Journal of Parkinson's Disease - Volume 11, issue 2

Authors: Fleury, Vanessa | Zekeridou, Alkisti | Lazarevic, Vladimir | Gaïa, Nadia | Giannopoulou, Catherine | Genton, Laurence | Cancela, José | Girard, Myriam | Goldstein, Rachel | Bally, Julien F. | Mombelli, Andrea | Schrenzel, Jacques | Burkhard, Pierre R.

Article Type: Research Article

Abstract: Background: Oral microbiota has largely escaped attention in Parkinson’s disease (PD), despite its pivotal role in maintaining oral and systemic health. Objective: The aim of our study was to examine the composition of the oral microbiota and the degree of oral inflammation in PD. Methods: Twenty PD patients were compared to 20 healthy controls. Neurological, periodontal and dental examinations were performed as well as dental scaling and gingival crevicular fluid sampling for cytokines measurement (interleukine (IL)-1β, IL-6, IL-1 receptor antagonist (RA), interferon-γ and tumor necrosis factor (TNF)-α). Two months later, oral microbiota was sampled from saliva …and subgingival dental plaque. A 16S rRNA gene amplicon sequencing was used to assess bacterial communities. Results: PD patients were in the early and mid-stage phases of their disease (Hoehn & Yahr 2–2.5). Dental and periodontal parameters did not differ between groups. The levels of IL-1β and IL-1RA were significantly increased in patients compared to controls with a trend for an increased level of TNF-α in patients. Both saliva and subgingival dental plaque microbiota differed between patients and controls. Streptococcus mutans , Kingella oralis , Actinomyces AFQC_s, Veillonella AFUJ_s, Scardovia , Lactobacillaceae, Negativicutes and Firmicutes were more abundant in patients, whereas Treponema KE332528_s, Lachnospiraceae AM420052_s, and phylum SR1 were less abundant. Conclusion: Our findings show that the oral microbiome is altered in early and mid-stage PD. Although PD patients had good dental and periodontal status, local inflammation was already present in the oral cavity. The relationship between oral dysbiosis, inflammation and the pathogenesis of PD requires further study. Show more

Keywords: Oral microbiome, inflammation, biomarker, non-motor symptoms, cytokine, Parkinson’s disease, microbiota

DOI: 10.3233/JPD-202459

Citation: Journal of Parkinson's Disease, vol. 11, no. 2, pp. 619-631, 2021

Authors: Bougea, Anastasia | Koros, Christos | Papagiannakis, Nikolaos | Simitsi, Athina-Maria | Prentakis, Andreas | Papadimitriou, Dimitra | Pachi, Ioanna | Antonelou, Roubina | Angelopoulou, Efthalia | Beratis, Ion | Bozi, Maria | Papageorgiou, Sokratis G. | Trapali, Xenia Geronicola | Stamelou, Maria | Stefanis, Leonidas

Article Type: Research Article

Abstract: Background: Previous studies have highlighted serum uric acid as a putative idiopathic Parkinson’s disease (iPD) biomarker. Only one study, so far, showed higher levels of serum uric acid in leucine-rich repeat kinase 2 (LRRK  + 2 ) carriers compared to those who developed PD, however a longitudinal comparison between LRRK2  + PD and healthy controls (HC) has not been performed. Objective: The aim of this study was to determine whether there are longitudinal differences in serum uric acid between iPD, LRRK2  + PD and HC and their association with motor and non-motor features. Methods: Longitudinal data of uric acid …of 282 de novo iPD, 144 LRRK2  + PD patients, and 195 age-matched HC were obtained from the Parkinson’s Progression Markers Initiative (PPMI) database. We also used longitudinal Montreal Cognitive Assessment (MoCA), Movement Disorder Society–Unified Parkinson’s Disease Rating Scale part III (MDS-UPDRS-III), Geriatric Depression Scale (GDS) scores, and DaTSCAN striatal binding ratios (SBRs). Results: Longitudinal uric acid measurements were significantly lower in LRRK2  + PD patients compared to HC up to 5 years follow-up. There was no significant impact or correlation of adjusted or unadjusted uric acid levels with MoCA, MDS-UPDRS III, or GDS scores, the presence of RBD or DAT-SCAN SBRs. Conclusion: LRRK2  + PD group had significantly lower uric acid concentrations compared to HC after adjusting for age, sex and baseline BMI up to 5 years follow-up. There were no significant associations between uric acid levels and indices of disease severity. These findings identify serum uric acid as a marker linked to LRRK2  + PD. Show more

Keywords: Leucine rich repeat kinase 2, LRRK2, Parkinson’s disease, Parkinson’s progression markers initiative, montreal cognitive assessment, movement disorder society–unified Parkinson’s disease rating scale part III

DOI: 10.3233/JPD-202337

Citation: Journal of Parkinson's Disease, vol. 11, no. 2, pp. 633-640, 2021

Authors: Mertsalmi, Tuomas H. | But, Anna | Pekkonen, Eero | Scheperjans, Filip

Article Type: Research Article

Abstract: Background: The gastrointestinal tract is considered as a potential origin of Parkinson’s disease (PD) pathology. Besides constipation, appendectomy and inflammatory bowel disease have also been associated with a higher PD-risk, but findings have been inconsistent. To date, there is only one previous study suggesting that irritable bowel syndrome (IBS) is associated with an increased risk of PD. Objective: To evaluate whether IBS is associated with a higher risk of PD. Methods: In this retrospective registry-based cohort study, we identified 28,150 patients that were diagnosed with IBS (IBS+) during the years 1998–2014, using data from the Finnish …Care Register for Health Care. In addition, 98,789 IBS-free reference subjects (IBS-) of same age and gender and living in the same municipality were included. The study subjects were followed until the end of the year 2014 to analyze the incidence of PD. The association between IBS and PD was assessed by a Cox proportional hazards model. Results: Diagnosis of IBS was associated with a higher hazard of PD with an adjusted hazard ratio (aHR) of 1.70 (95% CI 1.27–2.26). However, the ratio of hazard rates for PD between IBS+ and IBS- subjects was not constant over time. The Cox model with time-varying coefficient for IBS status showed that the hazard of PD was significantly higher in IBS patients only during the first two years of follow-up (aHR 2.96, 95% CI 1.78–4.92). Conclusion: Our findings indicate that the association between IBS and PD is likely explained by reverse causation and detection bias. It remains open whether IBS is an actual risk factor or a prodromal symptom of PD. Show more

Keywords: Parkinson’s disease, irritable bowel syndrome, gastrointestinal tract, epidemiology

DOI: 10.3233/JPD-202330

Citation: Journal of Parkinson's Disease, vol. 11, no. 2, pp. 641-651, 2021

Authors: Vitorio, Rodrigo | Hasegawa, Naoya | Carlson-Kuhta, Patricia | Nutt, John G. | Horak, Fay B. | Mancini, Martina | Shah, Vrutangkumar V.

Article Type: Research Article

Abstract: Background: There is a lack of recommendations for selecting the most appropriate gait measures of Parkinson’s disease (PD)-specific dual-task costs to use in clinical practice and research. Objective: We aimed to identify measures of dual-task costs of gait and turning that best discriminate performance in people with PD from healthy individuals. We also investigated the relationship between the most discriminative measures of dual-task costs of gait and turning with disease severity and disease duration. Methods: People with mild-to-moderate PD (n  = 144) and age-matched healthy individuals (n  = 79) wore 8 inertial sensors while walking under single and …dual-task (reciting every other letter of the alphabet) conditions. Outcome measures included 26 objective measures within four gait domains (upper/lower body, turning and variability). The area under the curve (AUC) from the receiver-operator characteristic plot was calculated to compare discriminative ability of dual-task costs on gait across outcome measures. Results: PD-specific, dual-task interference was identified for arm range of motion, foot strike angle, turn velocity and turn duration. Arm range of motion (AUC = 0.73) and foot strike angle (AUC = 0.68) had the largest AUCs across dual-task costs measures and they were associated with disease severity and/or disease duration. In contrast, the most commonly used dual-task gait measure, gait speed, showed an AUC of only 0.54. Conclusion: Findings suggest that people with PD rely more than healthy individuals on executive-attentional resources to control arm swing, foot strike, and turning, but not gait speed. The dual-task costs of arm range of motion best discriminated people with PD from healthy individuals. Show more

Keywords: Cognition, gait, locomotion, Parkinson’s disease

DOI: 10.3233/JPD-202289

Citation: Journal of Parkinson's Disease, vol. 11, no. 2, pp. 653-664, 2021

Authors: Umehara, Tadashi | Oka, Hisayoshi | Nakahara, Atsuo | Shiraishi, Tomotaka | Sato, Takeo | Matsuno, Hiromasa | Komatsu, Teppei | Omoto, Shusaku | Murakami, Hidetomo | Iguchi, Yasuyuki

Article Type: Research Article

Abstract: Background: Orthostatic hypotension (OH) at an early stage of Parkinson’s disease (PD) predicts poor prognosis, which may suggest degeneration of dopaminergic neurons affects sympathetic function, causing OH. Objective: We tested the hypothesis that striatal dopaminergic depletion is associated with OH in PD. Methods: Out of 99 patients with newly diagnosed untreated PD, 81 patients were enrolled according to our selection criteria. All patients underwent head-up tilt-table testing and striatal 123 I-2β-carbomethoxy-3β-(4-iodophenyl)-N -(3-fluoropropyl) nortropane (123 I-FP-CIT) dopamine transporter single photon emission computed tomography (DAT-SPECT). DaTQUANT software (GE Healthcare) was used as a semi-quantitative tool to analyze DAT-SPECT …data. The association between hemodynamic changes and 123 I-FP-CIT uptake was examined. Results: 123 I-FP-CIT uptake in the putamen, especially the anterior part and left side, was related not only to motor severity but also to OH. Change in systolic blood pressure correlated negatively with 123 I-FP-CIT uptake in bilateral anterior putamen (left: p  < 0.01, right: p  < 0.05) and left posterior putamen (p  < 0.05). Patients with OH had more severe dopamine depletion in left anterior (p  = 0.008) and posterior (p  = 0.007) putamen at a similar motor severity than did patients without OH even though both groups have similar baseline characteristics. An analysis of asymmetry index showed patients with OH had symmetrically decreased dopamine levels in anterior putamen when compared to those without OH (p  = 0.024). Conclusion: OH is closely related to striatal dopamine depletion in PD. This relation may help to account for the prognostic value of OH. Show more

Keywords: Autonomic nervous system, Parkinson’s disease, single photon emission tomography (SPECT), orthostatic hypotension, striatal dopamine depletion

DOI: 10.3233/JPD-202239

Citation: Journal of Parkinson's Disease, vol. 11, no. 2, pp. 665-673, 2021

Authors: Dahodwala, Nabila | Jahnke, Jordan | Pettit, Amy R. | Li, Pengxiang | Ladage, Vrushabh P. | Kandukuri, Prasanna L. | Bao, Yanjun | Zamudio, Jorge | Jalundhwala, Yash J. | Doshi, Jalpa A.

Article Type: Research Article

Abstract: Background: Increasing doses of oral antiparkinson medications are indicated in advanced Parkinson’s disease (PD), but little is known about sustainment of high-dose regimens. Objective: To investigate sustainment of high-dose oral medication regimens in Medicare beneficiaries with incident advanced PD. Methods: This retrospective cohort study utilized 100%fee-for-service Medicare claims from 2011–2013. We identified advanced PD using a pharmacy claims-based proxy and selected patients who initiated a new high-dose oral medication regimen (daily levodopa equivalent dose [LED] >1000 mg/day for ≥30 days) in 2012. In the following 12 months, we examined: 1) annual proportion of days covered (PDC)≥0.80 and …2) presence of a ≥ 90 day continuous gap at varying dosage thresholds: the initial >1000 mg/day, >800 mg/day, >500 mg/day, or >0 mg/day. Results: We identified 9,405 patients with advanced PD (mean age 77.4 [SD 6.8] years; 53%men). Only 5%maintained a regimen of >1000 mg/day at PDC ≥0.80; 75% had a ≥ 90-day gap in that dosage level. At a dosage threshold of >800 mg/day, 20% had a PDC ≥0.80 and 53% had a ≥ 90-day gap; at >500 mg/day, 56% had a PDC ≥0.80 and 19%had a ≥ 90-day gap; and at >0 mg/day (any dose), 76% had a PDC ≥0.80 and only 10%had a≥90-day gap. Conclusion: Few patients with advanced PD sustained a high-dose oral medication regimen in the year following initiation, but most sustained a substantially lower-dose regimen. Strategies to improve advanced PD treatment are needed. Show more

Keywords: Advanced Parkinson’s disease, prescribing patterns, discontinuation, Medicare, administrative claims

DOI: 10.3233/JPD-202147

Citation: Journal of Parkinson's Disease, vol. 11, no. 2, pp. 675-684, 2021

Authors: Pérez-Soriano, Alexandra | Giraldo, Darly M. | Ríos, Jose | Muñoz, Esteban | Compta, Yaroslau | Martí, María José | Catalán MSA Registry (CMSAR)

Collaborators: Pagonabarraga, Javier | Valldeoriola, Francesc | Hernández-Vara, Jorge | Classen, Serge Jauma | Puente, Victor | Pont, Claustre | Caballol, Núria | Tolosa, Eduardo | Bayes, Angels | Campdelacreu, Jaume | de Fábregues, Oriol | Ávila, Asunción | Calopa, Matilde | Gaig, Carles | Pastor, Pau | Pujol, Montserrat | Garrido, Alicia | Painous, Celia | Planellás, Lluís | Cámara, Ana

Article Type: Research Article

Abstract: Background/Objective: Multiple system atrophy (MSA) is a highly debilitating, rare neurodegenerative disorder with two clinical motor variants (parkinsonian or MSA-P and cerebellar or MSA-C). There is a wide span of motor and non-motor symptoms (NMS) that progress over time. We studied the cohort from the Catalan Multiple System Atrophy Registry (CMSAR) to determine which symptoms are most likely to progress throughout a 2-year follow-up. Methods: We analyzed baseline, 12-month, and 24-month follow-up evaluations from the 80 cases recruited by the CMSAR. Evaluations included the UMSARS assessment, cognitive and neuropsychiatric evaluations, and a non-motor scale (NMSS-PD). Statistical analysis was …done using a Generalized Estimated Equations (GEE) model. Results: Both UMSARS I and II sub-scores significantly increased at 12- and 24-month follow-ups (p  < 0.001), with a median total score increase of 11 and 12.5 points, respectively. Items on UMSARS I that significantly worsened were mostly motor affecting daily activities. NMS, including urinary and sexual dysfunction, as well as sleep difficulties showed a significant progression on the NMSS-PD; however, other NMS such as postural hypotension, gastrointestinal, and mood dysfunction, although prevalent, did not show a clear progression on clinical scales. Conclusion: Within 24 months and as early as 12 months, MSA cases may experience significant motor worsening, affecting basic daily activities. NMS are prevalent; however, not all clinical scales register a clear progression of symptoms, perhaps suggesting that they are not sensitive enough for non-motor evaluation. Show more

Keywords: MSA, prospective changes, motor symptoms, non-motor symptoms

DOI: 10.3233/JPD-202332

Citation: Journal of Parkinson's Disease, vol. 11, no. 2, pp. 685-694, 2021

Authors: van Wamelen, Daniel J. | Urso, Daniele | Ray Chaudhuri, K.

Article Type: Research Article

Abstract: Background: Several small-scale studies have shown that motor performance in Parkinson’s disease (PD) fluctuates throughout the day. Studies specifically focusing on de novo patients are, however, lacking. Objective: To evaluate the effect of clock time on motor performance in de novo drug-naïve patients with PD. Methods: We retrieved MDS-UPDRS III scores for 421 de novo PD patients from the PPMI cohort and stratified them into three groups based on time of assessment: group 1) 7:00–10:00; group 2) 10:00–13:00, and group 3) 13:00–18:00. Groups were compared using Kruskal-Wallis test and results corrected for multiple …testing. In addition, we obtained 27 wearable sensor reports, objectively capturing bradykinesia scores in a home setting over a 6-day continuous period, in 12 drug-naïve patients from the Parkinson’s Kinetigraph Registry held at King’s College Hospital London. Time spent in severe bradykinesia scores were broken down into five daytime (06:00–21:00) three-hourly epochs and scores compared using the Friedman test. Results: There were no group differences in demographic or other clinical variables for the cross-sectional analysis. MDS-UPDRS III total scores worsened significantly during the course of the day (median 18 (group 1); 20 (group 2); and 23 (group 3); p  = 0.001). In the longitudinal wearable sensor cohort, diurnal variations were present in percentage of time spent in severe bradykinesia (p  < 0.001) with the lowest percentage during the 09:00–12:00 epoch (69.56±16.68%), when most patients are awake and start daily activity, and the highest percentage during the 18:00–21:00 epoch (73.58±16.35%). Conclusion: This exploratory study shows the existence of a diurnal pattern of motor function in patients with de novo PD. The results obtained were corroborated by objective measurements in a small longitudinal cohort confirming a similar diurnal motor score variation. Show more

Keywords: Parkinson’s disease, circadian rhythm, diurnal rhythm, bradykinesia, motor

DOI: 10.3233/JPD-202352

Citation: Journal of Parkinson's Disease, vol. 11, no. 2, pp. 695-702, 2021

Authors: Wood, Kimberly H. | Memon, Adeel A. | Memon, Raima A. | Joop, Allen | Pilkington, Jennifer | Catiul, Corina | Gerstenecker, Adam | Triebel, Kristen | Cutter, Gary | Bamman, Marcas M. | Miocinovic, Svjetlana | Amara, Amy W.

Article Type: Research Article

Abstract: Background: Cognitive and sleep dysfunction are common non-motor symptoms in Parkinson’s disease (PD). Objective: Determine the relationship between slow wave sleep (SWS) and cognitive performance in PD. Methods: Thirty-two PD participants were evaluated with polysomnography and a comprehensive level II neurocognitive battery, as defined by the Movement Disorders Society Task Force for diagnosis of PD-mild cognitive impairment. Raw scores for each test were transformed into z -scores using normative data. Z-scores were averaged to obtain domain scores, and domain scores were averaged to determine the Composite Cognitive Score (CCS), the primary outcome. Participants were grouped by …percent of SWS into High SWS and Low SWS groups and compared on CCS and other outcomes using 2-sided t -tests or Mann-Whitney U . Correlations of cognitive outcomes with sleep architecture and EEG spectral power were performed. Results: Participants in the High SWS group demonstrated better global cognitive function (CCS) (p  = 0.01, effect size: r  = 0.45). In exploratory analyses, the High SWS group showed better performance in domains of executive function (effect size: Cohen’s d  = 1.05), language (d  = 0.95), and processing speed (d  = 1.12). Percentage of SWS was correlated with global cognition and executive function, language, and processing speed. Frontal EEG delta power during N3 was correlated with the CCS and executive function. Cognition was not correlated with subjective sleep quality. Conclusion: Increased SWS and higher delta spectral power are associated with better cognitive performance in PD. This demonstrates the significant relationship between sleep and cognitive function and suggests that interventions to improve sleep might improve cognition in individuals with PD. Show more

Keywords: Parkinson’s disease, slow wave sleep, sleep, cognition

DOI: 10.3233/JPD-202215

Citation: Journal of Parkinson's Disease, vol. 11, no. 2, pp. 703-714, 2021

Authors: Port, Rebecca J. | Rumsby, Martin | Brown, Graham | Harrison, Ian F. | Amjad, Anneesa | Bale, Claire J.

Article Type: Research Article

Abstract: Background: Parkinson’s disease (PD) is a neurodegenerative condition with a diverse and complex pattern of motor and non-motor symptoms which change over time with disease duration. Objective: The aims of the present study were to discover what symptoms matter most to people with the condition and to examine how these priorities change with disease duration. Methods: A simple free-text online survey (using SmartSurvey) was developed by Parkinson’s UK, which asked participants to identify up to three aspects of the condition they would most like to see improvement in. Results: 790 people participated reporting 2,295 …issues related to PD which were grouped into 24 broad symptom domains. Of these, 1,358 (59.1%) were categorised as motor symptoms, 859 (37.4%) as non-motor issues and 78 (3.4%) as medication problems. This study reveals how certain features of PD become more or less important to patients as the condition progresses. Non-motor symptoms were highly cited from the very earliest stages of PD. Problems with walking, balance and falls, speech problems, freezing and dyskinesia become increasingly important as the condition progresses whereas tremor, stiffness and psychological health become decreasingly important as the condition progresses. Conclusions: The data suggest that the priorities of people affected by PD for improving life are personal and change with duration of the condition. These findings have implications for developing person-centred management and care, as well as for directing future research to improve quality of life. Show more

Keywords: Parkinson’s disease, quality of life, symptoms, patient priorities, progression

DOI: 10.3233/JPD-202346

Citation: Journal of Parkinson's Disease, vol. 11, no. 2, pp. 715-724, 2021