Journal of Parkinson's Disease - Volume 5, issue 4

Authors: Skogseth, Ragnhild E. | Bronnick, Kolbjorn | Pereira, Joana B. | Mollenhauer, Brit | Weintraub, Daniel | Fladby, Tormod | Aarsland, Dag

Article Type: Research Article

Abstract: Background: Mild cognitive impairment and dementia are common, clinically important features of Parkinson’s disease (PD). The underlying disease pathology is heterogeneous and not yet well characterized. Biomarkers for cognitive impairment in PD could aid in diagnostic and prognostic evaluation and in the development of new cognitive enhancing treatments. Objective: To examine the relationship between CSF markers and cognition in a large, multicenter, cohort study of early, untreated PD, and compare marker concentrations between PD patients with and without MCI and healthy, age-matched controls. Methods: 414 early, untreated PD (34% with mild cognitive impairment) and 189 healthy, …cognitively intact controls with baseline neuropsychological testing and CSF abeta42, t-tau, p-tau181 and α -synuclein results were included. Multiple linear regression models were constructed with a composite cognition factor, or memory-, or visuospatial- or executive-attention domains as dependent variables, and CSF markers, demographic characteristics and MDS-UPDRS III score as predictors. Results: Lower α -synuclein was associated with reduced performance on the executive-attention domain and the composite cognition factor in the whole PD-group. Abeta42 was significantly decreased in PD with mild cognitive impairment compared with controls after adjusting for covariates, while values in PD without MCI were identical to healthy controls. Conclusions: The association between reduced CSF α -synuclein concentrations and cognition suggests that α -synuclein pathology contributes to early cognitive impairment in PD, in particular to executive-attentional dysfunction. Longitudinal analyses are needed to determine if this and other CSF biomarkers in early Parkinson’s disease are associated with the risk of future cognitive decline and dementia. Show more

Keywords: Parkinson disease, cerebrospinal fluid, Mild cognitive impairment, alpha-synuclein, amyloid beta-peptides, tau Proteins

DOI: 10.3233/JPD-150682

Citation: Journal of Parkinson's Disease, vol. 5, no. 4, pp. 783-792, 2015

Authors: Lucas-Jiménez, Olaia | Díez-Cirarda, María | Ojeda, Natalia | Peña, Javier | Cabrera-Zubizarreta, Alberto | Ibarretxe-Bilbao, Naroa

Article Type: Research Article

Abstract: Background: While significant progress has been made to determine the functional role of specific gray matter areas underlying verbal memory in Parkinson’s disease (PD), very little is known about the relationship between these regions and their underlying white matter structures. Objective: The objectives of this study were (1) to investigate verbal memory, fractional anisotropy and brain activation differences between PD patients and healthy controls (HC), (2) to explore the neuroanatomical and neurofunctional correlates of verbal memory in PD, and (3) to investigate the relationship between these neuroanatomical and neurofunctional verbal memory correlates in PD. Methods: Functional …magnetic resonance imaging (fMRI) while performing a verbal memory paradigm and diffusion tensor imaging data (DTI), were acquired in 37 PD patients and 15 age-, sex-, and education-matched HC. Results: PD patients showed verbal recognition memory impairment, lower fractional anisotropy in the anterior cingulate tract, and lower brain activation in the inferior orbitofrontal cortex compared to HC. Brain activation in the inferior orbitofrontal cortex correlated significantly with verbal recognition memory impairment in PD patients. In addition, a relationship between brain activation in the inferior orbitofrontal cortex and fractional anisotropy of the uncinate fasciculus was found in PD. Conclusions: These results reveal that deficits in verbal memory in PD are accompanied by functional brain activation changes, but also have specific structural correlates related to white matter microstructural integrity. Show more

Keywords: Parkinson’s disease, DTI, fMRI, verbal memory, recognition, learning

DOI: 10.3233/JPD-150623

Citation: Journal of Parkinson's Disease, vol. 5, no. 4, pp. 793-804, 2015

Authors: Béland, Sarah-Gabrielle | Postuma, Ronald B. | Latreille, Véronique | Bertrand, Josie-Anne | Panisset, Michel | Chouinard, Sylvain | Wolfson, Christina | Gagnon, Jean-François

Article Type: Research Article

Abstract: Background: Parkinson’s disease is characterized by numerous non-motor symptoms, including sleep disorders. Sleep apnea has been reported in a substantial proportion of patients with Parkinson’s disease, but it is unclear whether it has significant consequences for the quality of life of those affected or whether it is associated with other manifestations of the disease. Objective: To verify whether sleep apnea is associated with more severe motor and non-motor clinical features in Parkinson’s disease. Methods: Parkinson’s disease patients underwent polysomnography to diagnose the presence of sleep apnea (apnea-hypopnoea index >10). Participants also underwent an extensive assessment, blinded …to sleep apnea status, to determine disease severity, quantitative motor indices, motor subtypes, treatment complications, and sleep, autonomic, psychiatric, and sensory dysfunctions. Cognitive status was also determined with a complete neuropsychological assessment. Results were assessed using regression analysis adjusted for age, sex, and disease duration. Results: Of 92 patients examined, 19 had sleep apnea (21%) and 73 did not. We found no significant differences in motor and non-motor symptoms or signs between apneic and non-apneic Parkinson’s disease patients. The use of different apnea-hypopnoea index cut-offs (>5 and >15) produced similar results. Conclusions: Our results show that sleep apnea is not associated with more severe motor or non-motor manifestations in Parkinson’s disease. More studies including control groups are needed to confirm the implications of those results. Show more

Keywords: Parkinson’s disease, sleep apnea, non-motor symptoms, cognition

DOI: 10.3233/JPD-150602

Citation: Journal of Parkinson's Disease, vol. 5, no. 4, pp. 805-811, 2015

Authors: Sullivan, Kelly L. | Mortimer, James A. | Wang, Wei | Zesiewicz, Theresa A. | Brownlee, H.J. | Borenstein, Amy R.

Article Type: Research Article

Abstract: Background: Associations have been reported between the risk of Parkinson’s disease (PD) and employment in certain fields. Most studies have focused on toxic exposures as potential causal explanations. However, PD also has been associated with personality characteristics that may influence occupational choices and patterns. Objective: This study evaluates the role of personality as indicated by occupational choices and employment patterns in the risk for PD. Methods: In-person interviews were conducted to assess occupational histories and early-adult personality indicators among 89 PD patients and 99 controls. Results: PD cases had fewer lifetime jobs than controls …(mean for cases = 4.38 ± 2.20; mean for controls = 5.00 ± 2.26; p  = 0.03). Among women, PD was positively associated with more complex work with people (OR = 1.45, 95% CI 1.12–1.89), representing a 95% increased risk for PD comparing women with the greatest complexity of work with those requiring the least complexity of work with people. Women PD cases also performed less complex work with things compared with controls (OR = 0.69 (95% CI 0.53–0.90)), translating into a 13-fold increased risk for PD among women whose work involved the least complex work with things compared with the most. The numbers of jobs and job types were associated with taking more activity risks as a young-adult (r  = 0.19, p  = 0.02; r  = 0.26, p  = 0.001, respectively). Conclusions: Cases with PD held fewer lifetime jobs compared with controls. Occupational complexity was associated with the risk for PD among women, but not men. Further consideration of the possible influence of personality on occupational choices is warranted. Show more

Keywords: Employment, novelty-seeking, risk-taking, premorbid, risk factors

DOI: 10.3233/JPD-150635

Citation: Journal of Parkinson's Disease, vol. 5, no. 4, pp. 813-820, 2015

Authors: Yang, Panzao | Pavlovic, Darja | Waldvogel, Henry | Dragunow, Mike | Synek, Beth | Turner, Clinton | Faull, Richard | Guan, Jian

Article Type: Research Article

Abstract: Background: String vessels are collapsed basement membrane without endothelium and have no function in circulation. String vessel formation contributes to vascular degeneration in Alzheimer disease. By comparing to age-matched control cases we have recently reported endothelial degeneration in brain capillaries of human Parkinson disease (PD). Objective: Current study evaluated changes of basement membrane of capillaries, string vessel formation and their association with astrocytes, blood-brain-barrier integrity and neuronal degeneration in PD. Methods: Brain tissue from human cases of PD and age-matched controls was used. Immunohistochemical staining for collagen IV, GFAP, NeuN, tyrosine hydroxylase, fibrinogen and Factor VIII …was evaluated by image analysis in the substantia nigra, caudate nucleus and middle frontal gyrus. Results: While the basement-membrane-associated vessel density was similar between the two groups, the density of string vessels was significantly increased in the PD cases, particularly in the substantia nigra. Neuronal degeneration was found in all brain regions. Astrocytes and fibrinogen were increased in the caudate nuclei of PD cases compared with control cases. Conclusions: Endothelial degeneration and preservation of basement membrane result in an increase of string vessel formation in PD. The data may suggest a possible role for cerebral hypoperfusion in the neuronal degeneration characteristic of PD, which needs further investigation. Elevated astrocytosis in the caudate nucleus of PD cases could be associated with disruption of the blood-brain barrier in this brain region. Show more

Keywords: Capillaries, Parkinson’s disease, age and human

DOI: 10.3233/JPD-140454

Citation: Journal of Parkinson's Disease, vol. 5, no. 4, pp. 821-836, 2015

Authors: Nausieda, Paul A. | Hsu, Ann | Elmer, Lawrence | Gil, Ramon A. | Spiegel, Joerg | Singer, Carlos | Khanna, Sarita | Rubens, Robert | Kell, Sherron | Modi, Nishit B. | Gupta, Suneel

Article Type: Research Article

Abstract: Background: Due to the short half-life of levodopa, immediate-release carbidopa-levodopa (IR CD-LD) produces fluctuating LD concentrations, contributing to a risk of eventual motor complications. IPX066 was designed to rapidly attain therapeutic LD concentrations and maintain them to allow a dosing interval of ∼6 hours. Objective: To extensively analyze the dosing data collected in IPX066 studies during open-label conversions from IR CD-LD alone or with entacapone (CLE) and identify patterns relevant for managing conversion in the clinical setting. Methods: Patients had ≥2.5 hours/day of “off” time despite a stable IR or CLE regimen. Suggested initial dosing conversion …tables based on prior LD daily dosage were provided. Results: Of 450 patients previously treated with IR CD-LD and 110 with CLE, 87.3% and 82.7% completed conversion to IPX066, respectively. At the end of conversion, average IPX066 LD daily dosages were higher than pre-conversion dosages, with a mean conversion ratio of 2.1±0.6 for IR CD-LD and 2.8±0.8 for CLE; >90% of patients took IPX066 3 or 4 times/day, compared with a median of 5 times/day at baseline in both studies. After conversion, daily “off” time significantly decreased, with no significant increase in troublesome dyskinesia. The most common adverse event reported during conversion was nausea, with an incidence of 5.3% for conversion from IR and 7.3% from CLE. Conclusions: Among PD patients with substantial “off” time, a majority were safely converted to IPX066. The sustained LD profile from the IPX066 formulation allowed an increase in LD dose accompanied by improved motor functions, without increased troublesome dyskinesia. Show more

Keywords: Levodopa, Parkinson’s disease, dyskinesia, off-time, on-time, extended-release

DOI: 10.3233/JPD-150622

Citation: Journal of Parkinson's Disease, vol. 5, no. 4, pp. 837-845, 2015

Authors: Haaxma, Charlotte A. | Horstink, Martin W.I.M. | Zijlmans, Jan C. | Lemmens, Wim A.J.G. | Bloem, Bastiaan R. | Borm, George F.

Article Type: Research Article

Abstract: Background: Response fluctuations and dyskinesias develop during the use of both levodopa (LD) and dopamine agonists (DA), but may not be equally disabling. Objective: To compare the risk and time of onset of disabling response fluctuations and dyskinesias (DRFD) among patients with Parkinson’s disease (PD) who were initially treated with either LD or DA. Methods: Open cohort study of all consecutive de-novo PD patients in routine clinical practice, included over a period of 15 years (median follow-up: 8.1 years, range 1.1–17.7), since embarking on LD or DA. Older patients and patients with more severe PD were …started on LD (n  = 77), younger patients on a DA (n  = 50). Therapy was adjusted according to generally accepted guidelines. The primary endpoints were: the onset of response fluctuations, dyskinesias, and the moment when these complications became disabling (DRFD). Results: LD-starters developed response fluctuations 0.8 years earlier than DA-starters (p  = 0.07), while dyskinesias appeared around 2.5 years earlier (p  = 0.003). However, the risk and time of onset of DRFD did not differ statistically between the groups (LD-starters: 60% , median interval 7.3 years, DA-starters: 52% , 6.1 years, p  = 0.63). DA-starters displayed a 0.19 points lower adjusted mean improvement in motor scores than LD-starters (p  = 0.002). Adjustments for age and severity of PD at start of dopaminergic therapy did not change these results. Conclusions: In routine clinical practice, the risk and time of onset of DRFD is comparable for LD-starters versus DA-starters, but motor functioning is worse in DA-starters. These results support the use of LD as initial therapy for PD. Show more

Keywords: Parkinson’s disease, levodopa, dopamine agonists, dyskinesia, response fluctuations

DOI: 10.3233/JPD-150532

Citation: Journal of Parkinson's Disease, vol. 5, no. 4, pp. 847-853, 2015

Authors: Almeida, Lorena R.S. | Sherrington, Catherine | Allen, Natalie E. | Paul, Serene S. | Valenca, Guilherme T. | Oliveira-Filho, Jamary | Canning, Colleen G.

Article Type: Research Article

Abstract: Background: Predictors of falls in people with Parkinson’s disease (PD) who have not previously fallen are yet to be identified. Objectives: We aimed to identify predictors of all falls and recurrent falls in people with PD who had not fallen in the previous year and to explore the timing of falls in a 12-month follow-up period. Methods: Participants with PD (n  = 130) were assessed by disease-specific, self-report and balance measures. Falls were recorded prospectively for 12 months. Univariate and multivariate analyses were performed. Kaplan-Meier survival analysis was used to investigate time to falling. Results: …Forty participants (31%) had ≥1 fall during follow-up and 21 (16%) had ≥2 falls. Disability, reduced balance confidence and greater concern about falling were associated with ≥1 fall in univariate analyses. Additionally, PD duration and severity, freezing of gait and impaired balance were associated with ≥2 falls (p  <  0.05). Disability (Schwab and England scale, Odds Ratio [OR] = 0.56 per 10 points increase; 95% confidence interval [CI] 0.39–0.80; p  = 0.002) was associated with ≥1 fall in the final multivariate model (area under the receiver operating characteristic curve [AUC] = 0.65; 95% CI 0.55–0.76; p  = 0.005). Disability (Unified Parkinson’s Disease Rating Scale activities of daily living, OR = 1.20; 95% CI 1.07–1.34; p  = 0.001) and levodopa equivalent dose (OR = 1.11 per 100 mg increase; 95% CI 0.95–1.30; p  = 0.19) were associated with ≥2 falls in the final multivariate model (AUC = 0.72; 95% CI 0.60–0.84; p  = 0.001). Recurrent fallers experienced their first fall earlier than single fallers (p  <  0.05). Conclusions: Self-reported disability was the strongest single predictor of all falls and recurrent falls. Show more

Keywords: Parkinson’s disease, accidental falls, risk factors, postural balance

DOI: 10.3233/JPD-150651

Citation: Journal of Parkinson's Disease, vol. 5, no. 4, pp. 855-864, 2015

Authors: Tan, Ai Huey | Tan, Chong Tin | Marras, Connie | Loh, Kwong Weng | Wye Ho, Niki Wai | Lim, Quan Hziung | Tan, Pei Wen | Lim, Chee Chean | Cheong, Yee Weai | Kong, Sik Thien | Schee, Jie Ping | Tan, Kean Hoong | Soo, Suet Ker | Vanderschaaf, Cheryl | Lai Heong Lew, Sara | Mahamad, Ummi Affah | Goh, Khean Jin | Yong, Hoi Sen | Lim, Shen-Yang

Article Type: Research Article

Abstract: Background: Public knowledge regarding Parkinson’s disease (PD) is important to facilitate good health-seeking behavior, but the literature on this topic is scarce. Objective: We aimed to explore the level of public knowledge regarding PD in a large multiethnic urban Asian cohort, and (as a secondary aim) in a smaller cohort of PD patients and caregivers. Methods: A Knowledge of PD Questionnaire (KPDQ) was developed and administered to members of the Malaysian general public, and to PD patients and caregivers. The KPDQ tests recognition of PD symptoms and general knowledge regarding PD. Results: 1,258 members of …the general public completed the KPDQ. Tremor was the most widely recognized symptom (recognized by 79.0% of respondents); however, 83.7% incorrectly believed that all PD patients experience tremor. Memory problem was the most widely recognized NMS. Overall, motor symptoms were better recognized than NMS. Common misperceptions were that there is a cure for PD (49.8%) and that PD is usually familial (41.4%). Female gender, Chinese ethnicity, tertiary education, healthcare-related work, and knowing someone with PD were independently associated with higher KPDQ scores. PD patients (n  = 116) and caregivers (n  = 135) demonstrated superior knowledge compared with the general public group, but one-third of them believed that PD is currently curable. Conclusions: This is the only study on public knowledge regarding PD in Asia. Important gaps in knowledge were evident, which could present a barrier to early diagnosis and appropriate treatment of PD. This highlights the need for targeted education campaigns and further research in this area. Show more

Keywords: Parkinson’s disease, epidemiology, knowledge, awareness, education, cure, stem cells, Asia

DOI: 10.3233/JPD-150594

Citation: Journal of Parkinson's Disease, vol. 5, no. 4, pp. 865-879, 2015

Authors: Hall, Julie M. | Shine, James M. | O’Callaghan, Claire | Walton, Courtney C. | Gilat, Moran | Naismith, Sharon L. | Lewis, Simon J.G.

Article Type: Research Article

Abstract: Background: Freezing of gait is a common disabling symptom of Parkinson’s disease (PD) with limited treatment options. The pathophysiological mechanisms of freezing behaviour are still contentious. Objective: To investigate the prevalence of freezing of gait and its associations with increasing disease severity to gain a better understanding of the underlying pathophysiology. Methods: This exploratory study included 389 idiopathic PD patients, divided into four groups; early and advanced PD with freezing of gait, and early and advanced PD without freezing of gait. Motor, cognitive and affective symptoms, REM sleep behaviour disorder and autonomic function were assessed. …Results: Regardless of disease stage, patients with freezing of gait had more severe motor symptoms and a predominant non-tremor phenotype. In the early stages, freezers had a selective impairment in executive function and had more marked REM sleep behaviour disorder. Autonomic disturbances were not associated with freezing of gait across early or advanced disease stages. Conclusion: These findings support the notion that impairments across the frontostriatal pathways are intricately linked to the pathophysiology underlying freezing of gait across all stages of PD. Features of REM sleep behaviour disorder suggest a contribution to freezing from brainstem pathology but this does not extend to more general autonomic dysfunction. Show more

Keywords: Parkinson’s disease, freezing of gait, disease stage, pathophysiology, executive function

DOI: 10.3233/JPD-150581

Citation: Journal of Parkinson's Disease, vol. 5, no. 4, pp. 881-891, 2015

Authors: Price, Catherine C. | Levy, Shellie-Anne | Tanner, Jared | Garvan, Cyndi | Ward, Jade | Akbar, Farheen | Bowers, Dawn | Rice, Mark | Okun, Michael

Article Type: Research Article

Abstract: Background: Post-operative cognitive dysfunction (POCD) demarks cognitive decline after major surgery but has been studied to date in “healthy” adults. Although individuals with neurodegenerative disorders such as Parkinson’s disease (PD) commonly undergo elective surgery, these individuals have yet to be prospectively followed despite hypotheses of increased POCD risk. Objective: To conduct a pilot study examining cognitive change pre-post elective orthopedic surgery for PD relative to surgery and non-surgery peers. Methods: A prospective one-year longitudinal design. No-dementia idiopathic PD individuals were actively recruited along with non-PD “healthy” controls (HC) undergoing knee replacement surgery. Non-surgical PD and HC …controls were also recruited. Attention/processing speed, inhibitory function, memory recall, animal (semantic) fluency, and motor speed were assessed at baseline (pre-surgery), 3 weeks, 3 months, and 1 year post- orthopedic surgery. Reliable change methods examined individual changes for PD individuals relative to control surgery and control non-surgery peers. Results: Over two years we screened 152 older adult surgery or non-surgery candidates with 19 of these individuals having a diagnosis of PD. Final participants included 8 PD (5 surgery, 3 non-surgery), 47 Control Surgery, and 21 Control Non-Surgery. Eighty percent (4 of the 5) PD surgery declined greater than 1.645 standard deviations from their baseline performance on measures assessing processing speed and inhibitory function. This was not observed for the non-surgery PD individuals. Conclusion: This prospective pilot study demonstrated rationale and feasibility for examining cognitive decline in at-risk neurodegenerative populations. We discuss recruitment and design challenges for examining post-operative cognitive decline in neurodegenerative samples. Show more

Keywords: Orthopedics, arthroplasty, neurodegenerative, memory, executive function

DOI: 10.3233/JPD-150632

Citation: Journal of Parkinson's Disease, vol. 5, no. 4, pp. 893-905, 2015

Authors: Pirker, Susanne | Perju-Dumbrava, Laura | Kovacs, Gabor G. | Traub-Weidinger, Tatiana | Pirker, Walter

Article Type: Research Article

Abstract: Background: Corticobasal degeneration (CBD) is characterized by neuronal and glial deposition of 4-repeat tau in the frontal and parietal cerebral cortex, white matter and striatum. There is neuronal loss in affected cortical regions and in the substantia nigra (SN). Recent single photon emission tomography (SPECT) studies have reported normal striatal dopamine transporter (DAT) binding in individual patients with CBD. Objective: To study the pattern and course of DAT binding loss in CBD. Methods: We retrospectively analyzed DAT SPECT studies in two patients presenting with a corticobasal syndrome in whom a diagnosis of CBD was later confirmed …pathologically. Results: Baseline scans at 1.5 years after symptom onset revealed only mild abnormalities (reduced uptake in one putamen). Follow up scans at 4.5 years (Case 1) and 5 years (Case 2) after symptom onset showed a marked decline of striatal DAT binding. In both cases, there was a 37% binding reduction from the age-expected striatal binding value. Asymmetry of striatal DAT binding had increased from mild in the first SPECT studies to moderate at the time of their final imaging. Conclusion: CBD patients can have delayed neuronal loss in the SN. Follow up DAT imaging may be of value in patients with possible CBD and a normal baseline scan. Show more

Keywords: Atypical parkinsonism, corticobasal syndrome, corticobasal degeneration, dopamine transporter, single photon emission computerized tomography

DOI: 10.3233/JPD-150625

Citation: Journal of Parkinson's Disease, vol. 5, no. 4, pp. 907-912, 2015

Authors: Moccia, Marcello | Mollenhauer, Brit | Erro, Roberto | Picillo, Marina | Palladino, Raffaele | Barone, Paolo

Article Type: Research Article

Abstract: Background: Parkinson’s disease (PD) subjects are less likely to ever smoke and are more prone to quit smoking, as compared to controls. Therefore, smoking habits can be considered part of the non-motor phenotype, preceding the onset of motor PD by several years. Objective: To explore non-motor symptom (NMS) correlates of smoking habits in de novo PD. Methods: This cross-sectional study included 281 newly diagnosed, drug-naïve PD subjects, recruited in Naples (Italy) and in Kassel (Germany). All subjects completed the NMS Questionnaire (NMSQ), and were investigated for smoking status (never, current and former smokers) and intensity (pack-years). …Results: 140 PD subjects never smoked, 20 currently smoked, and 121 had quit smoking before PD diagnosis. NMSQ total score did not associate with smoking status, but with smoking intensity (p  = 0.028; coefficient = 0.088). A multinomial logistic regression stepwise model presenting never smoking as reference, selected as NMSQ correlates of current smoking: sex difficulties (p  = 0.002; OR = 5.254), daytime sleepiness (p  = 0.046; OR = 0.085), insomnia (p  = 0.025; OR = 0.135), and vivid dreams (p  = 0.040; OR = 3.110); and of former smoking: swallowing (p  = 0.013; OR = 0.311), nausea (p  = 0.027; OR = 7.157), unexplained pains (p  = 0.002; OR = 3.409), forgetfulness (p  = 0.005; OR = 2.592), sex interest (p  = 0.007; OR = 0.221), sex difficulties (p  = 0.038; OR = 4.215), and daytime sleepiness (p  = 0.05; OR = 0.372). An ordinal logistic regression stepwise model selected as NMSQ correlates of smoking intensity: nocturnal restlessness (p  = 0.027; coefficient = 0.974), and leg swelling (p  = 0.004; coefficient = 1.305). Conclusions: Certain NMSs are associated with different smoking status and intensity, suggesting a variety of adaptive mechanisms to cigarette smoking. Show more

Keywords: Parkinson, de novo, non-motor, smoking, nicotine, cigarette, motor

DOI: 10.3233/JPD-150639

Citation: Journal of Parkinson's Disease, vol. 5, no. 4, pp. 913-924, 2015

Authors: Fearon, Conor | Butler, John S. | Newman, Louise | Lynch, Timothy | Reilly, Richard B.

Article Type: Research Article

Abstract: Background: Sensory and perceptual disturbances progress with disease duration in Parkinson’s disease (PD) and probably contribute to motor deficits such as bradykinesia and gait disturbances, including freezing of gait (FOG). Simple reaction time tests are ideal to explore sensory processing, as they require little cognitive processing. Multisensory integration is the ability of the brain to integrate sensory information from multiple modalities into a single coherent percept, which is crucial for complex motor tasks such as gait. Objectives: The aims of this study were to: 1. Assess differences in unisensory (auditory and visual) and multisensory processing speed in people …with PD and age-matched healthy controls. 2. Compare relative differences in unisensory processing in people with PD with disease duration and freezing of gait status taking into account the motor delays, which are invariably present in PD. 3. Compare relative differences in multisensory (audiovisual) processing between the PD cohort and age-matched controls. Methods: 39 people with PD (23 with FOG) and 17 age-matched healthy controls performed a reaction time task in response to unisensory (auditory-alone, visual-alone) and multisensory (audiovisual) stimuli. Results: The PD group were significantly slower than controls for all conditions compared with healthy controls but auditory reaction times were significantly faster than visual for the PD group only. These relative unisensory differences are correlated with disease duration and divide the PD group by FOG status, but these factors are co-dependent. Although multisensory facilitation occurs in PD, it is significantly less enhanced than in healthy controls. Conclusion: There are significant unisensory and multisensory processing abnormalities in PD. The relative differences in unisensory processing are specific to PD progression, providing a link between these sensory abnormalities and a motor feature of PD. Sensory disturbances have previously been postulated to be central to FOG but this is the first study to predict audiovisual processing abnormalities using FOG status. The multisensory processing abnormalities are independent of disease duration and FOG status and may be a potential biomarker for the disease. Show more

Keywords: Parkinson’s disease, sensory processing, multisensory, auditory, visual

DOI: 10.3233/JPD-150655

Citation: Journal of Parkinson's Disease, vol. 5, no. 4, pp. 925-936, 2015

Authors: van der Eijk, Martijn | Bloem, Bastiaan R. | Nijhuis, Frouke A.P. | Koetsenruijter, Jan | Vrijhoef, Hubertus J.M. | Munneke, Marten | Wensing, Michel | Faber, Marjan J.

Article Type: Research Article

Abstract: Background: ParkinsonNet, a nationwide organization with regionally oriented professional health networks in TheNetherlands, aims to improve the quality of Parkinson care. Facilitation of multidisciplinary collaboration is a key objective of ParkinsonNet. Objectives: This study examined whether the concept enhances multidisciplinary collaboration between healthcare professionals involved in Parkinson care. Methods: A regional network involving 101 healthcare professionals was newly established. Participants received two questionnaires. One aimed at documenting direct working relationships (‘connections’) between professionals and the other aimed at evaluating multidisciplinary team performance. Additionally, thirteen healthcare professionals were interviewed to identify barriers and facilitators for multidisciplinary collaboration. …‘Social network analysis’ focused on sub-networks around three community hospitals at baseline and one year after the implementation. Results: The number of ‘knowing each other ’ connections increased from 1431 to 2175 (52% , p  <  0.001) and ‘professional contact ‘ connections increased from 664 to 891 (34% , p <  0.001). Large differences between sub-networks were found, positive changes being associated with a central role of neurologists and nurse specialists committed to multidisciplinary care. The perceived team performance did not change. Participants experienced problems with information exchange and interdisciplinary communication. Generally, participants were unaware of other healthcare professionals involved in individual patients and what treatments they provide simultaneously. Conclusions: ParkinsonNet partially enhanced multidisciplinary collaboration between healthcare professionals involved in Parkinson care. Crucial facilitators of this were a central role of nurse specialists and the commitment to collaborate with and refer to expert therapists among neurologists. Additional measures are needed to further improve multidisciplinary care across different institutions and around individual patients. Show more

Keywords: Parkinson disease, multidisciplinary communication, collaboration, social networking, community network

DOI: 10.3233/JPD-150673

Citation: Journal of Parkinson's Disease, vol. 5, no. 4, pp. 937-945, 2015

Authors: Malek, Naveed | Swallow, Diane M.A. | Grosset, Katherine A. | Lawton, Michael A. | Marrinan, Sarah L. | Lehn, Alexander C. | Bresner, Catherine | Bajaj, Nin | Barker, Roger A. | Ben-Shlomo, Yoav | Burn, David J. | Foltynie, Thomas | Hardy, John | Morris, Huw R. | Williams, Nigel M. | Wood, Nicholas | Grosset, Donald G. | on behalf of the PRoBaND clinical consortium

Article Type: Research Article

Abstract: Background: There is wide variation in the phenotypic expression of Parkinson’s disease (PD), which is driven by both genetic and epidemiological influences. Objectives: To define and explain variation in the clinical phenotype of PD, in relation to genotypic variation. Methods: Tracking Parkinson’s is a multicentre prospective longitudinal epidemiologic and biomarker study of PD. Patients attending specialist clinics in the United Kingdom with recent onset (<3.5 years) and young onset (diagnosed <50 years of age) PD were enrolled. Motor, non-motor and quality of life assessments were performed using validated scales. Cases are followed up 6 monthly up …to 4.5 years for recent onset PD, and up to 1 year for young onset PD. We present here baseline clinical data from this large and demographically representative cohort. Results: 2247 PD cases were recruited (1987 recent onset, 260 young onset). Recent onset cases had a mean (standard deviation, SD) age of 67.6 years (9.3) at study entry, 65.7% males, with disease duration 1.3 years (0.9), MDS-UPDRS 3 scores 22.9 (12.3), LEDD 295 mg/day (211) and PDQ-8 score 5.9 (4.8). Young onset cases were 53.5 years old (7.8) at study entry, 66.9% male, with disease duration 10.2 years (6.7), MDS-UPDRS 3 scores 27.4 (15.3), LEDD 926 mg/day (567) and PDQ-8 score 11.6 (6.1). Conclusions: We have established a large clinical PD cohort, consisting of young onset and recent onset cases, which is designed to evaluate variation in clinical expression, in relation to genetic influences, and which offers a platform for future imaging and biomarker research. Show more

Keywords: Parkinson’s disease, heterogeneity, genotype, phenotype

DOI: 10.3233/JPD-150662

Citation: Journal of Parkinson's Disease, vol. 5, no. 4, pp. 947-959, 2015

Authors: Cohen, Matthew L. | Schwab, Nadine A. | Price, Catherine C. | Heilman, Kenneth M.

Article Type: Research Article

Abstract: Background: Planned and initiated actions frequently need to be terminated in favor of another action. It is known that many individuals with Parkinson’s disease (PD) have more difficulty self-initiating movement (i.e., endogenously evoked movement) than moving in response to environmental stimuli (i.e., exogenously evoked movement). However, it is not known if individuals with PD display this same endogenous-exogenous asymmetry when needing to terminate, disengage, and reprogram movements. Objective: This study used a novel reaction time (RT) paradigm to test whether patients with mild PD have subclinical deficits of endogenous movement initiation and endogenous movement reprogramming. Methods: …Twelve non-demented individuals with PD on medication and 15 demographically similar healthy control (HC) participants completed an experimental paradigm that examined their RTs (key press) following self-selected valid action preparation (endogenous cues) versus valid exogenously presented cues. The paradigm also assessed participants’ ability to rapidly stop their endogenous or exogenous preparation following an invalid cue and execute an alternative action (key press). Results: Participants with PD produced similar RTs as controls following endogenous and exogenous valid cues, and following invalid exogenous cues. However, following invalid endogenous cues, PD participants were slower than HC participants to stop an endogenous preparation and execute an alternative action. Conclusions: Despite having mild disease and being on dopaminergic medication, these individuals with PD displayed deficits in motor disengagement and reprograming of self-selected actions. Future studies should examine how this phenomenon influences every day actions, as well as possible treatments for this deficit. Show more

DOI: 10.3233/JPD-150672

Citation: Journal of Parkinson's Disease, vol. 5, no. 4, pp. 961-970, 2015

Authors: Pirogovsky-Turk, Eva | Filoteo, J. Vincent | Litvan, Irene | Harrington, Deborah L.

Article Type: Research Article

Abstract: Background: Changes in episodic memory are common early in Parkinson’s disease (PD) and may be a risk factor for future cognitive decline. Although medial temporal lobe (MTL) memory and frontostriatal (FS) executive systems are thought to play different roles in distinct components of episodic memory impairment in PD, no study has investigated whether different aspects of memory functioning are differentially associated with MTL and FS volumes in nondemented patients without mild cognitive impairment (PD-woMCI). Objectives: The present study investigated MRI markers of different facets of memory functioning in 48 PD-woMCI patients and 42 controls. Methods: Regional …volumes were measured in structures comprising the MTL and FS systems and then correlated with key indices of memory from the California Verbal Learning Test. Results: In PD-woMCI patients, memory was impaired only for verbal learning, which was not associated with executive, attention/working memory, or visuospatial functioning. Despite an absence of cortical atrophy, smaller right MTL volumes in patients were associated with poorer verbal learning, long delayed free recall, long delayed cued recall, and recognition memory hits and false positives. Smaller right pars triangularis (inferior frontal) volumes were also associated with poorer long delayed cued recall and recognition memory hits. These relationships were not found in controls. Conclusions: The findings indicate that MTL volumes are sensitive to subtle changes in almost all facets of memory in PD-woMCI, whereas FS volumes are sensitive only to memory performances in cued-testing formats. Show more

Keywords: Parkinson’s disease, magnetic resonance imaging, memory, neuropsychology, medial temporal lobe system, frontostriatal system, cognitive functions

DOI: 10.3233/JPD-150652

Citation: Journal of Parkinson's Disease, vol. 5, no. 4, pp. 971-981, 2015

Authors: Nilsson, Maria H. | Iwarsson, Susanne | Thordardottir, Björg | Haak, Maria

Article Type: Research Article

Abstract: Background: Activity performance is marked by the degenerative nature of Parkinson’s disease (PD), but few qualitative studies have focused on how people with PD perceive participation in life situations. Objective: To identify and describe barriers and facilitators for participation from the perspective of people with PD. Methods: Qualitative data was obtained by the focus group method using a semi-structured interview guide. Participants were recruited by purposeful sampling until saturation was reached. Homogeneity within each focus group was based on self-rated PD severity (mild, moderate, severe). Nine focus groups (three per PD severity level) included a total …of 29 participants. Results: Complex dynamics between the individual and the physical and social environment create barriers and facilitators for participation as described in the four categories which emerged out of the focus group discussions. The category Ambiguity of attitudes and the support of others describes how attitudes and support of other people act both as facilitators and barriers for participation. PD specific complexity of the body and physical environment interaction describes barriers for participation. Facilitators emerged in the two categories PD expertise in health care and social services and Information and education foster PD specific understanding . Conclusions: Our findings imply several potential means to facilitate participation for people with PD, taking the person as well as the environment into account in person-centred interventions. This involves aspects such as having access to PD specific expertise, increasing the knowledge and thereby the understanding of PD as well as providing support for maintained work-life. Show more

Keywords: Activities, education, environment, falls, family, knowledge, patient involvement, self-help devices, transportation, work

DOI: 10.3233/JPD-150631

Citation: Journal of Parkinson's Disease, vol. 5, no. 4, pp. 983-992, 2015

Authors: Lamotte, Guillaume | Rafferty, Miriam R. | Prodoehl, Janey | Kohrt, Wendy M. | Comella, Cynthia L. | Simuni, Tanya | Corcos, Daniel M.

Article Type: Correction

DOI: 10.3233/JPD-159002

Citation: Journal of Parkinson's Disease, vol. 5, no. 4, pp. 993-993, 2015

Article Type: Other

Citation: Journal of Parkinson's Disease, vol. 5, no. 4, pp. 995-1004, 2015