Journal of Parkinson's Disease - Volume 9, issue 4

Authors: Houghton, Richard | Boess, Frank | Verselis, Lynne | Ding, Yingjie | Freitas, Rita | Constantinovici, Niculae | Ong, Rose

Article Type: Research Article

Abstract: Background: Treatment patterns in Parkinson’s disease (PD) have not been extensively studied for nearly two decades. Insurance claims are appropriate for such analysis. Objective: To understand the standard of care use of symptomatic treatments in new cases of PD and factors associated with treatment choice. Methods: Retrospective cohort study using claims data from the United States between 2008 and 2016. We used Kaplan–Meier methodology to estimate time to treatment start and switch or add-on therapy and Cox proportional hazards models to identify predictors. Results: We identified 68,532 patients eligible for treatment pattern analyses. Median …time from diagnosis until first treatment was 37 days (95% confidence interval: 36–38). Two distinct patterns of treatment initiation were identified: fast initiators and patients with delayed treatment start (or no recorded treatment). Levodopa therapies were the most commonly prescribed treatment class (52.6%). Increased age was associated with shorter time to start of treatment with levodopa. Younger age was associated with shorter time to initiation of dopamine agonists and other symptomatic treatments. Patients that initiated treatment with levodopa/combinations had the fewest switches/add-ons [30.4%; median time 7.29 (6.71, 8.13) years]. Older patients had fewer switch/add-on therapies, but only in the group that started with levodopa/combination therapy. Conclusions: Time from diagnosis to treatment start was relatively short, suggesting that PD diagnosis, as reflected in the database, is closely linked to start of symptomatic treatment. Levodopa treatment remains the most common treatment, especially for older patients. Delayed treatment start was associated with increased age and comorbidity. Show more

Keywords: Charlson comorbidities, claims data, Parkinson’s disease, treatment patterns, United States

DOI: 10.3233/JPD-191636

Citation: Journal of Parkinson's Disease, vol. 9, no. 4, pp. 749-759, 2019

Authors: Jeziorska, Maria | Atkinson, Andrew | Kass-Iliyya, Lewis | Kobylecki, Christopher | Gosal, David | Marshall, Andrew | Malik, Rayaz A. | Silverdale, Monty

Article Type: Short Communication

Abstract: We assessed small nerve fibre degeneration and regeneration in more and less affected sides in Parkinson’s disease (PD). Bilateral skin biopsies from 23 PD patients were immunostained for PGP9.5 for Intraepidermal Nerve Fibre Density (IENFD) and GAP-43 for mean axonal length (MAL), total epidermal (TNFL) and subepidermal nerve fibre length (SKTNFL). IENFD (p  < 0.001) and SKTNFL (p  < 0.001) were lower, whilst MAL (p  < 0.001) and TNFL (p  < 0.05) were higher in more affected versus less affected side. These results suggest increased small nerve fibre degeneration accompanied by enhanced nerve regeneration on the side more affected by PD and GAP-43 usefulness …in skin biopsy assessment. Show more

Keywords: Parkinson’s disease, peripheral neuropathy, intraepidermal nerve fibre

DOI: 10.3233/JPD-191697

Citation: Journal of Parkinson's Disease, vol. 9, no. 4, pp. 761-765, 2019

Authors: Hoogland, Jeroen | Post, Bart | de Bie, Rob M.A.

Article Type: Research Article

Abstract: Background: Earlier research showed that Parkinson’s disease is related to increased overall mortality, but it remains unclear which patient level factors are predictive of increased mortality in Parkinson’s disease. Objective: To jointly evaluate potential risk factors for overall and Parkinson’s disease (PD) related mortality, we collected detailed information from a cohort of newly diagnosed PD patients which was consequently followed for over a decade. Methods: A total of 133 consecutive patients with newly diagnosed PD were followed for at least 13 years. Survival analysis of observed mortality was used to evaluate risk factors for overall mortality, …whereas survival analysis of mortality as corrected for the general population was used to evaluate risk factors for PD-related mortality. Results: Overall mortality increased with age, male sex, higher levodopa equivalent dose, and presence of mild cognitive impairment. PD-related mortality increased with earlier onset of Parkinson’s disease, higher levodopa equivalent dose, and mild cognitive impairment. Conclusions: Our findings provide confirmation and extension of risk factors for overall mortality and generate new insights into PD-related mortality. Show more

Keywords: Parkinson disease, mortality, cohort studies, survival analyses

DOI: 10.3233/JPD-191652

Citation: Journal of Parkinson's Disease, vol. 9, no. 4, pp. 767-774, 2019

Authors: de Schipper, Laura J. | Hafkemeijer, Anne | van der Grond, Jeroen | Marinus, Johan | Henselmans, Johanna M.L. | van Hilten, Jacobus J.

Article Type: Research Article

Abstract: Background: Dementia with Lewy bodies (DLB) and Parkinson’s disease (PD) are considered subtypes of the α -synucleinopathy continuum that show similar and dissimilar clinical and morphological features. Objective: To further our understanding of brain abnormalities that might differentiate both disorders more clearly, we performed quantitative magnetic resonance (MR) imaging of the subcortical and cortical grey matter. Methods: Three-dimensional T1 weighted 3 tesla MR images of 14 DLB and 62 age- and gender-matched PD patients were examined to study cortical and subcortical grey matter structure. We used volumetric measurements to study total grey matter, and volumes of …the pallidum, amygdala, putamen, caudate nucleus, thalamus and hippocampus. Whole-brain and structural network-based methods were used to identify local differences in grey matter and vertex-based shape analysis was used to assess focal hippocampal changes. Results: Volumetric, whole-brain and network-based analyses showed reduced hippocampal (p  = 0.008) and right parahippocampal region volumes (p  = 0.030) in DLB compared to PD patients. Shape analysis showed atrophy in the head and body of the right (p  = 0.040) and in the head of the left (p  = 0.030) hippocampus of DLB patients. Conclusion: DLB patients showed atrophy of the hippocampus and parahippocampal gyrus compared to PD patients with a differential involvement of the head and body of the hippocampus. Further studies should examine if these group-based findings can be used to differentiate both disorders on an individual level. Show more

Keywords: Parkinson’s disease, Lewy body dementia, magnetic resonance imaging, hippocampus, structure, shape

DOI: 10.3233/JPD-191600

Citation: Journal of Parkinson's Disease, vol. 9, no. 4, pp. 775-783, 2019

Authors: Baille, Guillaume | Perez, Thierry | Devos, David | Machuron, François | Dujardin, Kathy | Chenivesse, Cécile | Defebvre, Luc | Moreau, Caroline

Article Type: Research Article

Abstract: Background: Dyspnea is a multidimensional sensation that is reported in Parkinson’s disease (PD). The multidimensional dyspnea profile (MDP) questionnaire can help to distinguish the perceptive dimension and the emotion response. Objective: The aim was to assess the clinical features associated with dyspnea using the MDP questionnaire in order to determine which aspects of the symptom was linked with anxiety, depression or motor severity of the disease. Methods: Non-demented patients were asked whether they experienced shortness of breath in the last month. In case of positive answer, dyspnea was assessed by the MDP. MDS-UPDRS, global cognitive performance, …non-motor symptoms and quality of life were assessed. Results: 60/163 patients were dyspneic since 4.6±2.4 years. The most frequent best sensory quality (SQ) described were: hyperpnoea (35%), physical breathing effort (25%) and air hunger (20%). Hyperpnoea and air hunger had the highest SQ intensity. Anxiety had the highest intensity in the emotional domain. Conclusion: Dyspnea is a frequent symptom in PD, with specific presentations and two main aspects: one related with anxiety and another with ventilation control impairment. Show more

Keywords: Parkinson’s disease, dyspnea, non-motor symptom, anxiety, ventilatory dysfunction

DOI: 10.3233/JPD-191713

Citation: Journal of Parkinson's Disease, vol. 9, no. 4, pp. 785-791, 2019

Authors: Hashimoto, Makoto | Ho, Gilbert | Takamatsu, Yoshiki | Wada, Ryoko | Sugama, Shuei | Takenouchi, Takato | Waragai, Masaaki | Masliah, Eliezer

Article Type: Research Article

Abstract: Aging-related neurodegenerative disorders are frequently associated with the aggregation of multiple amyloidogenic proteins (APs), although the reason why such detrimental phenomena have emerged in the post-reproductive human brain across evolution is unclear. Speculatively, APs might provide physiological benefits for the human brain during developmental/reproductive stages. Of relevance, it is noteworthy that cross-seeding (CS) of APs has recently been characterized in cellular and animal models of neurodegenerative disease, and that normal physiological CS of multiple APs has also been observed in lower organisms, including yeast and bacteria. In this context, our main objective is to discuss a possible involvement of the …CS of APs in promoting evolvability, a hypothetical view regarding the function of APs as an inheritance of acquired characteristics against human brain stressors, which are transgenerationally transmitted to offspring via germ cells. Mechanistically, the protofibrils formed by the CS of multiple APs might confer hormesis more potently than individual APs. By virtue of greater encoded stress information in parental brains being available, the brains of offspring can cope more efficiently with forth-coming stressors. On the other hand, subsequent neurodegeneration caused by APs in parental brain through the antagonistic pleiotropy mechanism in aging, may suggest that synergistically, multiple APs might be more detrimental compared to singular AP in neurodegeneration. Taken together, we suggest that the CS of multiple APs might be involved in both evolvability and neurodegenerative disease in human brain, which may be mechanistically and therapeutically important. Show more

Keywords: Alzheimer’s disease, Parkinson’s disease, amyloidogenic proteins, amyloid cascade hypothesis, evolvability hypothesis, cross-seeding, antimicrobial protection model

DOI: 10.3233/JPD-191675

Citation: Journal of Parkinson's Disease, vol. 9, no. 4, pp. 793-802, 2019

Authors: Ratti, Pietro-Luca | Faraci, Francesca | Hackethal, Sandra | Mascheroni, Alessandro | Ferlito, Clara | Caverzasio, Serena | Amato, Ninfa | Choe, Eun Kyoung | Luo, Yuhan | Nunes-Ferreira, Paulo-Edson | Galati, Salvatore | Puiatti, Alessandro | Kaelin-Lang, Alain

Article Type: Research Article

Abstract: Background: Subjective symptoms, which are retrospectively assessed during clinical interviews in the office, may be influenced by patient recall in Parkinson’s disease (PD). Prospective collection of subjective data might be an effective tool to overcome this bias. Objective: We investigated the correspondence between prospectively and retrospectively assessed motor symptoms in PD. Methods: Forty-two consecutive patients (9 females, 67±9.8 years old) with mild to moderate PD reported their symptoms four times a day for two weeks, using the “SleepFit ” application (app) for tablets. This app incorporates a new Visual Analogue Scale assessing global mobility (m-VAS), and …the Scales for Outcome in Parkinson Assessment Diary Card (SCOPA-DC). At day 14, the Movement Disorders Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) parts II and IV questionnaires were completed at the hospital. Agreement (root mean square difference) and the tendency to under- or overestimate their symptoms by patients (relative difference after normalization) were calculated to compare prospectively vs. retrospectively collected information. Results: Although agreement was good for overall scores (m-VAS: 10.0%; SCOPA-DC: 18.3%), and for single motor symptoms (involuntary movements, hand dexterity, walking, changing position; each <20%), some individuals with more advanced disease, higher fatigue or worse sleep quality showed poor symptom recall in retrospect. Moreover, a subgroup of patients (16.7%) either over- or underestimated symptom severity. Conclusions: Regular, prospective monitoring of motor symptoms is suitable in PD patients. SleepFit might be a useful tool in routine practice to identify patients tending to under- or overestimate their symptoms, and for their follow-up. Show more

Keywords: Parkinson disease, ecological momentary assessment, self report, symptom assessment, software

DOI: 10.3233/JPD-191662

Citation: Journal of Parkinson's Disease, vol. 9, no. 4, pp. 803-809, 2019

Authors: Tang, Peng | Hou, Chen | Liu, Yue | Liu, Peng | Zhang, Xin | Zhang, Lina | Chong, Li | Li, Rui

Article Type: Research Article

Abstract: Background/Objective: Easily applicable, quantitative assessment of movement is widely needed in various clinical settings, especially in the evaluation of Parkinson’s disease (PD). Methods: We developed a highly repeatable tablet computer-based finger movement assessment system (FMAS) to record finger movement profile in a visual-motor task both in PD (n  = 217) and healthy participants (n  = 221). Results: We found age-related declines in finger movement performance among the healthy participants but not in PD patients with the FMAS. Significant differences in movement time (MT) and latency/MT ratio but not in latency were observed in PD patients as compared with …healthy subjects (P  < 0.000). Meanwhile, we identified the latency/MT ratio as the optimal parameter to differentiate PD from age-matched healthy subjects in an age-independent manner (cut-off 1.08 with corresponding AUC = 0.861). In addition, a significant correlation was found between finger movement parameters and the Hoehn and Yahr scale (H-Y scale), UPDRS III score and the duration of the disease in PD patients (P  < 0.01). Conclusion: It was suggested that the tablet computer-based evaluation of finger movement provided an easily applicable quantitative method to assess the conditions of PD patients. Show more

Keywords: Parkinson’s disease, hypokinesia, finger movement profile, visual motor task, quantitative assessment

DOI: 10.3233/JPD-191695

Citation: Journal of Parkinson's Disease, vol. 9, no. 4, pp. 811-819, 2019

Authors: Gilat, Moran

Article Type: Short Communication

Abstract: Visually scoring freezing of gait (FOG) from video is increasingly recognized as the gold-standard for assessing FOG severity in Parkinson’s disease. Surprisingly, no guidelines exist on how to visually score FOG. Here, I present a free template that can be implemented in open-source software to annotate FOG from video. I provide a user guide on how to implement the template and standardize the scoring of FOG and the percentage of time spent with FOG (% FOG). It is hoped that by disseminating this method investigators will be better able to employ % FOG as an outcome in their studies and …therapeutic trials. Show more

Keywords: Parkinson’s disease, gait, gait analysis, outcome assessment, falls, software

DOI: 10.3233/JPD-191700

Citation: Journal of Parkinson's Disease, vol. 9, no. 4, pp. 821-824, 2019

Authors: Stephenson, Diane | Hill, Derek | Cedarbaum, Jesse M. | Tome, Maria | Vamvakas, Spiros | Romero, Klaus | Conrado, Daniela J. | Dexter, David T. | Seibyl, John | Jennings, Danna | Nicholas, Timothy | Matthews, Dawn | Xie, Zhiyong | Imam, Syed | Maguire, Paul | Russell, David | Gordon, Mark Forrest | Stebbins, Glenn T. | Somer, Ed | Gallagher, Jill | Roach, Arthur | Basseches, Peter | Grosset, Donald | Marek, Ken | on behalf of the Critical Path for Parkinson’s Consortium

Article Type: Correction

DOI: 10.3233/JPD-199003

Citation: Journal of Parkinson's Disease, vol. 9, no. 4, pp. 825-825, 2019