Journal of Parkinson's Disease - Volume 12, issue 2

Authors: Tan, Yu-Yan | Jenner, Peter | Chen, Sheng-Di

Article Type: Review Article

Abstract: Monoamine oxidase-B (MAO-B) inhibitors are commonly used for the symptomatic treatment of Parkinson’s disease (PD). MAO-B inhibitor monotherapy has been shown to be effective and safe for the treatment of early-stage PD, while MAO-B inhibitors as adjuvant drugs have been widely applied for the treatment of the advanced stages of the illness. MAO-B inhibitors can effectively improve patients’ motor and non-motor symptoms, reduce “OFF” time, and may potentially prevent/delay disease progression. In this review, we discuss the effects of MAO-B inhibitors on motor and non-motor symptoms in PD patients, their mechanism of action, and the future development of MAO-B inhibitor …therapy. Show more

Keywords: Monoamine oxidase-B inhibitors, Parkinson’s disease, selegiline, rasagiline, safinamide

DOI: 10.3233/JPD-212976

Citation: Journal of Parkinson's Disease, vol. 12, no. 2, pp. 477-493, 2022

Authors: Urbi, Berzenn | Corbett, Joel | Hughes, Ian | Owusu, Maame Amma | Thorning, Sarah | Broadley, Simon A. | Sabet, Arman | Heshmat, Saman

Article Type: Systematic Review

Abstract: The legalization of cannabis in many countries has allowed many Parkinson’s disease (PD) patients to turn to cannabis as a treatment. As such there is a growing interest from the PD community to be properly guided by evidence regarding potential treatment benefits of cannabis. This systematic review and meta-analysis aims to compile the best available evidence to help guide patients and their family, clinicians and researchers make informed decisions. A systematic search of the literature was conducted in June 2021. Five randomized controlled studies and eighteen non-randomized studies investigated cannabis treatment in PD patients. No compelling evidence was found to …recommend the use of cannabis in PD patients. However, a potential benefit was identified with respect to alleviation of PD related tremor, anxiety, pain, improvement of sleep quality and quality of life. Given the relative paucity of well-designed randomized studies, there is an identified need for further investigation, particularly in these areas. Show more

Keywords: Cannabis, Parkinson’s disease, efficacy of cannabis, tremor, UPDRS

DOI: 10.3233/JPD-212923

Citation: Journal of Parkinson's Disease, vol. 12, no. 2, pp. 495-508, 2022

Authors: Hanff, Anne-Marie | Leist, Anja K. | Fritz, Joëlle V. | Pauly, Claire | Krüger, Rejko | Halek, Margareta | on behalf of the NCER-PD Consortium

Article Type: Systematic Review

Abstract: Background: Self-stigma in people with Parkinson’s disease (PD) can substantially impact quality of life and possibilities for social participation. An integrative analysis of determinants of self-stigma has been lacking. Objective: We sought to explore which complementary insights from qualitative and quantitative studies, as well as from expert consultation, could be gained. Methods: An established mixed methods study design was employed to first conduct a mixed methods scoping review of published qualitative and quantitative literature, and then consult with experts to arrive at an exhaustive list of determinants of self-stigma after a thematic synthesis. Results: …A total of 87 unique determinants of self-stigma were identified. Quantitative studies and expert consultations mainly identified personal determinants of people with self-stigma (e.g., age, anxiety, or apathy). In contrast, qualitative studies identified social situations associated with self-stigma (e.g., joint meals of people with typical PD with others). Notably, self-stigma of people with PD was found to be particularly salient in unfamiliar places, at the working place or in contact with people without PD. Across methods, cognitive impairment, tremor, and abnormal walk and unsteady gait, respectively, were associated with self-stigma. Conclusion: The mixed method study design yielded complementary insights, but also factors commonly associated with self-stigma across methods. Future prioritization exercises may gain further insights into self-stigma of people with PD. Facilitating social encounters by both addressing needs of affected people and raising knowledge and public awareness may improve quality of life in people with PD. Show more

Keywords: Parkinson’s disease, social stigma, shame, social discrimination, review, international classification of functioning, disability and health

DOI: 10.3233/JPD-212869

Citation: Journal of Parkinson's Disease, vol. 12, no. 2, pp. 509-522, 2022

Authors: McFarthing, Kevin | Prakash, Neha | Simuni, Tanya

Article Type: Other

DOI: 10.3233/JPD-229001

Citation: Journal of Parkinson's Disease, vol. 12, no. 2, pp. 523-536, 2022

Authors: Liguori, Claudio | Stefani, Alessandro | Fernandes, Mariana | Cerroni, Rocco | Mercuri, Nicola Biagio | Pierantozzi, Mariangela

Article Type: Research Article

Abstract: Background: Several biomarkers have been evaluated in Parkinson’s disease (PD); cerebrospinal fluid (CSF) levels of lactate may reflect cerebral metabolism function and CSF amyloid-β42 (Aβ42 ), total tau (t-tau) and phosphorylated tau (p-tau) concentrations may detect an underlying neurodegenerative process. Objective: CSF levels of lactate, Aβ42 , t-tau, and p-tau were measured in patients with mild to moderate PD. CSF levels of dopamine (DA) and its metabolite 3,4-Dihydroxyphenylacetic acid (DOPAC) were also assessed, exploring their relations with the other CSF biomarkers. Methods: 101 drug-naive PD patients and 60 controls were included. Participants …underwent clinical assessments and CSF biomarker analysis. Patients were divided into subgroups according to their Hoehn & Yahr stage (PD-1, PD-2, PD-3). Results: PD patients showed higher lactate levels (M = 1.91; p  = 0.03) and lower Aβ42 (M = 595; p  < 0.001) and DA levels (M = 0.32; p  = 0.04) than controls (Mlactate  = 1.72; MAβ42  = 837; MDA  = 0.50), while no significant differences were found in t-tau, p-tau and DOPAC concentrations. Considering the subgroup analysis, PD-3 group had higher lactate (M = 2.12) and t-tau levels (M = 333) than both PD-1 (Mlactate  = 1.75, p  = 0.006; Mt - tau  = 176, p  = 0.008) and PD-2 groups (Mlactate  = 1.91, p  = 0.01; Mt - tau  = 176, p  = 0.03), as well as the controls (Mlactate  = 1.72, p  = 0.04; Mt - tau  = 205, p  = 0.04). PD-2 group showed higher lactate levels than PD-1 group (p  = 0.04) and controls (p  = 0.03). Finally, CSF lactate levels negatively correlated with DA (r = –0.42) and positively with t-tau CSF levels (r = 0.33). Conclusion: This CSF-based study shows that lactate levels in PD correlated with both clinical disease progression and neurodegeneration biomarkers, such as tau proteins and DA. Further studies should explore the clinical potential of measuring CSF biomarkers for better understanding the role of brain energy metabolism in PD, for research and therapeutic options. Show more

Keywords: Lactate, tau, amyloid-β42, dopamine, motor impairment

DOI: 10.3233/JPD-212936

Citation: Journal of Parkinson's Disease, vol. 12, no. 2, pp. 537-544, 2022

Authors: Chen, Gary K. | Yan, Qi | Paul, Kimberly C. | Kusters, Cynthia D.J. | Folle, Aline Duarte | Furlong, Melissa | Keener, Adrienne | Bronstein, Jeff | Horvath, Steve | Ritz, Beate

Article Type: Research Article

Abstract: Background: Stochastic epigenetic mutations (SEM) reflect a deviation from normal site-specific methylation patterns. Epigenetic mutation load (EML) captures the accumulation of SEMs across an individual’s genome and may reflect dysfunction of the epigenetic maintenance system in response to epigenetic challenges. Objective: We investigate whether EML is associated with PD risk and time to events (i.e., death and motor symptom decline). Methods: We employed logistic regression and Cox proportional hazards regression to assess the association between EML and several outcomes. Our analyses are based on 568 PD patients and 238 controls from the Parkinson’s disease, Environment and …Genes (PEG) study, for whom blood-based methylation data was available. Results: We found an association for PD onset and EML in all genes (OR = 1.90; 95%CI 1.52-2.37) and PD-related genes (OR = 1.87; 95%CI 1.50-2.32). EML was also associated with time to a minimum score of 35 points on the motor UPDRS exam (OR = 1.28; 95%CI 1.06-1.56) and time to death (OR = 1.29, 95%CI 1.11-1.49). An analysis of PD related genes only revealed five intragenic hotspots of high SEM density associated with PD risk. Conclusion: Our findings suggest an enrichment of methylation dysregulation in PD patients in general and specifically in five PD related genes. EML may also be associated with time to death and motor symptom progression in PD patients. Show more

Keywords: Parkinson’s disease, epigenetics

DOI: 10.3233/JPD-212834

Citation: Journal of Parkinson's Disease, vol. 12, no. 2, pp. 545-556, 2022

Authors: Peterschmitt, M. Judith | Saiki, Hidemoto | Hatano, Taku | Gasser, Thomas | Isaacson, Stuart H. | Gaemers, Sebastiaan J.M. | Minini, Pascal | Saubadu, Stéphane | Sharma, Jyoti | Walbillic, Samantha | Alcalay, Roy N. | Cutter, Gary | Hattori, Nobutaka | Höglinger, Günter U. | Marek, Kenneth | Schapira, Anthony H.V. | Scherzer, Clemens R. | Simuni, Tanya | Giladi, Nir | Sardi, Sergio Pablo | Fischer, Tanya Z. | on behalf of the MOVES-PD Investigators

Article Type: Research Article

Abstract: Background: Glucocerebrosidase gene (GBA ) mutations influence risk and prognosis of Parkinson’s disease (PD), possibly through accumulation of glycosphingolipids, including glucosylceramide (GL-1). Venglustat is a novel, brain penetrant glucosylceramide synthase inhibitor. Objective: Evaluate venglustat pharmacology, safety, and tolerability in patients with PD and GBA mutations (GBA -PD). Methods: Part 1 of the phase 2 MOVES-PD trial (NCT02906020) was a randomized, double-blinded, placebo-controlled, dose-escalation study performed in six countries. Eligible participants included Japanese and non-Japanese patients aged 18–80 years with PD diagnosis and heterozygous GBA mutation. Participants were randomized to three doses of once-daily oral …venglustat or placebo and were followed up to 36 weeks (Japanese participants: 52 weeks). Primary endpoint was venglustat safety and tolerability versus placebo. Secondary and exploratory endpoints included venglustat pharmacokinetics and pharmacodynamics. Results: Participants (N  = 29) received venglustat (Japanese, n  = 9; non-Japanese, n  = 13) or placebo (n  = 3; n  = 4). Eight (89%) Japanese and 12 (92%) non-Japanese venglustat-treated participants experienced at least one adverse event (AE) versus two (67%) and four (100%) participants from the respective placebo groups. Most AEs were mild or moderate; no serious AEs or deaths occurred. Two venglustat-treated non-Japanese participants discontinued due to AEs (confusional state and panic attack). Over 4 weeks, venglustat exposure in plasma and cerebrospinal fluid (CSF) increased, and GL-1 levels in plasma and CSF decreased, both in a dose-dependent manner. At the highest dose, CSF GL-1 decreased by 72.0% in Japanese and 74.3% in non-Japanese participants. Conclusion: Venglustat showed favorable safety and tolerability in MOVES-PD Part 1 and target engagement was achieved in CSF. Show more

Keywords: Parkinson’s disease, MOVES-PD, Venglustat (GZ/SAR402671), glucocerebrosidase gene (GBA), glucosylceramide (GL-1), glucosylceramide synthase (GCS) inhibition, GBA-PD

DOI: 10.3233/JPD-212714

Citation: Journal of Parkinson's Disease, vol. 12, no. 2, pp. 557-570, 2022

Authors: Ygland Rödström, Emil | Mattsson-Carlgren, Niklas | Janelidze, Shorena | Hansson, Oskar | Puschmann, Andreas

Article Type: Research Article

Abstract: Background: Biochemical and clinical biomarkers correlate with progression rate and disease severity in Parkinson’s disease (PD) but are not sufficiently studied in late PD. Objective: To examine how serum neurofilament light chain (S-NfL) alone or combined with clinical classifications predicts PD outcome in later disease stages. Methods: Eighty-five patients with 7.9±5.1 years of PD duration were included in an observational cohort. Clinical scores were obtained at two separate examinations 8.2±2.0 years apart. S-NfL levels were determined with single molecule array (SiMoA). Five predefined disease progression milestones were assessed. After affirming combination potential of S-NfL and either …of two clinical classifications, three combined models were constructed based on these factors and age at onset in different combinations. Results: S-NfL levels showed significant hazard ratios for four out of five disease progression milestones: walking-aid usage (HR 3.5; 95% CI 1.4–8.5), nursing home living (5.1; 2.1–12.5), motor end-stage (6.2; 2.1–17.8), and death (4.1; 1.7–9.7). Higher S-NfL levels were associated with lower ability in activities of daily living and poorer cognition at baseline and/or at follow-up. Combined models showed significantly improved area under receiver operating characteristic curves (0.77–0.91) compared to S-NfL levels alone (0.68–0.71) for predicting the five disease milestones. Conclusion: S-NfL levels stratified patients according to their likelihood to reach clinically relevant progression milestones during this long-term observational study. S-NfL alone reflected motor and social outcomes in later stages of PD. Combining S-NfL with clinical factors was possible and exploratory combined models improved prognostic accuracy. Show more

Keywords: Parkinson’s disease, biomarkers, dementia, neurofilament proteins, prognosis, mortality

DOI: 10.3233/JPD-212866

Citation: Journal of Parkinson's Disease, vol. 12, no. 2, pp. 571-584, 2022

Authors: Giannoccaro, Maria Pia | Avoni, Patrizia | Rizzo, Giovanni | Incensi, Alex | Infante, Rossella | Donadio, Vincenzo | Liguori, Rocco

Article Type: Research Article

Abstract: Background: Previous studies reported skin phosphorylated α-synuclein (p-syn) deposits in Parkinson’s disease (PD) patients but not in patients with parkinsonism due to tauopathies, although data on the latter are limited. Objective: We aimed to assess the presence of skin p-syn deposits in patients with clinical diagnosis of parkinsonism usually due to tauopathy and PD. Methods: We consecutively recruited 26 patients, 18 fulfilling clinical diagnostic criteria of progressive supranuclear palsy (PSP) and 8 of corticobasal syndrome (CBS), 26 patients with PD, and 26 healthy controls (HC). All subjects underwent skin biopsy to study p-syn deposits in skin …nerves by immunofluorescence. Results: Skin p-syn deposits were present in only two of the PSP/CBS patients and none of the HC. Conversely, all PD patients showed p-syn deposition (p  < 0.001, Chi-square). The two p-syn positive patients were diagnosed with PSP and CBS, respectively. Although clinical and MRI findings supported these diagnoses, both patients had some atypical features more typical of synucleinopathies. Conclusion: The detection of skin p-syn deposits may help in the differential diagnosis of parkinsonism. Indeed, in this study, all PD patients and only two out of 26 with a clinical diagnosis of PSP/CBS had skin p-syn deposits. Furthermore, these two patients showed clinical features that could suggest an atypical synucleinopathy presentation or a mixed pathology. Show more

Keywords: Alpha-synuclein, biomarker, corticobasal syndrome, Parkinson’s disease, parkinsonism, progressive supranuclear paly, skin biopsy

DOI: 10.3233/JPD-212904

Citation: Journal of Parkinson's Disease, vol. 12, no. 2, pp. 585-591, 2022

Authors: Steiner, Oliver | de Zeeuw, Jan | Stotz, Sophia | Bes, Frederik | Kunz, Dieter

Article Type: Short Communication

Abstract: Neurodegenerative processes in the brain are reflected by structural retinal changes. As a possible biomarker of cognitive state in prodromal α -synucleinopathies, we compared melanopsin-mediated post-illumination pupil response (PIPR) with cognition (CERAD-plus) in 69 patients with isolated REM-sleep behavior disorder. PIPR was significantly correlated with cognitive domains, especially executive functioning (r  = 0.417, p  < 0.001), which was more pronounced in patients with lower dopamine-transporter density, suggesting advanced neurodegenerative state (n  = 26; r  = 0.575, p  = 0.002). Patients with mild neurocognitive disorder (n  = 10) had significantly reduced PIPR (smaller melanopsin-mediated response) compared to those without (p  = 0.001). Thus, PIPR may be a functional—possibly …monitoring—marker for impaired cognitive state in (prodromal) α -synucleinopathies. Show more

Keywords: α-synucleinopathies, melanopsin, pupillometry, post-illumination pupil response, cognition, executive functioning, dopamine-transporter density, biomarker

DOI: 10.3233/JPD-212775

Citation: Journal of Parkinson's Disease, vol. 12, no. 2, pp. 593-598, 2022

Authors: Nawaz, Huma | Sargent, Lana | Quilon, Helengrace | Cloud, Leslie J. | Testa, Claudia M. | Snider, Jon D. | Lageman, Sarah K. | Baron, Mark S. | Berman, Brian D. | Zimmerman, Kristin | Price, Elvin T. | Mukhopadhyay, Nitai D. | Barrett, Matthew J.

Article Type: Research Article

Abstract: Background: Individuals with Parkinson’s disease (PD) may be especially vulnerable to future cognitive decline from anticholinergic medications. Objective: To characterize anticholinergic medication burden, determine the co-occurrence of anticholinergic and cholinesterase inhibitors, and to assess the correlations among anticholinergic burden scales in PD outpatients. Methods: We studied 670 PD outpatients enrolled in a clinic registry between 2012 and 2020. Anticholinergic burden was measured with the Anticholinergic Cognitive Burden Scale (ACB), Anticholinergic Drug Scale (ADS), Anticholinergic Risk Scale (ARS), and Drug Burden Index-Anticholinergic component (DBI-Ach). Correlations between scales were assessed with weighted kappa coefficients. Results: Between …31.5 to 46.3% of PD patients were taking medications with anticholinergic properties. Among the scales applied, the ACB produced the highest prevalence of medications with anticholinergic properties (46.3%). Considering only medications with definite anticholinergic activity (scores of 2 or 3 on ACB, ADS, or ARS), the most common anticholinergic drug classes were antiparkinsonian (8.2%), antipsychotic (6.4%), and urological (3.3%) medications. Cholinesterase inhibitors and medications with anticholinergic properties were co-prescribed to 5.4% of the total cohort. The most highly correlated scales were ACB and ADS (κ = 0.71), ACB and ARS (κ = 0.67), and ADS and ARS (κ = 0.55). Conclusion: A high proportion of PD patients (20%) were either taking antiparkinsonian, urological, or antipsychotic anticholinergic medications or were co-prescribed anticholinergic medications and cholinesterase inhibitors. By virtue of its detection of a high prevalence of anticholinergic medication usage and its high correlation with other scales, our data support use of the ACB scale to assess anticholinergic burden in PD patients. Show more

Keywords: Parkinson’s disease, Parkinson’s disease dementia, anticholinergic medications, cholinesterase inhibitors

DOI: 10.3233/JPD-212769

Citation: Journal of Parkinson's Disease, vol. 12, no. 2, pp. 599-606, 2022

Authors: Petrucci, Matthew N. | Amundsen-Huffmaster, Sommer | Chung, Jae Woo | Hsiao-Wecksler, Elizabeth T. | MacKinnon, Colum D.

Article Type: Research Article

Abstract: Background: An external cue can markedly improve gait initiation in people with Parkinson’s disease (PD) and is often used to overcome freezing of gait (FOG). It is unknown if the effects of external cueing are comparable if the imperative stimulus is triggered by the person receiving the cue (self-triggered) or an external source. Objective: Two experiments were conducted to compare the effects of self- versus externally triggered cueing on anticipatory postural adjustments (APAs) during gait initiation in people with PD. Methods: In experiment 1, 10 individuals with PD and FOG initiated gait without a cue or …in response to a stimulus triggered by the experimenter or by the participant. Experiment 2 compared self- versus externally triggered cueing across three groups: healthy young adults (n  = 16), healthy older adults (n  = 11), and a group with PD (n  = 10). Results: Experiment 1: Externally triggered cues significantly increased APA magnitudes compared to uncued stepping, but not when the same cue was self-triggered. Experiment 2: APAs were not significantly improved with a self-triggered cue compared to un-cued stepping in both the PD and healthy older adult groups, but the young adults showed a significant facilitation of APA magnitude. Conclusion: The effectiveness of an external cue on gait initiation in people with PD and older adults is critically dependent upon whether the source of the trigger is endogenous (self-produced) or exogenous (externally-generated). These results may explain why cueing interventions that rely upon self-triggering of the stimulus are often ineffective in people with PD. Show more

Keywords: Parkinson’s disease, cueing, aging, gait initiation, freezing of gait

DOI: 10.3233/JPD-212732

Citation: Journal of Parkinson's Disease, vol. 12, no. 2, pp. 607-619, 2022

Authors: Carroll, Louise M. | Morris, Meg. E. | O’Connor, William T. | Volpe, Daniele | Salsberg, Jon | Clifford, Amanda M.

Article Type: Research Article

Abstract: Background: Aquatic therapy is one therapy option for people living with Parkinson’s disease (PD). However, the optimal prescription, dosage, and delivery remain unclear. Objective: i) To generate consensus statements, ii) to establish evidence-based clinical practice aquatic therapy guidelines for PD. Methods: Seventy-three international experts were invited to participate in a 3-step modified Delphi study. Gaps in the aquatic therapy evidence, patient preferences, and stakeholder engagement were considered when developing the initial list of 43-statements identified by the research development group. Practice experts rated each statement on an 11-point Likert scale. Consensus for inclusion was set at …a priori of ≥70% of respondents scoring an item ≥7. Two rounds of Delphi questionnaires were completed online, and the expert comments were analyzed using content analysis. An online consensus meeting with an expert subgroup (n  = 10) then advised on the guideline’s acceptability and debated items until consensus for inclusion was reached. Results: Fifty experts participated in the Delphi round one (83% response rate) and 45 in round two (90% response rate), representing 15 countries. In round one, 35 statements met the criteria for consensus. Content analysis informed the revised statements in round two, where 12 of the remaining 16 statements met consensus. The final agreed aquatic therapy guidelines include key information about dosage, content, safety, contraindications, and the optimal aquatic therapy delivery throughout the disease course. Conclusion: Stakeholders, including international practice experts, informed a rigorous evidence-based approach to integrate the best available evidence, patient preferences, and practice expertise to inform these guidelines. Show more

Keywords: Aquatic therapy, guidelines, hydrotherapy, Parkinson’s disease, physical therapy, rehabilitation

DOI: 10.3233/JPD-212881

Citation: Journal of Parkinson's Disease, vol. 12, no. 2, pp. 621-637, 2022

Authors: Bourilhon, Julie | Olivier, Claire | You, Hana | Collomb-Clerc, Antoine | Grabli, David | Belaid, Hayat | Mullie, Yannick | François, Chantal | Czernecki, Virginie | Lau, Brian | Pérez-García, Fernando | Bardinet, Eric | Fernandez-Vidal, Sara | Karachi, Carine | Welter, Marie-Laure

Article Type: Research Article

Abstract: Background: Dopa-resistant freezing of gait (FOG) and falls represent the dominant motor disabilities in advanced Parkinson’s disease (PD). Objective: We investigate the effects of deep brain stimulation (DBS) of the mesencephalic locomotor region (MLR), comprised of the pedunculopontine (PPN) and cuneiform (CuN) nuclei, for treating gait and balance disorders, in a randomized double-blind cross-over trial. Methods: Six PD patients with dopa-resistant FOG and/or falls were operated for MLR-DBS. Patients received three DBS conditions, PPN, CuN, or Sham, in a randomized order for 2-months each, followed by an open-label phase. The primary outcome was the change in …anteroposterior anticipatory-postural-adjustments (APAs) during gait initiation on a force platform Results: The anteroposterior APAs were not significantly different between the DBS conditions (median displacement [1st–3rd quartile] of 3.07 [3.12–4.62] cm with sham-DBS, 1.95 [2.29–3.85] cm with PPN-DBS and 2.78 [1.66–4.04] cm with CuN-DBS; p  = 0.25). Step length and velocity were significantly higher with CuN-DBS vs. both sham-DBS and PPN-DBS. Conversely, step length and velocity were lower with PPN-DBS vs. sham-DBS, with greater double stance and gait initiation durations. One year after surgery, step length was significantly lower with PPN-DBS vs. inclusion. We did not find any significant change in clinical scales between DBS conditions or one year after surgery. Conclusion: Two months of PPN-DBS or CuN-DBS does not effectively improve clinically dopa-resistant gait and balance disorders in PD patients. Show more

Keywords: Mesencephalic locomotor region, Parkinson’s disease patients, freezing of gait, postural instability, deep brain stimulation

DOI: 10.3233/JPD-212793

Citation: Journal of Parkinson's Disease, vol. 12, no. 2, pp. 639-653, 2022

Authors: Lawson, Rachael A. | Richardson, Sarah J. | Kershaw, Daisy | Davis, Daniel | Stephan, Blossom C.M. | Robinson, Louise | Brayne, Carol | Barnes, Linda | Burn, David J. | Yarnall, Alison J. | Taylor, John-Paul | Parker, Stuart | Allan, Louise M.

Article Type: Research Article

Abstract: Background: Delirium is a serious acute neuropsychiatric condition associated with altered attention and arousal. Objective: To evaluate simple bedside tests for attention and arousal to detect delirium in those with and without Parkinson’s disease (PD) and dementia. Methods: Participants from two prospective delirium studies were pooled comprising 30 with PD without cognitive impairment, 24 with Lewy body cognitive impairment (PD dementia or dementia with Lewy bodies), 16 with another dementia and 179 PD and dementia-free older adults. Participants completed standardised delirium assessments including tests of attention: digit span, Memorial Delirium Assessment Scale (MDAS) attention and months …of the year backwards; and arousal: Glasgow Coma Scale (GSC), Observational Scale of Level of Arousal (OSLA), Modified Richmond Agitation Scale and MDAS consciousness. Delirium was diagnosed using the DSM-5 criteria. Results: On their first admission, 21.7%participants had prevalent delirium. Arousal measures accurately detected delirium in all participants (p  < 0.01 for all), but only selected attention measures detected delirium in PD and dementia. In PD and dementia-free older adults, impaired digit span and OSLA were the optimal tests to detect delirium (area under the curve [AUC] = 0.838, p  < 0.001) while in PD and dementia the optimal tests were MDAS attention and GCS (AUC=0.90 and 0.84, respectively, p  < 0.001 for both). Conclusion: Simple bedside tests of attention and arousal at a single visit could accurately detect delirium in PD, dementia and PD and dementia-free older adults; however, the optimal tests differed between groups. Combined attention and arousal scores increased accuracy, which could have clinical utility to aid the identification of delirium neurodegenerative disorders. Show more

Keywords: Delirium, Parkinson disease, dementia, attention, arousal, diganosis

DOI: 10.3233/JPD-212849

Citation: Journal of Parkinson's Disease, vol. 12, no. 2, pp. 655-665, 2022

Authors: Dommershuijsen, Lisanne J. | Ruiter, Rikje | Erler, Nicole S. | Rizopoulos, Dimitris | Ikram, M. Arfan | Ikram, M. Kamran

Article Type: Research Article

Abstract: Background: The immune system is known to be involved in Parkinson’s disease (PD) pathogenesis, but the temporal relationship between peripheral immune responses and PD remains unknown. Objective: We determined the association between peripheral immune cell numbers, C-reactive protein (CRP), and prevalent as well as incident PD. Methods: This study was embedded in the population-based setting of the Rotterdam Study. We repeatedly measured peripheral immune cell numbers (differential leukocyte count and platelet count, granulocyte-to-lymphocyte ratio [GLR], platelet-to-lymphocyte ratio [PLR], and adapted systemic immune-inflammation index [adapted SII]) and CRP between 1990 and 2016. Participants were continuously followed-up for …PD until 2018. We estimated the association of the markers with prevalent and incident PD using logistic regression models and joint models, respectively. Models were adjusted for age, sex, smoking, body mass index, and medication use. Odds ratios (OR) and hazard ratios (HR) are shown per doubling of the marker. Results: A total of 12,642 participants were included in this study. The mean age (standard deviation) was 65.1 (9.8) years and 57.5%were women. Participants with a higher lymphocyte count were less likely to have prevalent PD (adjusted OR: 0.34, 95%CI 0.17–0.68). Participants with a higher GLR, PLR, and adapted SII were more likely to have prevalent PD, but these effects were explained by the lymphocyte count. The peripheral immune cell numbers and CRP were not significantly associated with the risk of incident PD. Conclusion: We found participants with a higher lymphocyte count to be less likely to have prevalent PD, but we did not find an association between peripheral immune cell numbers nor CRP and the risk of incident PD. Show more

Keywords: Biomarkers, epidemiology, immunity, inflammation, lymphocytes, Parkinson’s disease

DOI: 10.3233/JPD-212914

Citation: Journal of Parkinson's Disease, vol. 12, no. 2, pp. 667-678, 2022

Authors: Hsu, Tien-Wei | Chu, Che-Sheng | Tsai, Shih-Jen | Cheng, Chih-Ming | Su, Tung-Ping | Chen, Tzeng-Ji | Bai, Ya-Mei | Liang, Chih-Sung | Chen, Mu-Hong

Article Type: Research Article

Abstract: Background: Increasing evidence suggests a potential relationship between viral infection and Parkinson’s disease (PD). Objective: Herein, we explore the association between infection by dengue virus and PD. Methods: Between 1997 and 2012, we recruited 1,422 patients with dengue fever and 14,220 matched controls (age, sex, time of enrollment, and medical and mental comorbidities) from the Taiwan National Health Insurance Research Database. We identified new onset of PD to the end of 2013. The Kaplan-Meier method was used to estimate the incidence rate of PD. Cox-regression analysis was applied to calculate the hazard ratios (HRs) with 95% …confidence intervals (CIs) after adjustment for confounders. Results: During the follow up period, the dengue group had higher incidence of PD than the control group (1.2% vs. 0.4% , p  = 0.001). Patients with dengue fever had a significantly higher risk of developing PD [HR, 2.59; 95% CI, 1.51–4.44] compared with the controls, after adjustments for demographic data, PD-related comorbidities, and all-cause clinical visits. The subgroup analysis, stratified by age and sex, found that higher risk for PD was statistically significant for male (HR, 3.51; 95% CI, 1.76–7.00) and patients aged >60 years (HR, 2.96; 95% CI, 1.62–5.41). Conclusion: The risk of PD was 2.59-fold higher in patients with dengue fever than in non-infected controls during the follow-up period. Clinicians need to monitor signs of PD during patient recovery from dengue fever. Additional studies are needed to confirm our results and investigate the mechanisms linking PD and dengue virus infection. Show more

Keywords: Dengue, Parkinson’s disease, virus infection, neurological sequelae, Taiwan

DOI: 10.3233/JPD-212938

Citation: Journal of Parkinson's Disease, vol. 12, no. 2, pp. 679-687, 2022

Authors: Waskowiak, Pauline | Koppelmans, Vincent | Ruitenberg, Marit F.L.

Article Type: Research Article

Abstract: Background: In addition to the well-known motor symptoms, patients with Parkinson’s disease (PD) also frequently experience disabling non-motor symptoms including impulse control disorders (ICDs). ICDs are characterized by a loss of voluntary control over impulses, drives, or temptations regarding excessive hedonic behavior. Objective: The present study examined whether depression and anxiety in de novo PD patients predict the prospective development of ICDs. Methods: We selected 330 de novo PD patients from the Parkinson’s Progression Markers Initiative database who were free of ICDs at the start of the study. ICD presence at baseline and follow-up …assessments was evaluated via the shortened version of the Questionnaire for Impulsive-Compulsive Disorders (QUIP-S). Baseline depression and anxiety were measured via the Geriatric Depression Scale (GDS-15) and State-Trait-Anxiety Inventory (STAI-Y), respectively. Results: A total of 149 participants (45.2%) developed an ICD at follow-up and average time of ICD onset was 35 months after baseline. Results of a Cox regression analysis showed that STAI-Y scores but not GDS-15 scores significantly predicted ICD presence. Specifically, scores reflecting higher trait anxiety were associated with an increased risk of developing an ICD. This effect was not confounded by age, gender or UPDRS motor score. We also replicated the well-established result that dopamine agonist use is predictive of ICDs. Conclusion: Our findings indicate that higher anxiety levels in de novo PD patients represent a risk factor for ICD development during the course of the disorder. This highlights the need for early and routine based anxiety screening in these patients. Show more

Keywords: Anxiety, depression, impulsivity, impulse control, Parkinson’s disease

DOI: 10.3233/JPD-212959

Citation: Journal of Parkinson's Disease, vol. 12, no. 2, pp. 689-697, 2022

Authors: Boussac, Mathilde | Arbus, Christophe | Klinger, Helene | Eusebio, Alexandre | Hainque, Elodie | Corvol, Jean Christophe | Rascol, Olivier | Rousseau, Vanessa | Harroch, Estelle | d’Apollonia, Charlotte Scotto | Croiset, Aurélie | Ory-Magne, Fabienne | De Barros, Amaury | Fabbri, Margherita | Moreau, Caroline | Rolland, Anne-Sophie | Benatru, Isabelle | Anheim, Mathieu | Marques, Ana-Raquel | Maltête, David | Drapier, Sophie | Jarraya, Béchir | Hubsch, Cécile | Guehl, Dominique | Meyer, Mylène | Rouaud, Tiphaine | Giordana, Bruno | Tir, Mélissa | Devos, David | Brefel-Courbon, Christine | for the PREDISTIM study group

Article Type: Research Article

Abstract: Background: Deep brain stimulation of the sub-thalamic nucleus (DBS-STN) reduces symptoms in Parkinson’s disease (PD) patients with motor fluctuations. However, some patients may not feel ameliorated afterwards, despite an objective motor improvement. It is thus important to find new predictors of patients’ quality of life (QoL) amelioration after DBS-STN. We hypothesized that personality dimensions might affect QoL after DBS-STN. Objective: To evaluate associations between personality dimensions and QoL improvement one year after DBS-STN. Methods: DBS-STN-PD patients (n  = 303) having answered the “Temperament and Character Inventory” (TCI) before surgery and the PDQ-39 before and one year after …surgery were included, from the cohort study PREDI-STIM. Linear regression models were used to evaluate associations between TCI dimensions and change in PDQ-39 scores after DBS-STN. Results: Novelty Seeking and Cooperativeness scores before surgery were positively associated with PDQ-39 scores improvement after DBS-STN (FDR-adjusted p  < 0.01). Moreover, paradoxically unimproved patients with deterioration of their PDQ-39 scores after DBS-STN despite improvement of their MDS-UPDRS-IV scores had lower Cooperativeness scores, while paradoxically improved patients with amelioration of their PDQ-39 scores despite deterioration of their MDS-UPDRS-IV scores had higher Reward Dependence scores. Conclusion: Some presurgical personality dimensions were significantly associated with QoL amelioration and discrepancy between motor state and QoL changes after DBS-STN in PD. Educational programs before DBS-STN should take in account patient personality dimensions to better deal with their expectations. Show more

Keywords: Cooperativeness, DBS-STN, novelty seeking, Parkinson’s disease, quality of life

DOI: 10.3233/JPD-212883

Citation: Journal of Parkinson's Disease, vol. 12, no. 2, pp. 699-711, 2022

Authors: Srivastava, Hemant | Joop, Allen | Memon, Raima A. | Pilkington, Jennifer | Wood, Kimberly H. | Natelson Love, Marissa | Amara, Amy W.

Article Type: Research Article

Abstract: Background: Cognitive impairment is common and disabling in Parkinson’s disease (PD). Cognitive testing can be time consuming in the clinical setting. One rapid test to detect cognitive impairment in non-PD populations is the Clock Drawing Test (CDT), which calls upon the brain’s executive and visuospatial abilities to draw a clock designating a certain time. Objective: Test the hypothesis that PD participants would perform worse on CDT compared to controls and that CDT would correlate with other measures of cognition. Methods: This study evaluated two independent CDT scoring systems and differences in CDT performance …between PD (N = 97) and control (N = 54) participants using a two-sample t -test. Pearson’s correlations were conducted between the CDT and tests of sleepiness (Epworth Sleepiness Scale) and vigilance (Psychomotor Vigilance Test); executive function (Trails B-A); and global cognition (Montreal Cognitive Assessment). Receiver operating characteristic curves were used to determine cut points on the CDT that identify individuals who need additional cognitive testing. Results: PD participants had worse performance on CDT compared to controls. The CDT was correlated with executive function (Trails B-A) and global cognition (Montreal Cognitive Assessment). The CDT correlated with vigilance (Psychomotor Vigilance Task) only in healthy controls. However, the CDT was not correlated with measures of sleepiness (Epworth Sleepiness Scale) in either group. A cut point of 9 on the Rouleau scale and 18 on the Mendez scale identified PD participants with cognitive impairment. Conclusion: The CDT is a rapid clinical cognitive assessment that is feasible in PD and correlates with other measures of cognition. Show more

Keywords: Clock drawing test, parkinson’s disease, cognition

DOI: 10.3233/JPD-212802

Citation: Journal of Parkinson's Disease, vol. 12, no. 2, pp. 713-722, 2022

Authors: Cheng, Tsai-Chin | Huang, Shih-Fong | Wu, Shang-Yu | Lin, Fu-Gong | Lin, Wang-Sheng | Tsai, Po-Yi

Article Type: Research Article

Abstract: Background: Emerging evidence has indicated the positive effects of repetitive transcranial magnetic stimulation (rTMS) on patients with Parkinson’s disease (PD) for the treatment of mild cognitive impairment (MCI). Objective: Investigating whether combining virtual reality (VR) training with rTMS can further enhance cognitive improvement induced by rTMS treatment. Methods: We randomly assigned 40 patients with PD and MCI into three groups, namely the rTMS-VR group (n  = 13), rTMS group (n  = 11), and sham rTMS group (n  = 16). rTMS was administered as 10 consecutive sessions of intermittent theta burst stimulation (iTBS) over the left dorsolateral prefrontal cortex. In …the rTMS-VR group, VR training was administered immediately after each rTMS session. Cognitive function was measured using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Montreal Cognitive Assessment (MoCA) at baseline, immediately after intervention, and at 3-month follow-up. Results: Compared with the rTMS group, the rTMS-VR group exhibited significantly more improvements in total and delayed memory scores of the RBANS and the visuospatial/executive function score of the MoCA after intervention (p  = 0.000∼0.046) and the delayed memory score of the RBANS at 3-month follow-up (p  = 0.028). Conclusion: The integrated rTMS-VR protocol achieved a superior outcome in global cognitive function, more effectively enhancing working memory and visuospatial executive function than did the rTMS protocol alone. The combination of VR and rTMS can be an effective regimen for improving the cognitive function of patients with PD. Show more

Keywords: Cognitive dysfunction, Parkinson’s disease, transcranial magnetic stimulation, virtual reality

DOI: 10.3233/JPD-212978

Citation: Journal of Parkinson's Disease, vol. 12, no. 2, pp. 723-736, 2022

Authors: Guimarães, Thiago Gonçalves | Cury, Rubens Gisbert

Article Type: Research Article

Abstract: Subthalamic nucleus deep brain stimulation (STN DBS) is an established therapy for a subset of patients with Parkinson’s disease, and the adjustment of DBS parameters is typically guided by the patients’ rigidity and tremor. Although these cardinal symptoms remain relatively stable over time, progressive worsening of axial symptoms compromise motor function and quality of life. Because many patients report improvements in their global mobility after gait improvement, we have been adjusting DBS parameters during the long-term after surgery based on gait analysis. Here, we describe a practical strategy for troubleshooting gait problems in PD DBS patients by revising stimulation parameters …through “hands-on” programming, which can be a useful alternative approach for improving patients’ outcomes after STN DBS. Show more

Keywords: Parkinson’s disease, deep brain stimulation, gait analysis, subthalamic nucleus, gait disorders

DOI: 10.3233/JPD-212771

Citation: Journal of Parkinson's Disease, vol. 12, no. 2, pp. 737-741, 2022