Journal of Parkinson's Disease - Volume 6, issue 3

Authors: Izumi, Yasuhiko | Kondo, Naoto | Takahashi, Ryosuke | Akaike, Akinori | Kume, Toshiaki

Article Type: Research Article

Abstract: Background: The formation of intracellular aggregates containing α-synuclein (α-syn) is a main pathological feature of Parkinson disease. The propagation of α-syn aggregation via cell-to-cell transmission has been implicated in the progression of Parkinson disease. Objective: Our aim is to clarify the molecular mechanisms underlying the formation of intracellular aggregation by extracellular α-syn. Methods: We investigated the effects of exogenous α-syn aggregates on intracellular α-syn immunoreactivity in α-syn-overexpressing SH-SY5Y cells using two antibodies to distinct epitopes of α-syn. To obtain α-syn aggregates, α-syn solution was aged with continuous agitation. Results: Immunoreactivity against the acidic …C-terminal domain of the intracellular α-syn was reduced by exposure to agedα-syn, whereas that against the hydrophobic non-amyloid component region was not changed. The reduction in immunoreactivity was not suppressed by protease inhibitors but was mimicked by neutralization of the negative charges on the C-terminal of the intracellular α-syn induced by spermine or extracellular acidification. Conclusions: These results suggest that the reduction in immunoreactivity is attributed not to proteolytic cleavage but to a conformational change at the C-terminus of the intracellular α-syn. The conformational change at the C-terminus of the intracellular α-syn might be involved in an initial step of fibril formation by exogenous α-syn aggregates. Show more

Keywords: α-synuclein, conformational change, fibril, Parkinson disease, proteolysis

DOI: 10.3233/JPD-160835

Citation: Journal of Parkinson's Disease, vol. 6, no. 3, pp. 569-579, 2016

Authors: Olsson, Yvonne | Clarén, Lena | Alvariza, Anette | Årestedt, Kristofer | Hagell, Peter

Article Type: Research Article

Abstract: Background: Being a family caregiver for a person with Parkinson’s disease (PD) can negatively impact health and wellbeing, but it appears less clear to what extent caregivers’ health/social service needs are met. Objective: We explored the extent to which PD family caregivers experience sufficient access to health/social services, as compared to age-matched controls; and the associations between this and demographic and health-related variables. Methods: A cross-sectional survey of 66 PD family caregivers and 79 age-matched control subjects including the SF-36 health survey, the Nottingham Health Profile Sleep section (NHP-Sleep), and questions regarding contacts with various …health/social related services and whether these were perceived as sufficient. Results: People reporting insufficient access (n  = 29) were more often PD family caregivers than controls (83% vs. 37%), did more often have a disease of their own (79% vs. 46%), and reported poorer health according to the SF-36 and the NHP-Sleep. Being a PD family caregiver (OR, 8.90), reporting more pain (OR, 1.02) and having an own disease (OR, 3.46) were independently associated with insufficient health/social service access. Conclusions: Our results imply that those in greatest need for health/social services (i.e., those with poorer health, an own disease, and who are PD family caregivers) are those whose health/social service needs are least met. Larger studies are needed for firmer conclusions and regarding how unmet health/social service needs impacts caregiver health and wellbeing. Health/social service providers should not only focus on patients but also consider their family members’ needs. Show more

Keywords: Caregivers, health, health services needs and demand, Parkinson disease

DOI: 10.3233/JPD-160811

Citation: Journal of Parkinson's Disease, vol. 6, no. 3, pp. 581-587, 2016

Authors: Szeto, Jennifer Y.Y. | Mowszowski, Loren | Gilat, Moran | Walton, Courtney C. | Naismith, Sharon L. | Lewis, Simon J.G.

Article Type: Research Article

Abstract: Background: Recent attempts to standardise the definition of Mild Cognitive Impairment (MCI) in Parkinson’s disease (PD) by the Movement Disorder Society Task Force has led to a greater understanding of this entity but to date, there has been a paucity of research regarding the impact of PD-MCI on caregiver outcomes. Objective: The aim of this study was to utilise the newly established PD-MCI diagnostic criteria to investigate caregiver outcomes in relation to four specific aspects: (1) caregiver burden, (2) quality of life (QoL), (3) caregiving experience, and (4) psychological distress. Methods: This study included a …total of 166 patient-caregiver dyads. Caregiver outcomes including quality of life, caregiver burden, mood disturbances, and caregiver experience were compared between caregivers of PD patients classified as having normal cognition (PD-NC) and PD-MCI. Results: Despite the two groups being matched on demographic and clinical features, caregivers of PD-MCI patients reported a lower level of QoL with regard to physical health and more interruptions with usual activities. On the other hand, a higher impact on finances was reported in caregivers of PD-NC patients, relative to caregivers of PD-MCI patients. Conclusions: This study has shown that even at earlier stages of cognitive impairment, PD-MCI caregivers already experience elevated levels of distress in the role of providing care to their care-recipients. These findings highlight the need to include management of caregiver distress and associated sequelae alongside the management of PD-MCI patients, early on in the disease course. Show more

Keywords: Mild cognitive impairment, Parkinson’s disease, caregiver burden, quality of life, caregiver outcomes

DOI: 10.3233/JPD-160823

Citation: Journal of Parkinson's Disease, vol. 6, no. 3, pp. 589-596, 2016

Authors: Ossig, Christiana | Sippel, Daniel | Fauser, Mareike | Gandor, Florin | Jost, Wolfgang H. | Ebersbach, Georg | Storch, Alexander

Article Type: Research Article

Abstract: Background: Since previous studies aimed to study nonmotor symptom (NMS) fluctuations in direct conjunction with motor oscillations, there are no data available on the temporal context of NMS fluctuations and motor oscillations in advanced Parkinson’s disease (PD). Objective: To evaluate circadian patterns and temporal connections of NMS and motor fluctuations in PD. Methods: 15 controls, 17 non-fluctuating and 15 fluctuating PD patients completed two diaries by rating 4 key psychiatric (anxiety, depressive mood, inner restlessness, concentration/attention deficits), fatigue and 4 autonomic NMS (excessive sweating, sialorrhea, bladder urgency, dizziness) absent or present and motor function (Off, …On with/without dyskinesia, and asleep) for every hour for 5 consecutive days. Results: NMS Off state hours (hours with NMS rated as present) were less frequent compared to motor Off state hours and NMS On-Off-switches were less prevalent compared to those of the motor state. Off time and number of On-Off-switches of psychiatric NMS were moderately correlated with motor Off time and number of motor On-Off switches on the individual patient level. Changes in NMS state occurred largely independent of changes in motor states with concordance rates of only 26–43% of all NMS changes for psychiatric and 7–17% for autonomic NMS. In controls and non-fluctuating PD patients, there were no NMS state switches in concordance to motor state switches. Conclusion: We provide first data on the temporal context of NMS fluctuations showing similar frequencies of psychiatric NMS Off, fatigue Off and motor Off times as well as their On-Off-fluctuations, but low concordance rates of NMS with motor On-Off-state switches. We found no evidence for NMS fluctuations in non-fluctuating PD patients. Our data implicate similar fluctuation patterns of mood NMS and motor function without close timing and/or different kinetics. Show more

Keywords: Nonmotor symptoms, nonmotor fluctuations, motor complications, psychiatric symptoms, autonomic dysfunction, Parkinson’s disease

DOI: 10.3233/JPD-150764

Citation: Journal of Parkinson's Disease, vol. 6, no. 3, pp. 597-607, 2016

Authors: Johnson, Andrew R. | Lawrence, Blake J. | Corti, Emily J. | Booth, Leon | Gasson, N. | Thomas, Meghan G. | Loftus, A.M. | Bucks, Romola S.

Article Type: Research Article

Abstract: Background: The Depression, Anxiety, and Stress Scale –21 (DASS-21) is a frequently used measure of emotional disturbance symptoms in Parkinson’s disease (PD). However, the factor structure of the DASS-21 in PD has yet to be explored. Objective: To assess whether the scale is measuring these symptoms in PD in the same way as the general population. Methods: The present study fit a series of established DASS-21 factor structures with both confirmatory factor analysis (CFA) and exploratory structural equation modelling (ESEM) using data from 251 participants with PD. Results: The 3-factor ESEM provided the …best fit. The depression and stress scales fit well, however, few items on the anxiety subscale loaded clearly, with several items significantly loading onto the depression or stress factors. Conclusions: Whilst the depression and stress subscales appear suitable in PD, poor loadings and internal consistency indicate the anxiety subscale may not accurately assess anxiety symptomology in PD. This may be due to the scale’s reliance on physiological symptoms as indicators of anxiety, when many of these are present in PD. Thus, the anxiety subscale of the DASS-21 may not be a suitable measure of anxiety in PD. Show more

Keywords: Parkinson’s disease, DASS-21, ESEM, structure

DOI: 10.3233/JPD-160842

Citation: Journal of Parkinson's Disease, vol. 6, no. 3, pp. 609-616, 2016

Authors: Chekani, Farid | Bali, Vishal | Aparasu, Rajender R.

Article Type: Research Article

Abstract: Background: Parkinson’s disease (PD) is a debilitating neurological disorder that has a significant impact on activities of daily living (ADL). Limited data exists regarding the functional status of nursing home residents with PD. Objective: The study examined the nature, extent, and predictors of limitation of ADL in patients with PD residing in nursing homes. Methods: This study used cross-sectional design involving data from the National Nursing Home Survey (NNHS). The dependent variable was the total number of ADL for which the patient needed assistance. Assistance for ADL comprised of five items of transferring, dressing, eating, …toileting and bathing. Multivariable linear regression was used to examine the individual, biological and environmental factors associated with assistance needed for ADL. Results: The nationally representative study sample was of 98,093 nursing home residents with PD for an overall prevalence of 6.57%. The mean age of the study sample was 81.03±0.34 years. Mood symptoms (45%), behavioral symptoms (24%)and dementia (8%) were common among PD patients. Assistance needed for each ADL ranged from 68.24% for eating to 99.25% for bathing. Older age, being married, living in metropolitan statistical area (MSA), living in other place prior to admission, and presence of mood symptoms were positively related to assistance for ADL. Presence of behavioral symptoms and use of levodopa combination therapy were negatively related to assistance for ADL. Conclusions: Majority of the nursing home residents with PD had disability in all the five items of ADL. Various individual, environmental and biological factors were associated with ADL in nursing home residents with PD. Show more

Keywords: Parkinson’s disease, activities of daily living, ADL, nursing home patients, nursing home residents, elderly

DOI: 10.3233/JPD-160822

Citation: Journal of Parkinson's Disease, vol. 6, no. 3, pp. 617-624, 2016

Authors: Gunnery, Sarah D. | Habermann, Barbara | Saint-Hilaire, Marie | Thomas, Cathi A. | Tickle-Degnen, Linda

Article Type: Research Article

Abstract: Background: Though hypomimia, also called facial masking , is experienced by many people with Parkinson’s disease (PD), little is known about how the experience of this motor impairment relates to their own and their care partners’ (CP) social life and relationship quality. Objective: To test if the experience of facial masking relates to social wellbeing in people with PD and their CPs. Method: Forty individuals with PD and their CPs rated PD’s difficulty showing facial expression (facial masking), and completed questionnaires about their own social wellbeing and depression. Results: PD-reported and CP-reported facial …masking of PD were positively correlated with experience of social rejection in both partners, though this relationship was diminished when controlling for depression. CPs’ rating of their partner’s facial masking was negatively associated with enjoyment interacting with their partner. This relationship remained when controlling for CP and PD depression. Conclusions: The findings suggest that the experience of facial masking is negatively associated with social wellbeing particularly for the CPs, and especially so for the quality of CPs interpersonal relationship with their partner with PD. Show more

Keywords: Parkinson’s disease, caregivers, facial expression, quality of life

DOI: 10.3233/JPD-160782

Citation: Journal of Parkinson's Disease, vol. 6, no. 3, pp. 625-630, 2016

Authors: Heldman, Dustin A. | Giuffrida, Joseph P. | Cubo, Esther

Article Type: Research Article

Abstract: Background: Advanced therapies, such as deep brain stimulation and levodopa-carbidopa intestinal gel, can significantly improve quality of life in advanced Parkinson’s disease (PD). However, determining who should be referred for advanced therapy is a challenging problem. Objective: The objective was to determine the impact of remote monitoring using objective, wearable sensors on the advanced therapy referral rate in patients with advanced PD and if sensor data differed in patients who were referred and those who were not. Methods: A retrospective, exploratory, secondary analysis was performed on data collected in a study that followed forty individuals …with advanced PD for one year with half receiving standard care and half using motion sensor-based remote monitoring once per month in conjunction with standard care. Advanced therapy referral rates were compared between groups. For the group who underwent remote monitoring, objective motor features representing symptoms, dyskinesias, and fluctuations were examined to determine if objective kinematic features differed between patients who were and were not recommended for advanced therapy. Results: The advanced therapy referral rate was significantly higher for patients when a clinician had access to remote monitoring reports compared to standard care alone (63.6% versus 11.8%, p  < 0.01). Bradykinesia severity, bradykinesia fluctuations, and dyskinesia severity differed significantly (p  < 10e-8, p  < 10e-5, and p  < 0.01, respectively) between patients recommended and not recommended for advanced therapy. Conclusions: Remote monitoring technologies can capture motor features that may be clinically useful in identifying patients who may be candidates for advanced therapy. This could lead to development of automated screening algorithms, improve referral efficiency, and expand access to advanced therapies for patients with advanced PD. Show more

Keywords: Parkinson’s disease, telemedicine, deep brain stimulation, levodopa-carbidopa intestinal gel

DOI: 10.3233/JPD-160830

Citation: Journal of Parkinson's Disease, vol. 6, no. 3, pp. 631-638, 2016

Authors: Mak, Margaret K.Y. | Cheung, Vinci | Ma, Shuangye | Lu, Zhong L. | Wang, Defeng | Lou, Wutao | Shi, Lin | Mok, Vincent C.T. | Chu, Winnie C.W. | Hallett, Mark

Article Type: Research Article

Abstract: Background: Previous studies employed demanding and complex hand tasks to study the brain activation in people with Parkinson’s Disease (PD). There is inconsistent finding about the cerebellar activity during movement execution of this patient population. Objectives: This study aimed to examine the brain activation patterns of PD individuals in the on-state and healthy control subjects in a simple finger tapping task. Methods: Twenty-seven patients with PD and 22 age-matched healthy subjects were recruited for the study. Subjects were instructed to perform simple finger tapping tasks under self- and cue-initiated conditions in separate runs while their …brain activations were captured using fMRI. Results: Healthy subjects had higher brain activity in contralateral precentral gyrus during the self-initiated task, and higher brain activity in the ipsilateral middle occipital gyrus during the cue-initiated task. PD patients had higher brain activity in the cerebellum Crus I (bilateral) and lobules VI (ipsilateral) during the self-initiated task and higher brain activity in the contralateral middle frontal gyrus during the cue-initiated task. When compared with healthy controls, PD patients had lower brain activity in the contralateral inferior parietal lobule during the self-initiated task, and lower brain activity in the ipsilateral cerebellum lobule VIII, lobule VIIB and vermis VIII, and thalamus during the cue-initiated task. Conjunction analysis indicated that both groups had activation in bilateral cerebellum and SMA and ipsilateral precentral gyrus and postcentral gyrus during both self- and cue-initiated movement. Individuals with PD exhibited higher brain activity in the executive zone (cerebellum Crus I and II) during self-initiated movement, and lower brain activity in the sensorimotor zone (i.e. lobule VIIb and VIII of the cerebellum) during cue-initiated movement. Discussions: The findings suggest that individuals with PD may use more executive control when performing simple movements. Show more

Keywords: Cerebellum, cognition, fMRI, movement disorders, Parkinson’s disease

DOI: 10.3233/JPD-160849

Citation: Journal of Parkinson's Disease, vol. 6, no. 3, pp. 639-650, 2016

Authors: Carriere, Nicolas | Bourriez, Jean-Louis | Delval, Arnaud | Derambure, Philippe | Defebvre, Luc | Dujardin, Kathy

Article Type: Research Article

Abstract: Background: Impulse control disorders (ICDs) in Parkinson’s disease (PD) are related to treatment with dopamine agonists, which is thought to deregulate the dopaminergic mesolimbic pathway and impair reward evaluation. EEG studies in healthy controls (HCs) have suggested that the increase in theta power observed after negative outcome is a marker of reward processing. Objective: To compare outcome-locked, event-related spectral perturbation in a gambling task in PD patients with and without ICDs and in HCs. Methods: Twelve PD patients with ICDs, 12 PD patients without ICDs and 14 HCs underwent EEG while performing a gambling task. …The groups were compared in terms of (i) the peak EEG power in the theta (4–7 Hz), alpha (8–14 Hz) and beta (15–30 Hz) frequency bands between 200 and 500 ms after the outcome, and (ii) time-frequency plots at Fz, FCz and Cz. Results: Positive outcomes were associated with greater theta power than negative outcomes in patients without ICDs and in HCs, but not in patients with ICDs. Patients with ICDs and HCs displayed greater theta power following unexpectedly high outcomes. HCs displayed greater beta power following high amplitude than low amplitude outcomes, whereas patients with ICD showed the opposite pattern. Conclusions: In PD, ICDs are associated with (i) weaker modulation of frontocentral theta power by reward valence, (ii) greater frontocentral theta power following unexpected, high outcomes, and (iii) a reversal of the effect of risk on beta oscillations. These observations are consistent with an impairment in prediction error computation in the medial prefrontal cortex. Show more

Keywords: Parkinson disease, disruptive, impulse control, and conduct disorders, electroencephalography, brain waves, gambling, reward

DOI: 10.3233/JPD-160828

Citation: Journal of Parkinson's Disease, vol. 6, no. 3, pp. 651-666, 2016