Journal of Parkinson's Disease - Volume 10, issue 3

Authors: Hommel, Adrianus L.A.J. | Meinders, Marjan J. | Weerkamp, Nico J. | Richinger, Carmen | Schmotz, Christian | Lorenzl, Stefan | Dodel, Richard | Coelho, Miguel | Ferreira, Joaquim J. | Tison, Francois | Boraud, Thomas | Meissner, Wassilios G. | Rosqvist, Kristina | Timpka, Jonathan | Odin, Per | Wittenberg, Michael | Bloem, Bas R. | Koopmans, Raymond T. | Schragand, Anette | the CLaSP consortium

Article Type: Research Article

Abstract: Background: Treatment of patients with late-stage parkinsonism is often sub-optimal. Objective: To test the effectiveness of recommendations by a movement disorder specialist with expertise in late-stage parkinsonism. Methods: Ninety-one patients with late-stage parkinsonism considered undertreated were included in apragmatic a pragmatic multi-center randomized-controlled trial with six-month follow-up. The intervention group received a letter with treatment recommendations to their primary clinician based on an extensive clinical assessment. Controls received care as usual. The primary outcome was the Unified Parkinson Disease Rating Scale (UPDRS)part-II (Activities of Daily Living). Other outcomes included quality-of-life (PDQ-8), mental health (UPDRS-I), motor function …(UPDRS-III), treatment complications (UPDRS-IV), cognition (Mini-mental-state-examination), non-motor symptoms (Non-Motor-Symptoms-scale), health status (EQ-5D-5L) and levodopa-equivalent-daily-dose (LEDD). We also assessed adherence to recommendations. In addition to intention-to-treat analyses, a per-protocol analysis was conducted. Results: Sample size calculation required 288 patients, but only 91 patients could be included. Treating physicians followed recommendations fully in 16 (28%) and partially in 21 (36%) patients. The intention-to-treat analysis showed no difference in primary outcome (between-group difference = –1.2, p  = 0.45), but there was greater improvement for PDQ-8 in the intervention group (between-group difference = –3.7, p  = 0.02). The per-protocol analysis confirmed these findings, and showed less deterioration in UPDRS-part I, greater improvement on UPDRS-total score and greater increase in LEDD in the intervention group. Conclusions: The findings suggest that therapeutic gains may be reached even in this vulnerable group of patients with late-stage parkinsonism, but also emphasize that specialist recommendations need to be accompanied by better strategies to implement these to further improve outcomes. Show more

Keywords: Parkinsonian disorders, randomized controlled trial, treatment, activities of daily living, quality of life

DOI: 10.3233/JPD-202033

Citation: Journal of Parkinson's Disease, vol. 10, no. 3, pp. 1171-1184, 2020

Authors: Mantri, Sneha | Klawson, Emily | Albert, Steven | Nabieva, Karina | Lepore, Madeline | Kahl, Stephen | Daeschler, Margaret | Mamikonyan, Eugenia | Kopil, Catherine | Marras, Connie | Chahine, Lana M.

Article Type: Research Article

Abstract: Background: Fatigue in Parkinson’s disease (PD) is multifaceted and associated with reduced quality of life. In turn, the language used by people with PD to describe fatigue is variable and poorly understood. We sought to elucidate the lexicon of fatigue using a qualitative grounded theory approach. Objective: The objective of this study was to understand how patients with PD describe fatigue. Methods: A pre-study phase of online journaling (Phase 1) provided information regarding topics of importance to patients. Following this, two independent samples of fatigued subjects were studied. Individuals with PD participated in a telephone interview …(Phase 2); interview transcripts were analyzed to develop a detailed codebook. To ensure trustworthiness of the findings, an online survey (Phase 3) was administered to individuals with self-reported PD participating in the online study Fox Insight. The survey included the following question: “How do you define fatigue? Please provide your definition in the space below.” The codebook developed from Phase 2 was applied to the Phase 3 responses. Results: Fifteen individuals participated in Phase 2 and 413 individuals completed Phase 3. Fatigue was subdivided into three domains: cognitive, emotional, and physical. Nearly all individuals experienced more than one domain of fatigue. The most common themes included tiredness, lack of energy, and negative motivation. Conclusion: Fatigue in PD is multidimensional. Questionnaires that only assess the physical impact of fatigue may not be adequate to capture the broad range of experiences of fatigue among people with PD. Show more

Keywords: Fatigue, Parkinson’s disease, qualitative research

DOI: 10.3233/JPD-202029

Citation: Journal of Parkinson's Disease, vol. 10, no. 3, pp. 1185-1193, 2020

Authors: Schneider, Ruth B. | Myers, Taylor L. | Rowbotham, Helen M. | Luff, Marie K. | Amodeo, Katherine | Sharma, Saloni | Wilson, Renee | Jensen-Roberts, Stella | Auinger, Peggy | McDermott, Michael P. | Alcalay, Roy N. | Biglan, Kevin | Kinel, Daniel | Tanner, Caroline | Winter-Evans, Reni | Augustine, Erika F. | Cannon, Paul | 23andMe Research Team | Holloway, Robert G. | Dorsey, E. Ray

Article Type: Research Article

Abstract: Background: The rise of direct-to-consumer genetic testing has enabled many to learn of their possible increased risk for rare diseases, some of which may be suitable for gene-targeted therapies. However, recruiting a large and representative population for rare diseases or genetically defined sub-populations of common diseases is slow, difficult, and expensive. Objective: To assess the feasibility of recruiting and retaining a cohort of individuals who carry a genetic mutation linked to Parkinson’s disease (G2019S variant of LRRK2 ); to characterize this cohort relative to the characteristics of traditional, in-person studies; and to evaluate this model’s ability to create …an engaged study cohort interested in future clinical trials of gene-directed therapies. Methods: This single-site,3-year national longitudinal observational study will recruit between 250 to 350 LRRK2 carriers without Parkinson’s disease and approximately 50 with the condition. Participants must have undergone genetic testing by the personal genetics company, 23andMe, Inc., have knowledge of their carrier status, and consent to be contacted for research studies. All participants undergo standardized assessments, including video-based cognitive and motor examination, and complete patient-reported outcomes on an annual basis. Results: 263 individuals living in 33 states have enrolled. The cohort has a mean (SD) age of 56.0 (15.9) years, 59% are female, and 76% are of Ashkenazi Jewish descent. 233 have completed the baseline visit: 47 with self-reported Parkinson’s disease and 186 without. Conclusions: This study establishes a promising model for developing a geographically dispersed and well-characterized cohort ready for participation in future clinical trials of gene-directed therapies. Show more

Keywords: Clinical trials as topic, cohort studies, genetic testing, LRRK2, Parkinson’s disease, rare disease, remote consultation, telemedicine

DOI: 10.3233/JPD-202019

Citation: Journal of Parkinson's Disease, vol. 10, no. 3, pp. 1195-1207, 2020

Authors: Tang, Yilin | Liang, Xiaoniu | Han, Linlin | Peng, Fang | Shen, Bo | Yu, Huiling | Shen, Yan | Shen, Cong | Yu, Jintai | Wang, Jian

Article Type: Research Article

Abstract: Background: Parkinson’s disease with mild cognitive impairment (PD-MCI) or dementia (PDD) has been shown to be correlated with poor quality of life (QoL). The association between specific cognitive domains and QoL is less clear. Objective: To determine how the cognitive domains affect QoL in different cognitive states in PD. Methods: We recruited 600 PD patients, including 185 PD patients with normal cognition (PD-NC), 336 PD-MCI patients, and 79 PDD patients. All patients underwent a scale-based assessment (PDQ-39) for QoL, as well as clinical evaluations and neuropsychological tests. Results: Compared to PD-NC group, QoL became …more impaired in the PD-MCI and PDD groups. Generalized linear model revealed that no neuropsychological test was significantly associated with QoL in PD-NC group; neuropsychological tests in attention and language domains were significantly associated with QoL in PD-MCI patients; neuropsychological tests in memory and language domains were significantly associated with QoL in PDD patients. Conclusions: Cognitive domains contribute differently to QoL in PD. These findings may prompt clinicians to target specific cognitive domains for improving QoL in the PD patients. Show more

Keywords: Parkinson’s disease, mild cognitive impairment, dementia, quality of life

DOI: 10.3233/JPD-202097

Citation: Journal of Parkinson's Disease, vol. 10, no. 3, pp. 1209-1216, 2020

Authors: Tamplin, Jeanette | Morris, Meg E. | Marigliani, Caterina | Baker, Felicity A. | Noffs, Gustavo | Vogel, Adam P.

Article Type: Research Article

Abstract: Background: Parkinson’s disease (PD) frequently causes progressive deterioration in speech, voice and cognitive aspects of communication. These affect wellbeing and quality of life and are associated with caregiver strain and burden. Therapeutic singing groups can ameliorate PD-related communication disorders and increase social interaction and wellbeing for caregivers and care recipients. Objective: To analyse the effects of ParkinSong group singing sessions on Parkinson’s communication and wellbeing outcomes for people with PD and caregivers over 12 months. Methods: A 4-armed controlled clinical trial compared ParkinSong with active non-singing control conditions over 12 months. Two dosage levels (weekly versus …monthly) were available for each condition. ParkinSong comprised high-effort vocal, respiratory and speech exercises, group singing, and social interaction. PD-specific outcomes included vocal loudness, speech intelligibility, maximum phonation time, respiratory muscle strength, and voice related quality of life (QoL). Wellbeing outcomes were also measured for caregivers and care recipients. Results: We recruited 75 people with PD and 44 caregivers who attended weekly ParkinSong, monthly ParkinSong, weekly control or monthly control groups. We found significant improvements in the primary outcome of vocal loudness (p  = 0.032), with weekly singers 5.13 dB louder (p  = 0.044) and monthly singers 5.69 dB louder (p  = 0.015) than monthly controls at 12 months. ParkinSong participants also showed greater improvements in voice-related QoL and anxiety. Caregivers who attended ParkinSong showed greater reductions in depression and stress scores. Conclusions: This 12-month controlled clinical trial of ParkinSong demonstrated improvements in speech loudness and voice-related QoL for participants with PD, and enhanced wellbeing for both caregivers and care recipients. No adverse effects were reported over 12 months and improvements were sustained. Show more

Keywords: Clinical Trial Registry number: ACTRN12617000528358, Parkinson’s disease, movement disorders, rehabilitation, communication, speech, loudness, singing, music therapy, voice-related quality of life, non-motor symptoms

DOI: 10.3233/JPD-191838

Citation: Journal of Parkinson's Disease, vol. 10, no. 3, pp. 1217-1230, 2020

Authors: Aye, Yin Minn | Liew, Gerald M. | Ng, Samuel Y.E. | Wen, Ming-Ching | Lim, Linda L.H. | Chua, Shu-Ting | Chotphoksap, Usanee | Chao, Yinxia | Ng, Adeline S.Y. | Tan, Eng King | Tan, Louis Chew Seng | Xu, Zheyu

Article Type: Research Article

Abstract: Background: Mild parkinsonian signs (MPS) are common in the older adult and associated with a wide range of adverse health outcomes. There is limited data on the prevalence of MPS and its significance. Objective: To determine the prevalence of MPS in the community ambulant population and to evaluate the relationship of MPS with prodromal features of Parkinson’s disease (PD) and cognition. Methods: This cross-sectional community-based study involved participants aged ≥50 years. Parkinsonian signs were assessed using the modified Unified Parkinson’s Disease Rating Scale (mUPDRS) and cognition using the Montreal Cognitive Assessment (MoCA). Premotor symptoms of PD …were screened using a self-reported questionnaire. Linear regression was used to assess the association of MPS with premotor symptoms of PD and cognitive impairment. Results: Of 392 eligible participants, MPS was present in 105 (26.8%). Mean age of participants with MPS was 68.8±6.9 years and without MPS was 66.1±5.9 years (p  < 0.001). Multivariate analysis revealed that MoCA scores were significantly lower in the MPS group (β= –0.152, 95% CI = –0.009, –0.138, p  < 0.05). A significant correlation between the presence of REM sleep behavior disorder (RBD) and total MPS scores (β= 0.107, 95% CI = 0.053, 1.490, p  < 0.05) was also found. Neither vascular risk factors nor other premotor symptoms were significantly associated with MPS. Conclusion: MPS is common and closely related to cognitive impairment and increasing age. Presence of RBD is predictive of higher MPS scores. This study highlights the necessity of other investigations or sensitive risk markers to identify subjects at future risk of PD. Show more

Keywords: Mild parkinsonian signs, REM sleep behavior disorder (RBD), premotor symptoms

DOI: 10.3233/JPD-191849

Citation: Journal of Parkinson's Disease, vol. 10, no. 3, pp. 1231-1237, 2020

Authors: Javidnia, Monica | Shoulson, Ira | Kieburtz, Karl | Venuto, Charles S.

Article Type: Short Communication

Abstract: Parkinson’s disease (PD) patients experience a range of non-motor symptoms that are believed to be related to disease pathophysiology, many of which are treatable by medications. Among newly-diagnosed PD participants in the Parkinson’s Progression Markers Initiative study, we describe (1) the frequency of medication use for common non-motor symptoms, and (2) when non-motor symptomatic treatment was initiated relative to PD diagnosis. Non-motor medication use was reported by 73% of participants, most commonly for depression, constipation, and anxiety. Treatment of some non-motor symptoms, notably depression, antedated diagnosis. These data may be useful for studies of non-motor symptoms in PD.

Keywords: Non-motor symptoms, pharmacotherapies, anxiety, depression, sleep

DOI: 10.3233/JPD-201973

Citation: Journal of Parkinson's Disease, vol. 10, no. 3, pp. 1239-1243, 2020

Authors: Nonnekes, Jorik | Bloem, Bastiaan R.

Article Type: Short Communication

Abstract:  The relation between freezing of gait in Parkinson’s disease and levodopa is complex. Here, we describe a new phenotype of freezing of gait, namely levodopa-induced freezing of gait with a biphasic pattern. Our observation supports the idea that freezing of gait might emerge because of a mismatch between cognitive/limbic loops and motor loops involved in gait control. Moreover, it underscores the importance of assessing the influence of dopaminergic medication in daily clinical practice, including objective assessment in all three dopaminergic states. The possibility of biphasic freezing will only emerge after such a comprehensive evaluation, and will have immediate therapeutic consequences.

Keywords: Gait, freezing of gait, levodopa, Parkinson’s disease, parkinsonism, biphasic

DOI: 10.3233/JPD-201997

Citation: Journal of Parkinson's Disease, vol. 10, no. 3, pp. 1245-1248, 2020

Authors: Fedorova, Tatyana D. | Knudsen, Karoline | Sommerauer, Michael | Svendsen, Kristina B. | Otto, Marit | Borghammer, Per

Article Type: Short Communication

Abstract: Isolated REM sleep behaviour disorder (iRBD) is a predictive marker of prodromal Lewy body disease. iRBD prevalence in the general population is around 1%, but it remains under-diagnosed, even though symptoms are alleviated by medication. We developed a population screening strategy and identified 16 iRBD patients by conducting telephone interviews and polysomnography examinations. We compared our population-screened cohort with sleep-center referred patients and found higher MoCA scores and lower MDS-UPDRS-III scores in our patients. In conclusion, screening can be used to identify iRBD patients in a cost-effective manner with the benefit of identifying patients at a very early disease stage.

Keywords: REM sleep behavior disorder, Lewy body disease, Parkinson’s disease, screening, polysomnography

DOI: 10.3233/JPD-202020

Citation: Journal of Parkinson's Disease, vol. 10, no. 3, pp. 1249-1253, 2020

Authors: Vorderwülbecke, Bernd J. | Lehmann, Rebekka | Breuer, Eva

Article Type: Short Communication

Abstract: REM sleep behavior disorder (RBD) might render patients with Parkinson’s disease prone to sleep-disordered breathing. This retrospective polysomonographic study assessed the prevalence of sleep-disordered breathing in 108 consecutive patients with either both Parkinson’s disease and RBD (n  = 37), Parkinson’s disease without RBD (n  = 21), or isolated RBD (n  = 50). Across all patients, 25% had at least moderate sleep-related breathing disorder, without significant differences between groups. Following multivariable analysis, RBD influenced sleep-related breathing parameters modestly but not significantly, whereas body mass index had a prominent impact. Further studies with larger patient cohorts are needed, and confounders like body mass index must …adequately be controlled for. Show more

Keywords: Body mass index, Parkinson’s disease, REM sleep behavior disorder, sleep apnea syndromes

DOI: 10.3233/JPD-201996

Citation: Journal of Parkinson's Disease, vol. 10, no. 3, pp. 1255-1259, 2020