Journal of Parkinson's Disease - Volume 12, issue 1

Authors: Brolin, Kajsa | Bandres-Ciga, Sara | Blauwendraat, Cornelis | Widner, Håkan | Odin, Per | Hansson, Oskar | Puschmann, Andreas | Swanberg, Maria

Article Type: Research Article

Abstract: Background: Risk factors for Parkinson’s disease (PD) can be more or less relevant to a population due to population-specific genetic architecture, local lifestyle habits, and environmental exposures. Therefore, it is essential to study PD at a local, regional, and continental scale in order to increase the knowledge on disease etiology. Objective: We aimed to investigate the contribution of genetic and environmental factors to PD in a new Swedish case-control cohort. Methods: PD patients (n  = 929) and matched population-based controls (n  = 935) from the southernmost county in Sweden were included in the cohort. Information on environmental exposures …was obtained using questionnaires at inclusion. Genetic analyses included a genome-wide association study (GWAS), haplotype assessment, and a risk profile analysis using cumulative genetic risk scores. Results: The cohort is a representative PD case-control cohort (64% men, mean age at diagnosis = 67 years, median Hoehn and Yahr score 2.0), in which previously reported associations between PD and environmental factors, such as tobacco, could be confirmed. We describe the first GWAS of PD solely composed of PD patients from Sweden, and confirm associations to well-established risk alleles in SNCA . In addition, we nominate an unconfirmed and potentially population-specific genome-wide significant association in the PLPP4 locus (rs12771445). Conclusion: This work provides an in-depth description of a new PD case-control cohort from southern Sweden, giving insights into environmental and genetic risk factors for PD in the Swedish population. Show more

Keywords: Parkinson’s disease, Sweden, case-control studies, risk factors, genome-wide association study, haplotypes

DOI: 10.3233/JPD-212818

Citation: Journal of Parkinson's Disease, vol. 12, no. 1, pp. 153-171, 2022

Authors: Chiu, Shu-Fen | Wu, Yih-Ru | Tsay, Pei-Kwei | Chiu, Yi-Chen

Article Type: Research Article

Abstract: Background: Parkinson’s disease (PD), a degenerative disease with irreversible motor dysfunction, impacts patients’ quality of life (QoL). Spirituality can provide a sense of hope and meaning when individuals are faced with adverse life events, such as a diagnosis of PD. However, few studies have examined the relationship between spiritual well-being and QoL for persons with PD. Objective: To explore the relationships between the disease characteristics, spirituality and QoL for persons with PD, and verify the mediating effects of spirituality on the relationship. Methods: This cross-sectional study recruited patients with PD (n  = 110) by convenience sampling from …a neurological clinic in northern Taiwan. Variables were measured using the Spirituality Index of Well-Being Chinese version (SIWB-C) and the 39-item Parkinson’s disease Quality of Life Questionnaire Chinese version (PDQ-39-C) self-report questionnaires. Descriptive analysis and linear hierarchical regression were conducted to examine the studied variables and explore the mediating effect of spiritual wellbeing. Results: Those whose scores were significantly better in PDQ-39 were younger, employed, with shorter disease duration and less severe condition with better functioning on their early stages and lower LEDD; additionally, those who had better quality of life also experienced better spiritual wellbeing than the counterparts. The regression model demonstrated spiritual self-efficacy had mediating effects between disease characteristics and QoL, explaining 69.8%of the variance (adjusted R 2  = 65.3%). Conclusion: The results can be the references for future strategies and interventions, focusing on increasing spiritual self-efficacy and reducing the impact of disease severity to improve QoL for persons with PD. Show more

Keywords: Parkinson’s disease, spiritual well-being, self-efficacy, quality of life

DOI: 10.3233/JPD-212764

Citation: Journal of Parkinson's Disease, vol. 12, no. 1, pp. 173-184, 2022

Authors: Chuang, Yu-Han | Tan, Chun-Hsiang | Su, Hui-Chen | Chien, Chung-Yao | Sung, Pi-Shan | Lee, Tsung-Lin | Yu, Rwei-Ling

Article Type: Research Article

Abstract: Background: Hypomimia is a clinical feature of Parkinson’s disease (PD). Based on the embodied simulation theory, the impairment of facial mimicry may worsen facial emotion recognition; however, the empirical results are inconclusive. Objective: We aimed to explore the worsening of emotion recognition by hypomimia. We further explored the relationship between the hypomimia, emotion recognition, and social functioning. Methods: A total of 114 participants were recruited. The patients with PD and normal controls (NCs) were matched for demographic characteristics. All the participants completed the Mini-Mental State Examination and the Chinese Multi-modalities Emotion Recognition Test. In addition to …the above tests, the patients were assessed with the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale and Parkinson’s Disease Social Functioning Scale (PDSFS). Results: Patients with PD with hypomimia had worse recognition of disgust than NCs (p  = 0.018). The severity of hypomimia was predictive of the recognition of disgust (β= –0.275, p  = 0.028). Facial emotion recognition was predictive of the PDSFS score of PD patients (β= 0.433, p  = 0.001). We also found that recognizing disgust could mediate the relationship between hypomimia and the PDSFS score (β= 0.264, p  = 0.045). Conclusion: Patients with hypomimia had the worst disgust facial recognition. Hypomimia may affect the social function of PD patients, which is related to recognizing the expression of disgust. Emotion recognition training may improve the social function of patients with PD. Show more

Keywords: Parkinson’s disease, hypomimia, embodied simulation theory, emotion recognition, social function

DOI: 10.3233/JPD-212830

Citation: Journal of Parkinson's Disease, vol. 12, no. 1, pp. 185-197, 2022

Authors: Sinai, Alon | Nassar, Maria | Sprecher, Elliot | Constantinescu, Marius | Zaaroor, Menashe | Schlesinger, Ilana

Article Type: Research Article

Abstract: Background: MRI-guided focused ultrasound (FUS) has established short-term efficacy in tremor relief. Objective: We report our long-term experience of treating tremor with unilateral FUS unilateral VIM-thalamotomy in tremor dominant Parkinson’s disease (TDPD) patients. Methods: We report outcome of FUS thalamotomy in TDPD patients with 1–5 years of follow-up. Outcomes: tremor reduction assessed with Clinical Rating Scale for Tremor (CRST) and Unified Parkinson’s Disease Rating Scale (UPDRS part III) overall and in the treated hemibody and safety. Results: Twenty-six TDPD patients completed 1–5 years of follow-up (median follow-up 36 months, range 12–60 months). Median age …was 60 years (range 46–79), with median disease duration of 6 years (range 2–16). Immediately, treatment resulted in 100%improvement in tremor in the treated arm in 23 patients and 90%improvement in 3 patients. In 15 patients with leg tremor, 2 patients with chin tremor and 1 patient with head tremor, tremor was significantly improved. Up to 5 years, median CRST score, median UPDRS score, overall and in treated hemibody, decreased significantly as compared with baseline (p  < 0.0001). In 2 patients tremor returned completely and in 8 patients there was partial return of tremor. Adverse events were mild and resolved within 3 months. At baseline 4 patients were not receiving any medication vs. 3 at last follow-up and 15 were not taking levodopa vs.9 at last follow-up. Conclusion: Unilateral FUS VIM-thalamotomy in TDPD patients was effective and safe and provided long-term tremor relief in most patients. FUS thalamotomy for tremor may delay initiation of levodopa treatment. Show more

Keywords: Parkinson’s disease, treatment, tremor, ultrasound, surgery

DOI: 10.3233/JPD-212810

Citation: Journal of Parkinson's Disease, vol. 12, no. 1, pp. 199-206, 2022

Authors: Lennaerts-Kats, Herma | Ebenau, Anne | van der Steen, Jenny T. | Munneke, Marten | Bloem, Bastiaan R. | Vissers, Kris C.P. | Meinders, Marjan J. | Groot, Marieke M.

Article Type: Research Article

Abstract: Background: Palliative care for persons with Parkinson’s disease (PD) is developing. However, little is known about the experiences of patients with PD in the palliative phase and of their family caregivers. Objective: To explore needs of patients with PD in the palliative phase and of their family caregivers. Methods: A mixed methods case study design. Health care professionals included patients for whom the answer on the question “Would you be surprised if this patient died in the next 12 months?” was negative. At baseline, and after six and twelve months, we conducted semi-structured interviews with patients …and caregivers. Participants completed questionnaires on quality of life, disease burden, caregiver burden, grief, and positive aspects of caregiving. We analyzed quantitative data using descriptive statistics, while we used thematic analysis for qualitative data. Results: Ten patients and eight family caregivers participated, of whom five patients died during the study period. While the quantitative data reflected a moderate disease burden, the qualitative findings indicated a higher disease burden. Longitudinal results showed small differences and changes in time. Patients reported a diverse range of symptoms, such as fatigue, immobility, cognitive changes, and hallucinations, which had a tremendous impact on their lives. Nevertheless, they rated their overall quality of life as moderate to positive. Family caregivers gradually learned to cope with difficult situations such delirium, fluctuations in functioning and hallucinations. They had great expertise in caring for the person with PD but did not automatically share this with health care professionals. Patients sensed a lack of time to discuss their complex needs with clinicians. Furthermore, palliative care was rarely discussed, and none of these patients had been referred to specialist palliative care services. Conclusion: Patients with PD experienced many difficulties in daily living. Patients seems to adapt to living with PD as they rated their quality of life as moderate to positive. Family caregivers became experts in the care for their loved one, but often learned on their own. An early implementation of the palliative care approach can be beneficial in addressing the needs of patients with PD and their family caregivers. Show more

Keywords: Parkinson’s disease, case study, palliative care, family caregivers, patients, mixed methods

DOI: 10.3233/JPD-212742

Citation: Journal of Parkinson's Disease, vol. 12, no. 1, pp. 207-219, 2022

Authors: McDaniels, Bradley | Lee, Chun-Lung | Bishop, Malachy

Article Type: Research Article

Abstract: Background: Positive personality resources have demonstrated the ability to positively impact health outcomes. Objective: To examine the psychometric properties of the original Psychological Capital Questionnaire (PCQ-24) in patients with Parkinson’s disease (PD). Methods: A sample of 114 individuals with PD completed the PCQ-24, and via a latent factor modeling framework exploratory and confirmatory factor analyses were conducted to evaluate the psychometric properties in people with PD. Results: Exploratory factor analysis (EFA) revealed that both the efficacy and hope scales were reliable (Cronbach’s alpha = 0.87 and 0.86, respectively) and had statistically acceptable validity with strong factor …loadings all above the practical threshold of 0.60. The resilience and optimism scales were also reliable (Cronbach’s alpha = 0.78 and 0.73, respectively) but had only moderately acceptable validity in part due to three reverse-scored items (i.e., No. 13, 20, & 23) with weak factor loadings of 0.26, 0.46, and 0.50, respectively. After excluding these at-risk items, the overall factor loadings for resilience and optimism were significantly improved at the acceptable above 0.60. The CFA results confirm a statistically acceptable model fit for the modified version (only 21-items) of the PCQ in the PD sample. Conclusion: Both EFA and CFA analyses provide statistical evidence supporting the modified PCQ version and demonstrate better test validity and reliability for the PD population. The refined PCQ form is both effectively shorter and psychometrically superior to the original and has promise in investigating health outcomes in people with PD. Show more

Keywords: Factor analysis, latent factor modeling, Parkinson’s disease, positive psychological capital, positive psychology, quality of life

DOI: 10.3233/JPD-212772

Citation: Journal of Parkinson's Disease, vol. 12, no. 1, pp. 221-228, 2022

Authors: Rémillard-Pelchat, David | Rahayel, Shady | Gaubert, Malo | Postuma, Ronald B. | Montplaisir, Jacques | Pelletier, Amélie | Monchi, Oury | Brambati, Simona Maria | Carrier, Julie | Gagnon, Jean-François

Article Type: Research Article

Abstract: Background: Rapid-eye-movement sleep behavior disorder (RBD) is a major risk factor for Parkinson’s disease and dementia with Lewy bodies. More than a third of RBD patients have mild cognitive impairment (MCI), but their specific structural brain alterations remain poorly understood. Objective: This study aimed to investigate the local deformation and volume of gray and white matter tissue underlying MCI in RBD. Methods: Fifty-two idiopathic RBD patients, including 17 with MCI (33%), underwent polysomnography, neuropsychological, neurological, and magnetic resonance imaging assessments. MCI diagnosis was based on a subjective complaint, cognitive impairment on the neuropsychological battery, and preserved …daily functioning. Forty-one controls were also included. Deformation-based morphometry (DBM), voxel-based morphometry (VBM), and regional volume analyses of the corpus callosum and cholinergic basal forebrain were performed. Multiple regression models were also computed using anatomical, cognitive (composite z scores), and motor parameters. Results: Globally, patients with MCI displayed a widespread pattern of local deformation and volume atrophy in the cortical (bilateral insula, cingulate cortex, precuneus, frontal, temporal and occipital regions, right angular gyrus, and mid-posterior segment of the corpus callosum) and subcortical (brainstem, corona radiata, basal ganglia, thalamus, amygdala, and right hippocampus) regions compared to patients without MCI (DBM) or controls (DBM and VBM). Moreover, brain deformation (DBM) in patients were associated with lower performance in attention and executive functions, visuospatial abilities, and higher motor symptoms severity. Conclusion: The present study identified novel brain structural alterations in RBD patients with MCI which correlated with poorer cognitive performance. These results are consistent with those reported in patients with synucleinopathies-related cognitive impairment. Show more

Keywords: REM sleep behavior disorder, mild cognitive impairment, Parkinson’s disease/parkinsonism, dementia with Lewy bodies, magnetic resonance imaging

DOI: 10.3233/JPD-212691

Citation: Journal of Parkinson's Disease, vol. 12, no. 1, pp. 229-241, 2022

Authors: Sosnik, Ronen | Danziger-Schragenheim, Shani | Possti, Daniel | Fahoum, Firas | Giladi, Nir | Hausdorff, Jeffrey M. | Mirelman, Anat | Maidan, Inbal

Article Type: Research Article

Abstract: Background: The performance on a visual Go/NoGo (VGNG) task during walking has been used to evaluate the effect of gait on response inhibition in young and older adults; however, no work has yet included Parkinson’s disease (PD) patients for whom such changes may be even more enhanced. Objective: In this study, we aimed to explore the effect of gait on automatic and cognitive inhibitory control phases in PD patients and the associated changes in neural activity and compared them with young and older adults. Methods: 30 PD patients, 30 older adults, and 11 young adults performed …a visual Go/NoGo task in a sitting position and during walking on a treadmill while their EEG activity and gait were recorded. Brain electrical activity was evaluated by the amplitude, latency, and scalp distribution of N2 and P300 event related potentials. Mix model analysis was used to examine group and condition effects on task performance and brain activity. Results: The VGNG accuracy rates in PD patients during walking were lower than in young and older adults (F  = 5.619, p  = 0.006). For all groups, N2 latency during walking was significantly longer than during sitting (p  = 0.013). In addition, P300 latency was significantly longer in PD patients (p  < 0.001) and older adults (p  = 0.032) during walking compared to sitting and during ‘NoGo’ trials compared with ‘Go’ trials. Moreover, the young adults showed the smallest number of electrodes for which a significant differential activation between sit to walk was observed, while PD patients showed the largest with N2 being more strongly manifested in bilateral parietal electrodes during walking and in frontocentral electrodes while seated. Conclusion: The results show that response inhibition during walking is impaired in older subjects and PD patients and that increased cognitive load during dual-task walking relates to significant change in scalp electrical activity, mainly in parietal and frontocentral channels. Show more

Keywords: Parkinson’s disease, inhibitory control, EEG, dual task, gait

DOI: 10.3233/JPD-212776

Citation: Journal of Parkinson's Disease, vol. 12, no. 1, pp. 243-256, 2022

Authors: Zolfaghari, Sheida | Yao, Chun W. | Wolfson, Christina | Pelletier, Amelie | Postuma, Ronald B.

Article Type: Research Article

Abstract: Background: Earlier detection of parkinsonism, specifically during its prodromal stage, may be key to preventing its progression. Previous studies have produced contradictory results on the association between sleep symptoms and prodromal parkinsonism. Objective: We conducted a prospective study within the Canadian Longitudinal Study on Aging (CLSA) to determine whether self-reported symptoms of insomnia, somnolence, apnea, and restless legs syndrome predate the diagnosis of parkinsonism after three years of follow-up. Methods: At baseline, amongst other information, participants completed a questionnaire for difficulty initiating or maintaining sleep, daytime somnolence, snoring or stopping breathing during sleep, and symptoms of …restless legs syndrome. After 3 years of follow-up, baseline responses from participants who self-reported a new diagnosis of parkinsonism (cases) were compared to those who did not (controls). For each case, 10 controls were individually matched by age, sex, education, BMI, caffeine, smoking, and alcohol. Binary unconditional logistic regression models were used to estimate the association between sleep symptoms and new-onset parkinsonism, adjusting for age, sex, education, BMI, smoking, alcohol, and caffeine. Results: We identified 58 incident-parkinsonism cases and 580 matched controls (65.5%male, mean age = 69.60, SD = 8.0). Baseline symptoms of sleep-onset insomnia (12.1%vs. 13.0%, Adjusted OR[95%CI] = 0.87[0.32,2.33]), sleep-maintenance insomnia (24.1%vs. 20.2%, AOR = 1.01[0.46,2.20]), daytime somnolence (8.6%vs. 7.4%, AOR = 1.11[0.37,3.39]), obstructive sleep apnea (27.3%vs. 26.2%, AOR = 0.84[0.40,1.79]), and restless leg syndrome (20.6%vs. 9.9%, AOR = 1.34[0.42,4.25]) were similar among those who developed parkinsonism and those who did not. Conclusion: Symptoms of insomnia, somnolence, apnea, and restless legs did not predate a new diagnosis of parkinsonism over 3 years. Show more

Keywords: Parkinsonism, insomnia, daytime somnolence, obstructive sleep apnea, restless leg syndrome, CLSA

DOI: 10.3233/JPD-212796

Citation: Journal of Parkinson's Disease, vol. 12, no. 1, pp. 257-266, 2022

Authors: Domenighetti, Cloé | Sugier, Pierre-Emmanuel | Sreelatha, Ashwin Ashok Kumar | Schulte, Claudia | Grover, Sandeep | Mohamed, Océane | Portugal, Berta | May, Patrick | Bobbili, Dheeraj R. | Radivojkov-Blagojevic, Milena | Lichtner, Peter | Singleton, Andrew B. | Hernandez, Dena G. | Edsall, Connor | Mellick, George D. | Zimprich, Alexander | Pirker, Walter | Rogaeva, Ekaterina | Lang, Anthony E. | Koks, Sulev | Taba, Pille | Lesage, Suzanne | Brice, Alexis | Corvol, Jean-Christophe | Chartier-Harlin, Marie-Christine | Mutez, Eugénie | Brockmann, Kathrin | Deutschländer, Angela B. | Hadjigeorgiou, Georges M. | Dardiotis, Efthimos | Stefanis, Leonidas | Simitsi, Athina Maria | Valente, Enza Maria | Petrucci, Simona | Duga, Stefano | Straniero, Letizia | Zecchinelli, Anna | Pezzoli, Gianni | Brighina, Laura | Ferrarese, Carlo | Annesi, Grazia | Quattrone, Andrea | Gagliardi, Monica | Matsuo, Hirotaka | Kawamura, Yusuke | Hattori, Nobutaka | Nishioka, Kenya | Chung, Sun Ju | Kim, Yun Joong | Kolber, Pierre | van de Warrenburg, Bart PC | Bloem, Bastiaan R. | Aasly, Jan | Toft, Mathias | Pihlstrøm, Lasse | Guedes, Leonor Correia | Ferreira, Joaquim J. | Bardien, Soraya | Carr, Jonathan | Tolosa, Eduardo | Ezquerra, Mario | Pastor, Pau | Diez-Fairen, Monica | Wirdefeldt, Karin | Pedersen, Nancy L. | Ran, Caroline | Belin, Andrea C. | Puschmann, Andreas | Hellberg, Clara | Clarke, Carl E. | Morrison, Karen E. | Tan, Manuela | Krainc, Dimitri | Burbulla, Lena F. | Farrer, Matt J. | Krüger, Rejko | Gasser, Thomas | Sharma, Manu | Elbaz, Alexis | on behalf of the Comprehensive Unbiaised Risk Factor Assessment for Genetics and Environment in Parkinson’s Disease (Courage-PD) consortium

Article Type: Research Article

Abstract: Background: Previous studies showed that lifestyle behaviors (cigarette smoking, alcohol, coffee) are inversely associated with Parkinson’s disease (PD). The prodromal phase of PD raises the possibility that these associations may be explained by reverse causation. Objective: To examine associations of lifestyle behaviors with PD using two-sample Mendelian randomisation (MR) and the potential for survival and incidence-prevalence biases. Methods: We used summary statistics from publicly available studies to estimate the association of genetic polymorphisms with lifestyle behaviors, and from Courage-PD (7,369 cases, 7,018 controls; European ancestry) to estimate the association of these variants with PD. We used …the inverse-variance weighted method to compute odds ratios (ORIVW ) of PD and 95%confidence intervals (CI). Significance was determined using a Bonferroni-corrected significance threshold (p  = 0.017). Results: We found a significant inverse association between smoking initiation and PD (ORIVW per 1-SD increase in the prevalence of ever smoking = 0.74, 95%CI = 0.60–0.93, p  = 0.009) without significant directional pleiotropy. Associations in participants ≤67 years old and cases with disease duration ≤7 years were of a similar size. No significant associations were observed for alcohol and coffee drinking. In reverse MR, genetic liability toward PD was not associated with smoking or coffee drinking but was positively associated with alcohol drinking. Conclusion: Our findings are in favor of an inverse association between smoking and PD that is not explained by reverse causation, confounding, and survival or incidence-prevalence biases. Genetic liability toward PD was positively associated with alcohol drinking. Conclusions on the association of alcohol and coffee drinking with PD are hampered by insufficient statistical power. Show more

Keywords: Smoking, alcohol, coffee, Parkinson’s disease, Mendelian randomisation

DOI: 10.3233/JPD-212851

Citation: Journal of Parkinson's Disease, vol. 12, no. 1, pp. 267-282, 2022

Authors: Ragothaman, Anjanibhargavi | Miranda-Dominguez, Oscar | Brumbach, Barbara H. | Giritharan, Andrew | Fair, Damien A. | Nutt, John G. | Mancini, Martina | Horak, Fay B.

Article Type: Research Article

Abstract: Background: Instrumented measures of balance and gait measure more specific balance and gait impairments than clinical rating scales. No prior studies have used objective balance/gait measures to examine associations with ventricular and brain volumes in people with Parkinson’s disease (PD). Objective: To test the hypothesis that larger ventricular and smaller cortical and subcortical volumes are associated with impaired balance and gait in people with PD. Methods: Regional volumes from structural brain images were included from 96 PD and 50 control subjects. Wearable inertial sensors quantified gait, anticipatory postural adjustments prior to step initiation (APAs), postural responses …to a manual push, and standing postural sway on a foam surface. Multiple linear regression models assessed the relationship between brain volumes and balance/gait and their interactions in PD and controls, controlling for sex, age and corrected for multiple comparisons. Results: Smaller brainstem and subcortical gray matter volumes were associated with larger sway area in people with PD, but not healthy controls. In contrast, larger ventricle volume was associated with smaller APAs in healthy controls, but not in people with PD. A sub-analysis in PD showed significant interactions between freezers and non-freezers, in several subcortical areas with stride time variability, gait speed and step initiation. Conclusion: Our models indicate that smaller subcortical and brainstem volumes may be indicators of standing balance dysfunction in people with PD whereas enlarged ventricles may be related to step initiation difficulties in healthy aging. Also, multiple subcortical region atrophy may be associated with freezing of gait in PD. Show more

Keywords: Balance, brain volume, gait, Parkinson’s disease

DOI: 10.3233/JPD-202403

Citation: Journal of Parkinson's Disease, vol. 12, no. 1, pp. 283-294, 2022

Authors: Ren, Chao | He, Kai-Jie | Hu, Hua | Zhang, Jin-Bao | Dong, Li-Guo | Li, Dan | Chen, Jing | Mao, Cheng-Jie | Wang, Fen | Liu, Chun-Feng

Article Type: Research Article

Abstract: Background: Previous investigations have suggested that decreased expression of glutamate transporter-1 (GLT-1) is involved in glutamate excitotoxicity and contribute to the development of Parkinson’s disease (PD), GLT-1 is decreased in animal models of PD. GLT-1 is mainly expressed in astrocytes, and the striatum is a GLT-1-rich brain area. Objective: The aim was to explore the function and mechanism of astrocytic GLT-1 in PD-like changes. Methods: In the study, PD-like changes and their molecular mechanism in rodents were tested by a behavioral assessment, micro-positron emission tomography/computed tomography (PET/CT), western blotting, immunohistochemical and immunofluorescence staining, and high performance …liquid chromatography pre-column derivatization with O-pthaldialdehida after downregulating astrocytic GLT-1 in vivo and in vitro . Results: In vivo , after 6 weeks of brain stereotactic injection of adeno-associated virus into the striatum, rats in the astrocytic GLT-1 knockdown group showed poorer motor performance, abnormal gait, and depression-like feature; but no olfactory disorders. The results of micro-PET/CT and western blotting indicated that the dopaminergic system was impaired in astrocytic GLT-1 knockdown rats. Similarly, tyrosine hydroxylase (TH) positive immune-staining in neurons of astrocytic GLT-1 knockdown rats showed deficit in cell count. In vitro , knockdown of astrocytic GLT-1 via RNA interference led to morphological injury of TH-positive neurons, which may be related to the abnormal calcium signal induced by glutamate accumulation after GLT-1 knockdown. Furthermore, the GLT-1 agonist ceftriaxone showed a protective effect on TH-positive neuron impairment. Conclusion: The present findings may shed new light in the future prevention and treatment of PD based on blocking glutamate excitotoxicity. Show more

Keywords: GLT-1, astrocyte, Parkinson’s disease, glutamate, calcium signaling

DOI: 10.3233/JPD-212640

Citation: Journal of Parkinson's Disease, vol. 12, no. 1, pp. 295-314, 2022

Authors: Santos García, Diego | García Roca, Lucía | de Deus Fonticoba, Teresa | Cores Bartolomé, Carlos | Naya Ríos, Lucía | Canfield, Héctor | Paz González, Jose M. | Martínez Miró, Cristina | Jesús, Silvia | Aguilar, Miquel | Pastor, Pau | 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 | 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 L, Luis M. | McAfee, Darrian | Martinez-Martin, Pablo | Mir, Pablo | COPPADIS Study Group

Article Type: Research Article

Abstract: Background: Constipation has been linked to cognitive impairment development in Parkinson’s disease (PD). Objective: Our aim was to analyze cognitive changes observed in PD patients and controls from a Spanish cohort with regards to the presence or not of constipation. Methods: PD patients and controls recruited from 35 centers of Spain from the COPPADIS cohort from January 2016 to November 2017 were followed-up during 2 years. The change in cognitive status from baseline (V0) to 2-year follow-up was assessed with the PD-CRS (Parkinson’s Disease Cognitive Rating Scale). Subjects with a score ≥1 on item 21 of …the NMSS (Non-Motor Symptoms Scale) at baseline (V0) were considered as “with constipation”. Regression analyses were applied for determining the contribution of constipation in cognitive changes. Results: At V0, 39.7% (198/499) of PD patients presented constipation compared to 11.4% of controls (14/123) (p  < 0.0001). No change was observed in cognitive status (PD-CRS total score) neither in controls without constipation (from 100.24±13.72 to 100.27±13.68; p  = 0.971) and with constipation (from 94.71±10.96 to 93.93±13.03; p  = 0.615). The PD-CRS total score decreased significantly in PD patients with constipation (from 89.14±15.36 to 85.97±18.09; p  < 0.0001; Coehn’s effect = –0.35) compared to patients without constipation (from 93.92±15.58 to 93.14±17.52; p  = 0.250) (p  = 0.018). In PD patients, to suffer from constipation at V0 was associated with a decrease in the PD-CRS total score from V0 to V2 (β= –0.1; 95% CI, –4.36 – –0.27; p  = 0.026) and having cognitive impairment at V2 (OR = 1.79; 95% CI, 1.01 – 3.17; p  = 0.045). Conclusion: Constipation is associated with cognitive decline in PD patients but not in controls. Show more

Keywords: Cognition, constipation, impairment, non-motor symptoms, Parkinson’s disease

DOI: 10.3233/JPD-212868

Citation: Journal of Parkinson's Disease, vol. 12, no. 1, pp. 315-331, 2022

Authors: Sosero, Yuri L. | Yu, Eric | Estiar, Mehrdad A. | Krohn, Lynne | Mufti, Kheireddin | Rudakou, Uladzislau | Ruskey, Jennifer A. | Asayesh, Farnaz | Laurent, Sandra B. | Spiegelman, Dan | Trempe, Jean-François | Quinnell, Timothy G. | Oscroft, Nicholas | Arnulf, Isabelle | Montplaisir, Jacques Y. | Gagnon, Jean-François | Desautels, Alex | Dauvilliers, Yves | Gigli, Gian Luigi | Valente, Mariarosaria | Janes, Francesco | Bernardini, Andrea | Sonka, Karel | Kemlink, David | Oertel, Wolfgang | Janzen, Annette | Plazzi, Giuseppe | Antelmi, Elena | Biscarini, Francesco | Figorilli, Michela | Puligheddu, Monica | Mollenhauer, Brit | Trenkwalder, Claudia | Sixel-Döring, Friederike | Cochen De Cock, Valérie | Monaca, Christelle Charley | Heidbreder, Anna | Ferini-Strambi, Luigi | Dijkstra, Femke | Viaene, Mineke | Abril, Beatriz | Boeve, Bradley F. | Postuma, Ronald B. | Rouleau, Guy A. | Ibrahim, Abubaker | Stefani, Ambra | Högl, Birgit | Hu, Michele T.M. | Gan-Or, Ziv

Article Type: Research Article

Abstract: Background: PSAP encodes saposin C, the co-activator of glucocerebrosidase, encoded by GBA . GBA mutations are associated with idiopathic/isolated REM sleep behavior disorder (iRBD), a prodromal stage of synucleinopathy. Objective: To examine the role of PSAP mutations in iRBD. Methods: We fully sequenced PSAP and performed Optimized Sequence Kernel Association Test in 1,113 iRBD patients and 2,324 controls. We identified loss-of-function (LoF) mutations, which are very rare in PSAP , in three iRBD patients and none in controls (uncorrected p  = 0.018). Results: Two variants were stop mutations, p.Gln260Ter and …p.Glu166Ter, and one was an in-frame deletion, p.332_333del. All three mutations have a deleterious effect on saposin C, based on in silico analysis. In addition, the two carriers of p.Glu166Ter and p.332_333del mutations also carried a GBA variant, p.Arg349Ter and p.Glu326Lys, respectively. The co-occurrence of these extremely rare PSAP LoF mutations in two (0.2%) GBA variant carriers in the iRBD cohort, is unlikely to occur by chance (estimated co-occurrence in the general population based on gnomAD data is 0.00035%). Although none of the three iRBD patients with PSAP LoF mutations have phenoconverted to an overt synucleinopathy at their last follow-up, all manifested initial signs suggestive of motor dysfunction, two were diagnosed with mild cognitive impairment and all showed prodromal clinical markers other than RBD. Their probability of prodromal PD, according to the Movement Disorder Society research criteria, was 98% or more. Conclusion: These results suggest a possible role of PSAP variants in iRBD and potential genetic interaction with GBA , which requires additional studies. Show more

Keywords: REM sleep behavior disorder, PSAP, saposin C, Parkinson’s disease, GBA, glucocerebrosidase, genetics

DOI: 10.3233/JPD-212867

Citation: Journal of Parkinson's Disease, vol. 12, no. 1, pp. 333-340, 2022

Authors: Karabayir, Ibrahim | Butler, Liam | Goldman, Samuel M. | Kamaleswaran, Rishikesan | Gunturkun, Fatma | Davis, Robert L. | Ross, G. Webster | Petrovitch, Helen | Masaki, Kamal | Tanner, Caroline M. | Tsivgoulis, Georgios | Alexandrov, Andrei V. | Chinthala, Lokesh K. | Akbilgic, Oguz

Article Type: Research Article

Abstract: Background: Parkinson’s disease (PD) is a chronic, disabling neurodegenerative disorder. Objective: To predict a future diagnosis of PD using questionnaires and simple non-invasive clinical tests. Methods: Participants in the prospective Kuakini Honolulu-Asia Aging Study (HAAS) were evaluated biannually between 1995–2017 by PD experts using standard diagnostic criteria. Autopsies were sought on all deaths. We input simple clinical and risk factor variables into an ensemble-tree based machine learning algorithm and derived models to predict the probability of developing PD. We also investigated relationships of predictive models and neuropathologic features such as nigral neuron density. Results: …The study sample included 292 subjects, 25 of whom developed PD within 3 years and 41 by 5 years. 116 (46%) of 251 subjects not diagnosed with PD underwent autopsy. Light Gradient Boosting Machine modeling of 12 predictors correctly classified a high proportion of individuals who developed PD within 3 years (area under the curve (AUC) 0.82, 95%CI 0.76–0.89) or 5 years (AUC 0.77, 95%CI 0.71–0.84). A large proportion of controls who were misclassified as PD had Lewy pathology at autopsy, including 79%of those who died within 3 years. PD probability estimates correlated inversely with nigral neuron density and were strongest in autopsies conducted within 3 years of index date (r  = –0.57, p  < 0.01). Conclusion: Machine learning can identify persons likely to develop PD during the prodromal period using questionnaires and simple non-invasive tests. Correlation with neuropathology suggests that true model accuracy may be considerably higher than estimates based solely on clinical diagnosis. Show more

Keywords: Parkinson’s disease, Lewy body pathology, neuron density, machine learning

DOI: 10.3233/JPD-212876

Citation: Journal of Parkinson's Disease, vol. 12, no. 1, pp. 341-351, 2022

Authors: Yoon, Seo Yeon | Heo, Seok-Jae | Kim, Yong Wook | Yang, Seung Nam | Moon, Hyun Im

Article Type: Research Article

Abstract: Background: Ankylosing spondylitis (AS) is an immune-mediated, chronic inflammatory rheumatic disorder. The etiology of Parkinson’s disease (PD) is multifactorial; however, inflammation is receiving an increasing amount of attention as an underlying cause of the neurodegenerative process of PD. Objective: We performed a nationwide longitudinal, population-based matched cohort study to assess the association with the later development of parkinsonism in Korea. Methods: This study was conducted using records from the Health Insurance Review and Assessment Service database. The cumulative incidence rate of PD was estimated. Fine–Gray subdistribution hazard models were used to identify hazards associated with PD …development based on the presence of AS. Exposure to anti-inflammatory drugs was measured and analyzed to determine the protective effect of these medications. Additionally, the hazard ratio (HR) for atypical parkinsonism was estimated. Results: The results of the Fine–Gray subdistribution hazard model revealed that the HR for PD development in the AS group was 1.82 (95%confidence interval [CI], 1.38–2.39, p  < 0.001). A significant decrease in PD development was observed in patients with AS taking non-steroidal anti-inflammatory drugs (NSAIDs). The HR for atypical parkinsonism in the AS group was 3.86 (95%CI, 1.08–13.78, p  < 0.05). Conclusion: We found that AS was associated with an increased risk of PD and atypical parkinsonism. NSAIDs used for AS control have some protective effects against PD. Further studies assessing whether biological treatment mitigates PD risk in patients with high activity are warranted. Show more

Keywords: Ankylosing spondylitis, Parkinson’s disease, population-based cohort, National Health Insurance

DOI: 10.3233/JPD-212878

Citation: Journal of Parkinson's Disease, vol. 12, no. 1, pp. 353-360, 2022

Authors: Thieken, Franziska | Timmermann, Lars | Sohrabi, Keywan | Woopen, Christiane | Schmitz-Luhn, Björn | Janhsen, Anna | Eggers, Carsten

Article Type: Research Article

Abstract: Background: Parkinsonian syndromes are heterogeneous chronic neurodegenerative disorders associated with both motor and non-motor symptoms. The symptoms have major psychosocial effects on the quality of life of patients and can be a burden for caregivers. So far, several questionnaires have been developed to assess quality of life in Parkinsonism, but none of these include the positive sides on well-being such as personal and social resilience factors. Objective: The aim of this study is to develop a digital framework for a longitudinal assessment of quality of life during the progression of Parkinson’s disease. Methods: …The CHAPO model (Challenges and Potentials) has been established in a vast study by Wagner et al. to assess the quality of life of older people. This model includes environmental and individual factors, life chances, and life results, such as individual life evaluation, from a subjective as well as an objective point of view. Therefore, it has been adapted in several development steps to include the specific aspects that affect quality of life in Parkinsonian syndromes. The development process included 6 steps: definition, refinement, operationalization, piloting/debriefing, adjustment, and integration. Results: The development of the CHAPO-PD model has been completed and it represents the first main result of this study. Conclusion: By taking a holistic understanding of quality of life into account, we expect to detect previously unrecognized factors, which correlate to the subjective well-being of Parkinson’s disease patients, and aim to use these findings to improve the health care structures for patients with Parkinson’s disease and related disorders. Show more

Keywords: Parkinson’s disease, health-related quality of life, holistic, assessment tool, prognostication, personalized care

DOI: 10.3233/JPD-202391

Citation: Journal of Parkinson's Disease, vol. 12, no. 1, pp. 361-370, 2022

Authors: Myers, Taylor L. | Augustine, Erika F. | Baloga, Elizabeth | Daeschler, Margaret | Cannon, Paul | Rowbotham, Helen | Chanoff, Eli | 23andMe Research Team | Jensen-Roberts, Stella | Soto, Julia | Holloway, Robert G. | Marras, Connie | Tanner, Caroline M. | Dorsey, E. Ray | Schneider, Ruth B.

Article Type: Research Article

Abstract: Background: Traditional in-person Parkinson’s disease (PD) research studies are often slow to recruit and place unnecessary burden on participants. The ongoing COVID-19 pandemic has added new impetus to the development of new research models. Objective: To compare recruitment processes and outcomes of three remote decentralized observational PD studies with video visits. Methods: We examined the number of participants recruited, speed of recruitment, geographic distribution of participants, and strategies used to enhance recruitment in FIVE, a cross-sectional study of Fox Insight participants with and without PD (n  = 203); VALOR-PD, a longitudinal study of 23andMe, Inc. research participants …carrying the LRRK2 G2019S variant with and without PD (n  = 277); and AT-HOME PD, a longitudinal study of former phase III clinical trial participants with PD (n  = 226). Results: Across the three studies, 706 participants from 45 U.S. states and Canada enrolled at a mean per study rate of 4.9 participants per week over an average of 51 weeks. The cohorts were demographically homogenous with regard to race (over 95%white) and level of education (over 90%with more than a high school education). The number of participants living in primary care Health Professional Shortage Areas in each study ranged from 30.3–42.9%. Participants reported interest in future observational (98.5–99.6%) and interventional (76.1–87.6%) research studies with remote video visits. Conclusion: Recruitment of large, geographically dispersed remote cohorts from a single location is feasible. Interest in participation in future remote decentralized PD studies is high. More work is needed to identify best practices for recruitment, particularly of diverse participants. Show more

Keywords: Parkinson’s disease, telemedicine, recruitment, decentralized

DOI: 10.3233/JPD-212935

Citation: Journal of Parkinson's Disease, vol. 12, no. 1, pp. 371-380, 2022

Authors: Bange, Manuel | Gonzalez-Escamilla, Gabriel | Marquardt, Tabea | Radetz, Angela | Dresel, Christian | Herz, Damian | Schöllhorn, Wolfgang Immanuel | Groppa, Sergiu | Muthuraman, Muthuraman

Article Type: Research Article

Abstract: Background: Movement execution is impaired in patients with Parkinson’s disease. Evolving neurodegeneration leads to altered connectivity between distinct regions of the brain and altered activity at interconnected areas. How connectivity alterations influence complex movements like drawing spirals in Parkinson’s disease patients remains largely unexplored. Objective: We investigated whether deteriorations in interregional connectivity relate to impaired execution of drawing. Methods: Twenty-nine patients and 31 age-matched healthy control participants drew spirals with both hands on a digital graphics tablet, and the regularity of drawing execution was evaluated by sample entropy. We recorded resting-state fMRI and task-related EEG, and …calculated the time-resolved partial directed coherence to estimate effective connectivity for both imaging modalities to determine the extent and directionality of interregional interactions. Results: Movement performance in Parkinson’s disease patients was characterized by increased sample entropy, corresponding to enhanced irregularities in task execution. Effective connectivity between the motor cortices of both hemispheres, derived from resting-state fMRI, was significantly reduced in Parkinson’s disease patients in comparison to controls. The connectivity strength in the nondominant to dominant hemisphere direction in both modalities was inversely correlated with irregularities during drawing, but not with the clinical state. Conclusion: Our findings suggest that interhemispheric connections are affected both at rest and during drawing movements by Parkinson’s disease. This provides novel evidence that disruptions of interhemispheric information exchange play a pivotal role for impairments of complex movement execution in Parkinson’s disease patients. Show more

Keywords: Parkinson’s disease, motor control, neural effective connectivity, fMRI

DOI: 10.3233/JPD-212840

Citation: Journal of Parkinson's Disease, vol. 12, no. 1, pp. 381-395, 2022

Authors: Marques, Ana | Taylor, Natasha L. | Roquet, Daniel | Beze, Steven | Chassain, Carine | Pereira, Bruno | O’Callaghan, Claire | Lewis, Simon J.G. | Durif, Franck

Article Type: Research Article

Abstract: Background: Visual illusions (VI) in Parkinson’s disease (PD) are generally considered as an early feature of the psychosis spectrum leading to fully formed visual hallucinations (VH), although this sequential relationship has not been clearly demonstrated. Objective: We aimed to determine whether there are any overlapping, potentially graded patterns of structural and functional connectivity abnormalities in PD with VI and with VH. Such a finding would argue for a continuum between these entities, whereas distinct imaging features would suggest different neural underpinnings for the phenomena. Methods: In this case control study, we compared structural and resting state …functional MRI brain patterns of PD patients with VH (PD-H, n  = 20), with VI (PD-I, n  = 19), and without VH or VI (PD-C, n  = 23). Results: 1) PD-H had hypo-connectivity between the ILO and anterior cingulate precuneus and parahippocampal gyrus compared to PD-C and PD-I; 2) In contrast, PD-I had hyper-connectivity between the inferior frontal gyrus and the postcentral gyrus compared to PD-C and PD-H. Moreover, PD-I had higher levels of functional connectivity between the amygdala, hippocampus, insula, and fronto-temporal regions compared to PD-H, together with divergent patterns toward the cingulate. 3) Both PD-I and PD-H had functional hypo-connectivity between the lingual gyrus and the parahippocampal region vs. PD-C, and no significant grey matter volume differences was observed between PD-I and PD-H. Conclusion: Distinct patterns of functional connectivity characterized VI and VH in PD, suggesting that these two perceptual experiences, while probably linked and driven by at least some similar mechanisms, could reflect differing neural dysfunction. Show more

Keywords: Parkinson’s disease, hallucinations, illusions, neuroimaging, visuo-perception

DOI: 10.3233/JPD-212838

Citation: Journal of Parkinson's Disease, vol. 12, no. 1, pp. 397-409, 2022

Authors: Okunoye, Olaitan | Horsfall, Laura | Marston, Louise | Walters, Kate | Schrag, Anette

Article Type: Research Article

Abstract: Background: Hospitalization in Parkinson’s disease (PD) is associated with reduced quality of life, caregiver burden and high costs. However, no large-scale studies of rate and causes of hospitalizations in patients with PD have been published. Objective: To investigate the rate and reasons for hospitalization and factors associated with hospitalization among people with PD compared to the general population. Methods: We examined rate and causes of admission in PD patients and matched controls in The Health Improvement Network from 2006 to 2016. Multivariable Poisson regression was used to explore the effects of age, gender, social deprivation, urbanicity …and practice geographic location on hospitalization. Results: In the longitudinal data from 9,998 newly diagnosed individuals with PD and 55,554 controls without PD aged ≥50 years, 39% of PD patients and 28% of controls were hospitalised over a median follow-up of 5.1 years. The adjusted incidence rate ratio (IRR) of hospitalization in PD compared to controls was 1.33 (95% CI:1.29–1.37) and rose with increased follow-up duration. Hospitalization rate was overall higher in the older age groups, but the adjusted IRR of hospitalization compared to controls was highest in the youngest age group. PD patients were more often admitted with falls/fractures, infections, gastrointestinal complications, PD, dementia, psychosis/hallucinations, postural hypotension, electrolyte disturbances, stroke and surgical procedures and slightly less often due to hypertension. Conclusion: People with PD have an increased hospitalization rate compared to controls, particularly in the younger age groups, and it increases with longer disease duration. The complications of motor and non-motor features of PD are amongst the main reasons for admission, some of which could be managed preventatively to avoid admissions. Show more

Keywords: Parkinson’s disease, hospitalization, incidence, reasons, primary care

DOI: 10.3233/JPD-212874

Citation: Journal of Parkinson's Disease, vol. 12, no. 1, pp. 411-420, 2022

Authors: Picillo, Marina | LaFontant, David-Erick | Bressman, Susan | Caspell-Garcia, Chelsea | Coffey, Christopher | Cho, Hyunkeun Ryan | Burghardt, Elliot L. | Dahodwala, Nabila | Saunders-Pullman, Rachel | Tanner, Caroline M. | Amara, Amy W. | for the Parkinson’s Progression Markers Initiative

Article Type: Research Article

Abstract: Background: Investigation of sex-related motor and non-motor differences and biological markers in Parkinson’s disease (PD) may improve precision medicine approach. Objective: To examine sex-related longitudinal changes in motor and non-motor features and biologic biomarkers in early PD. Methods: We compared 5-year longitudinal changes in de novo, untreated PD men and women (at baseline N  = 423; 65.5%male) of the Parkinson’s Progression Markers Initiative (PPMI), assessing motor and non-motor manifestations of disease; and biologic measures in cerebrospinal fluid (CSF) and dopamine transporter deficit on DaTscanTM uptake. Results: Men experienced greater longitudinal decline in self-reported motor …(p  < 0.001) and non-motor (p  = 0.009) aspects of experiences of daily living, such that men had a yearly increase in MDS-UPDRS part II by a multiplicative factor of 1.27 compared to women at 0.7, while men had a yearly increase in MDS-UPDRS part I by a multiplicative factor of 0.98, compared to women at 0.67. Compared to women, men had more longitudinal progression in clinician-assessed motor features in the ON medication state (p  = 0.010) and required higher dopaminergic medication dosages over time (p  = 0.014). Time to reach specific disease milestones and longitudinal changes in CSF biomarkers and DaTscanTM uptake were not different by sex. Conclusion: Men showed higher self-assessed motor and non-motor burden of disease, with possible contributions from suboptimal dopaminergic therapeutic response in men. However, motor features of disease evaluated with clinician-based scales in the OFF medication state, as well as biological biomarkers do not show specific sex-related progression patterns. Show more

Keywords: DaTScan, motor, non-motor, Parkinson’s disease, sex

DOI: 10.3233/JPD-212892

Citation: Journal of Parkinson's Disease, vol. 12, no. 1, pp. 421-436, 2022

Authors: Bartl, Michael | Dakna, Mohammed | Schade, Sebastian | Wicke, Tamara | Lang, Elisabeth | Ebentheuer, Jens | Weber, Sandrina | Trenkwalder, Claudia | Mollenhauer, Brit

Article Type: Research Article

Abstract: Background: The MDS-Unified Parkinson’s disease (PD) Rating Scale (MDS-UPDRS) is the most used scale in clinical trials. Little is known about the predictive potential of its single items. Objective: To systematically dissect MDS-UPDRS to predict PD progression. Methods: 574 de novo PD patients and 305 healthy controls were investigated at baseline (BL) in the single-center DeNoPa (6-year follow-up) and multi-center PPMI (8-year follow-up) cohorts. We calculated cumulative link mixed models of single MDS-UPDRS items for odds ratios (OR) for class change within the scale. Models were adjusted for age, sex, time, and levodopa equivalent daily dose. …Annual change and progression of the square roots of the MDS-UDPRS subscores and Total Score were estimated by linear mixed modeling. Results: Baseline demographics revealed more common tremor dominant subtype in DeNoPa and postural instability and gait disorders-subtype and multiethnicity in PPMI. Subscore progression estimates were higher in PPMI but showed similar slopes and progression in both cohorts. Increased ORs for faster progression were found from BL subscores I and II (activities of daily living; ADL) most marked for subscore III (rigidity of neck/lower extremities, agility of the legs, gait, hands, and global spontaneity of movements). Tremor items showed low ORs/negative values. Conclusion: Higher scores at baseline for ADL, freezing, and rigidity were predictors of faster deterioration in both cohorts. Precision and predictability of the MDS-UPDRS were higher in the single-center setting, indicating the need for rigorous training and/or video documentation to improve its use in multi-center cohorts, for example, clinical trials. Show more

Keywords: MDS-UPDRS, Parkinson’s disease, progression, predictors, DeNoPa, PPMI

DOI: 10.3233/JPD-212860

Citation: Journal of Parkinson's Disease, vol. 12, no. 1, pp. 437-452, 2022

Authors: Sauerbier, Anna | Bachon, Pia | Ambrosio, Leire | Loehrer, Philipp A. | Rizos, Alexandra | Jost, Stefanie T. | Gronostay, Alexandra | Konitsioti, Agni | Barbe, Michael T. | Fink, Gereon R. | Ashkan, Keyoumars | Nimsky, Christopher | Visser-Vandewalle, Veerle | Chaudhuri, K. Ray | Timmermann, Lars | Martinez-Martin, Pablo | 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: The satisfaction with life and, in particular, with treatment in Parkinson’s disease (PD) is understudied. Objective: To explore a new 7-item rating tool assessing satisfaction with life and treatment (SLTS-7) in PD. Methods: In this cross-sectional, multi-center study, including patients screened for advanced therapies, psychometric characteristics of the SLTS-7 were analyzed. An exploratory factor analysis identified the underlying factorial structure of the SLTS-7. Results: 117 patients were included, and the data quality of the SLTS-7 was excellent (computable data 100%), and acceptability measures satisfied standard criteria. Besides the global assessment (item 1), the …exploratory factor analysis produced item 2 (physical satisfaction) as an independent item and two factors among the remaining items: items 3–5 (psycho-social satisfaction), and items 6 and 7 (treatment satisfaction). Cronbach’s alpha was 0.89, indicative of high internal consistency. The SLTS-7 total score correlated moderately with motor symptoms and weakly with non-motor symptoms total scores. SLTS-7 showed the highest correlations with the European Quality of Life with 5 items (EQ-5D) visual analog scale (0.43–0.58, p  < 0.01), indicating a moderate convergent validity. The SLTS-7 significantly increased with higher non-motor symptoms burden levels (p  = 0.002). Conclusion: Life satisfaction in PD covers three specific aspects, namely physical, psycho-social, and treatment satisfaction. The new SLTS-7 is a valid, reliable, and easy-to-use tool to assess satisfaction with life and treatment in patients with PD screened for advanced therapies. Longitudinal studies analyzing the effect of advanced PD treatment on life and treatment satisfaction are warranted. Show more

Keywords: Non-motor symptoms, patient-reported outcomes, quality of life, satisfaction with life, satisfaction with treatment

DOI: 10.3233/JPD-212823

Citation: Journal of Parkinson's Disease, vol. 12, no. 1, pp. 453-464, 2022

Authors: Brock, Peter | Oates, Lloyd L. | Gray, William K. | Henderson, Emily J. | Mann, Helen | Haunton, Victoria J. | Skelly, Rob | Hand, Annette | Davies, Matthew L | Walker, Richard W.

Article Type: Research Article

Abstract: Background: Parkinson’s disease (PD) is a multi-system disorder that can impact on driving ability. Little is known about how these changes in driving ability affect people with PD, making it difficult for clinicians and carers to offer appropriate support. Objective: To assess patient views concerning the effect of PD on their driving ability, the impact of these changes and how they manage them. Method: An online survey was created by a team of clinicians, people with PD, their carers, and representatives from Parkinson’s UK. People with PD throughout the United Kingdom were invited to participate through …Parkinson’s UK’s website, newsletter and Parkinson’s Excellence Network email list. Results: 805 people with PD took part in the survey. We found that the loss of a driving licence had an adverse impact on employment, socialisation, travel costs and spontaneous lifestyle choices. Multiple changes in driving ability related to PD were described, including that impulse control disorders can have an adverse impact on driving. Changes in driving ability caused people to change their driving practices including taking shorter journeys and being less likely to drive at night. Participants advised managing changes in driving ability through planning, vehicle adaptions, maintaining skills and self-assessment. Conclusion: This study demonstrates the impact that changes in driving ability can have on the lifestyle of people with PD and reveals the strategies that individuals adopt to manage these changes. Show more

Keywords: Parkinson’s disease, automobile driving, impulsive behavior, quality of life, survey

DOI: 10.3233/JPD-212686

Citation: Journal of Parkinson's Disease, vol. 12, no. 1, pp. 465-471, 2022

Authors: Abbruzzese, Giovanni | Kulisevsky, Jaime | Bergmans, Bruno | Gomez-Esteban, Juan C. | Kägi, Georg | Raw, Jason | Stefani, Alessandro | Warnecke, Tobias | Jost, Wolfgang H. | the SYNAPSES Study Investigators Group

Article Type: Correction

DOI: 10.3233/JPD-219007

Citation: Journal of Parkinson's Disease, vol. 12, no. 1, pp. 473-473, 2022

Article Type: Correction

DOI: 10.3233/JPD-219009

Citation: Journal of Parkinson's Disease, vol. 12, no. 1, pp. 475-475, 2022