Journal of Parkinson's Disease - Volume 12, issue 5

Authors: Devignes, Quentin | Daoudi, Sami | Viard, Romain | Lopes, Renaud | Betrouni, Nacim | Kuchcinski, Gregory | Rolland, Anne-Sophie | Moreau, Caroline | Defebvre, Luc | Bardinet, Eric | Bonnet, Marie | Brefel-Courbon, Christine | Delmaire, Christine | El Mountassir, Fouzia | Fluchère, Frédérique | Fradet, Anne | Giordana, Caroline | Hainque, Elodie | Houvenaghel, Jean-François | Jarraya, Béchir | Klinger, Hélène | Maltête, David | Marques, Ana | Meyer, Mylène | Rascol, Olivier | Rouaud, Tiphaine | Tir, Melissa | Wirth, Thomas | Corvol, Jean-Christophe | Devos, David | Dujardin, Kathy | for the PREDISTIM working group

Article Type: Research Article

Abstract: Background: Parkinson’s disease mild cognitive impairment (PD-MCI) is frequent and heterogenous. There is no consensus about its influence on subthalamic deep brain stimulation (STN-DBS) outcomes. Objective: To determine the prevalence of PD-MCI and its subtypes in candidates to STN-DBS. Secondarily, we sought to identify MRI structural markers associated with cognitive impairment in these subgroups. Methods: Baseline data from the French multicentric PREDISTIM cohort were used. Candidates to STN-DBS were classified according to their cognitive performance in normal cognition (PD-NC) or PD-MCI. The latter included frontostriatal (PD-FS) and posterior cortical (PD-PC) subtypes. Between-group comparisons were performed on …demographical and clinical variables as well as on T1-weighted MRI sequences at the cortical and subcortical levels. Results: 320 patients were included: 167 (52%) PD-NC and 153 (48%) PD-MCI patients. The latter group included 123 (80%) PD-FS and 30 (20%) PD-PC patients. There was no between-group difference regarding demographic and clinical variables. PD-PC patients had significantly lower global efficiency than PD-FS patients and significantly worse performance on visuospatial functions, episodic memory, and language. Compared to PD-NC, PD-MCI patients had cortical thinning and radiomic-based changes in the left caudate nucleus and hippocampus. There were no significant differences between the PD-MCI subtypes. Conclusion: Among the candidates to STN-DBS, a significant proportion has PD-MCI which is associated with cortical and subcortical alterations. Some PD-MCI patients have posterior cortical deficits, a subtype known to be at higher risk of dementia. Show more

Keywords: Cortical thickness, dual syndrome hypothesis, radiomics, shape analysis, voxel-based morphometry

DOI: 10.3233/JPD-223232

Citation: Journal of Parkinson's Disease, vol. 12, no. 5, pp. 1507-1526, 2022

Authors: Gibson, Lucy L. | Pollak, Thomas A. | Heslegrave, Amanda | Hye, Abdul | Batzu, Lucia | Rota, Silvia | Trivedi, Dhaval | Nicholson, Timothy R. | ffytche, Dominic | Zetterberg, Henrik | Chaudhuri, K. Ray | Aarsland, Dag

Article Type: Research Article

Abstract: Background: Neuropsychiatric symptoms are common and important to people with Parkinson’s disease (PD), but their etiology is poorly understood. Plasma neurofilament light (NfL) and p-tau181 are biomarkers of neuro-axonal degeneration and tau pathology respectively, which have yet to be explored in association with the affective and psychotic symptoms in PD. Objective: To investigate the relationship between plasma NfL and p-tau181 with the affective and psychotic symptoms in PD. Methods: We assessed the baseline concentration of plasma NfL and p-tau181 in a cohort of 108 patients with PD and 38 healthy controls. A subgroup of patients (n … = 63) were assessed annually with clinical measures for up to 7 years. Psychotic symptoms were assessed using the Non-Motor Symptom Scale and affective symptoms were measured in the Hospital Anxiety and Depression Scale. Results: Baseline plasma NfL was a significant predictor of psychotic symptoms longitudinally across the study adjusted for age, Hoehn and Yahr stage, duration of follow up, duration of disease, baseline levodopa and dopamine agonist medication, and baseline cognition: (OR 8.15 [95% CI 1.40–47.4], p  = 0.020). There was no association between NfL concentration and the cumulative prevalence of affective symptoms. Plasma p-tau181 concentration was not associated with psychotic or affective symptoms. Conclusion: These findings suggest psychotic symptoms are associated with greater neurodegeneration in PD. Further studies are needed to explore NfL as a potential biomarker for psychosis in PD. Show more

Keywords: Neurofilament light, p-tau, psychosis, neuropsychiatric symptoms, biomarker, Parkinson’s disease

DOI: 10.3233/JPD-223182

Citation: Journal of Parkinson's Disease, vol. 12, no. 5, pp. 1527-1538, 2022

Authors: Usnich, Tatiana | Hanssen, Henrike | Lohmann, Katja | Lohse, Christina | Klein, Christine | Kasten, Meike | Brüggemann, Norbert | on behalf of the EPIPARK Study Group

Article Type: Short Communication

Abstract: Patients with Parkinson’s disease (PD) carrying variants in the Glucocerebrosidase (GBA) gene (GBA -PD) suffer from orthostatic symptoms more frequently than idiopathic PD patients (IPD). Systematic measurements of the blood pressure have not yet been performed. In the present study, a prospective analysis of 33 GBA -PD and 313 IPD patients was carried out. Systolic blood pressure upon changing from the supine to the upright position dropped more strongly in GBA -PD compared to IPD patients. Diastolic blood pressure and heart rate did not differ between groups. This study provides further evidence for a pronounced involvement of the autonomic …nervous system in GBA -PD. Show more

Keywords: Autonomic symptoms, GBA, orthostatic hypotension, Parkinson’s disease

DOI: 10.3233/JPD-223197

Citation: Journal of Parkinson's Disease, vol. 12, no. 5, pp. 1539-1544, 2022

Authors: Tseng, Kuan-Yin | Kuo, Tung-Tai | Wang, Vicki | Huang, Eagle Yi-Kung | Ma, Kuo-Hsing | Olson, Lars | Hoffer, Barry J. | Chen, Yuan-Hao

Article Type: Research Article

Abstract: Background: L-DOPA-induced dyskinesia (LID), occurring with aberrant processing of exogenous L-DOPA in the dopamine-denervated striatum, is a main complication of levodopa treatment in Parkinson’s disease. Objective: To characterize the effects of the vesicular antagonist tetrabenazine (TBZ) on L-DOPA-induced behavior, neurochemical signals, and underlying protein expressions in an animal model of Parkinson’s disease. Methods: 20-week-old MitoPark mice were co-treated or separately administered TBZ and L-DOPA for 14 days. Abnormal involuntary movements (AIMs) and locomotor activity were analyzed. To explore dopamine (DA) transmission, fast scan cyclic voltammetry was used to assess presynaptic DA dynamics in striatal slices following …treatments. PET imaging with 4-[18F]-PE2I, ADAM and immunoblotting assays were used to detect receptor protein changes in the DA-denervated striatum. Finally, nigrostriatal tissues were collected for HPLC measures of DA, serotonin and their metabolites. Results: A single injection of TBZ given in the interval between the two L-DOPA/Carbidopa treatments significantly attenuated L-DOPA-induced AIMs expression and locomotor hyperactivity. TBZ was shown to reduce tonic and phasic release of DA following L-DOPA treatment in DA-denervated striatal tissue. In the DA-depleted striatum, TBZ decreased the expression of L-DOPA-enhanced D1 receptors and the serotonin reuptake transporter. Neurochemical analysis indicated that TBZ attenuated L-DOPA-induced surges of DA levels by promoting DA turnover in the nigrostriatal system. Conclusions: Our findings demonstrate that TBZ diminishes abnormal striatal DA transmission, which involves the ability of TBZ to modulate the presymptomatic dynamics of DA, and then mitigate aberrant release of exogenous L-DOPA from nerve terminals. The results support the potential of repositioning TBZ to counteract LID development. Show more

Keywords: Parkinson’s disease, dopamine, L-DOPA-induced dyskinesia, tetrabenazine, serotonin transporter

DOI: 10.3233/JPD-223195

Citation: Journal of Parkinson's Disease, vol. 12, no. 5, pp. 1545-1565, 2022

Authors: Sampedro, Frederic | Martínez-Horta, Saul | Marín-Lahoz, Juan | Pagonabarraga, Javier | Kulisevsky, Jaime

Article Type: Research Article

Abstract: Background: Apathy represents a core neuropsychiatric symptom in Parkinson’s disease (PD). As there is currently no established effective treatment for apathy in PD, further investigating the biological origin of this symptom is needed to design novel therapeutic strategies. Among the multiple neurotransmitter alterations that have been associated with apathy, the involvement of extra-striatal dopaminergic degeneration remains to be fully explored. Objective: To investigate whether apathy in PD reflects increased dopaminergic degeneration extending beyond striatal regions. Methods: In the de novo PD cohort of the Parkinson’s Progression Markers Initiative (PPMI), we performed whole-brain I123 -Ioflupane Single Photon …Emission Computed Tomography (DAT-SPECT) analyses to characterize cross-sectional and longitudinal differences in DAT uptake associated with the presence of apathy. We also assessed the relationship between apathy and cognition in this sample, as apathy has been suggested to herald cognitive decline. Results: Apathetic PD patients (N  = 70) had similar sociodemographic, clinical, and biomarker profiles compared to the non-apathetic group (N  = 333) at baseline. However, apathy was associated with an increased risk of developing cognitive impairment after a four-year follow-up period (p  = 0.006). Compared to non-apathetic patients, apathetic patients showed a widespread reduction of extra-striatal DAT uptake at baseline as well as an increased longitudinal loss of DAT uptake (corrected p  < 0.05). Conclusions: Isolated apathy in PD is associated with extra-striatal dopaminergic degeneration. As this abnormal dopamine depletion was in turn related to cognitive performance, this might explain, at least partially, the increased risk of apathetic PD patients to develop cognitive impairment or dementia. Show more

Keywords: Apathy, DAT, extra-striatal, Parkinson’s disease

DOI: 10.3233/JPD-223223

Citation: Journal of Parkinson's Disease, vol. 12, no. 5, pp. 1567-1574, 2022

Authors: Bange, Manuel | Gonzalez-Escamilla, Gabriel | Lang, Nadine Sandra Claudia | Ding, Hao | Radetz, Angela | Herz, Damian Marc | Schöllhorn, Wolfgang Immanuel | Muthuraman, Muthuraman | Groppa, Sergiu

Article Type: Research Article

Abstract: Background: Gait impairments are common in Parkinson’s disease (PD). The pathological mechanisms are complex and not thoroughly elucidated, thus quantitative and objective parameters that closely relate to gait characteristics are critically needed to improve the diagnostic assessments and monitor disease progression. The substantia nigra is a relay structure within basal ganglia brainstem loops that is centrally involved in gait modulation. Objective: We tested the hypothesis that quantitative gait biomechanics are related to the microstructural integrity of the substantia nigra and PD-relevant gait abnormalities are independent from bradykinesia-linked speed reductions. Methods: Thirty-eight PD patients and 33 age-matched …control participants walked on a treadmill at fixed speeds. Gait parameters were fed into a principal component analysis to delineate relevant features. We applied the neurite orientation dispersion and density imaging (NODDI) model on diffusion-weighted MR-images to calculate the free-water content as an advanced marker of microstructural integrity of the substantia nigra and tested its associations with gait parameters. Results: Patients showed increased duration of stance phase, load response, pre-swing, and double support time, as well as reduced duration of single support and swing time. Gait rhythmic alterations associated positively with the free-water content in the right substantia nigra in PD, indicating that patients with more severe neurodegeneration extend the duration of stance phase, load response, and pre-swing. Conclusion: The results provide evidence that gait alterations are not merely a byproduct of bradykinesia-related reduced walking speed. The data-supported association between free-water and the rhythmic component highlights the potential of substantia nigra microstructure imaging as a measure of gait-dysfunction and disease-progression. Show more

Keywords: Parkinson’s disease, gait, substantia nigra, free-water, diffusion-weighted imaging

DOI: 10.3233/JPD-223225

Citation: Journal of Parkinson's Disease, vol. 12, no. 5, pp. 1575-1590, 2022

Authors: Kehagia, Angie A. | North, Tracie K. | Grose, Jane | Jeffery, Alison N. | Cocking, Laura | Chapman, Rebecca | Carroll, Camille

Article Type: Research Article

Abstract: Background: Recruitment and retention of participants in clinical trials for Parkinson’s disease (PD) is challenging. A qualitative study embedded in the PD STAT multi-centre randomised controlled trial of simvastatin for neuroprotection in PD explored the motivators, barriers and challenges of participants, care partners and research staff. Objective: To outline a set of considerations informing a patient-centred approach to trial recruitment, retention, and delivery. Method: We performed semi-structured interviews and focus groups with a subset of trial participants and their care partners. Quantitative and qualitative data were obtained through surveys circulated among the 235 participants across 23 UK …sites at the beginning, middle and end of the 2-year trial. We also interviewed and surveyed research staff at trial closure. Results: Twenty-seven people with PD, 6 care partners and 9 researchers participated in interviews and focus groups. A total of 463 trial participant survey datasets were obtained across three timepoints, and 53 staff survey datasets at trial closure. Trial participants discussed the physical and psychological challenges they faced, especially in the context of OFF state assessments, relationships, and communication with research staff. Care partners shared their insights into OFF state challenges, and the value of being heard by research teams. Research staff echoed many concerns with suggestions on flexible, person-centred approaches to maximising convenience, comfort, and privacy. Conclusion: These considerations, in favour of person-centred research protocols informed by the variable needs of participants, care partners and staff, could be developed into a set of recommendations for future trials. Show more

Keywords: Parkinson’s disease, clinical trial, participation, recruitment, retention, OFF assessment, consent, patient-centred, qualitative, PPI

DOI: 10.3233/JPD-212987

Citation: Journal of Parkinson's Disease, vol. 12, no. 5, pp. 1591-1604, 2022

Authors: Day, Jacob O. | Smith, Stephen | Noyce, Alastair J. | Alty, Jane | Jeffery, Alison | Chapman, Rebecca | Carroll, Camille

Article Type: Short Communication

Abstract: Digital health technologies (DHTs) have great potential for use as clinical trial outcomes; however, practical issues need to be addressed in order to maximise their benefit. We describe our experience of incorporating two DHTs as secondary/exploratory outcome measures in PD STAT, a randomised clinical trial of simvastatin in people with Parkinson’s disease. We found much higher rates of missing data in the DHTs than the traditional outcome measures, in particular due to technical and software difficulties. We discuss methods to address these obstacles in terms of protocol design, workforce training and data management.

Keywords: Parkinson’s disease, clinical trials, digital outcomes, sensors, data management

DOI: 10.3233/JPD-223162

Citation: Journal of Parkinson's Disease, vol. 12, no. 5, pp. 1605-1609, 2022

Authors: Wuehr, Max | Schmidmeier, Florian | Katzdobler, Sabrina | Fietzek, Urban M. | Levin, Johannes | Zwergal, Andreas

Article Type: Research Article

Abstract: Background: Postural instability is a major disabling factor in patients with advanced Parkinson’s disease (PD) and often resistant to treatment. Previous studies indicated that imbalance in PD may be reduced by low-intensity noisy galvanic vestibular stimulation (nGVS). Objective: To investigate the potential mode of action of this therapeutic effect. In particular, we examined whether nGVS-induced reductions of body sway in PD are compatible with stochastic resonance (SR), a mechanism by which weak sensory noise stimulation can paradoxically enhance sensory information transfer. Methods: Effects of nGVS of varying intensities (0–0.7 mA) on body sway were examined in 15 …patients with PD standing with eye closed on a posturographic force plate. We assumed a bell-shaped response curve with maximal reductions of sway at intermediate nGVS intensities to be indicative of SR. An established SR-curve model was fitted on individual patient outcomes and three experienced human raters had to judge whether responses to nGVS were consistent with the exhibition of SR. Results: nGVS-induced reductions of body sway compatible with SR were found in 10 patients (67%) with optimal improvements of 23±13%. In 7 patients (47%), nGVS-induced sway reductions exceeded the minimally important clinical difference (optimal improvement: 30±10%), indicative of strong SR. This beneficial effect was more likely in patients with advanced PD (R  = 0.45; p  = 0.045). Conclusions: At least half of the assessed patients showed robust improvements in postural balance compatible with SR when treated with low-intensity nGVS. In particular, patients with more advanced disease stages and imbalance may benefit from the non-invasive and well-tolerated treatment with nGVS. Show more

Keywords: Balance, body sway, galvanic vestibular stimulation, Parkinson’s disease, stochastic resonance

DOI: 10.3233/JPD-213127

Citation: Journal of Parkinson's Disease, vol. 12, no. 5, pp. 1611-1618, 2022

Authors: Kawada, Tomoyuki

Article Type: Letter

Abstract: I discussed the risk of phenoconversions from idiopathic/isolated REM sleep behavior disorder (iRBD). Comorbidity with iRBD, such as obstructive sleep apnea, may accerelate the risk of α-synuclein-related neurodegenerative diseases. Further studies are needed to specify the risk factors of phenoconversion from iRBD.

Keywords: α-synuclein-related neurodegenerative diseases, rapid eye movement sleep behavior disorder, risk factors

DOI: 10.3233/JPD-223306

Citation: Journal of Parkinson's Disease, vol. 12, no. 5, pp. 1619-1620, 2022

Authors: Templeton, John Michael | Poellabauer, Christian | Schneider, Sandra

Article Type: Research Article

Abstract: Background: Mobile devices and their capabilities (e.g., device sensors and human-device interactions) are increasingly being considered for use in clinical assessments and disease monitoring due to their ability to provide objective, repeatable, and more accurate measures of neurocognitive performance. These mobile-based assessments also provide a foundation for the design of intervention recommendations. Objective: The purpose of this work was to assess the benefits of various physical intervention programs as they relate to Parkinson’s disease (PD), its symptoms, and stages (Hoehn and Yahr (H&Y) Stages 1–5). Methods: Ninety-five participants (n  = 70 PD; n  = 25 control) completed 14 …tablet-based neurocognitive functional tests (e.g., motor, memory, speech, executive, and multi-function) and standardized health questionnaires. 208 symptom-specific digital features were normalized to assess the benefits of various physical intervention programs (e.g., aerobic activity, non-contact boxing, functional strength, and yoga) for individuals with PD. While previous studies have shown that physical interventions improve both motor and non-motor PD symptoms, this paper expands on previous works by mapping symptom-specific neurocognitive functionalities to specific physical intervention programs across stages of PD. Results: For early-stage PD (e.g., H&Y Stages 1 & 2), functional strength activities provided the largest overall significant delta improvement (Δ = 0.1883; p  = 0.0265), whereas aerobic activity provided the largest overall significant delta improvement (Δ = 0.2700; p  = 0.0364) for advanced stages of PD (e.g., H&Y Stages 3–5). Conclusions: As mobile-based digital health technology allows for the collection of larger, labeled, objective datasets, new ways to analyze and interpret patterns in this data emerge which can ultimately lead to new personalized medicine programs. Show more

Keywords: Intervention recommendation, mobile applications, neurocognitive assessment, Parkinson’s disease, physical activity

DOI: 10.3233/JPD-223214

Citation: Journal of Parkinson's Disease, vol. 12, no. 5, pp. 1621-1631, 2022

Authors: Pengo, Marta | Murueta-Goyena, Ane | Teijeira-Portas, Sara | Acera, Marian | Del Pino, Rocio | Sáez-Atxukarro, Oihane | Diez-Cirarda, Maria | Tijero, Beatriz | Fernández-Valle, Tamara | Gómez Esteban, Juan Carlos | Gabilondo, Iñigo

Article Type: Research Article

Abstract: Background: Visual impairment is frequent and highly disabling in Parkinson’s disease (PD); however, few studies have comprehensively evaluated its impact on vision-related quality of life. Objective: To evaluate the relationship between visual function tests and the visual impairment perceived by PD patients in daily living activities. Methods: We cross-sectionally evaluated 62 PD patients and 33 healthy controls (HC). Visual disability was measured with a comprehensive battery of primary visual function and visual cognition tests (visual outcomes), and vision-related quality of life was evaluated with the National Eye Institute 25-Item Visual Function Questionnaire (NEI VFQ-25). The relationship …between visual outcomes and NEI VFQ-25 sub-scores was analyzed with Pearson’s correlations and stepwise linear regression. Results: In PD patients, and not in HC, most NEI VFQ-25 sub-scores were significantly correlated with Cube Analysis and Dot Counting from Visual Object and Space Perception (VOSP) battery (visual perception), Clock Drawing Test (visuoconstructive capacity) and Trail Making Test part-A (visual attention and processing speed) and to a lesser extent with high- and low-contrast visual acuity. Dot Counting (VOSP) was the test primarily associated with most NEI VFQ-25 sub-scores (5 out of 12). Roth-28 color test was the one that best explained the variance of Peripheral Vision (R2 : 0.21) and Role Difficulties (R2 : 0.36) sub-scores of NEI VFQ-25, while photopic contrast sensitivity explained 41% of Driving sub-score variance. Conclusion: Vision-related quality of life in PD is mainly influenced by alterations in visual perception, visuoconstructive capacity and visual attention and processing speed. Future studies are warranted to confirm and further extend our findings. Show more

Keywords: Activities of daily living, visual acuity, contrast sensitivity, visual cognition, Parkinson’s disease

DOI: 10.3233/JPD-213143

Citation: Journal of Parkinson's Disease, vol. 12, no. 5, pp. 1633-1643, 2022

Authors: Lee, Susan J. | Shaw, Peter M. | Thornton, Bob | Kumar, Amit | Eizik, Michal | Goldstaub, Dan | Braun, Tali | Teper, Gally | Pai, Jennifer K. | Chodick, Gabriel | Bienfait, Karina | Levitan, Diane | Beller, Daniella | Chris Min, K. | Jonathan, Daniel | Voss, Tiffini | Fox, Caroline S. | Aubrey Stoch, S. | Struyk, Arie F. | Vainstein, Gabriel

Article Type: Research Article

Abstract: Background: More efficient screening methods are needed to improve the ability to identify and follow genetic cohorts in Parkinson’s disease (PD). Objective: To explore the use of the electronic medical records (EMRs) to identify participants with PD. Methods: Using an algorithm previously developed in collaboration with Maccabi Healthcare Services (MHS), approximately 5,200 participants with PD were identified, more than 3,200 were screened, and 837 participants were enrolled and genotyped for leucine-rich repeat kinase 2 (LRRK2 ) and beta-glucocerebrosidase (GBA) variants. Questionnaires were completed to ascertain Ashkenazi Jewish (AJ) ancestry and family history of PD. …Results: Among 837 participants with PD, 82% were 65 years and older and 72% had a family history of AJ ancestry. Among those with AJ ancestry, 15.6% reported having relatives with PD. The frequency of observed mutations for LRRK2 and GBA genes combined was approximately 15.4%. The frequency of observed LRRK2 mutation was 6.1% overall and 7.2% from those with AJ ancestry; and for GBA mutation was 9.3% overall and 11.2% from those with AJ ancestry. Conclusion: Although the frequency of observed mutations in this study was lower than anticipated, mutation carriers were enriched among those with a family history of AJ ancestry increasing nearly 2-3-fold, from 3% –7% (LRRK2 ) and 4% –11% (GBA ). The identification (and selection) of PD patients through EMRs prior to genotyping is a viable approach, to establish a genetically defined cohort of patients with PD for clinical research. Show more

Keywords: Parkinson’s disease, glucocerebrosidase, Parkinson mutations, genetic testing

DOI: 10.3233/JPD-212703

Citation: Journal of Parkinson's Disease, vol. 12, no. 5, pp. 1645-1653, 2022

Authors: van den Heuvel, Lieneke | Hoefsloot, Wibe | Post, Bart | Meinders, Marjan J. | Bloem, Bastiaan R. | Stiggelbout, Anne M. | van Til, Janine A.

Article Type: Research Article

Abstract: Background: In Parkinson’s disease (PD), several disease-modifying treatments are being tested in (pre-)clinical trials. To successfully implement such treatments, it is important to have insight into factors influencing the professionals’ decision to start disease-modifying treatments in persons who are in the prodromal stage of PD. Objective: We aim to identify factors that professionals deem important in deciding to a start disease-modifying treatment in the prodromal stage of PD. Methods: We used a discrete choice experiment (DCE) to elicit preferences of neurologists and last-year neurology residents regarding treatment in the prodromal phase of PD. The DCE contained …16 hypothetical choice sets in which participants were asked to choose between two treatment options. The presented attributes included treatment effect, risk of severe side-effects, risk of mild side-effects, route of administration, and annual costs. Results: We included 64 neurologists and 18 last year neurology residents. Participants attached most importance to treatment effect and to the risk of severe side-effects. Participants indicated that they would discuss one of the presented treatments in daily practice more often in persons with a high risk of being in the prodromal phase compared to those with a moderate risk. Other important factors for deciding to start treatment included the amount of evidence supporting the putative treatment effect, the preferences of the person in the prodromal phase, and the life expectancy. Conclusion: This study provides important insights in factors that influence decision making by professionals about starting treatment in the prodromal phase of PD. Show more

Keywords: Decision making, disease-modifying treatment, Parkinson’s disease, prodromal PD, professional’s preference

DOI: 10.3233/JPD-223208

Citation: Journal of Parkinson's Disease, vol. 12, no. 5, pp. 1655-1664, 2022

Authors: Meira, Bruna | Lhommée, Eugénie | Schmitt, Emmanuelle | Klinger, Hélène | Bichon, Amélie | Pélissier, Pierre | Anheim, Mathieu | Tranchant, Christine | Fraix, Valérie | Meoni, Sara | Durif, Franck | Houeto, Jean-Luc | Azulay, Jean Philippe | Moro, Elena | Thobois, Stéphane | Krack, Paul | Castrioto, Anna | for the Honeymoon study group

Article Type: Research Article

Abstract: Background: Previous studies described a parkinsonian personality characterized as rigid, introverted, and cautious; however, little is known about personality traits in de novo Parkinson’s disease (PD) patients and their relationships with motor and neuropsychiatric symptoms. Objective: To investigate personality in de novo PD and explore its relationship with PD symptoms. Methods: Using Cloninger’s biosocial model, we assessed personality in 193 de novo PD patients. Motor and non-motor symptoms were measured using several validated scales. Cluster analysis was conducted to investigate the interrelationship of personality traits, motor, and non-motor symptoms. Results: PD …patients showed low novelty seeking, high harm avoidance, and normal reward dependence and persistence scores. Harm avoidance was positively correlated with the severity of depression, anxiety, and apathy (rs  = [0.435, 0.676], p  < 0.001) and negatively correlated with quality of life (rs  = –0.492, p  < 0.001). Novelty seeking, reward dependence, and persistence were negatively correlated with apathy (rs  = [–0.274, –0.375], p  < 0.001). Classification of patients according to personality and PD symptoms revealed 3 distinct clusters: i) neuropsychiatric phenotype (with high harm avoidance and low novelty seeking, hypodopaminergic neuropsychiatric symptoms and higher impulsivity), ii) motor phenotype (with low novelty seeking and higher motor severity), iii) benign phenotype (with low harm avoidance and high novelty seeking, reward dependence, and persistence traits clustered with lower symptoms severity and low impulsivity). Conclusion: Personality in early PD patients allows us to recognize 3 patients’ phenotypes. Identification of such subgroups may help to better understand their natural history. Their longitudinal follow-up will allow confirming whether some personality features might influence disease evolution and treatment. Show more

Keywords: Neuropsychiatric symptoms, non-motor symptoms, Parkinson’s disease, personality

DOI: 10.3233/JPD-213070

Citation: Journal of Parkinson's Disease, vol. 12, no. 5, pp. 1665-1676, 2022

Authors: van de Wetering-van Dongen, Veerle A. | Nijkrake, Maarten J. | Koenders, Niek | van der Wees, Philip J. | Bloem, Bastiaan R. | Kalf, Johanna G.

Article Type: Research Article

Abstract: Background: Abnormal respiratory function tests can be observed early in the course of Parkinson’s disease (PD). A better understanding of the impact of respiratory dysfunction on daily life in PD is needed to prevent later occurring complications as a (aspiration) pneumonia. Objective: To explain which respiratory symptoms people with PD or a form of atypical parkinsonism experience and how these symptoms impact on their daily lives. Methods: This qualitative study used a grounded theory approach. A purposeful sample strategy was used to capture information-rich cases. Data were collected in semi-structured interviews with participants diagnosed with either …PD (n  = 11) or atypical parkinsonism (n  = 3), all of whom had confirmed respiratory symptoms. Data were analyzed using grounded theory analysis by creating codes, categories, theoretical themes, and, ultimately, a conceptual model. Results: Four respiratory profiles emerged, describing different types of respiratory dysfunction, with various positive and negative influencing factors. First, a loss of breathing automatism was experienced. Second, episodes of breathlessness or a rapid, shallow breathing pattern were triggered by either physical exertion, fatigue, or postural deformities. Third, stress and anxiety also triggered episodes of breathlessness. Fourth, a decreased cough strength and frequent coughing. Based on these findings, we constructed a conceptual model that visualizes the relations between these four types of respiratory dysfunction and their impact on daily life, with ‘discomfort’ and ‘avoidance of social activities’ as crucial elements. Conclusion: A tailored approach for each profile of respiratory dysfunction is recommended to improve respiratory dysfunction and to reduce its social impact in people with PD. Show more

Keywords: Respiratory function, respiratory symptoms, Parkinson’s disease, qualitative research, multidisciplinary

DOI: 10.3233/JPD-213121

Citation: Journal of Parkinson's Disease, vol. 12, no. 5, pp. 1677-1691, 2022

Authors: Nie, Jia | Liu, Chunyu | Yu, Canqing | Guo, Yu | Pei, Pei | Yang, Ling | Chen, Yiping | Du, Huaidong | Zhu, Kaifei | Schmidt, Danile | Avery, Daniel | Chen, Junshi | Chen, Zhengming | Lv, Jun | Li, Liming | for the China Kadoorie Biobank (CKB) Collaborative Group

Article Type: Research Article

Abstract: Background: Existing limited evidence suggests that smoking and tea consumption may be associated with a lower risk of Parkinson’s disease (PD). However, less is known about the independent and joint roles of these two habits, which are often clustered among Chinese, on PD risk. Objective: To prospectively examine the independent and joint association of tea consumption and smoking with the risk of PD. Methods: The China Kadoorie Biobank (CKB) study recruited 512,725 participants aged 30 to 79 years from ten areas across China since 2004. Information on smoking and tea consumption was collected at baseline, and PD …cases were ascertained by linkage to the national health insurance system and death registry. Cox proportional hazards models were used to estimate the multivariable-adjusted hazard ratios (HRs) and corresponding 95%confidence intervals (CIs). Results: During a median of 10.8 years of follow-up, 922 PD cases were recorded. Compared with participants who never consumed tea, the HR (95%CI) for daily consumers was 0.68 (0.55, 0.84). Compared with participants who never or occasionally smoked, the HR (95%CI) for current smokers was 0.66 (0.53, 0.82). Those who had a clustering habit of smoking and tea consumption had a 38%(HR = 0.62; 95%CI: 0.49, 0.79) lower PD risk than those who consumed none. However, there were no statistically significant multiplicative or additive interaction for tea consumption and smoking on PD risk. Conclusion: We found that smoking and daily tea consumption were independently inversely associated with the risk of PD. Show more

Keywords: Chinese, Parkinson’s disease, prospective study, smoking, tea consumption

DOI: 10.3233/JPD-223148

Citation: Journal of Parkinson's Disease, vol. 12, no. 5, pp. 1693-1702, 2022