Journal of Parkinson's Disease - Volume 12, issue 3

Authors: Hiramatsu, Satoe | Morizane, Asuka | Kikuchi, Tetsuhiro | Doi, Daisuke | Yoshida, Kenji | Takahashi, Jun

Article Type: Research Article

Abstract: Background: Pluripotent stem cell (PSC)-derived dopaminergic (DA) neurons are an expected source of cell therapy for Parkinson’s disease. The transplantation of cell aggregates or neurospheres, instead of a single cell suspension has several advantages, such as keeping the 3D structure of the donor cells and ease of handling. For this PSC-based therapy to become a widely available treatment, cryopreservation of the final product is critical in the manufacturing process. However, cryopreserving cell aggregates is more complicated than cryopreserving single cell suspensions. Previous studies showed poor survival of the DA neurons after the transplantation of cryopreserved fetal ventral-mesencephalic tissues. …Objective: To achieve the cryopreservation of induced pluripotent stem cell (iPSC)-derived DA neurospheres toward clinical application. Methods: We cryopreserved iPSC-derived DA neurospheres in various clinically applicable cryopreservation media and freezing protocols and assessed viability and neurite extension. We evaluated the population and neuronal function of cryopreserved cells by the selected method in vitro . We also injected the cells into 6-hydroxydopamine (6-OHDA) lesioned rats, and assessed their survival, maturation and function in vivo. Results: The iPSC-derived DA neurospheres cryopreserved by Proton Freezer in the cryopreservation medium Bambanker hRM (BBK) showed favorable viability after thawing and had equivalent expression of DA-specific markers, dopamine secretion, and electrophysiological activity as fresh spheres. When transplanted into 6-OHDA-lesioned rats, the cryopreserved cells survived and differentiated into mature DA neurons, resulting in improved abnormal rotational behavior. Conclusion: These results show that the combination of BBK and Proton Freezer is suitable for the cryopreservation of iPSC-derived DA neurospheres. Show more

Keywords: Cryopreservation, cell-based therapy, neurosphere, dopaminergic neuron, induced pluripotent stem cells, Parkinson’s disease

DOI: 10.3233/JPD-212934

Citation: Journal of Parkinson's Disease, vol. 12, no. 3, pp. 871-884, 2022

Authors: Leimbach, Friederike | Atkinson-Clement, Cyril | Socorro, Pieter | Jahanshahi, Marjan

Article Type: Research Article

Abstract: Background: Parkinson’s disease (PD) and subthalamic nucleus deep brain stimulation (STN-DBS) are both known to induce cognitive changes. Objective: The aim of our study was to investigate the impact of STN-DBS on two forms of conditional associative learning (CAL), trial and error or corrective feedback learning, which differed in difficulty to test the load-dependency hypothesis of the cognitive effects of STN-DBS in PD. Methods: We recruited two groups of PD patients, those who had STN-DBS surgery bilaterally (n  = 24) and a second unoperated group (n  = 9) who were assessed on two versions of a task of …visual CAL involving either a more difficult trial and error learning or a relatively easier corrective feedback learning. Each task was completed twice by both groups, On and Off STN-DBS for the operated group and a first and second time by the unoperated group. Results: With STN-DBS Off , corrective feedback learning was superior to trial and error CAL, but not with STN-DBS On . The unoperated PD group had improved performance during the second assessment. To control for the improvement observed with repeated assessment in the PD control group, we split the STN-DBS group into two subgroups based on the condition of the first assessment (Off first vs. On first). While we found no STN-DBS effects for the Off first subgroup (N = 14), we observed improved performance during the second STN-DBS Off session for the On first subgroup (N = 10). Conclusion: The findings suggest that in PD, STN-DBS interferes with use of corrective feedback and its integration in the conditional associative learning process. Also STN stimulation affected the ability of operated patients to resolve proactive interference during learning of the arbitrary visual associations by trial and error or with corrective feedback. Show more

Keywords: Conditional associative learning, deep brain stimulation, Parkinson’s disease, subthalamic nucleus

DOI: 10.3233/JPD-212843

Citation: Journal of Parkinson's Disease, vol. 12, no. 3, pp. 885-896, 2022

Authors: Zheng, Zhe | Zhu, Zhoule | Ying, Yuqi | Jiang, Hongjie | Wu, Hemmings | Tian, Jun | Luo, Wei | Zhu, Junming

Article Type: Research Article

Abstract: Background: Accurate electrode targeting was essential for the efficacy of deep brain stimulation (DBS). There is ongoing debate about the necessary of microelectrode recording (MER) in subthalamic nucleus (STN)-DBS surgery for accurate targeting. Objective: This study aimed to analyze the accuracy of imaging-guided awake DBS with MER in STN for Parkinson’s disease in a single center. Methods: The authors performed a retrospective analysis of 161 Parkinson’s disease patients undergoing STN-DBS at our center from March 2013 to June 2021. The implantation was performed by preoperative magnetic resonance imaging (MRI)-based direct targeting with intraoperative MER and macrostimulation …testing. 285 electrode tracks with preoperative and postoperative coordinates were included to calculate the placement error in STN targeting. Results: 85.9% of electrodes guided by preoperative MRI were implanted without intraoperative adjustment. 31 (10.2%) and 12 (3.9%) electrodes underwent intraoperative adjustment due to MER and intraoperative testing, respectively. We found 86.2% (245/285) of electrodes with trajectory error ≤2 mm. The MER physiological signals length < 4 mm and ≥4 mm group showed trajectory error > 2 mm in 38.0% and 8.8% of electrodes, respectively. Compared to non-adjustment electrodes, the final positioning of MER-adjusted electrodes deviated from the center of STN. Conclusion: The preoperative MRI guided STN targeting results in approximately 14% cases that require electrode repositioning. MER physiological signals length < 4 mm at first penetration implied deviation off planned target. MER combined with intraoperative awake testing served to rescue such deviation based on MRI alone. Show more

Keywords: Accuracy, deep brain stimulation, microelectrode recording, Parkinson’s disease, subthalamic nucleus

DOI: 10.3233/JPD-213095

Citation: Journal of Parkinson's Disease, vol. 12, no. 3, pp. 897-903, 2022

Authors: Michels, Jennifer | van der Wurp, Hendrik | Kalbe, Elke | Rehberg, Sarah | Storch, Alexander | Linse, Katharina | Schneider, Christine | Gräber, Susanne | Berg, Daniela | Dams, Judith | Balzer-Geldsetzer, Monika | Hilker-Roggendorf, Rüdiger | Oberschmidt, Carola | Baudrexel, Simon | Witt, Karsten | Schmidt, Nele | Deuschl, Günther | Mollenhauer, Brit | Trenkwalder, Claudia | Liepelt-Scarfone, Inga | Spottke, Annika | Roeske, Sandra | Wüllner, Ullrich | Wittchen, Hans-Ulrich | Riedel, Oliver | Kassubek, Jan | Dodel, Richard | Schulz, Jörg Bernhard | Costa, Ana Sofia | Reetz, Kathrin

Article Type: Research Article

Abstract: Background: Parkinson’s disease (PD) is associated with various non-motor symptoms, including cognitive deterioration. Objective: Here, we used data from the DEMPARK/LANDSCAPE cohort to describe the association between progression of cognitive profiles and the PD motor phenotypes: postural instability and gait disorder (PIGD), tremor-dominant (TR-D), and not-determined (ND). Methods: Demographic, clinical, and neuropsychological six-year longitudinal data of 711 PD-patients were included (age: M  = 67.57; 67.4% males). We computed z-transformed composite scores for a priori defined cognitive domains. Analyses were controlled for age, gender, education, and disease duration. To minimize missing data and drop-outs, three-year follow-up data …of 442 PD-patients was assessed with regard to the specific role of motor phenotype on cognitive decline using linear mixed modelling (age: M  = 66.10; 68.6% males). Results: Our study showed that in the course of the disease motor symptoms increased while MMSE and PANDA remained stable in all subgroups. After three-year follow-up, significant decline of overall cognitive performance for PIGD-patients were present and we found differences for motor phenotypes in attention (β = –0.08, SE = 0.003, p  < 0.006) and memory functions showing that PIGD-patients deteriorate per months by –0.006 compared to the ND-group (SE = 0.003, p  = 0.046). Furthermore, PIGD-patients experienced more often difficulties in daily living. Conclusion: Over a period of three years, we identified distinct neuropsychological progression patterns with respect to different PD motor phenotypes, with early executive deficits yielding to a more amnestic profile in the later course. Here, in particular PIGD-patients worsened over time compared to TR-D and ND-patients, highlighting the greater risk of dementia for this motor phenotype. Show more

Keywords: Cognitive decline, dementia, longitudinal, mild cognitive impairment, Parkinson’s disease, postural instability and gait disorder, progression, tremor-dominant

DOI: 10.3233/JPD-212787

Citation: Journal of Parkinson's Disease, vol. 12, no. 3, pp. 905-916, 2022

Authors: Kovács, Norbert | Bergmann, Lars | Anca-Herschkovitsch, Marieta | Cubo, Esther | Davis, Thomas L. | Iansek, Robert | Siddiqui, Mustafa S. | Simu, Mihaela | Standaert, David G. | Chaudhuri, K. Ray | Bourgeois, Paul | Gao, Tianming | Kukreja, Pavnit | Pontieri, Francesco E. | Aldred, Jason

Article Type: Research Article

Abstract: 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 non-motor 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 non-motor 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. Show more

Keywords: Dyskinesia, health-related quality of life, levodopa-carbidopa intestinal gel, non-motor symptoms, Parkinson’s disease

DOI: 10.3233/JPD-212979

Citation: Journal of Parkinson's Disease, vol. 12, no. 3, pp. 917-926, 2022

Authors: Zolfaghari, Sheida | Lewandowski, Natalia | Pelletier, Amelie | Naeimi, Seyed Ali | Gagnon, Jean-François | Brillon-Corbeil, Marina | Montplaisir, Jacques Y. | Postuma, Ronald B.

Article Type: Short Communication

Abstract: Several studies have suggested that atherosclerotic diseases and diabetes may be risk factors for α -synucleinopathies. This prospective cohort study evaluated whether cardiovascular diseases and metabolic risk factors alter the rate or type of phenoconversion from idiopathic/isolated REM sleep behavior disorder (iRBD) to parkinsonism or dementia. Polysomnography-confirmed iRBD patients recruited between 2004 and 2020 were followed annually. Baseline history of cardiovascular disorders, hypertension, hypercholesterolemia, and diabetes were compared among patients who developed outcomes versus those who remained outcome-free. No atherosclerotic risk factors were associated with development of α -synucleinopathies. Patients with hypercholesterolemia were somewhat more likely to develop dementia with …Lewy bodies rather than Parkinson’s disease. Show more

Keywords: REM sleep behavior disorder, cardiovascular disease, hypertension, diabetes, hypercholesterolemia, α-synucleinopathies, Parkinson’s disease, dementia with Lewy bodies, cohort

DOI: 10.3233/JPD-212984

Citation: Journal of Parkinson's Disease, vol. 12, no. 3, pp. 927-933, 2022

Authors: Santos García, Diego | Canfield, Hector | de Deus Fonticoba, Teresa | Cores Bartolomé, Carlos | Naya Ríos, Lucía | García Roca, Lucía | Martínez Miró, Cristina | Jesús, Silvia | Aguilar, Miquel | Pastor, Pau | Cosgaya, Marina | García Caldentey, Juan | Caballol, Nuria | Legarda, Inés | Hernández Vara, Jorge | Cabo, Iria | López Manzanares, Lydia | González Aramburu, Isabel | Ávila Rivera, María A. | Gómez Mayordomo, Víctor | Nogueira, Víctor | Puente, Víctor | Dotor, 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 | Blázquez Estrada, Marta | Seijo, Manuel | Rúiz Martínez, Javier | Valero, Caridad | Kurtis, Mónica | de Fábregues, Oriol | González Ardura, Jessica | Alonso Redondo, Ruben | Ordás, Carlos | López Díaz, Luis M. | McAfee, Darrian | Martinez-Martin, Pablo | Mir, Pablo | COPPADIS Study Group

Article Type: Research Article

Abstract: Background: Motor phenotype (MP) can be associated with a different prognosis in Parkinson’s disease (PD), but it is not fixed and can change over time. Objective: Our aim was to analyze how the MP changed over time and to identify factors associated with the changes in PD patients from a multicenter Spanish PD cohort. Methods: PD patients who were recruited from January-2016 to November-2017 (baseline visit; V0) and evaluated again at a 2-year±30 days follow-up (V2) from 35 centers of Spain from the COPPADIS cohort, were included in this study.MP was calculated at both visits based …on Jankovic classification in TD (tremor dominant), IND (indeterminate), or PIGD (postural instability and gait difficulty). Sociodemographic and clinical data were collected, including serum biomarkers. Results: Five hundred eleven patients (62.57±8.59 years old; 59.2%males) were included in the study. At V0, MP was: 47.4%(242/511) TD; 36.6%(187/511) PIGD; 16%(82/511) IND. Up to 38%(194/511) of the patients changed their phenotype from V0 to V2, being the most frequent from TD to IND (8.4%) and from TD to PIGD (6.7%). A worse cognitive status (OR = 0.966) and less autonomy for activities of daily living (OR  =  0.937) at V0 and a greater increase in the globalNMS burden (OR  =  1.011) from V0 to V2 were associated with changing from TD to another phenotype after 2-year follow-up. Conclusion: The MP in PD can change over time. With disease progression, the percentage of cases with non-tremoric MP increases. PD patients who changed from TD to postural instability and gait difficulty increased NMS burden significantly. Show more

Keywords: Changes, motor, Parkinson’s disease, phenotype, postural instability, gait difficulty, tremor

DOI: 10.3233/JPD-213004

Citation: Journal of Parkinson's Disease, vol. 12, no. 3, pp. 935-955, 2022

Authors: Soh, Emily Ming Li | Neo, Shermyn | Saffari, Seyed Ehsan | Wong, Aidan Sheng Yong | Ganesan, Ganga | Li, Wei | Ng, Hwee Lan | Xu, Zheyu | Tay, Kay Yaw | Au, Wing Lok | Tan, Kelvin Bryan | Tan, Louis Chew Seng

Article Type: Research Article

Abstract: Background: There is currently insufficient long-term data on costs of treatment in patients with Parkinson’s disease (PD), which is chronic and progressive, and associated with substantial healthcare costs. Identifying patterns in healthcare utilization and cost may illuminate further discussion on early intervention. Objective: To characterize long-term healthcare utilization and costs of PD in newly diagnosed patients managed by movement disorder specialists. Methods: Using a longitudinal matched-cohort study of linked data from the National Neuroscience Institute Parkinson’s disease and Movement Disorder and healthcare administrative databases in Singapore from 2008–2017, we compared healthcare utilization and costs between patients …and controls matched on age, sex, race, and Charlson Comorbidity Index score. Results: 1,162 patients met study inclusion criteria and 1,157 matched controls were identified. The total mean annual healthcare cost (at 2017 costs) was significantly increased in patients compared to controls from years 1–9 post-diagnosis. The increased cost was observed 2 years before diagnosis (USD2322 vs. 2052; p  < 0.001). Mean annual cost attributable to PD increased from USD1854 at 1-year post-diagnosis to USD2652 at 9 years. Over 9 years, average costs were significantly higher across all domains of healthcare utilization except primary care—cost of intermediate and long-term care was increased by a factor of 2.5, specialist care by 2.3, emergency department visits by 1.6, and hospital admissions by 1.3. Conclusion: PD results in higher healthcare utilization and costs. Pre-diagnosis increase in healthcare utilization observed in patients supports the presence of prodromal PD symptoms and may present an opportunity for early diagnosis. Show more

Keywords: Parkinson’s disease, cost-of-illness, healthcare, utilization

DOI: 10.3233/JPD-212982

Citation: Journal of Parkinson's Disease, vol. 12, no. 3, pp. 957-966, 2022

Authors: Roos, Dareia S. | Klein, Martin | Deeg, Dorly J.H. | Doty, Richard L. | Berendse, Henk W.

Article Type: Research Article

Abstract: Background: The prodromal phase of Parkinson’s disease (PD) can last up to 20 years and is characterized by a variety of non-motor symptoms. Objective: To determine the prevalence of a selection of non-motor symptoms known to be associated with an increased risk of developing PD in a late middle-aged population-based sample and to determine their association with motor function. Methods: At a mean age of 60.3 years, 775 subjects were recruited from the Longitudinal Aging Study Amsterdam (LASA). Hyposmia, cognitive impairment, patient-reported constipation, possible REM-sleep behavior disorder, depression, and anxiety were indexed as known PD risk …factors. Additionally, 1) the PD screening questionnaire, 2) four physical performance tests, and 3) a functional limitations questionnaire, were used to determine whether the presence of two or more PD risk factors was associated with reduced motor function. Results: The prevalence of single risk factors ranged between 3 and 13%. Approximately 11% of subjects had two or more PD risk factors. Motor functioning of subjects with two or more PD risk factors was significantly worse than performance of subjects without or with a single risk factor (all p values≤0.001). Conclusion: Approximately 11% of the late middle-aged population has two or more known PD risk factors. Among these subjects self-perceived PD symptoms and reduced physical performance are more prevalent, suggesting that at least some of these subjects may be in the prodromal phase of PD. Show more

Keywords: Parkinson’s disease, prodromal symptoms, hyposmia, risk factors

DOI: 10.3233/JPD-213007

Citation: Journal of Parkinson's Disease, vol. 12, no. 3, pp. 967-974, 2022

Authors: Lau, Yue Hui | Podlewska, Aleksandra | Ocloo, Josephine | Gupta, Atul | Gonde, Christopher | Bloem, Bastiaan R. | Chaudhuri, K. Ray

Article Type: Research Article

Abstract: Background: Lack of participation of black and minority ethnic communities (BAME) in registered clinical trials is a concern as data emerging from these studies are used to licence new drugs or other interventions, even though findings made in such selected study populations have limited external validity in the aforesaid ethnic groups. Objective: We used Parkinson’s disease (PD), the fastest rising neurodegenerative disorder in the world, as an exemplar condition to test our hypothesis that participants from BAME communities are underrepresented in clinical trials. Methods: A systematic search of clinical trials registered on a Clinicaltrials.gov database which …queried for PD with racial distribution data from 2017 to 2021. Results: Out of 266 trials considered, 54 trials were published in peer reviewed journals. Among these, only 23 (42.65%) publications reported data regarding the racial distribution of the participants. Out of these, five studies involved mixed racial participation and two trials included black subjects. Conclusion: We found that inclusion of under-represented BAME groups in recently published clinical trials is low, at only 21.57%, and is not even considered in most studies. Out of the reviewed trials, only 5 (21.75%) studies reported detailed demographic categories with black minorities enrolment. This constitutes a severe under-representation when compared to the proportion of Black or African American in the UK population (3%). Results of this study identified the need for better reporting of racial composition in clinical trials. We strongly recommend that future studies should consider ethnicity and other issues around diversity when designing and implementing the clinical trials, not only in the PD field but also beyond. Show more

Keywords: Clinical trials, diversity, ethnicity, Parkinson’s disease

DOI: 10.3233/JPD-213113

Citation: Journal of Parkinson's Disease, vol. 12, no. 3, pp. 975-981, 2022

Authors: Postuma, Ronald B. | Pelletier, Amelie | Gagnon, Jean-Francois | Montplaisir, Jaccques

Article Type: Research Article

Abstract: Background: Prodromal multiple system atrophy (MSA) has been characterized mainly by retrospective chart reviews. Direct observation and tracking of prodromal markers in MSA have been very limited Objective: To report the baseline characteristics and evolution of prodromal markers of MSA as they were prospectively measured in patients with idiopathic/isolated REM sleep behavior disorder (iRBD) Methods: Patients with iRBD were evaluated as part of a comprehensive protocol repeated annually. The protocol included assessment of motor, sleep, psychiatric, and autonomic symptoms supplemented by motor examination, quantitative motor testing, neuropsychological examination, orthostatic blood pressure measurement, and tests of olfaction …and color vision. Patients who eventually developed MSA were described and compared with those who phenoconverted to Lewy body disease (Parkinson’s disease and dementia with Lewy bodies). Results: Of 67 phenocoverters, 4 developed MSA-P and 63 developed Lewy body disease. An additional 2 MSA-C patients were seen at baseline, already with cerebellar signs. Compared to those with Lewy body disease, those with MSA-P were younger, had less severe loss of tonic REM sleep atonia, more insomnia symptoms, and better olfaction. Clinically-evident autonomic dysfunction was not invariable in prodromal stages, often developing proximate to or after motor phenoconversion. Of the autonomic symptoms, genitourinary dysfunction was the first to develop in all cases. Olfaction and cognition remained normal throughout the prodromal and clinical disease course, in clear contrast to patients with Lewy body disease. Conclusion: Prodromal MSA progresses rapidly, often without substantial autonomic dysfunction, and with preserved olfaction and cognition throughout its prodromal course. Show more

Keywords: Multiple system atrophy, prodromal

DOI: 10.3233/JPD-213039

Citation: Journal of Parkinson's Disease, vol. 12, no. 3, pp. 983-991, 2022

Authors: Stott, Simon | Broza, Yoav Y. | Gharra, Alaa | Wang, Zhen | Barker, Roger A. | Haick, Hossam

Article Type: Research Article

Abstract: Background: The analysis of volatile organic compounds (VOCs) collected in breath samples has the potential to be a rapid, non-invasive test to aid in the clinical diagnosis and tracking of chronic conditions such as Parkinson’s disease (PD). Objective: To assess the feasibility and utility of breath sample analysis done, both at point of collection in clinic and when sent away to be analyzed remotely, to diagnose, stratify and monitor disease course in a moderately large cohort of patients with PD. Methods: Breath samples were collected from 177 people with PD and 37 healthy matched control individuals …followed over time. Standard clinical data (MDS-UPDRS & cognitive assessments) from the PD patients were collected at the same time as the breath sample was taken, these measures were then correlated with the breath test analysis of exhaled VOCs. Results: The breath test was able to distinguish patients with PD from healthy control participants and correlated with disease stage. The off-line system (remote analysis) gave good results with overall classification accuracies across a range of clinical measures of between 73.6% to 95.6%. The on-line (in clinic) system showed comparable results but with lower levels of correlation, varying between 33.5% to 82.4%. Chemical analysis identified 29 potential molecules that were different and which may relate to pathogenic pathways in PD. Conclusion: Breath analysis shows potential for PD diagnostics and monitoring. Both off-line and on-line sensor systems were easy to do and provided comparable results which will enable this technique to be easily adopted in clinic if larger studies confirm our findings. Show more

Keywords: Diagnosis, breath tests, biomarkers, volatile organic compounds, sensing materials, point of care testing, nanoparticles

DOI: 10.3233/JPD-213133

Citation: Journal of Parkinson's Disease, vol. 12, no. 3, pp. 993-1002, 2022

Authors: Goldberg, Alon

Article Type: Research Article

Abstract: Background: Parkinson’s disease (PD) is one of the most common chronic, progressive neurodegenerative diseases, with well-developed research focusing on the caregiver-spouse showing low well-being along with predeath grief and feelings of loss among caregivers. However, offspring of a parent diagnosed with PD may also suffer predeath grief and loss even if they are not their parent‘s main caregiver. Yet, this research is not well developed. Objective: The objective of the current study was to examine offspring’s coming to terms with their parent’s PD and the well-being of the offspring, within the conceptual framework of attachment theory. …Methods: Seventy-one Israeli adult children of parents with PD participated in the study and completed self-report questionnaires assessing their resolution of their parent‘s PD, attachment, well-being, and the severity of the PD symptoms. Results: Results showed that attachment anxiety negatively associated with higher resolution of the parent’s disease, beyond the effect of the PD symptoms’ severity. In addition, resolution of the parent’s disease was positively associated with the offspring‘s well-being. Conclusion: Resolution of a parent’s PD is highly challenging for offspring with attachment anxiety. Therefore, targeting these individuals within the offspring of parents diagnosed with PD may assist them with coping during this challenging period. This may be especially impactful, as research shows that those offspring who resolve their parent’s PD also have higher well-being. Show more

Keywords: Parkinson disease, resolution of disease, attachment, well-being

DOI: 10.3233/JPD-212931

Citation: Journal of Parkinson's Disease, vol. 12, no. 3, pp. 1003-1012, 2022

Authors: Pauly, Laure | Pauly, Claire | Hansen, Maxime | Schröder, Valerie E. | Rauschenberger, Armin | Leist, Anja K. | Krüger, Rejko | on behalf of the NCER-PD Consortium

Article Type: Research Article

Abstract: Background: The analysis of the procedural memory is particularly relevant in neurodegenerative disorders like Parkinson’s disease, due to the central role of the basal ganglia in procedural memory. It has been shown that anterograde procedural memory, the ability to learn a new skill, is impaired in Parkinson’s disease. However, retrograde procedural memory, the long-term retention and execution of skills learned in earlier life stages, has not yet been systematically investigated in Parkinson’s disease. Objective: This study aims to investigate retrograde procedural memory in people with Parkinson’s disease. We hypothesized that retrograde procedural memory is impaired in …people with Parkinson’s disease compared to an age- and gender-matched control group. Methods: First, we developed the CUPRO evaluation system, an extended evaluation system based on the Cube Copying Test, to distinguish the cube copying procedure, representing functioning of retrograde procedural memory, and the final result, representing the visuo-constructive abilities. Development of the evaluation system included tests of discriminant validity. Results: Comparing people with typical Parkinson’s disease (n  = 201) with age- and gender-matched control subjects (n  = 201), we identified cube copying performance to be significantly impaired in people with Parkinson’s disease (p  = 0.008). No significant correlation was observed between retrograde procedural memory and disease duration. Conclusion: We demonstrated lower cube copying performance in people with Parkinson’s disease compared to control subjects, which suggests an impaired functioning of retrograde procedural memory in Parkinson’s disease. Show more

Keywords: Parkinson’s disease, neurodegenerative disorder, cognitive impairment, memory, habits, neuropsychology

DOI: 10.3233/JPD-213081

Citation: Journal of Parkinson's Disease, vol. 12, no. 3, pp. 1013-1022, 2022

Authors: Goh, Zhao H.K. | Cheong, Julia L.Y. | Marras, Connie | Tanner, Caroline M. | Kasten, Meike | Korczyn, Amos D. | Chahine, Lana | Lo, Raymond | Noyce, Alastair J. | on behalf of the Movement Disorders Society Epidemiology Study Group

Article Type: Research Article

Abstract: Background: Parkinson’s disease (PD) is a debilitating neurodegenerative disease with both motor and non-motor manifestations. Available treatment reduces symptoms and is critical for improving quality of life. Treatment options include drugs, device-aided therapies, and non-pharmacological therapies. Complementary and alternative therapies (CATs) are also used in some countries. Objective: To examine the availability of PD treatment by country, and differences by national income as defined by the World Bank (high income countries (HICs), upper middle income countries (UMICs), lower middle income countries (LMICs) and low income countries (LICs)). Methods: This study was conducted by surveying International Parkinson …and Movement Disorders Society members about availability of PD treatment. LMICs and LICs (LMICs/LICs) were analysed together. Results: There were 352 valid responses from 76 countries (41.5% from HICs, 30.4% from UMICs, and 28.1% from LMICs/LICs). Levodopa was widely available across all income groups (99%). Availability of other PD drugs decreased with national income. Availability of device-aided therapies decreased with national income (100% availability in HICs, 92.5% among UMICs, and 57.6% among LMICs/LICs). A similar trend was observed for CATs (37.0% availability in HICs, 31.8% in UMICs, and 19.2% in LMIC/LICs). Physiotherapy was the most available non-pharmacological therapy (> 90% respondents). Occupational therapy and SALT were less available in LMIC/LICs (49.5% and 55.6% respectively) compared to HICs (80.1% and 84.9% respectively). Conclusion: Our survey highlights significant discrepancies in availability of PD treatments between countries and income groups. This is concerning given the symptomatic benefit patients gain from treatment. Improving equitable access to PD treatment should be prioritised. Show more

Keywords: Access, epidemiology, medication, Parkinson’s disease

DOI: 10.3233/JPD-213006

Citation: Journal of Parkinson's Disease, vol. 12, no. 3, pp. 1023-1034, 2022

Authors: Osler, Merete | Okholm, Gunhild Tidemann | Villumsen, Marie | Rozing, Maarten Pieter | Jørgensen, Terese Sara Høj

Article Type: Research Article

Abstract: Background: The underlying disease mechanisms of Parkinson’s disease (PD) are still unknown and knowledge about risk and prognostic factors is sparse. Objective: To examine the association between intelligence, education, body height, and body mass index (BMI) in young adulthood and risk of PD and subsequent survival. Methods: In total, 656,751 men born 1939–1959 with information from conscription examinations around age 19 years were followed for PD and mortality from 1977–2018 in Danish registries. Cox proportional hazard regression was used to conduct the analyses. Results: During follow-up, 5,264 (0.8%) men were …diagnosed with PD. Higher intelligence, education, and body height conferred a higher hazard of PD, independent of age at disease onset. BMI above compared to below the mean (22.8 kg/m2 ) was associated with slightly higher hazard of late-onset PD (>60 years). During follow-up, 2,125 (40.5%) men with PD died, corresponding to a 2.55 (95% confidence interval:2.44–2.66) times higher mortality compared to men without PD. Intelligence was inversely associated with mortality in men with and without PD. Higher education and body height were also inversely associated with mortality in men without PD, whereas the estimates were less pronounced and imprecisely estimated for men with PD. Having an obese BMI was associated with higher mortality in men with PD. Conclusion: Intelligence, education, and body height in young adulthood are positively associated with risk of PD later in life among men. BMI above the mean only confer a higher risk for late-onset PD. For men diagnosed with PD, high intelligence is the only early life indicator associated with better survival, whereas obese BMI predicts poorer survival. Show more

Keywords: Parkinson’s disease, survival, early living conditions, cohort study

DOI: 10.3233/JPD-213102

Citation: Journal of Parkinson's Disease, vol. 12, no. 3, pp. 1035-1043, 2022

Authors: Zapf, Alexandra C. | Folkerts, Ann-Kristin | Kahler, Larissa | Schnitzler, Alfons | Reker, Paul | Barbe, Michael T. | Florin, Esther | Kalbe, Elke

Article Type: Research Article

Abstract: Background: Parkinson’s disease (PD) has been associated with a tendency towards more risky decisions. However, the commonly used paradigms typically neglect the social context. Objective: Here, we investigated social decision-making and self-estimation in a competitive experimental task. Methods: A computerized experimental setting was used in which 86 PD patients (age = 66.5 [50–79], 62.8% male, H&Y = 2 [1.5–3]) and 44 healthy controls (HC; age = 67 [54–79], 54.4% male) in groups of four performed mathematical addition tasks in which they were asked to calculate as many sums as possible in five minutes. Participants had to choose their preferred compensation scheme (“piece …rate” versus “tournament”) and retrospectively rank their performance in comparison to the suspected performance of the others. A comprehensive neuropsychological test battery was also conducted. Results: No significant difference was found in overall social decision-making and self-estimation between PD patients and HC. However, for those individuals who made inadequate decisions, PD patients engaged in significantly more risk-averse and HC in more risky decisions. Concerning those inadequate decisions, the PD patients made more extreme decisions (severity of social decision-making) in both directions (risk-averse, risk-seeking). Conclusion: Our data indicate that social decision-making behavior and self-estimation are largely intact in PD patients with mild to moderate disease stages and intact global cognition, executive functions, and social cognition. Future studies with more heterogeneous PD samples regarding their neuropsychological profile will have to examine at which state social decision-making may be affected and by which factors this behavior might be influenced. Show more

Keywords: Parkinson’s disease, social decision-making, self-estimation, social behavior, social cognition

DOI: 10.3233/JPD-212960

Citation: Journal of Parkinson's Disease, vol. 12, no. 3, pp. 1045-1057, 2022

Authors: Sklerov, Miriam | Browner, Nina | Dayan, Eran | Rubinow, David | Frohlich, Flavio

Article Type: Research Article

Abstract: Background: Autonomic dysfunction and depression are common non-motor symptoms of Parkinson’s disease (PD) that confer poorer prognosis. These PD symptoms may have overlapping pathophysiologic underpinnings. Objective: To investigate associations between autonomic and depression symptoms in early PD, and their evolution over time. Methods: We obtained data from the Parkinson’s Progression Markers Initiative, a prospective open-access database of early PD. Regression analyses were used to model effects of depression on autonomic symptoms in controls and in PD at baseline, visit 6 (24 months after baseline), and visit 12 (60 months after baseline), correcting for multiple comparisons. …Results: Data from 421 people with PD at baseline, 360 at visit 6, 300 at visit 12, and 193 controls were included. When controlling for age, depression, and anti-hypertensive medications, depression predicted autonomic symptoms in all groups. Accounting for motor symptoms did not alter these associations. When comparing groups, the influence of depression on autonomic symptoms was stronger in all PD groups compared to controls, and strongest in PD at visit 12. Depression predicted the presence of orthostatic hypotension only in the PD group at visit 12. Conclusion: We demonstrated the important impact of depression on autonomic symptoms in early and middle stages of PD, which are independent of motor symptoms. Though the physiologic basis of these two PD symptoms are not fully understood, our findings add to pathologic evidence of a shared mechanistic substrate, separate from that responsible for PD motor symptoms. These findings may influence clinical management and development of novel therapies. Show more

Keywords: Parkinson’s disease, non-motor symptoms, depression, autonomic dysfunction, autonomic symptoms

DOI: 10.3233/JPD-213075

Citation: Journal of Parkinson's Disease, vol. 12, no. 3, pp. 1059-1067, 2022