Journal of Parkinson's Disease - Volume 11, issue 1

Authors: Lee, Yang Hyun | Lee, Wha Jin | Chung, Seok Jong | Yoo, Han Soo | Jung, Jin Ho | Baik, Kyoungwon | Sohn, Young H. | Seong, Joon-Kyung | Lee, Phil Hyu

Article Type: Research Article

Abstract: Background: The different effects of white matter hyperintensity (WMH) severity and WMH-associated microstructural connectivity on cognition in the early stages of Parkinson’s disease (PD) have not been investigated. Objective: To investigate the differential effect of WMH severity and WMH-associated microstructural connectivity on cognition in early stages of PD. Methods: A total of 136 de novo PD patients were enrolled and divided into groups based on total WMH visual rating scores as follows: mild, moderate, and severe. Microstructural connectivity was measured using graph theoretical analysis according to WMH severity. Additionally, correlation coefficients between WMH-associated microstructural connectivity or …WMH scores and cognitive performance were assessed. Results: Patients with severe WMHs demonstrated poorer performance in language function than those with moderate WMHs, and in frontal/executive and visual memory function than those with mild WMHs. Areas of microstructural connectivity were more extensive in patients with severe WMHs compared to those with mild and moderate WMHs, involving frontal and parieto-temporal regions. WMH-associated right fronto-temporo-parietal microstructural disintegration was correlated with cognitive dysfunction in attention, frontal/executive, and memory domains, whereas there was no correlation between WMH scores and any cognitive domains. Conclusion: These data suggest that disruption of microstructural networks by WMHs, rather than WMH burden itself, contributed more to cognitive impairment in PD. Show more

Keywords: Cognition, diffusion tensor imaging, microstructural connectivity, Parkinson’s disease, white matter hyperintensities

DOI: 10.3233/JPD-202312

Citation: Journal of Parkinson's Disease, vol. 11, no. 1, pp. 239-249, 2021

Authors: Netser, Roni | Demmin, Docia L. | Dobkin, Roseanne | Goldstein, Ariel | Roché, Matthew | Netser Zernik, Amitai | Silverstein, Steven M.

Article Type: Research Article

Abstract: Background: Parkinson’s disease (PD) is known to affect retinal structure and activity. As such, retinal evaluations may be used to develop objective and possibly early PD diagnostic tools. Objective: The aim of this study was to investigate the effects of Parkinson’s disease (PD) manifestation and treatment on retinal activity. Methods: Data were collected on 21 participants diagnosed with PD, including the number of medications taken, clinical scales and flash electroretinography (fERG) measurements, under light-adapted and dark-adapted conditions. The fERG parameters measured included a-wave and b-wave amplitude and implicit time (i.e., latency). First, we investigated correlations between …symptom measure scores and the fERG parameters. Next, we divided participants into two groups based on their antiparkinsonian medication load and analyzed differences between these groups’ fERG parameters. Results: fERG parameters were strongly correlated with a number of clinical variables, including motor and non-motor symptoms and age at PD onset. Photoreceptor cell implicit time was longer among participants taking one or less antiparkinsonian medication as compared to those taking two or more. However, overall there was not strong evidence of a relationship between the number of antiparkinsonian medications taken and the fERG parameters. Conclusion: Findings suggest that fERG may be a useful, non-intrusive measure of retinal, and, perhaps overall CNS function, in PD. However, additional studies in larger samples are needed to clarify this association. Show more

Keywords: Parkinson’s disease, electroretinography, retina, electrophysiology, biomarker

DOI: 10.3233/JPD-191830

Citation: Journal of Parkinson's Disease, vol. 11, no. 1, pp. 251-259, 2021

Authors: Fearon, Conor | Lees, Andrew J. | McKinley, John J. | McCarthy, Allan | Smyth, Shane | Farrell, Michael | Lynch, Timothy

Article Type: Other

Abstract: Clinical, neuropathological and neuroimaging research suggests that pathological changes in Parkinson’s disease (PD) start many years before the emergence of motor signs. Since disease-modifying treatments are likely to be most effective when initiated early in the disease process, there has been significant interest in characterizing prodromal PD. Some people with PD describe autonomic symptoms at the time of diagnosis suggesting that autonomic dysfunction is a common feature of prodromal PD. Furthermore, subtle motor signs may be present and emerge prior to the time of diagnosis. We present a series of patients who, in the prodromal phase of PD, experienced the …emergence of tremor initially only while yawning or straining at stool and discuss how early involvement of autonomic brainstem nuclei could lead to these previously unreported phenomena. The hypothalamic paraventricular nucleus (PVN) plays a central role in autonomic control including bowel/bladder function, cardiovascular homeostasis and yawning and innervates multiple brainstem nuclei involved in autonomic functions (including brainstem reticular formation, locus ceruleus, dorsal raphe nucleus and motor nucleus of the vagus). The PVN is affected in PD and evidence from related phenomena suggest that the PVN could increase tremor either by increasing downstream cholinergic activity on brainstem nuclei such as the reticular formation or by stimulating the locus ceruleus to activate the cerebellothalamocortical network via the ventrolateral nucleus of the thalamus. Aberrant cholinergic/noradrenergic transmission between these brainstem nuclei early in PD couldlead to tremor before the emergence of other parkinsonian signs, representing an early clinical clue to prodromal PD. Show more

Keywords: Parkinson’s disease, tremor, yawning, dopamine

DOI: 10.3233/JPD-202322

Citation: Journal of Parkinson's Disease, vol. 11, no. 1, pp. 261-269, 2021

Authors: Economou, Kristin | Quek, Dione | MacDougall, Hamish | Lewis, Simon J.G. | Ehgoetz Martens, Kaylena A.

Article Type: Research Article

Abstract: Background: Freezing of gait (FOG) in Parkinson’s disease (PD) has been shown to be more frequent in stressful situations, implicating anxiety. Heart rate (HR) has been shown to increase prior to a FOG episode supporting the notion that elevated stress levels may trigger FOG. However, no studies to date have investigated whether elevated HR precedes all subtypes of FOG or only those episodes that are driven by anxiety. Objective: The present study sought to investigate whether 1) HR increases prior to FOG episodes in nonspecific environments (Experiment 1), and if 2) HR increases prior to FOG when provoked …in high but not low threat environments using a virtual reality paradigm (Experiment 2). Methods: In Experiment 1, 10 of 19 participants with PD and FOG (PD + FOG) experienced FOG during a series of walking trials. In Experiment 2, 12 of 23 participants with PD + FOG experienced FOG while walking across an elevated and ground level narrow plank in virtual reality. HR was collected throughout the duration of both experiments, while FOG was quantified by experts using video review and tagging. Results: HR significantly increased 2–3 seconds prior to a FOG episode during Experiment 1. In Experiment 2, HR significantly increased 4–6 seconds prior to a FOG episode, specifically while navigating the elevated plank. However, there were no significant increases in HR prior to FOG episodes when participants navigated the ground plank. Conclusion: This study extends previous work further demonstrating that increases in HR prior to FOG episodes appear linked to elevated anxiety levels. Show more

Keywords: Freezing of gait, psychophysiology, heart rate, Parkinson’s disease, anxiety, threat

DOI: 10.3233/JPD-202146

Citation: Journal of Parkinson's Disease, vol. 11, no. 1, pp. 271-282, 2021

Authors: Crowley, Samuel J. | Banan, Guita | Amin, Manish | Tanner, Jared J. | Hizel, Loren | Nguyen, Peter | Brumback, Babette | Rodriguez, Katie | McFarland, Nikolaus | Bowers, Dawn | Ding, Mingzhou | Mareci, Thomas A. | Price, Catherine C.

Article Type: Research Article

Abstract: Background: Some individuals with Parkinson’s disease (PD) experience working memory and inhibitory difficulties, others learning and memory difficulties, while some only minimal to no cognitive deficits for many years. Objective: To statistically derive PD executive and memory phenotypes, and compare PD phenotypes on disease and demographic variables, vascular risk factors, and specific neuroimaging variables with known associations to executive and memory function relative to non-PD peers. Methods: Non-demented individuals with PD (n  = 116) and non-PD peers (n  = 62) were recruited to complete neuropsychology measures, blood draw, and structural magnetic resonance imaging. Tests representing the cognitive domains …of interest (4 executive function, 3 memory) were included in a k-means cluster analysis comprised of the PD participants. Resulting clusters were compared demographic and disease-related variables, vascular risk markers, gray/white regions of interest, and white matter connectivity between known regions involved in executive and memory functions (dorsolateral prefrontal cortices to caudate nuclei; entorhinal cortices to hippocampi). Results: Clusters showed: 1) PD Executive, n  = 25; 2) PD Memory, n  = 35; 3) PD Cognitively Well; n  = 56. Even after disease variable corrections, PD Executive had less subcortical gray matter, white matter, and fewer bilateral dorsolateral-prefrontal cortex to caudate nucleus connections; PD Memory showed bilaterally reduced entorhinal-hippocampal connections. PD Cognitively Well showed only reduced putamen volume and right entorhinal cortex to hippocampi connections relative to non-PD peers. Groups did not statistically differ on cortical integrity measures or cerebrovascular disease markers. Conclusion: PD cognitive phenotypes showed different structural gray and white matter patterns. We discuss data relative to phenotype demographics, cognitive patterns, and structural brain profiles. Show more

Keywords: Entorhinal cortex, white matter, hippocampus, prefrontal cortex, dementia, executive function, memory

DOI: 10.3233/JPD-202166

Citation: Journal of Parkinson's Disease, vol. 11, no. 1, pp. 283-297, 2021

Authors: Sauerbier, Anna | Schrag, Anette | Brown, Richard | Martinez-Martin, Pablo | Aarsland, Dag | Mulholland, Nicola | Vivian, Gill | Dafsari, Haidar S. | Rizos, Alexandra | Corcoran, Ben | Jarosz, Jozef | Siakallis, Loizos | Ray Chaudhuri, K.

Article Type: Research Article

Abstract: Background: Ethnic phenotypic differences in Parkinson’s disease (PD) are important to understand the heterogeneity of PD and develop biomarkers and clinical trials. Objective: To investigate (i) whether there are non-motor symptoms (NMS)- and comorbidity-based phenotypic differences between Black, Asian and Minority Ethnic (BAME) and White PD patients and (ii) whether clinically available biomarkers may help differentiate and explain the differences between the groups. Methods: This is a multicentre (four sites, London), real-life, cross-sectional study including PD patients of BAME or White ethnicity. The primary outcome was a detailed NMS assessment; additional measurements included disease and motor …stage, comorbidity, sociodemographic parameters and brain MRI imaging. Results: 271 PD patients (54 Asian, 71 Black, and 146 White) were included balanced for age, gender, and disease severity (HY). Black patients had a shorter disease duration compared to White and Asian populations. The SCOPA-Motor activities of daily living scores as well as the NMSS scores were significantly higher in both Black (total score and domain “miscellaneous”) and Asian (total score and domains “sleep/fatigue”, “mood/apathy” and “perception/hallucinations”) than White individuals. Both BAME populations had higher prevalence of arterial hypertension, and the Black population had a higher prevalence of diabetes mellitus. Brain MRI revealed a greater severity of white matter changes in Black compared to the White and Asian cohorts. Conclusion: These findings suggest differences in phenotype of PD in BAME populations with greater burden of NMS and motor disability and a higher rate of cardiovascular comorbidities. Show more

Keywords: Parkinson’s disease, ethnicity, BAME, non-motor symptoms

DOI: 10.3233/JPD-202218

Citation: Journal of Parkinson's Disease, vol. 11, no. 1, pp. 299-307, 2021

Authors: Yenilmez, Ferhat | Fründt, Odette | Hidding, Ute | Buhmann, Carsten

Article Type: Research Article

Abstract: Background: Little is known about the patients’ view on treatment with medical cannabis (MC) for Parkinson’s disease (PD). Objective: To assess the PD community’s perception of MC and patients’ experience with MC. Methods: Applying a questionnaire-based survey, we evaluated general knowledge and interest in MC as well as the frequency, modalities, efficacy, and tolerability of application. Questionnaires were distributed nationwide via the membership journal of the German Parkinson Association and locally in our clinic to control for report bias. Results: Overall, 1.348 questionnaires (1.123 nationwide, 225 local) were analysed. 51% of participants were …aware of the legality of MC application, 28% of various routes of administration (ROA) and 9% of the difference between delta9-tetrahydrocannabinol (Δ9 -THC) and cannabidiol (CBD). PD-related cannabis use was reported by 8.4% of patients and associated with younger age, living in large cities and better knowledge about the legal and clinical aspects of MC. Reduction of pain and muscle cramps was reported by more than 40% of cannabis users. Stiffness/akinesia, freezing, tremor, depression, anxiety and restless legs syndrome subjectively improved for more than 20% and overall tolerability was good. Improvement of symptoms was reported by 54% of users applying oral CBD and 68% inhaling THC-containing cannabis. Compared to CBD intake, inhalation of THC was more frequently reported to reduce akinesia and stiffness (50.0% vs. 35.4%; p  < 0.05). Interest in using MC was reported by 65% of non-users. Conclusion: MC is considered as a therapeutic option by many PD patients. Nevertheless, efficacy and different ROA should further be investigated. Show more

Keywords: Cannabis, THC, cannabidiol, Parkinson’s disease, therapy, survey, patient

DOI: 10.3233/JPD-202260

Citation: Journal of Parkinson's Disease, vol. 11, no. 1, pp. 309-321, 2021

Authors: Jost, Stefanie T. | Ray Chaudhuri, K. | Ashkan, Keyoumars | Loehrer, Philipp A. | Silverdale, Monty | Rizos, Alexandra | Evans, Julian | Petry-Schmelzer, Jan Niklas | Barbe, Michael T. | Sauerbier, Anna | Fink, Gereon R. | Visser-Vandewalle, Veerle | Antonini, Angelo | Martinez-Martin, Pablo | Timmermann, Lars | Dafsari, Haidar S. | On behalf of EUROPAR and the International Parkinson and Movement Disorders Society Non-Motor Parkinson’s Disease Study Group

Article Type: Research Article

Abstract: Background: Sleep disturbances and neuropsychiatric symptoms are some of the most common nonmotor symptoms in Parkinson’s disease (PD). The effect of subthalamic stimulation (STN-DBS) on these symptoms beyond a short-term follow-up is unclear. Objective: To examine 36-month effects of bilateral STN-DBS on quality of sleep, depression, anxiety, and quality of life (QoL) compared to standard-of-care medical therapy (MED) in PD. Methods: In this prospective, controlled, observational, propensity score matched, international multicenter study, we assessed sleep disturbances using the PDSleep Scale-1 (PDSS), QoL employing the PDQuestionnaire-8 (PDQ-8), motor disorder with the Scales for Outcomes in PD (SCOPA), …anxiety and depression with the Hospital Anxiety and Depression Scale (HADS), and dopaminergic medication requirements (LEDD). Within-group longitudinal outcome changes were tested using Wilcoxon signed-rank and between-group longitudinal differences of change scores with Mann-Whitney U tests. Spearman correlations analyzed the relationships of outcome parameter changes at follow-up. Results: Propensity score matching applied on 159 patients (STN-DBS n  = 75, MED n  = 84) resulted in 40 patients in each treatment group. At 36-month follow-up, STN-DBS led to significantly better PDSS and PDQ-8 change scores, which were significantly correlated. We observed no significant effects for HADS and no significant correlations between change scores in PDSS, HADS, and LEDD. Conclusions: We report Class IIb evidence of beneficial effects of STN-DBS on quality of sleep at 36-month follow-up, which were associated with QoL improvement independent of depression and dopaminergic medication. Our study highlights the importance of sleep for assessments of DBS outcomes. Show more

Keywords: Deep brain stimulation, sleep dysfunction, subthalamic nucleus, quality of life, nonmotor symptoms

DOI: 10.3233/JPD-202278

Citation: Journal of Parkinson's Disease, vol. 11, no. 1, pp. 323-335, 2021

Authors: Liu, Yi-Hsuan | Jensen, Gordon L. | Na, Muzi | Mitchell, Diane C. | Wood, G. Craig | Still, Christopher D. | Gao, Xiang

Article Type: Research Article

Abstract: Background: Several dietary components have been shown to be neuroprotective against risk of neurodegeneration. However, limited observational studies have examined the role of overall diet quality on risk of Parkinson’s disease. Objectives: We examined the associations between diet quality and risk of Parkinson’s disease in a prospective cohort study and meta-analysis. Methods: Included in the cohort study were 3,653 participants (1,519 men and 2,134 women; mean age: 81.5 years) in the Geisinger Rural Aging Study longitudinal cohort in Pennsylvania. Diet quality was assessed using a validated dietary screening tool containing 25 food- and behavior-specific questions in …2009. Potential Parkinson’s cases were identified using electronic health records based on ICD9 (332.*), ICD10 (G20), and Parkinson-related treatments. Hazard ratios (HRs) and 95% confidence intervals (CIs) across diet quality tertiles were calculated using Cox proportional hazards models after adjusting for potential confounders. We further performed a meta-analysis by pooling our study with four published papers on this topic. Random-effects model was utilized to calculate the pooled risk ratios and 95% CIs. Results: During a mean of 6.94 years of follow-up, 47 incident Parkinson’s cases were documented. Having high diet quality at baseline was associated with lower Parkinson’s disease risk (adjusted HR for the highest vs the lowest diet quality tertile = 0.39; 95% CI: 0.17, 0.89; p -trend = 0.02). The meta-analysis including 140,617 individuals also showed that adherence to high diet quality or a healthy dietary pattern was associated with lower risk of Parkinson’s disease (pooled risk ratio = 0.64; 95% CI: 0.49, 0.83). Conclusion: Having high diet quality or a healthy dietary pattern was associated with lower future risk of Parkinson’s disease. Show more

Keywords: Diet quality, Parkinson’s disease, prospective study, meta-analysis

DOI: 10.3233/JPD-202290

Citation: Journal of Parkinson's Disease, vol. 11, no. 1, pp. 337-347, 2021

Authors: Thomsen, Trine Hørmann | Jørgensen, Lene Bastrup | Kjær, Troels Wesenberg | Winge, Kristian | Haahr, Anita

Article Type: Research Article

Abstract: Background: People with Parkinson’s disease suffer from a range of various symptoms. Altered movement patterns frequently represent the prevailing symptom experience and influence the everyday life of the affected persons. Objective: This qualitative study explores how persons with Parkinson‘s disease experience everyday life with a complex symptom profile and how they manage the consequential challenges in their daily life, as well as the motivation and consequences of these coping behaviours. Methods: Thirty-four patients with Parkinson’s disease were interviewed as an integrated part of the method Video-based Narrative. The interviews were analysed by means of qualitative content …analysis according to Graneheim & Lundman. Results: The analysis identified six predominant coping types with different behavioural traits: The convincing behaviour , The economizing behaviour , The encapsulating behaviour , The evasive behaviour , The adaptable behaviour , and The dynamic behaviour . The strategies embedded in each of the six types are diverse, but all participants seek to maintain their integrity in different ways leading to the main motivation “To stay the same person ”. Conclusion: Healthcare professionals should be aware of the patients‘ various coping behaviour in order to offer a person-centred approach. Psychoeducational interventions to promote coping skills may be essential in incorporating disease-related changes in the conduct of everyday life with Parkinson’s disease to maintain integrity. Show more

Keywords: Parkinson’s disease, coping behaviour, transition, conduct of everyday life, health-promotion, person-centred approach, qualitative research

DOI: 10.3233/JPD-202217

Citation: Journal of Parkinson's Disease, vol. 11, no. 1, pp. 349-361, 2021