Journal of Parkinson's Disease - Volume 5, issue 2

Authors: Hassan, Anhar | Wu, Samuel S. | Schmidt, Peter | Simuni, Tanya | Giladi, Nir | Miyasaki, Janis M. | Bloem, Bastiaan R. | Malaty, Irene A. | Okun, Michael S.

Article Type: Research Article

Abstract: Background: Parkinson’s disease (PD) patients with 20 years or more survival (PD-20) are not well characterized. Objective: To evaluate PD-20 patient characteristics and identify areas for improvement of their health care. Methods: The international, multicenter National Parkinson’s Foundation Quality Improvement Initiative (NPF-QII) study database was queried to identify PD-20 subjects. Demographic and clinical data were analyzed. Results: We identified 187 PD-20 subjects (55% men) representing 4% (187/4,619) of all NPF-QII participants. Subjects were mean age 69.5 years; mean age at PD onset was 44.0 years. The majority (75%) had 20-25 years of PD duration, …the longest duration being 49 years. They were median Hoehn and Yahr stage 3, and 75% had motor fluctuations. Half (54%) reported exercising. The majority (89%) were living at home and required a caregiver (88%). They were mildly cognitively impaired for age (Montreal Cognitive Assessment estimate 22.6±3.7), with most deficits in verbal fluency and delayed recall. Quality of life (Parkinson’s Disease Quality of Life Questionnaire index 36±15%) was mild to moderately impaired, with most impairment in mobility and activities of daily living. Caregiver strain measured by the Multidimensional Caregiver Strain Index (27±16%), recorded highest subscores in social constraint. PD-20 subjects aged <70 years versus ≥70 only differed significantly by worse cognition (P  <  0.0001). Conclusions: PD-20 subjects reflect an elite group of PD survivors with early-onset disease and relatively mild cognitive disability despite long disease duration. Interventions for caregivers, mobility, and activities of daily living are areas that could improve caregiver burden and patient quality of life. Show more

Keywords: Advanced, complications, Parkinson’s disease, quality-of-life

DOI: 10.3233/JPD-140515

Citation: Journal of Parkinson's Disease, vol. 5, no. 2, pp. 313-319, 2015

Authors: Williams, Isobel Anne | Wilkinson, Leonora | Limousin, Patricia | Jahanshahi, Marjan

Article Type: Research Article

Abstract: Background: Deep brain stimulation of the subthalamic nucleus (STN DBS) ameliorates the motor symptoms of Parkinson’s disease (PD). However, some aspects of executive control are impaired with STN DBS. Objective: We tested the prediction that (i) STN DBS interferes with switching from automatic to controlled processing during fast-paced random number generation (RNG) (ii) STN DBS-induced cognitive control changes are load-dependent. Methods: Fifteen PD patients with bilateral STN DBS performed paced-RNG, under three levels of cognitive load synchronised with a pacing stimulus presented at 1, 0.5 and 0.33 Hz (faster rates require greater cognitive control), with DBS …on or off. Measures of output randomness were calculated. Countscore 1 (CS1) indicates habitual counting in steps of one (CS1). Countscore 2 (CS2) indicates a more controlled strategy of counting in twos. Results: The fastest rate was associated with an increased CS1 score with STN DBS on compared to off. At the slowest rate, patients had higher CS2 scores with DBS off than on, such that the differences between CS1 and CS2 scores disappeared. Conclusions: We provide evidence for a load-dependent effect of STN DBS on paced RNG in PD. Patients could switch to more controlled RNG strategies during conditions of low cognitive load at slower rates only when the STN stimulators were off, but when STN stimulation was on, they engaged in more automatic habitual counting under increased cognitive load. These findings are consistent with the proposal that the STN implements a switch signal from the medial frontal cortex which enables a shift from automatic to controlled processing. Show more

Keywords: Subthalamic nucleus, deep brain stimulation, Parkinson’s disease, controlled processing, automatic, impulse control disorders

DOI: 10.3233/JPD-140355

Citation: Journal of Parkinson's Disease, vol. 5, no. 2, pp. 321-331, 2015

Authors: Rahimi, Jasmin | Milenkovic, Ivan | Kovacs, Gabor G.

Article Type: Research Article

Abstract: Background: Spreading of misfolded proteins has been suggested for neurodegenerative diseases. The hierarchical distribution of protein deposits in Alzheimer‘s (AD) and Parkinson’s disease (PD) supports this concept. Objectives: To evaluate α-synuclein and tau-deposition in the optic pathway as an excellent anatomical model, which follows a strict trajectory including a cortico-geniculate feedback connection. Methods: We immunostained the optic nerve, lateral geniculate nucleus (LGN), and occipital cortex for AT8 (phosphorylated tau), α-synuclein, and disease-associated prion protein (PrP) in 47 cases with tau pathology (AD type, argyrophilic grain disease, or progressive supranuclear palsy), 16 PD, and 5 Creutzfeldt-Jakob disease …(CJD) cases, respectively. Results: We detected immunoreactivity for all proteins along the optic pathway. The optic nerve showed immunopositivity only in cases with tau (6/8, 75%) or α-synuclein (5/7, 71%) pathology. The LGN was involved also frequently (tau: 22/47, 46.8% ; α-synuclein: 15/16, 93.7% ; PrP 5/5, 100%). The occipital cortex was variably affected by tau or α-synuclein pathology, but always showed PrP immunoreactivity in the CJD cases. Tau pathology in the LGN correlated with tau immunoreactivity in the occipital cortex and Braak stages of neurofibrillary degeneration. In tauopathies, which do not involve the occipital cortex, like argyrophilic grain disease or progressive supranuclear palsy, tau pathology was more frequently astrocytic in the LGN. Conclusions: Our results have implications 1) for the understanding of disease spreading along neural pathways and 2) for the diagnostic evaluation of the visual system in neurodegenerative proteinopathies as a potential biomarker to evaluate disease progression or subgrouping of cases. Show more

Keywords: Lateral geniculate body, neurodegeneration, prion-like spreading, prion protein, α-synuclein, tau; visual system

DOI: 10.3233/JPD-140485

Citation: Journal of Parkinson's Disease, vol. 5, no. 2, pp. 333-340, 2015

Authors: Jonasson, Stina B. | Ullén, Susann | Iwarsson, Susanne | Lexell, Jan | Nilsson, Maria H.

Article Type: Research Article

Abstract: Background: Fear of falling can be conceptualized in different ways, e.g., as concerns about falling or low fall-related self-efficacy. It is common in people with Parkinson’s disease (PD), and there is growing knowledge about its contributing factors. However, previous multivariate studies have mainly focused on fear of falling in relation to PD-related disabilities, and less is known about the associations between fear of falling and personal and environmental factors. Objective: To identify explanatory factors of concerns about falling in people with PD by focusing on personal and environmental factors as well as PD-related disabilities. Methods: Data …were collected from 241 persons with PD (39% women, median age 70 years, PD duration 8 years). Concerns about falling (assessed with the Falls Efficacy Scale-International, FES-I; categorized into low, moderate, or high concerns) were used as the dependent variable in a multivariate ordinal regression analysis. Personal factors, environmental factors and PD-related disabilities constituted independent variables. Results: Low, moderate and high concerns about falling were reported by 29% , 24% and 47% of the participants, respectively. Walking difficulties, orthostatism, motor symptoms, age, and fatigue (presented in order of importance) were significant (p  <  0.05) explanatory factors of concerns about falling. Conclusions: Several factors significantly explained concerns about falling in people with PD. Walking difficulties was by far the strongest explanatory factor. This suggests that minimizing walking difficulties should be a primary target when aiming at reducing concerns about falling in people with PD. Show more

Keywords: Accidental falls, fear, multivariate analysis, Parkinson disease, regression analysis, self efficacy

DOI: 10.3233/JPD-140524

Citation: Journal of Parkinson's Disease, vol. 5, no. 2, pp. 341-349, 2015

Authors: Cohen, Matthew L. | Aita, Stephen | Mari, Zoltan | Brandt, Jason

Article Type: Research Article

Abstract: Background: Apathy and depression are associated with poor cognition in patients with Parkinson’s disease (PD). However, the cognitive signature of each syndrome is not well understood. The cognitive consequences of having apathy or depression, versus apathy and depression, are also unclear. Objective: This study investigated the unique and combined effects of apathy and depression on cognition in PD patients. Methods: PD patients were identified from a clinical research database as having self-reported apathy (n  = 21), depression (n  = 11), or both (n  = 43). PD patients without apathy or depression served as the Control group (n  = 49). The …groups were of similar age, education, disease severity, age of symptom onset, and medication status. A multivariate analysis of variance (MANOVA) compared the groups on 17 neuropsychological test scores in the domains of attention, motor and psychomotor speed, construction, language, episodic memory, and executive functioning. Results: There was a significant overall effect of group: F (18,276) = 2.12, p  = 0.006, η p 2 = 0.12 . Univariate analyses and planned contrasts revealed medium-sized effects distinguishing only the control group and the group with both apathy and depression (η p 2 = 0.06 – 0.12 ) on measures of verbal fluency and manual, processing, and psychomotor speed. Conclusions: PD patients with apathy alone or depression alone did not perform worse than PD controls on neuropsychological tests. Patients with apathy and depression performed worse than controls, but only on speed-based measures. This suggests that apathy and depression are associated with the same or similar circuits as those of cognitive and motor speed. Show more

Keywords: Parkinson’s disease, cognition, apathy, depression

DOI: 10.3233/JPD-140484

Citation: Journal of Parkinson's Disease, vol. 5, no. 2, pp. 351-359, 2015

Authors: Deli, Gabriella | Aschermann, Zsuzsanna | Ács, Péter | Bosnyák, Edit | Janszky, József | Faludi, Béla | Makkos, Attila | Kovács, Márton | Komoly, Sámuel | Balás, István | Dóczi, Tamás | Kovács, Norbert

Article Type: Research Article

Abstract: Background: Sleep problems are among the most common non-motor symptoms of Parkinson’s disease (PD). The PD Sleep Scale 2nd version (PDSS-2) improved the original PDSS by adding more items on different aspects of sleep problems, making it a more robust tool to evaluate the severity of sleep disturbances. However, previous studies on deep brain stimulation (DBS) have not used the PDSS-2. Objective: To determine if the PDSS-2 could detect improvement reliably in sleep problems after bilateral subthalamic nucleus DBS for PD. Methods: In this prospective study, 25 consecutive patients undergoing DBS implantation were enrolled. Patients were …examined twice: 1 week prior to the DBS implantation (baseline) and 12 months postoperatively. Severity of PD symptoms were assessed by the Movement Disorders Society Unified PD Rating Scale (MDS-UPDRS) and the Non-Motor Symptoms Scale (NMSS). Presence and severity of sleep disturbances were specifically measured by PDSS-2. Results: Total score of MDS-UPDRS improved from 81 (median, interquartile-range: 63-103) to 55 points (median, IQR: 46-75, p  <  0.001). Health-related quality of life, measured by PDQ-39, also improved from 29 (IQR: 18-40) to 15 (IQR: 9-28) points (p  = 0.002). Most domains of NMSS also improved. At baseline 13 patients reported sleep problems, but 1 year after DBS implantation only 3 did (p  = 0.012). Although only 6 out of 15 items showed a significant decrease after DBS implantation, the total score of PDSS-2 decreased from 24 (IQR: 17-32) to 10 (IQR: 7-18) points (P  <  0.001). Conclusions: Based on our results, PDSS-2 can detect improvements in sleep quality reliably after DBS implantation. Show more

Keywords: Sleep, non-motor symptoms, subthalamic deep brain stimulation, restless legs syndrome

DOI: 10.3233/JPD-150540

Citation: Journal of Parkinson's Disease, vol. 5, no. 2, pp. 361-368, 2015

Authors: Zhao, Yan | Heida, Tjitske | van Wegen, Erwin E.H. | Bloem, Bastiaan R. | van Wezel, Richard J.A.

Article Type: Research Article

Abstract: Recent advances in smart glasses, wearable computers in the form of glasses, bring new therapeutic and monitoring possibilities for people with Parkinson’s disease (PD). For example, it can provide visual and auditory cues during activities of daily living that have long been used to improve gait disturbances. Furthermore, smart glasses can personalize therapies based on the state of the user and/or the user environment in real-time using object recognition and motion tracking. To provide guidelines for developers in creating new PD applications for smart glasses, a self-reported questionnaire was designed to survey the requirements, constraints, and attitudes of people with …PD with respect to this new technology. The survey was advertised online over an 11 month period on the website of the Parkinson Vereninging. The results were derived from 62 participants (54.8% men and 45.2% women, average age of 65.7 ± 9.1), representing a response rate of 79.5% . The participants were overall very enthusiastic about smart glasses as an assistive technology to facilitate daily living activities, especially its potential to self-manage motor problems and provide navigational guidance, thereby restoring their confidence and independence. The reported level of usage of mobile technologies like tablets and smartphones suggests that smart glasses could be adopted relatively easily, especially by younger people with PD. However, the respondents were concerned about the cost, appearance, efficacy, and potential side effects of smart glasses. To accommodate a wide range of symptoms, personal preferences, and comfort level with technology, smart glasses should be designed to allow simple operation and personalization. Show more

Keywords: Health care technology, medical informatics, mobile applications, self-management, cues, virtual reality exposure therapy

DOI: 10.3233/JPD-150568

Citation: Journal of Parkinson's Disease, vol. 5, no. 2, pp. 369-378, 2015

Authors: Tard, Céline | Delval, Arnaud | Duhamel, Alain | Moreau, Caroline | Devos, David | Defebvre, Luc | Dujardin, Kathy

Article Type: Research Article

Abstract: Background: Due to its high prevalence in dual-task paradigms, freezing of gait in Parkinson’s disease is thought to be associated with dysexecutive syndrome and attentional disorders. However, the role of specific attentional disorders in patients with freezing of gait is still unclear. Objective: Here, we sought to specifically determine which basic attentional modalities are impaired in patients with freezing of gait. Methods: Seventy-eight parkinsonian patients performed a computer-controlled reaction-time paradigm designed to measure the different attentional subcomponents, controlled for visuospatial processing and motor participation. Results: The freezer (n  = 42) and non-freezer (n  = 36) groups …were matched for age, educational level, MMSE and Mattis Dementia Rating Scale. There were no intergroup differences in simple reaction times, whereas choice reaction times were higher in the freezer group than in the non-freezer group for divided attention (p  = 0.023). Conclusions: At equivalent levels of overall cognitive efficiency, freezer patients showed a greater slowdown than non-freezer patients with a specific impairment in divided attention. Show more

Keywords: Focusing, dual-task, Parkinsonism, attention, divided attention

DOI: 10.3233/JPD-140498

Citation: Journal of Parkinson's Disease, vol. 5, no. 2, pp. 379-387, 2015

Authors: Jiao, Yun | Dou, Yuchen | Lockwood, Georgina | Pani, Amar | Smeyne, Richard Jay

Article Type: Research Article

Abstract: Background: MPTP and paraquat are two compounds that have been used to model Parkinson’s disease in mice. Previous studies in two non-traditional strains of mice have shown that a single dose of MPTP can induce changes in body temperature, while the effects of paraquat have not been examined. Examination of body temperature is important since small fluctuations in an animal’s core temperature can significantly affect drug metabolism, and if significant enough can even culminate in an animal’s death. Objective: To determine how external heating can alter the survival of C57BL/6J mice following MPTP administration. Methods: In …this study, we examine the effects of MPTP (4×20 mg/kg, 2 hours apart) and paraquat (2×10 mg/kg/week for 3 weeks) on core temperature of C57BL/6J mice. Correlations of purine and catecholamine levels were also done in mice treated with MPTP. Results: We find that MPTP induces a significant hypothermia in C57BL/6J mice that reduces their core temperature below the limit of fatal hypothermia. Unlike MPTP, paraquat did not induce a significant hypothermia. Placement of animals on heating pads significantly abrogates the loss of core temperature. In both heated and non-heated conditions, mice treated with MPTP showed a significant depletion of ATP within 2 hours of administration in both striatum and SN that started to recover 2 hours after MPTP administration was complete. Striatal DA and DOPAC are significantly reduced starting 4–6 hours after MPTP. Conclusions: The fatal hypothermic effects of MPTP can be abrogated through use of external heating. Show more

Keywords: Mouse strain, MPTP, paraquat, temperature, fatal hypothermic temperature

DOI: 10.3233/JPD-140424

Citation: Journal of Parkinson's Disease, vol. 5, no. 2, pp. 389-401, 2015

Authors: Ellis, Charles | Crosson, Bruce | Gonzalez Rothi, Leslie J. | Okun, Michael S. | Rosenbek, John C.

Article Type: Research Article

Abstract: Background: Models of basal ganglia (BG) function suggest that expressive language deficits will likely and consistently present in BG disease. Disparities currently exist between the predictions of models of BG function in expressive language and data from studies of BG disease. Traditional expressive language assessment methodologies that emphasize measures of language form (word and sentence productivity) while not carefully considering how language is used, may only partially account for these disparities. Objective: To use measures of cohesion to examine the use of cohesive markers in narrative discourse. Methods: Twelve individuals with idiopathic Parkinson’s disease (PD) were …compared to 12 matched neurologically intact controls on measures of discourse performance. Three discourse samples (typical day, memorable vacation and family) were analyzed for measures of narrative productivity, number of cohesive ties and cohesive adequacy. Mixed model analyses were completed for group comparisons. Results: Group differences were not observed on measures of language form as measured by narrative productivity, communication units, and number of cohesive ties produced. In contrast, group differences were observed in cohesive adequacy as individuals with PD produced a higher percentage of incomplete and erroneous cohesive ties relative the control subjects across narratives. Conclusions: These results support the conclusion that the BG in PD may have an executive role in expressive language use that can be disrupted without impacting language form. Show more

Keywords: Basal ganglia, Parkinson’s disease, language, discourse, cohesion

DOI: 10.3233/JPD-140476

Citation: Journal of Parkinson's Disease, vol. 5, no. 2, pp. 403-411, 2015