MAO-B and COMT inhibitors, dopamine agonists, amantadine, or on-demand treatments such as subcutaneous or sublingual apomorphine and inhaled levodopa as well as with continuous infusions of levodopa or apomorphine will improve off period tremor episodes. For patients with drug-refractory PD tremor despite levodopa optimization deep brain stimulation and focused ultrasound are first-line considerations. Surgery can also be highly effective for the treatment medication-refractory tremor in selected patients without motor fluctuations. The present review highlights the clinical essentials of parkinsonian tremor, critically examines available trial data on the effects of medication and surgical approaches and provides guidance for the choice of treatments to control PD tremor in clinical practice. Show more

Keywords: Parkinson’s disease, tremor, treatment, levodopa, levodopa-resistance

DOI: 10.3233/JPD-225060

Citation: Journal of Parkinson's Disease, vol. 13, no. 2, pp. 127-144, 2023

Authors: Yazar, Volkan | Dawson, Valina L. | Dawson, Ted M. | Kang, Sung-Ung

Article Type: Review Article

Abstract: Regulation of gene expression by epigenetic modifications means lasting and heritable changes in the function of genes without alterations in the DNA sequence. Of all epigenetic mechanisms identified thus far, DNA methylation has been of particular interest in both aging and age-related disease research over the last decade given the consistency of site-specific DNA methylation changes during aging that can predict future health and lifespan. An increasing line of evidence has implied the dynamic nature of DNA (de)methylation events that occur throughout the lifespan has a role in the pathophysiology of aging and age-associated neurodegenerative conditions, including Parkinson’s disease (PD). …In this regard, PD methylome shows, to some extent, similar genome-wide changes observed in the methylome of healthy individuals of matching age. In this review, we start by providing a brief overview of studies outlining global patterns of DNA methylation, then its mechanisms and regulation, within the context of aging and PD. Considering diverging lines of evidence from different experimental and animal models of neurodegeneration and how they combine to shape our current understanding of tissue-specific changes in DNA methylome in health and disease, we report a high-level comparison of the genomic methylation landscapes of brain, with an emphasis on dopaminergic neurons in PD and in natural aging. We believe this will be particularly useful for systematically dissecting overlapping genome-wide alterations in DNA methylation during PD and healthy aging, and for improving our knowledge of PD-specific changes in methylation patterns independent of aging process. Show more

Keywords: Parkinson’s disease, aging, DNA methylation, substantia nigra, brain, epigenome

DOI: 10.3233/JPD-223517

Citation: Journal of Parkinson's Disease, vol. 13, no. 2, pp. 145-164, 2023

Authors: Wang, Yue | Yu, Ningbo | Lu, Jiewei | Zhang, Xinyuan | Wang, Jin | Shu, Zhilin | Cheng, Yuanyuan | Zhu, Zhizhong | Yu, Yang | Liu, Peipei | Han, Jianda | Wu, Jialing

Article Type: Research Article

Abstract: Background: In Parkinson’s disease (PD), walking may depend on the activation of the cerebral cortex. Understanding the patterns of interaction between cortical regions during walking tasks is of great importance. Objective: This study investigated differences in the effective connectivity (EC) of the cerebral cortex during walking tasks in individuals with PD and healthy controls. Methods: We evaluated 30 individuals with PD (62.4±7.2 years) and 22 age-matched healthy controls (61.0±6.4 years). A mobile functional near-infrared spectroscopy (fNIRS) was used to record cerebral oxygenation signals in the left prefrontal cortex (LPFC), right prefrontal cortex (RPFC), left parietal lobe …(LPL), and right parietal lobe (RPL) and analyze the EC of the cerebral cortex. A wireless movement monitor was used to measure the gait parameters. Results: Individuals with PD demonstrated a primary coupling direction from LPL to LPFC during walking tasks, whereas healthy controls did not demonstrate any main coupling direction. Compared with healthy controls, individuals with PD showed statistically significantly increased EC coupling strength from LPL to LPFC, from LPL to RPFC, and from LPL to RPL. Individuals with PD showed decreased gait speed and stride length and increased variability in speed and stride length. The EC coupling strength from LPL to RPFC negatively correlated with speed and positively correlated with speed variability in individuals with PD. Conclusion: In individuals with PD, the left prefrontal cortex may be regulated by the left parietal lobe during walking. This may be the result of functional compensation in the left parietal lobe. Show more

Keywords: Effective connectivity, functional near-infrared spectroscopy, gait automaticity, Parkinson’s disease, cerebral cortex

DOI: 10.3233/JPD-223564

Citation: Journal of Parkinson's Disease, vol. 13, no. 2, pp. 165-178, 2023

Authors: Xylaki, Mary | Paiva, Isabel | Al-Azzani, Mohammed | Gerhardt, Ellen | Jain, Gaurav | Islam, Md Rezaul | Vasili, Eftychia | Wassouf, Zinah | Schulze-Hentrich, Julia M. | Fischer, André | Outeiro, Tiago Fleming

Article Type: Research Article

Abstract: Background: Synucleinopathies are disorders characterized by the abnormal accumulation of α -synuclein (aSyn). Synaptic compromise is observed in synucleinopathies parallel to aSyn aggregation and is accompanied by transcript deregulation. Objective: We sought to identify microRNAs associated with synaptic processes that may contribute to synaptic dysfunction and degeneration in synucleinopathies. Methods: We performed small RNA-sequencing of midbrain from 6-month-old transgenic mice expressing A30P mutant aSyn, followed by comparative expression analysis. We then used real-time quantitative polymerase chain reaction (qPCR) for validation. Functional analysis was performed in primary neurons by biochemical assays and imaging. Results: We …found several deregulated biological processes linked to the synapse. miR-101a-3p was validated as a synaptic miRNA upregulated in aSyn Tg mice and in the cortex of dementia with Lewy bodies patients. Mice and primary cultured neurons overexpressing miR-101a-3p showed downregulation of postsynaptic proteins GABA Ab2 and SAPAP3 and altered dendritic morphology resembling synaptic plasticity impairments and/or synaptic damage. Interestingly, primary cultured neuron exposure to recombinant wild-type aSyn species efficiently increased miR-101a-3p levels. Finally, a dynamic role of miR-101a-3p in synapse plasticity was shown by identifying downregulation of miR-101a-3p in a condition of enhanced synaptic plasticity modelled in Wt animals housed in enriched environment. Conclusion: To conclude, we correlated pathologic aSyn with high levels of miR-101a-3p and a novel dynamic role of the miRNA in synaptic plasticity. Show more

Keywords: Alpha-synuclein, dendritic spines, miRNA, neuronal plasticity, synucleinopathy

DOI: 10.3233/JPD-225055

Citation: Journal of Parkinson's Disease, vol. 13, no. 2, pp. 179-196, 2023

Authors: von der Recke, Felix | Warmerdam, Elke | Hansen, Clint | Romijnders, Robbin | Maetzler, Walter

Article Type: Short Communication

Abstract: Reduced range of gait speed (RGS) may lead to decreased environmental adaptability in persons with Parkinson’s disease (PwPD). Therefore, lab-measured gait speed, step time, and step length during slow, preferred, and fast walking were assessed in 24 PwPD, 19 stroke patients, and 19 older adults and compared with 31 young adults. Only PwPD, but not the other groups, showed significantly reduced RGS compared to young adults, driven by step time in the low and step length in the high gait speed range. These results suggest that reduced RGS may occur as a PD-specific symptom, and different gait components seem to …contribute. Show more

Keywords: Parkinson’s disease, range of gait speed, disease-specific, older adults, adaptability

DOI: 10.3233/JPD-223535

Citation: Journal of Parkinson's Disease, vol. 13, no. 2, pp. 197-202, 2023

Authors: Dorsey, E. Ray | Zafar, Maryam | Lettenberger, Samantha E. | Pawlik, Meghan E. | Kinel, Dan | Frissen, Myrthe | Schneider, Ruth B. | Kieburtz, Karl | Tanner, Caroline M. | De Miranda, Briana R. | Goldman, Samuel M. | Bloem, Bastiaan R.

Article Type: Research Article

Abstract: The etiologies of Parkinson’s disease (PD) remain unclear. Some, such as certain genetic mutations and head trauma, are widely known or easily identified. However, these causes or risk factors do not account for the majority of cases. Other, less visible factors must be at play. Among these is a widely used industrial solvent and common environmental contaminant little recognized for its likely role in PD: trichloroethylene (TCE). TCE is a simple, six-atom molecule that can decaffeinate coffee, degrease metal parts, and dry clean clothes. The colorless chemical was first linked to parkinsonism in 1969. Since then, four case studies involving …eight individuals have linked occupational exposure to TCE to PD. In addition, a small epidemiological study found that occupational or hobby exposure to the solvent was associated with a 500% increased risk of developing PD. In multiple animal studies, the chemical reproduces the pathological features of PD. Exposure is not confined to those who work with the chemical. TCE pollutes outdoor air, taints groundwater, and contaminates indoor air. The molecule, like radon, evaporates from underlying soil and groundwater and enters homes, workplaces, or schools, often undetected. Despite widespread contamination and increasing industrial, commercial, and military use, clinical investigations of TCE and PD have been limited. Here, through a literature review and seven illustrative cases, we postulate that this ubiquitous chemical is contributing to the global rise of PD and that TCE is one of its invisible and highly preventable causes. Further research is now necessary to examine this hypothesis. Show more

Keywords: Air pollution, indoor air pollution, environment, Parkinson’s disease, solvents, tetrachloroethylene, trichloroethylene, water pollution, chemical water pollution

DOI: 10.3233/JPD-225047

Citation: Journal of Parkinson's Disease, vol. 13, no. 2, pp. 203-218, 2023

Authors: Santos-García, Diego | de Deus Fonticoba, Teresa | Cores Bartolomé, Carlos | Feal Painceiras, Maria J. | Íñiguez-Alvarado, Maria Cristina | García Díaz, Iago | Jesús, Silvia | Buongiorno, Maria Teresa | Planellas, Lluís | Cosgaya, Marina | García Caldentey, Juan | Caballol, Nuria | Legarda, Ines | Hernández Vara, Jorge | Cabo, Iria | López Manzanares, Lydia | González Aramburu, Isabel | Ávila Rivera, Maria A. | Gómez Mayordomo, Víctor | Nogueira, Víctor | Puente, Víctor | Dotor García-Soto, Julio | Borrué, Carmen | Solano Vila, Berta | Álvarez Sauco, María | Vela, Lydia | Escalante, Sonia | Cubo, Esther | Carrillo Padilla, Francisco | Martínez Castrillo, Juan C. | Sánchez Alonso, Pilar | Alonso Losada, Maria G. | López Ariztegui, Nuria | Gastón, Itziar | Kulisevsky, Jaime | Menéndez González, Manuel | Seijo, Manuel | Rúiz Martínez, Javier | Valero, Caridad | Kurtis, Mónica | González Ardura, Jessica | Alonso Redondo, Ruben | Ordás, Carlos | López Díaz, Luis M. | McAfee, Darrian | Martinez-Martin, Pablo | Mir, Pablo

Article Type: Research Article

Keywords: Caregiver, longitudinal, mood, Parkinson’s disease, quality of life

DOI: 10.3233/JPD-225014

Citation: Journal of Parkinson's Disease, vol. 13, no. 2, pp. 219-231, 2023

Authors: Welton, Thomas | Hartono, Septian | Shih, Yao-Chia | Lee, Weiling | Chai, Pik Hsien | Chong, Say Lee | Ng, Samuel Yong Ern | Chia, Nicole Shuang Yu | Choi, Xinyi | Heng, Dede Liana | Tan, Eng-King | Tan, Louis C.S. | Chan, Ling-Ling

Article Type: Research Article

Abstract: Background: Diffusion kurtosis imaging provides in vivo measurement of microstructural tissue characteristics and could help guide management of Parkinson’s disease. Objective: To investigate longitudinal diffusion kurtosis imaging changes on magnetic resonance imaging in the deep grey nuclei in people with early Parkinson’s disease over two years, and whether they correlate with disease progression. Methods: We conducted a longitudinal case-control study of early Parkinson’s disease. 262 people (Parkinson’s disease: n  = 185, aged 67.5±9.1 years; 43% female; healthy controls: n  = 77, aged 66.6±8.1 years; 53% female) underwent diffusion kurtosis imaging and clinical assessment at baseline and two-year …timepoints. We automatically segmented five nuclei, comparing the mean kurtosis and other diffusion kurtosis imaging indices between groups and over time using repeated-measures analysis of variance, and Pearson correlation with the two-year change in Movement Disorder Society Unified Parkinson’s Disease Rating Scale Part III. Results: At baseline, mean kurtosis was higher in Parkinson’s disease than controls in the substantia nigra, putamen, thalamus and globus pallidus when adjusting for age, sex, and levodopa equivalent daily dose (p < 0.027). These differences grew over two years, with mean kurtosis increasing for the Parkinson’s disease group while remaining stable for the control group; evident in significant “group ×time” interaction effects for the putamen, thalamus and globus pallidus ( η p 2 = 0.08–0.11, p < 0.015). However, we did not detect significant correlations between increasing mean kurtosis and declining motor function in the Parkinson’s disease group. Conclusion: Diffusion kurtosis imaging of specific grey matter structures shows abnormal microstructure in PD at baseline and abnormal progression in PD over two years. Show more

Keywords: Magnetic resonance imaging, diffusion kurtosis imaging, Parkinson’s disease, movement disorders, microstructure, interaction, substantia nigra, longitudinal

DOI: 10.3233/JPD-225095

Citation: Journal of Parkinson's Disease, vol. 13, no. 2, pp. 233-242, 2023

Authors: Chang, Yu-Tzu | Huang, Chi-Wei | Chang, Hsin-I | Hsu, Shih-Wei | Lee, Chen-Chang | Huang, Shu-Hua | Wang, Pei-Ning | Chang, Chiung-Chih

Article Type: Research Article

Abstract: Background: A better understanding of factors associated with caregiver burden might facilitate the construction of coping strategies to improve their clinical outcomes and the comprehensive care model for dementia. Objective: To investigate the cognitive and neuropsychiatric domains that contribute to caregiver burden in three types of neurodegenerative disorders: Parkinson’s disease (PD), Alzheimer’s disease (AD), and frontotemporal disease (FTD). Methods: Eight hundred and fourteen patients and their caregivers were invited to participate; among them, 235 had PD with cognitive impairment; 429 had AD, and 150 had FTD. The evaluation protocol included the Neuropsychiatric Inventory (NPI), the Mini-Mental …State Examination, the Chinese Version Verbal Learning Test, the modified Trail Making Test B, semantic fluency, and a geriatric depression score. Statistical comparisons of the cognitive tests, NPI total scores, and caregiver burden among the three diagnosed types of dementia, matched for a Clinical Dementia Rating (CDR) of 0.5 or 1, were performed, and multivariate linear regression models were used to evaluate the parameter significance. Results: Caregivers for patients with PD and FTD showed significant burden increments when the CDR scores changes from 0.5 to 1. For CDR = 0.5, the PD group had significantly lower caregiver burdens than the AD group, but the NPI total scores were significantly higher. Factors related to caregiver burden were the presence of delusion among all diagnosis groups, while the impact of NPI total scores related to caregiver burden was the highest in FTD, followed by AD and PD. Conclusions: At the mild to moderate stages, our results suggested different degrees of significance in terms of the cognitive test scores or NPI subdomains for predicting caregiver stress among the three types of dementia. Show more

Keywords: Parkinson’s disease, Alzheimer’s disease, frontotemporal disease, caregiver stress, neuropsychiatric inventory

DOI: 10.3233/JPD-223550

Citation: Journal of Parkinson's Disease, vol. 13, no. 2, pp. 243-254, 2023