Effect of Intensive Voice Treatment on Tone-Language Speakers with Parkinson's Disease

ERIC Educational Resources Information Center

Whitehill, Tara L.; Wong, Lina L. -N.

2007-01-01

The aim of this study was to investigate the effect of intensive voice therapy on Cantonese speakers with Parkinson's disease. The effect of the treatment on lexical tone was of particular interest. Four Cantonese speakers with idiopathic Parkinson's disease received treatment based on the principles of Lee Silverman Voice Treatment (LSVT).…

Associations of specific psychiatric disorders with isolated focal dystonia, and monogenic and idiopathic Parkinson's disease.

PubMed

Steinlechner, Susanne; Hagenah, Johann; Rumpf, Hans-Jürgen; Meyer, Christian; John, Ulrich; Bäumer, Tobias; Brüggemann, Norbert; Kasten, Meike; Münchau, Alexander; Klein, Christine; Lencer, Rebekka

2017-06-01

Comorbidity of psychiatric disorders in patients with movement disorders is common. Often, psychiatric symptoms manifest before the onset of the movement disorder, thus not representing a mere reaction to its burden. How the disease mechanisms of psychiatric and movement disorders are related is still poorly understood. The aim of the present study was to compare prevalence rates of specific psychiatric disorders between different movement disorders including isolated focal dystonia (IFD, N = 91), monogenic Parkinson's disease (PD, N = 41), idiopathic PD (N = 45), and a sample from a Northern Germany general population (TACOS Study; N = 4075). Our results indicate an odds ratio (OR) of 2.6 [confidence interval (CI) 1.7-4.0] for general axis I disorders in IFD, an OR of 2.5 (CI 1.4-4.7) in monogenic PD, and an OR of 1.4 (CI 0.8-2.6) in idiopathic PD. More specifically, the monogenic PD group showed the highest ORs for affective disorders including depression (OR = 4.9), bipolar disorder (OR = 17.4), and hypomanic episodes (OR = 17.0), whereas IFD expressed the highest rates of anxiety disorders (OR = 3.3). Psychotic symptoms were only observed in the PD groups but not in IFD. Our findings underline the notion that psychiatric disorders are part of the phenotypic spectrum of movement disorders. Moreover, they suggest that IFD, monogenic PD, and idiopathic PD are associated with specific psychiatric disorders indicating disturbances in a different neural circuitry for sensorimotor control.

Effects of Intensive Voice Treatment (the Lee Silverman Voice Treatment [LSVT]) on Vowel Articulation in Dysarthric Individuals with Idiopathic Parkinson Disease: Acoustic and Perceptual Findings

ERIC Educational Resources Information Center

Sapir, Shimon; Spielman, Jennifer L.; Ramig, Lorraine O.; Story, Brad H.; Fox, Cynthia

2007-01-01

Purpose: To evaluate the effects of intensive voice treatment targeting vocal loudness (the Lee Silverman Voice Treatment [LSVT]) on vowel articulation in dysarthric individuals with idiopathic Parkinson's disease (PD). Method: A group of individuals with PD receiving LSVT (n = 14) was compared to a group of individuals with PD not receiving LSVT…

Genetic analysis of SCA2, 3 and 17 in idiopathic Parkinson's disease.

PubMed

Lim, S W; Zhao, Y; Chua, E; Law, H Y; Yuen, Y; Pavanni, R; Wong, M C; Ng, I S; Yoon, C S; Puong, K Y; Lim, S H; Tan, E K

2006-07-31

Recent reports of SCA2 and SCA3 patients who presented with levodopa responsive parkinsonism have generated considerable interest as they have implications for genetic testing. It is unclear whether ethnic race alone or founder effects within certain geographical region explain such an association. In this study, we conducted genetic analysis of SCA2, 3, 17 in an ethnic Chinese cohort with early onset and familial Parkinson's disease (PD) and healthy controls. A total of 191 subjects comprising of 91 PD and 100 healthy controls were examined. We identified one positive case of SCA2 in an early-onset sporadic PD patient who had CAG 36 repeats, yielding a prevalence of 2.2% in early-onset sporadic PD patients and less than 1.0% in our study PD population. The size of the repeats was lower than the expanded repeats (38-57) in SCA2 patients with ataxia in our population. All the children of the patient were physically normal even though some of them carried the repeat expansion of similar size. No cases and controls were positive for SCA3 and SCA17. We do not think routine screening of SCA2, SCA3 and SCA17 for all idiopathic PD patients is cost-effective in our ethnic Chinese population. However, SCA2 should be a differential diagnosis in young onset sporadic PD when genetic mutations of other known PD genes have been excluded.

Reliability and Validity of the Persian Version of the Fatigue Severity Scale in Idiopathic Parkinson's Disease Patients

PubMed Central

Hadizadeh, Hasti; Farhadi, Farzaneh; Delbari, Ahmad; Lökk, Johan

2013-01-01

As one of the most frequent symptoms, measurement of fatigue is an issue of interest in Parkinson's disease (PD). The fatigue severity scale (FSS) is one of the recommended questionnaires for this purpose. The aim of our study was to evaluate psychometric properties of the Persian version of the FSS (FSS-Per) to assess fatigue in PD patients. Ninety nondemented idiopathic Parkinson's disease (IPD) patients were consecutively recruited from an outpatient referral movement disorder clinic. In addition to the disease severity scales, the FSS-Per was used for fatigue measurement. The internal consistency coefficient was larger than 0.8 for all of the items with a total Cronbach's alpha of 0.96 (95% CI: 0.95–0.97). The FSS-Per score correlated with the UPDRS score (r = 0.55, P < 0.001) and the “Hoehn and Yahr” (HY) stage (r = 0.48, P < 0.001). The total score of the FSS-Per significantly discriminated IPD patients with more severe disability (HY stage > 2) versus those with less severe disease (HY stage ≤2) (AUC = 0.81 (95% CI: 0.72–0.90)). The FSS-Per fulfilled a high internal consistency and construct validity to measure the severity of fatigue in Iranian IPD patients. These acceptable psychometric properties were reproducible in subgroups of IPD patients regarding different levels of education, disease severity, sex and age groups. PMID:24089644

Gastrointestinal dysfunction in idiopathic Parkinsonism: A narrative review

PubMed Central

Salari, Mehri; Fayyazi, Emad; Mirmosayyeb, Omid

2016-01-01

Currently, gastrointestinal (GI) dysfunctions in Parkinson's disease (PD) are well-recognized problems and are known to be the initial symptoms in the pathological process that eventually results in PD. Many types of PD-associated GI dysfunctions have been identified, including weight loss, nausea, hypersalivation, dysphagia, dyspepsia, abdominal pain, intestinal pseudo-obstruction, constipation, defecatory dysfunction, and small intestinal bacterial overgrowth. These symptoms can influence on other PD symptoms and are the second most significant predictor of the quality of life of these patients. Recognition of GI symptoms requires vigilance on the part of clinicians. Health-care providers should routinely ask direct questions about GI symptoms during office visits so that efforts can be directed at appropriate management of these distressing manifestations. Multiple system atrophy (MSA) and progressive supranuclear palsy are two forms of neurodegenerative Parkinsonism. Symptoms of autonomic dysfunctions such as GI dysfunction are common in patients with parkinsonian disorders. Despite recent progress in the recognition of GI dysfunctions, there are a few reviews on the management of GI dysfunction and GI symptoms in idiopathic Parkinsonism. In this review, the clinical presentation, pathophysiology, and treatment of each GI symptom in PD, MSA, and prostate-specific antigen will be discussed. PMID:28331512

Early detection of probable idiopathic Parkinson's disease: I. development of a diagnostic test battery.

PubMed

Montgomery, Erwin B; Koller, William C; LaMantia, Theodora J K; Newman, Mary C; Swanson-Hyland, Elizabeth; Kaszniak, Alfred W; Lyons, Kelly

2000-05-01

We developed a test battery as an inexpensive and objective aid for the early diagnosis of idiopathic Parkinson's disease (iPD) and its differential diagnoses. The test battery incorporates tests of motor function, olfaction, and mood. In the motor task, a wrist flexion-and-extension task to different targets, movement velocities were recorded. Olfaction was tested with the University of Pennsylvania Smell Identification Test. Mood was assessed with the Beck Depression Inventory. An initial regression model was developed from the results of 19 normal control subjects and 18 patients with early, mild, probable iPD. Prospective application to an independent validation set of 122 normal control subjects and 103 patients resulted in an 88% specificity rate and 69% sensitivity rate, with an area under the Receiver Operator Characteristic curve of 0.87. Copyright © 2000 Movement Disorder Society.

Positron emission tomography suggests that the rate of progression of idiopathic parkinsonism is slow

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bhatt, M.H.; Snow, B.J.; Martin, W.R.

1991-06-01

The authors performed sequential positron emission tomography scans with 6-(18F)fluoro-L-dopa in 9 patients with idiopathic parkinsonism and 7 age-matched normal control subjects to compare changes in the nigrostriatal dopaminergic pathway over time. The mean interval between the scans was 3.3 years for the group with idiopathic parkinsonism and 3.9 years for the control subjects. The scans were analyzed by calculating the ratio of striatal to background radioactivity. Both groups showed statistically significant reductions of striatal uptake over the interval. The rate of decrease was almost identical in each group (p = 0.6). They infer that the usual rate of lossmore » of integrity of the dopaminergic nigrostriatal pathway in patients with idiopathic parkinsonism is slow and the rate of change between the two groups was comparable.« less

Asymmetrical Pedaling Patterns in Parkinson's Disease Patients

PubMed Central

Penko, Amanda L.; Hirsch, Joshua R.; Voelcker-Rehage, Claudia; Martin, Philip E.; Blackburn, Gordon; Alberts, Jay L.

2015-01-01

Background Approximately 1.5 million Americans are affected by Parkinson's disease [1] which includes the symptoms of postural instability and gait dysfunction. Currently, clinical evaluations of postural instability and gait dysfunction consist of a subjective rater assessment of gait patterns using items from the Unified Parkinson's Disease Rating Scale, and assessments can be insensitive to the effectiveness of medical interventions. Current research suggests the importance of cycling for Parkinson's disease patients, and while Parkinson's gait has been evaluated in previous studies, little is known about lower extremity control during cycling. The purpose of this study is to examine the lower extremity coordination patterns of Parkinson's patients during cycling. Methods Twenty five participants, ages 44-72, with a clinical diagnosis of idiopathic Parkinson's disease participated in an exercise test on a cycle ergometer that was equipped with pedal force measurements. Crank torque, crank angle and power produced by right and left leg were measured throughout the test to calculate Symmetry Index at three stages of exercise (20 Watt, 60 Watt, maximum performance). Findings Decreases in Symmetry Index were observed for average power output in Parkinson's patients as workload increased. Maximum power Symmetry Index showed a significant difference in symmetry between performance at both the 20 Watt and 60 Watt stage and the maximal resistance stage. Minimum power Symmetry Index did not show significant differences across the stages of the test. While lower extremity asymmetries were present in Parkinson's patients during pedaling, these asymmetries did not correlate to postural instability and gait dysfunction Unified Parkinson's Disease Rating Scale scores. Interpretation This pedaling analysis allows for a more sensitive measure of lower extremity function than the Unified Parkinson's Disease Rating Scale and may help to provide unique insight into current and

Analysis of blood-based gene expression in idiopathic Parkinson disease.

PubMed

Shamir, Ron; Klein, Christine; Amar, David; Vollstedt, Eva-Juliane; Bonin, Michael; Usenovic, Marija; Wong, Yvette C; Maver, Ales; Poths, Sven; Safer, Hershel; Corvol, Jean-Christophe; Lesage, Suzanne; Lavi, Ofer; Deuschl, Günther; Kuhlenbaeumer, Gregor; Pawlack, Heike; Ulitsky, Igor; Kasten, Meike; Riess, Olaf; Brice, Alexis; Peterlin, Borut; Krainc, Dimitri

2017-10-17

To examine whether gene expression analysis of a large-scale Parkinson disease (PD) patient cohort produces a robust blood-based PD gene signature compared to previous studies that have used relatively small cohorts (≤220 samples). Whole-blood gene expression profiles were collected from a total of 523 individuals. After preprocessing, the data contained 486 gene profiles (n = 205 PD, n = 233 controls, n = 48 other neurodegenerative diseases) that were partitioned into training, validation, and independent test cohorts to identify and validate a gene signature. Batch-effect reduction and cross-validation were performed to ensure signature reliability. Finally, functional and pathway enrichment analyses were applied to the signature to identify PD-associated gene networks. A gene signature of 100 probes that mapped to 87 genes, corresponding to 64 upregulated and 23 downregulated genes differentiating between patients with idiopathic PD and controls, was identified with the training cohort and successfully replicated in both an independent validation cohort (area under the curve [AUC] = 0.79, p = 7.13E-6) and a subsequent independent test cohort (AUC = 0.74, p = 4.2E-4). Network analysis of the signature revealed gene enrichment in pathways, including metabolism, oxidation, and ubiquitination/proteasomal activity, and misregulation of mitochondria-localized genes, including downregulation of COX4I1 , ATP5A1 , and VDAC3 . We present a large-scale study of PD gene expression profiling. This work identifies a reliable blood-based PD signature and highlights the importance of large-scale patient cohorts in developing potential PD biomarkers. © 2017 American Academy of Neurology.

Striatal and Hippocampal Atrophy in Idiopathic Parkinson's Disease Patients without Dementia: A Morphometric Analysis.

PubMed

Tanner, Jared J; McFarland, Nikolaus R; Price, Catherine C

2017-01-01

Analyses of subcortical gray structure volumes in non-demented idiopathic Parkinson's disease (PD) often, but not always, show volume loss of the putamen, caudate nucleus, nucleus accumbens, and hippocampus. There is building evidence that structure morphometry might be more sensitive to disease-related processes than volume. To assess morphometric differences of subcortical structures (putamen, caudate nucleus, thalamus, globus pallidus, nucleus accumbens, and amygdala) as well as the hippocampus in non-demented individuals with PD relative to age and education matched non-PD peers. Prospective recruitment of idiopathic no-dementia PD and non-PD peers as part of a federally funded investigation. T1-weighted isovoxel metrics acquired via 3-T Siemens Verio for all individuals [PD n  = 72 (left side onset n  = 27, right side onset n  = 45); non-PD n  = 48]. FIRST (FMRIB Software Library) applications provided volumetric and vertex analyses on group differences for structure size and morphometry. Group volume differences were observed only for putamen and hippocampi (PD < non-PD) with hippocampal volume significantly associating with disease duration. Group shape differences were observed for bilateral putamen, caudate nucleus, and hippocampus with greater striatal atrophy contralateral to side of motor symptom onset. Hippocampal shape differences disappeared when removing the effects of volume. The putamen was the primary structure to show both volume and shape differences in PD, indicating that the putamen is the predominant site of basal ganglia atrophy in early- to mid-stage PD. Side of PD symptom onset associates with contralateral striatal atrophy. Left-onset PD might experience more extensive striatal atrophy than right-onset PD. Hippocampus morphometric results suggest possible primary atrophy of CA3/4 and dentate gyrus.

Impaired Emotion Recognition in Music in Parkinson's Disease

ERIC Educational Resources Information Center

van Tricht, Mirjam J.; Smeding, Harriet M. M.; Speelman, Johannes D.; Schmand, Ben A.

2010-01-01

Music has the potential to evoke strong emotions and plays a significant role in the lives of many people. Music might therefore be an ideal medium to assess emotion recognition. We investigated emotion recognition in music in 20 patients with idiopathic Parkinson's disease (PD) and 20 matched healthy volunteers. The role of cognitive dysfunction…

Magnetic resonance spectroscopic study of parkinsonism related to boxing.

PubMed

Davie, C A; Pirtosek, Z; Barker, G J; Kingsley, D P; Miller, P H; Lees, A J

1995-06-01

Proton magnetic resonance spectroscopy, localised to the lentiform nucleus, was carried out in three ex-professional boxers who developed a parkinsonian syndrome, six patients with idiopathic Parkinson's disease, and six age matched controls. The three ex-boxers all showed a pronounced reduction in the absolute concentration of N-acetylaspartate compared with the patients with idiopathic Parkinson's disease and the control group. This reduction is likely to reflect neuronal loss occurring in the putamen and globus pallidus and supports the hypothesis that the extrapyramidal syndrome that may occur in ex-boxers is a distinct entity from idiopathic Parkinson's disease.

Magnetic resonance spectroscopic study of parkinsonism related to boxing.

PubMed Central

Davie, C A; Pirtosek, Z; Barker, G J; Kingsley, D P; Miller, P H; Lees, A J

1995-01-01

Proton magnetic resonance spectroscopy, localised to the lentiform nucleus, was carried out in three ex-professional boxers who developed a parkinsonian syndrome, six patients with idiopathic Parkinson's disease, and six age matched controls. The three ex-boxers all showed a pronounced reduction in the absolute concentration of N-acetylaspartate compared with the patients with idiopathic Parkinson's disease and the control group. This reduction is likely to reflect neuronal loss occurring in the putamen and globus pallidus and supports the hypothesis that the extrapyramidal syndrome that may occur in ex-boxers is a distinct entity from idiopathic Parkinson's disease. Images PMID:7608666

Parkinson's Disease

MedlinePlus

... Staying Safe Videos for Educators Search English Español Parkinson's Disease KidsHealth / For Kids / Parkinson's Disease What's in this ... symptoms of something called Parkinson's disease. What Is Parkinson's Disease? Parkinson's disease is a disorder of the central ...

The effect of LRRK2 mutations on the cholinergic system in manifest and premanifest stages of Parkinson's disease: a cross-sectional PET study.

PubMed

Liu, Shu-Ying; Wile, Daryl J; Fu, Jessie Fanglu; Valerio, Jason; Shahinfard, Elham; McCormick, Siobhan; Mabrouk, Rostom; Vafai, Nasim; McKenzie, Jess; Neilson, Nicole; Perez-Soriano, Alexandra; Arena, Julieta E; Cherkasova, Mariya; Chan, Piu; Zhang, Jing; Zabetian, Cyrus P; Aasly, Jan O; Wszolek, Zbigniew K; McKeown, Martin J; Adam, Michael J; Ruth, Thomas J; Schulzer, Michael; Sossi, Vesna; Stoessl, A Jon

2018-04-01

Markers of neuroinflammation are increased in some patients with LRRK2 Parkinson's disease compared with individuals with idiopathic Parkinson's disease, suggesting possible differences in disease pathogenesis. Previous PET studies have suggested amplified dopamine turnover and preserved serotonergic innervation in LRRK2 mutation carriers. We postulated that patients with LRRK2 mutations might show abnormalities of central cholinergic activity, even before the diagnosis of Parkinson's disease. Between June, 2009, and December, 2015, we recruited participants from four movement disorder clinics in Canada, Norway, and the USA. Patients with Parkinson's disease were diagnosed by movement disorder neurologists on the basis of the UK Parkinson's Disease Society Brain Bank criteria. LRRK2 carrier status was confirmed by bidirectional Sanger sequencing. We used the PET tracer N- 11 C-methyl-piperidin-4-yl propionate to scan for acetylcholinesterase activity. The primary outcome measure was rate of acetylcholinesterase hydrolysis, calculated using the striatal input method. We compared acetylcholinesterase hydrolysis rates between groups using ANCOVA, with adjustment for age based on the results of linear regression analysis. We recruited 14 patients with LRRK2 Parkinson's disease, 16 LRRK2 mutation carriers without Parkinson's disease, eight patients with idiopathic Parkinson's disease, and 11 healthy controls. We noted significant between-group differences in rates of acetylcholinesterase hydrolysis in cortical regions (average cortex p=0·009, default mode network-related regions p=0·006, limbic network-related regions p=0·020) and the thalamus (p=0·008). LRRK2 mutation carriers without Parkinson's disease had increased acetylcholinesterase hydrolysis rates compared with healthy controls in the cortex (average cortex, p=0·046). Patients with LRRK2 Parkinson's disease had significantly higher acetylcholinesterase activity in some cortical regions (average cortex p=0�

Structural and physiological neurovascular changes in idiopathic Parkinson's disease and its clinical phenotypes.

PubMed

Al-Bachari, Sarah; Vidyasagar, Rishma; Emsley, Hedley Ca; Parkes, Laura M

2017-10-01

Neurovascular changes are likely to interact importantly with the neurodegenerative process in idiopathic Parkinson's disease (IPD). Markers of neurovascular status (NVS) include white matter lesion (WML) burden and arterial spin labelling (ASL) measurements of cerebral blood flow (CBF) and arterial arrival time (AAT). We investigated NVS in IPD, including an analysis of IPD clinical phenotypes, by comparison with two control groups, one with a history of clinical cerebrovascular disease (CVD) (control positive, CP) and one without CVD (control negative, CN). Fifty-one patients with IPD (mean age 69.0 ± 7.7 years) (21 tremor dominant (TD), 24 postural instability and gait disorder (PIGD) and six intermediates), 18 CP (mean age 70.1 ± 8.0 years) and 34 CN subjects (mean age 67.4 ± 7.6 years) completed a 3T MRI scan protocol including T 2 -weighted fluid-attenuated inversion recovery (FLAIR) and ASL. IPD patients showed diffuse regions of significantly prolonged AAT, small regions of lower CBF and greater WML burden by comparison with CN subjects. TD patients showed lower WML volume by comparison with PIGD patients. These imaging data thus show altered NVS in IPD, with some evidence for IPD phenotype-specific differences.

Impact of specialist palliative care on coping with Parkinson's disease: patients and carers.

PubMed

Badger, Nathan J; Frizelle, Dorothy; Adams, Debi; Johnson, Miriam J

2018-06-01

UK guidelines recommend palliative care access for people with Parkinson's disease; however, this remains sporadic, and it is unknown whether specialist palliative care helps patients and carers cope with this distressing condition. This study aimed to explore whether, and how, access to specialist palliative care services affected patients' and carers' coping with Parkinson's disease. Semistructured interviews were conducted, audio-recorded and verbatim transcribed. Data were analysed using interpretative phenomenological analysis. Participants were patients with advanced idiopathic Parkinson's disease (n=3), and carers of people with Parkinson's disease (n=5, however, one diagnosis was reviewed) receiving care from an integrated specialist palliative care and Parkinson's disease service in North East England. Access to specialist palliative care helped participants cope with some aspects of advanced Parkinson's disease. Three superordinate themes were developed:' managing uncertainty', 'impacts on the self' and 'specialist palliative care maintaining a positive outlook'. Specialist palliative care helped patients and carers cope with advanced Parkinson's disease. Specialist palliative care is a complex intervention that acknowledges the complex and holistic nature of Parkinson's disease, enabling health in some domains despite continued presence of pathology. These exploratory findings support the utility of this approach for people living with Parkinson's disease. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Constipation and paradoxical puborectalis contraction in anismus and Parkinson's disease: a dystonic phenomenon?

PubMed

Mathers, S E; Kempster, P A; Swash, M; Lees, A J

1988-12-01

Anismus, or constipation due to functional obstruction at the pelvic outlet by paradoxical contraction of the striated sphincter muscles during defaecation straining, is described in ten constipated patients and four patients with Parkinson's disease and constipation. The dysfunctional pattern of muscle recruitment resembled that characteristic of dystonia elsewhere in the body and was indistinguishable in patients with idiopathic anismus and those with extrapyramidal motor disturbance due to Parkinson's disease. These findings suggest that anismus may be a focal dystonic phenomenon.

Constipation and paradoxical puborectalis contraction in anismus and Parkinson's disease: a dystonic phenomenon?

PubMed Central

Mathers, S E; Kempster, P A; Swash, M; Lees, A J

1988-01-01

Anismus, or constipation due to functional obstruction at the pelvic outlet by paradoxical contraction of the striated sphincter muscles during defaecation straining, is described in ten constipated patients and four patients with Parkinson's disease and constipation. The dysfunctional pattern of muscle recruitment resembled that characteristic of dystonia elsewhere in the body and was indistinguishable in patients with idiopathic anismus and those with extrapyramidal motor disturbance due to Parkinson's disease. These findings suggest that anismus may be a focal dystonic phenomenon. PMID:3221217

[REM sleep behavior disorders in Parkinson's disease].

PubMed

Liashenko, E A; Poluéktov, M G; Levin, O S

2014-01-01

The article presents a literature review on REM sleep behavior disorder (RBD). The loss of REM atonia of sleep, such that patients act out the contents of their dreams, is described. The most important implication of research into this area is that patients with idiopathic RBD are at very high risk of developing synuclein-mediated neurodegenerative disease (Parkinson's disease, dementia with Lewy bodies and multiple system atrophy), with risk estimates that approximate 40-65% at 10 years. Thus, RBD is a reliable marker of prodromal synucleinopathy that open possibilities for neuroprotective therapy.

Variability in Fundamental Frequency during Speech in Prodromal and Incipient Parkinson's Disease: A Longitudinal Case Study

ERIC Educational Resources Information Center

Harel, Brian; Cannizzaro, Michael; Snyder, Peter J.

2004-01-01

Nearly two centuries ago, Parkinson (1817) first observed that a particular pattern of speech changes occur in patients with idiopathic Parkinson's disease (PD). Numerous studies have documented these changes using a wide variety of acoustic measures, and yet few studies have attempted to quantify any such changes longitudinally, through the early…

Nonmotor symptoms in a malaysian Parkinson's disease population.

PubMed

Azmin, Shahrul; Khairul Anuar, Abdul Manaf; Tan, Hui Jan; Nafisah, Wan Yahya; Raymond, Azman Ali; Hanita, Othman; Shah, Shamsul Azhar; Norlinah, Mohamed Ibrahim

2014-01-01

Background. The nonmotor symptoms are important determinants of health and quality of life in Parkinson's disease but are not well recognized and addressed in clinical practice. This study was conducted to determine the prevalence of nonmotor symptoms and their impact on quality of life in patients with Parkinson's disease. Methods. This was a cross-sectional study among patients with idiopathic Parkinson's disease. Exclusion criteria were a Mini Mental State Examination score of <21/30. Prevalence of nonmotor symptoms was determined using the NMSQuest. The severity of nonmotor symptoms and the quality of life were assessed using validated disease-specific questionnaires (PDQ-39 and NMSS). Results. A total of 113 patients consisting of 60 males and 53 females were recruited. The median duration of illness was 5.0 (2.0-8.0) years. The prevalence rate of nonmotor symptoms in our cohort was 97.3%. The most common reported nonmotor symptom in our cohort was gastrointestinal (76.1%). We found that the severity of the nonmotor symptoms was associated with poorer quality of life scores (r s : 0.727, P < 0.001). Conclusions. Nonmotor symptoms were highly prevalent in our patients with Parkinson's disease and adversely affected the quality of life of our patients. In contrast to western studies, the most common nonmotor symptom is gastrointestinal. The possibility of an Asian diet playing a role in this observation requires further study.

Arterial spin labelling reveals prolonged arterial arrival time in idiopathic Parkinson's disease.

PubMed

Al-Bachari, Sarah; Parkes, Laura M; Vidyasagar, Rishma; Hanby, Martha F; Tharaken, Vivek; Leroi, Iracema; Emsley, Hedley C A

2014-01-01

Idiopathic Parkinson's disease (IPD) is the second most common neurodegenerative disease, yet effective disease modifying treatments are still lacking. Neurodegeneration involves multiple interacting pathological pathways. The extent to which neurovascular mechanisms are involved is not well defined in IPD. We aimed to determine whether novel magnetic resonance imaging (MRI) techniques, including arterial spin labelling (ASL) quantification of cerebral perfusion, can reveal altered neurovascular status (NVS) in IPD. Fourteen participants with IPD (mean ± SD age 65.1 ± 5.9 years) and 14 age and cardiovascular risk factor matched control participants (mean ± SD age 64.6 ± 4.2 years) underwent a 3T MRI scan protocol. ASL images were collected before, during and after a 6 minute hypercapnic challenge. FLAIR images were used to determine white matter lesion score. Quantitative images of cerebral blood flow (CBF) and arterial arrival time (AAT) were calculated from the ASL data both at rest and during hypercapnia. Cerebrovascular reactivity (CVR) images were calculated, depicting the change in CBF and AAT relative to the change in end-tidal CO2. A significant (p = 0.005) increase in whole brain averaged baseline AAT was observed in IPD participants (mean ± SD age 1532 ± 138 ms) compared to controls (mean ± SD age 1335 ± 165 ms). Voxel-wise analysis revealed this to be widespread across the brain. However, there were no statistically significant differences in white matter lesion score, CBF, or CVR between patients and controls. Regional CBF, but not AAT, in the IPD group was found to correlate positively with Montreal cognitive assessment (MoCA) scores. These findings provide further evidence of alterations in NVS in IPD.

Safety and efficacy of rasagiline in addition to levodopa for the treatment of idiopathic Parkinson's disease: a meta-analysis of randomised controlled trials.

PubMed

Cai, Jiang-Ping; Chen, Wan-Jin; Lin, Yu; Cai, Bin; Wang, Ning

2015-01-01

To assess the safety and efficacy of rasagiline for the treatment of Parkinson's disease (PD) among individuals currently receiving levodopa. A systematic literature search was conducted to identify randomised controlled trials (RCT) comparing rasagiline with placebo/no treatment in individuals with PD currently receiving levodopa. Outcome measures included improvement in motor functions; symptomatic improvement; improvement in quality of life; adverse effects. Random-effect meta-analytical techniques were conducted for the outcome measure and subgroup analyses. Three RCTs were included (n = 1002). The results showed significantly greater improvements in daily 'on' time without dyskinesia in levodopa-treated participants with idiopathic PD receiving 1 mg/day rasagiline compared to placebo (n = 712, 2 RCTs, MD 0.80, CI 0.45 to 1.15; p < 0.00001), and significantly greater improvements in Unified Parkinson's Disease Rating Scale motor performance scores during 'on' time in participants receiving 0.5-1 mg/day rasagiline (0.5 mg/day: n = 282, MD -2.91, CI -4.59 to -1.23; p = 0.0007; 1 mg/day: n = 712, 2 RCTs, MD -2.91, CI -4.02 to -1.80; p < 0.00001). There were no significant differences in adverse effects. 0.5 to 1 mg/day rasagiline in addition to levodopa is a safe and well-tolerated combination therapy for individuals with Parkinson's disease.

Quantitative Susceptibility Mapping in Parkinson's Disease.

PubMed

Langkammer, Christian; Pirpamer, Lukas; Seiler, Stephan; Deistung, Andreas; Schweser, Ferdinand; Franthal, Sebastian; Homayoon, Nina; Katschnig-Winter, Petra; Koegl-Wallner, Mariella; Pendl, Tamara; Stoegerer, Eva Maria; Wenzel, Karoline; Fazekas, Franz; Ropele, Stefan; Reichenbach, Jürgen Rainer; Schmidt, Reinhold; Schwingenschuh, Petra

2016-01-01

Quantitative susceptibility mapping (QSM) and R2* relaxation rate mapping have demonstrated increased iron deposition in the substantia nigra of patients with idiopathic Parkinson's disease (PD). However, the findings in other subcortical deep gray matter nuclei are converse and the sensitivity of QSM and R2* for morphological changes and their relation to clinical measures of disease severity has so far been investigated only sparsely. The local ethics committee approved this study and all subjects gave written informed consent. 66 patients with idiopathic Parkinson's disease and 58 control subjects underwent quantitative MRI at 3T. Susceptibility and R2* maps were reconstructed from a spoiled multi-echo 3D gradient echo sequence. Mean susceptibilities and R2* rates were measured in subcortical deep gray matter nuclei and compared between patients with PD and controls as well as related to clinical variables. Compared to control subjects, patients with PD had increased R2* values in the substantia nigra. QSM also showed higher susceptibilities in patients with PD in substantia nigra, in the nucleus ruber, thalamus, and globus pallidus. Magnetic susceptibility of several of these structures was correlated with the levodopa-equivalent daily dose (LEDD) and clinical markers of motor and non-motor disease severity (total MDS-UPDRS, MDS-UPDRS-I and II). Disease severity as assessed by the Hoehn & Yahr scale was correlated with magnetic susceptibility in the substantia nigra. The established finding of higher R2* rates in the substantia nigra was extended by QSM showing superior sensitivity for PD-related tissue changes in nigrostriatal dopaminergic pathways. QSM additionally reflected the levodopa-dosage and disease severity. These results suggest a more widespread pathologic involvement and QSM as a novel means for its investigation, more sensitive than current MRI techniques.

The Relationship between Speech Production and Speech Perception Deficits in Parkinson's Disease

ERIC Educational Resources Information Center

De Keyser, Kim; Santens, Patrick; Bockstael, Annelies; Botteldooren, Dick; Talsma, Durk; De Vos, Stefanie; Van Cauwenberghe, Mieke; Verheugen, Femke; Corthals, Paul; De Letter, Miet

2016-01-01

Purpose: This study investigated the possible relationship between hypokinetic speech production and speech intensity perception in patients with Parkinson's disease (PD). Method: Participants included 14 patients with idiopathic PD and 14 matched healthy controls (HCs) with normal hearing and cognition. First, speech production was objectified…

Beta-blocker therapy for tremor in Parkinson's disease.

PubMed

Crosby, N J; Deane, K H O; Clarke, C E

2003-01-01

The tremor of Parkinson's disease can cause considerable disability for the individual concerned. Traditional antiparkinsonian therapies such as levodopa have only a minor effect on tremor. Beta-blockers are used to attenuate other forms of tremor such as Essential Tremor or the tremor associated with anxiety. It is thought that beta-blockers may be of use in controlling the tremor of Parkinson's disease. To compare the efficacy and safety of adjuvant beta-blocker therapy against placebo for the treatment of tremor in patients with Parkinson's disease. Electronic searches of MEDLINE, EMBASE, SCISEARCH, BIOSIS, GEROLIT, OLDMEDLINE, LILACS, MedCarib, PASCAL, JICST-EPLUS, RUSSMED, DISSERTATION ABSTRACTS, SIGLE, ISI-ISTP, Aslib Index to Theses, The Cochrane Controlled Trials Register, Clinicaltrials.gov, metaRegister of Controlled Trials, NIDRR, NRR and CENTRAL were conducted. Grey literature was hand searched and the reference lists of identified studies and reviews examined. The manufacturers of beta-blockers were contacted. Randomised controlled trials of adjuvant beta-blocker therapy versus placebo in patients with a clinical diagnosis of idiopathic Parkinson's disease. Data was abstracted independently by two of the authors onto standardised forms and disagreements were resolved by discussion. Four randomised controlled trials were found comparing beta-blocker therapy with placebo in patients with idiopathic Parkinson's disease. These were double-blind cross-over studies involving a total of 72 patients. Three studies did not present data from the first arm, instead presenting results as combined data from both treatment arms and both placebo arms. The risk of a carry-over effect into the second arm meant that these results were not analysed. The fourth study presented data from each arm. This was in the form of a mean total score for tremor for each group. Details of the baseline scores, the numbers of patients in each group and standard deviations were not

On the role of endogenous neurotoxins and neuroprotection in Parkinson's disease.

PubMed

Segura-Aguilar, Juan

2017-06-01

For 50 years ago was introduced L-3,4-dihydroxyphenylalanine (L-dopa) in Parkinson's disease treatment and during this significant advances has been done but what trigger the degeneration of the nigrostriatal system remain unknown. There is a general agreement in the scientific community that mitochondrial dysfunction, protein degradation dysfunction, alpha-synuclein aggregation to neurotoxic oligomers, neuroinflammation, oxidative and endoplasmic reticulum stress are involved in the loss of dopaminergic neurons containing neuromelanin in Parkinson's disease. The question is what triggers these mechanisms. The age of normal onset in idiopathic Parkinson's disease suggests that environmental factors such as metals, pollutants or genetic mutations cannot be involved because these factors are related to early onset of Parkinsonism. Therefore, we have to search for endogenous neurotoxins and neuroprotection in order to understand what trigger the loss of dopaminergic neurons. One important feature of Parkinson's disease is the rate of the degenerative process before the motor symptoms are evident and during the disease progression. The extremely slow rate of Parkinson's disease suggests that the neurotoxins and the neuroprotection have to be related to dopamine metabolism. Possible candidates for endogenous neurotoxins are alpha-synuclein neurotoxic oligomers, 4-dihydroxyphenylacetaldehyde and ortho-quinones formed during dopamine oxidation to neuromelanin. Vesicular monoamine transporter-2, DT-diaphorase and glutathione transferase M2-2 seems to be the most important neuroprotective mechanism to prevent neurotoxic mechanism during dopamine oxidation.

[Inferior frontal region hypoperfusion in Parkinson disease with dementia].

PubMed

Ochudło, Stanisław; Opala, Grzegorz; Jasińska-Myga, Barbara; Siuda, Joanna; Nowak, Stanisław

2003-01-01

Dementia is more frequent in patients suffering from Parkinson's disease (PD) then in general population. The mechanism for mental deterioration in PD remains controversial. The aim of our study was comparison of the regional cerebral perfusion quantified by single photon emission computed tomography in patients suffering from idiopathic Parkinson's disease with and without dementia. We examined 49 PD patients: 22 PD patients with dementia and 27 PD patients without dementia. Dementia was recognized according to ICD-10 and DSM-IV criteria. Cognitive functions were executed by means of the Mini Mental State Examination (MMSE) and neuropsychological assessment. The Unified Parkinson's Disease Rating Scale (UPDRS) and Modified Hoehn & Yahr Scale was used to quantify the severity of PD. SPECT was performed with Siemens Diacam single--head rotating gamma camera after intravenous application of technetium 99m hexamethylpropylene amine oxime (99mTc-HMPAO). The perfusion values were expressed as cortical or basal ganglia regions of interest (ROIs)/cerebellum activity ratios. In both examined group of patients the lowest uptake was in basal ganglia region, while the highest uptake was in occipital region. In the subgroup of PD patients with dementia significant hypoperfusion affecting the inferior frontal cortices was observed. In Parkinson's disease with dementia hypoperfusion in inferior frontal region can be found.

Large-scale assessment of polyglutamine repeat expansions in Parkinson disease

PubMed Central

Wang, Lisa; Aasly, Jan O.; Annesi, Grazia; Bardien, Soraya; Bozi, Maria; Brice, Alexis; Carr, Jonathan; Chung, Sun J.; Clarke, Carl; Crosiers, David; Deutschländer, Angela; Eckstein, Gertrud; Farrer, Matthew J.; Goldwurm, Stefano; Garraux, Gaetan; Hadjigeorgiou, Georgios M.; Hicks, Andrew A.; Hattori, Nobutaka; Klein, Christine; Jeon, Beom; Kim, Yun J.; Lesage, Suzanne; Lin, Juei-Jueng; Lynch, Timothy; Lichtner, Peter; Lang, Anthony E.; Mok, Vincent; Jasinska-Myga, Barbara; Mellick, George D.; Morrison, Karen E.; Opala, Grzegorz; Pihlstrøm, Lasse; Pramstaller, Peter P.; Park, Sung S.; Quattrone, Aldo; Rogaeva, Ekaterina; Ross, Owen A.; Stefanis, Leonidas; Stockton, Joanne D.; Silburn, Peter A.; Theuns, Jessie; Tan, Eng K.; Tomiyama, Hiroyuki; Toft, Mathias; Van Broeckhoven, Christine; Uitti, Ryan J.; Wirdefeldt, Karin; Wszolek, Zbigniew; Xiromerisiou, Georgia; Yueh, Kuo-Chu; Zhao, Yi; Gasser, Thomas; Maraganore, Demetrius M.; Krüger, Rejko

2015-01-01

Objectives: We aim to clarify the pathogenic role of intermediate size repeat expansions of SCA2, SCA3, SCA6, and SCA17 as risk factors for idiopathic Parkinson disease (PD). Methods: We invited researchers from the Genetic Epidemiology of Parkinson's Disease Consortium to participate in the study. There were 12,346 cases and 8,164 controls genotyped, for a total of 4 repeats within the SCA2, SCA3, SCA6, and SCA17 genes. Fixed- and random-effects models were used to estimate the summary risk estimates for the genes. We investigated between-study heterogeneity and heterogeneity between different ethnic populations. Results: We did not observe any definite pathogenic repeat expansions for SCA2, SCA3, SCA6, and SCA17 genes in patients with idiopathic PD from Caucasian and Asian populations. Furthermore, overall analysis did not reveal any significant association between intermediate repeats and PD. The effect estimates (odds ratio) ranged from 0.93 to 1.01 in the overall cohort for the SCA2, SCA3, SCA6, and SCA17 loci. Conclusions: Our study did not support a major role for definite pathogenic repeat expansions in SCA2, SCA3, SCA6, and SCA17 genes for idiopathic PD. Thus, results of this large study do not support diagnostic screening of SCA2, SCA3, SCA6, and SCA17 gene repeats in the common idiopathic form of PD. Likewise, this largest multicentered study performed to date excludes the role of intermediate repeats of these genes as a risk factor for PD. PMID:26354989

Acupuncture as Adjuvant Therapy for Sleep Disorders in Parkinson's Disease.

PubMed

Aroxa, Fábio Henrique de Amorim; Gondim, Ihana Thaís Guerra de Oliveira; Santos, Elba Lúcia Wanderley; Coriolano, Maria das Graças Wanderley de Sales; Asano, Amdore Guescel C; Asano, Nadja Maria Jorge

2017-01-01

There are few studies which attest the efficacy of acupuncture on treatment of sleep disturbs in Parkinson disease. The aimed of this randomized clinical trial was to evaluate the effects of acupuncture on sleep disturbs of 22 patients with diagnosis of idiopathic Parkinson disease (Hoehn-Yahr 1 to 3) who have assistance on the Pro-Parkinson Program of Clinical Hospital at Federal University of Pernambuco in Brazil. All participants were evaluated by Parkinson Disease Sleep Scale (PDSS) before and after 8 weeks. The experimental group was submitted to 8 sections (once a week) which had duration of 30 minutes. The control group had no intervention. The intervention was executed using the acupuncture points LR3 (Taichong), SP6 (Sanyinjiao), LI4 (Hegu), TE5 (Wai-Guan), HT7 (Shenmen), PC6 (Neiguan), LI11 (Quchi), GB20 (Fengchi). Paired analyses were obtained by Wilcoxon test and independent analyses were made according to Mann-Whitney test. This study presented a potential therapeutic benefit of acupuncture on sleep disturbs of Parkinson's disease patients. This study showed a possible therapeutic benefit through acupuncture in sleep disorders in patients with PD. However, we propose new studies related to the effects of acupuncture on the clinical symptoms and evolution of the disease. Copyright © 2017 Medical Association of Pharmacopuncture Institute. Published by Elsevier B.V. All rights reserved.

Temporal Lobe and Frontal-Subcortical Dissociations in Non-Demented Parkinson's Disease with Verbal Memory Impairment.

PubMed

Tanner, Jared J; Mareci, Thomas H; Okun, Michael S; Bowers, Dawn; Libon, David J; Price, Catherine C

2015-01-01

The current investigation examined verbal memory in idiopathic non-dementia Parkinson's disease and the significance of the left entorhinal cortex and left entorhinal-retrosplenial region connections (via temporal cingulum) on memory impairment in Parkinson's disease. Forty non-demented Parkinson's disease patients and forty non-Parkinson's disease controls completed two verbal memory tests--a wordlist measure (Philadelphia repeatable Verbal Memory Test) and a story measure (Logical Memory). All participants received T1-weighted and diffusion magnetic resonance imaging (3T; Siemens) sequences. Left entorhinal volume and left entorhinal-retrosplenial connectivity (temporal cingulum edge weight) were the primary imaging variables of interest with frontal lobe thickness and subcortical structure volumes as dissociating variables. Individuals with Parkinson's disease showed worse verbal memory, smaller entorhinal volumes, but did not differ in entorhinal-retrosplenial connectivity. For Parkinson's disease entorhinal-retrosplenial edge weight had the strongest associations with verbal memory. A subset of Parkinson's disease patients (23%) had deficits (z-scores < -1.5) across both memory measures. Relative to non-impaired Parkinson's peers, this memory-impaired group had smaller entorhinal volumes. Although entorhinal cortex volume was significantly reduced in Parkinson's disease patients relative to non-Parkinson's peers, only white matter connections associated with the entorhinal cortex were significantly associated with verbal memory performance in our sample. There was also no suggestion of contribution from frontal-subcortical gray or frontal white matter regions. These findings argue for additional investigation into medial temporal lobe gray and white matter connectivity for understanding memory in Parkinson's disease.

Sensory neuropathic symptoms in idiopathic Parkinson's disease: prevalence and impact on quality of life.

PubMed

Adewusi, Joy K; Hadjivassiliou, Marios; Vinagre-Aragón, Ana; O'Connor, Karen Ruth; Khan, Aijaz; Grünewald, Richard Adam; Zis, Panagiotis

2018-05-23

Neuropathic symptoms are commonly reported in Parkinson's disease (PD), but robust data on the epidemiology of such symptoms are lacking. The present study sought to investigate the prevalence and determinants of peripheral sensory neuropathic symptoms (PSNS) in idiopathic PD (IPD) and ascertain the effects of such symptoms on the patients' quality of life (QoL). Patients with IPD and age-matched and gender-matched controls were screened for neuropathic symptoms using the Michigan Neuropathy Screening Instrument. The impact of neuropathic symptoms on QoL was investigated using the 36-Item Short Form Survey. Fifty-two patients and 52 age-matched and gender-matched controls were recruited. PSNS were reported more frequently in patients with IPD than in the control subjects (57.7 versus 28.8%, p = 0.003). No significant relationships were found between PD-related clinical characteristics (i.e. disease severity and duration, duration of exposure to levodopa) and the presence of PSNS. Significant correlations were found between the number of PSNS and physical functioning (Spearman's Rho - 0.351), even after adjusting for age, gender and Hoehn and Yahr score. Our results support the notion of a greater prevalence of PSNS in IPD patients as compared to the general population, which, at least in part, may be secondary to large and/or small fibre peripheral neuropathy. This warrants further investigation in larger studies that include detailed neurophysiological assessments.

Glucocerebrosidase Mutations in Parkinson Disease.

PubMed

O'Regan, Grace; deSouza, Ruth-Mary; Balestrino, Roberta; Schapira, Anthony H

2017-01-01

Following the discovery of a higher than expected incidence of Parkinson Disease (PD) in Gaucher disease, a lysosomal storage disorder, mutations in the glucocerebrocidase (GBA) gene, which encodes a lysosomal enzyme involved in sphingolipid degradation were explored in the context of idiopathic PD. GBA mutations are now known to be the single largest risk factor for development of idiopathic PD. Clinically, on imaging and pharmacologically, GBA PD is almost identical to idiopathic PD, other than certain features that can be identified in the specialist research setting but not in routine clinical practice. In patients with a known GBA mutation, it is possible to monitor for prodromal signs of PD. The clinical similarity with idiopathic PD and the chance to identify PD at a pre-clinical stage provides a unique opportunity to research therapeutic options for early PD, before major irreversible neurodegeneration occurs. However, to date, the molecular mechanisms which lead to this increased PD risk in GBA mutation carriers are not fully elucidated. Experimental models to define the molecular mechanisms and test therapeutic options include cell culture, transgenic mice and other in vivo models amenable to genetic manipulation, such as drosophilia. Some key pathological pathways of interest in the context of GBA mutations include alpha synuclein aggregation, lysosomal-autophagy axis changes and endoplasmic reticulum stress. Therapeutic agents that exploit these pathways are being developed and include the small molecule chaperone Ambroxol. This review aims to summarise the main features of GBA-PD and provide insights into the pathological relevance of GBA mutations on molecular pathways and the therapeutic implications for PD resulting from investigation of the role of GBA in PD.

Voice- and swallow-related quality of life in idiopathic Parkinson's disease.

PubMed

van Hooren, Michel R A; Baijens, Laura W J; Vos, Rein; Pilz, Walmari; Kuijpers, Laura M F; Kremer, Bernd; Michou, Emilia

2016-02-01

This study explores whether changes in voice- and swallow-related QoL are associated with progression of idiopathic Parkinson's disease (IPD). Furthermore, it examines the relationship between patients' perception of both voice and swallowing disorders in IPD. Prospective clinical study, quality of life (QoL). One-hundred mentally competent IPD patients with voice and swallowing complaints were asked to answer four QoL questionnaires (Voice Handicap Index, MD Anderson Dysphagia Inventory, Visual Analog Scale [VAS] voice, and Dysphagia Severity Scale [DSS]). Differences in means for the QoL questionnaires and their subscales within Hoehn and Yahr stage groups were calculated using one-way analysis of variance. The relationship between voice- and swallow-related QoL questionnaires was determined with the Spearman correlation coefficient. Scores on both voice and swallow questionnaires suggest an overall decrease in QoL with progression of IPD. A plateau in QoL for VAS voice and the DSS was seen in the early Hoehn and Yahr stages. Finally, scores on voice-related QoL questionnaires were significantly correlated with swallow-related QoL outcomes. Voice- and swallow-related QoL decreases with progression of IPD. A significant association was found between voice- and swallow-related QoL questionnaires. Healthcare professionals can benefit from voice- and swallow-related QoL questionnaires in a multidimensional voice- or swallow-assessment protocol. The patient's perception of his/her voice and swallowing disorders and its impact on QoL in IPD should not be disregarded. 2b. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

Mitochondrial dysfunctions in Parkinson's disease.

PubMed

Gautier, C A; Corti, O; Brice, A

2014-05-01

Neurodegenerative disorders (ND) include a wide spectrum of diseases characterized by progressive neuronal dysfunctions or degeneration. With an estimated cost of 135 billion € in 2010 in the European Union (Olesen et al., 2012), they put an enormous economic as well as social burden on modern societies. Hence, they have been the subject of a huge amount of research for the last fifty years. For many of these diseases, our understanding of their profound causes is incomplete and this hinders the discovery of efficient therapies. ND form a highly heterogeneous group of diseases affecting various neuronal subpopulations reflecting different origins and different pathological mechanisms. However, some common themes in the physiopathology of these disorders are emerging. There is growing evidence that mitochondrial dysfunctions play a pivotal role at some point in the course of neurodegeneration. In some cases (e.g. Alzheimer's disease, amyotrophic lateral sclerosis), impairment of mitochondrial functions probably occurs late in the course of the disease. In a subset of ND, current evidence suggests that mitochondrial dysfunctions play a more seminal role in neuronal demise. Parkinson's disease (PD) presents one of the strongest cases based in part on post-mortem studies that have shown mitochondrial impairment (e.g. reduced complex I activity) and oxidative damage in idiopathic PD brains. The occurrence of PD is largely sporadic, but clinical syndromes resembling sporadic PD have been linked to specific environmental insults or to mutations in at least 5 distinct genes (α-synuclein, parkin, DJ-1, PINK1 and LRRK2). It is postulated that the elucidation of the pathogenic mechanisms underlying the selective dopaminergic degeneration in familial and environmental Parkinsonism should provide important clues to the pathogenic mechanisms responsible for idiopathic PD. Hence, numerous cellular and animal models of the disease have been generated that mimic these

White matter lesions in Parkinson disease

PubMed Central

Bohnen, Nicolaas I.; Albin, Roger L.

2013-01-01

Pure vascular parkinsonism without evidence of nigral Lewy body pathology may occur as a distinct clinicopathological entity, but a much more frequent occurrence is the comorbid presence of age-associated white matter lesions (WMLs) in idiopathic Parkinson disease (PD). WMLs are associated with motor and cognitive symptoms in otherwise normal elderly individuals. Comorbid WMLs are, therefore, expected to contribute to clinical symptoms in PD. Studies of WMLs in PD differ with regard to methods of assessment of WML burden and the patient populations selected for analysis, but converging evidence suggests that postural stability and gait motor functions are predominantly affected. WMLs are described to contribute to dementia in Alzheimer disease, and emerging but inconclusive evidence indicates similar effects in PD. In this article, we review the literature addressing the occurrence and impact of WMLs in PD, and suggest that WMLs may exacerbate or contribute to some motor and cognitive deficits associated with PD. We review existing and emerging methods for studying white matter pathology in vivo, and propose future research directions. PMID:21343896

Parallel appearance of compulsive behaviors and artistic creativity in Parkinson's disease.

PubMed

Joutsa, Juho; Martikainen, Kirsti; Kaasinen, Valtteri

2012-01-01

A 55-year-old male with idiopathic Parkinson's disease developed three behavioral changes under combination therapy with selegiline, cabergoline and levodopa. Co-existent behaviors included severe pathological gambling, punding and novel skills in writing poetry (published poetry books). Brain [(18)F]fluorodopa PET imaging showed decreased tracer uptake in the striatum contralateral to the predominant motor symptoms, consistent with the clinical diagnosis of Parkinson's disease. Uptake in the ventral striatum was markedly high. Brain MRI before and after behavioral changes showed no pathological findings. The patient was diagnosed as having Parkinson's disease together with DSM-IV criteria-fulfilling pathological gambling and punding-like stereotyped behavior. There are no established criteria for the classification of emerged artistic creativity, although there are descriptions of the phenomenon in the literature. Inspired by the case, we conducted a preliminary survey - including 290 patients with Parkinson's disease - exploring the possible relationship between creativity and impulsive-compulsive behaviors. The case, supported by the results of the survey, adds to the cumulative evidence of the association between dopaminergic medication and enhanced creativity, and suggests a possible linkage between increased artistic creativity and impulsive-compulsive behaviors in Parkinson's disease. Furthermore, it could be speculated that the high mesolimbic dopamine function might relate to the behavioral changes observed in this patient, and is suggestive of the overlapping neurobiological mechanisms of compulsive behaviors and artistic creativity.

Parallel Appearance of Compulsive Behaviors and Artistic Creativity in Parkinson's Disease

PubMed Central

Joutsa, Juho; Martikainen, Kirsti; Kaasinen, Valtteri

2012-01-01

A 55-year-old male with idiopathic Parkinson's disease developed three behavioral changes under combination therapy with selegiline, cabergoline and levodopa. Co-existent behaviors included severe pathological gambling, punding and novel skills in writing poetry (published poetry books). Brain [18F]fluorodopa PET imaging showed decreased tracer uptake in the striatum contralateral to the predominant motor symptoms, consistent with the clinical diagnosis of Parkinson's disease. Uptake in the ventral striatum was markedly high. Brain MRI before and after behavioral changes showed no pathological findings. The patient was diagnosed as having Parkinson's disease together with DSM-IV criteria-fulfilling pathological gambling and punding-like stereotyped behavior. There are no established criteria for the classification of emerged artistic creativity, although there are descriptions of the phenomenon in the literature. Inspired by the case, we conducted a preliminary survey – including 290 patients with Parkinson's disease – exploring the possible relationship between creativity and impulsive-compulsive behaviors. The case, supported by the results of the survey, adds to the cumulative evidence of the association between dopaminergic medication and enhanced creativity, and suggests a possible linkage between increased artistic creativity and impulsive-compulsive behaviors in Parkinson's disease. Furthermore, it could be speculated that the high mesolimbic dopamine function might relate to the behavioral changes observed in this patient, and is suggestive of the overlapping neurobiological mechanisms of compulsive behaviors and artistic creativity. PMID:22679432

Toxin Models of Mitochondrial Dysfunction in Parkinson's Disease

PubMed Central

Martinez, Terina N.

2012-01-01

Abstract Significance: Parkinson's disease (PD) is a neurodegenerative disorder characterized, in part, by the progressive and selective loss of dopaminergic neuron cell bodies within the substantia nigra pars compacta (SNpc) and the associated deficiency of the neurotransmitter dopamine (DA) in the striatum, which gives rise to the typical motor symptoms of PD. The mechanisms that contribute to the induction and progressive cell death of dopaminergic neurons in PD are multi-faceted and remain incompletely understood. Data from epidemiological studies in humans and molecular studies in genetic, as well as toxin-induced animal models of parkinsonism, indicate that mitochondrial dysfunction occurs early in the pathogenesis of both familial and idiopathic PD. In this review, we provide an overview of toxin models of mitochondrial dysfunction in experimental Parkinson's disease and discuss mitochondrial mechanisms of neurotoxicity. Recent Advances: A new toxin model using the mitochondrial toxin trichloroethylene was recently described and novel methods, such as intranasal exposure to toxins, have been explored. Additionally, recent research conducted in toxin models of parkinsonism provides an emerging emphasis on extranigral aspects of PD pathology. Critical Issues: Unfortunately, none of the existing animal models of experimental PD completely mimics the etiology, progression, and pathology of human PD. Future Directions: Continued efforts to optimize established animal models of parkinsonism, as well as the development and characterization of new animal models are essential, as there still remains a disconnect in terms of translating mechanistic observations in animal models of experimental PD into bona fide disease-modifying therapeutics for human PD patients. Antioxid. Redox Signal. 16, 920–934. PMID:21554057

Motor assessment in Parkinson`s disease.

PubMed

Opara, Józef; Małecki, Andrzej; Małecka, Elżbieta; Socha, Teresa

2017-09-21

Parkinson's disease (PD) is one of most disabling disorders of the central nervous system. The motor symptoms of Parkinson's disease: shaking, rigidity, slowness of movement, postural instability and difficulty with walking and gait, are difficult to measure. When disease symptoms become more pronounced, the patient experiences difficulties with hand function and walking, and is prone to falls. Baseline motor impairment and cognitive impairment are probable predictors of more rapid motor decline and disability. An additional difficulty is the variability of the symptoms caused by adverse effects of drugs, especially levodopa. Motor assessment of Parkinson`s Disease can be divided into clinimetrics, assessment of balance and posture, arm and hand function, and gait/walking. These are many clinimetric scales used in Parkinson`s Disease, the most popular being the Hoehn and Yahr stages of progression of the disease and Unified Parkinson's Disease Rating Scale. Balance and posture can be assessed by clinimetric scales like the Berg BS, Tinetti, Brunel BA, and Timed Up and Go Test, or measured by posturometric platforms. Among skill tests, the best known are: the Purdue Pegboard Test, Nine-Hole Peg Test, Jebsen and Taylor test, Pig- Tail Test, Frenchay Arm Test, Action Research Arm Test, Wolf FMT and Finger-Tapping Test. Among motricity scales, the most popular are: the Fugl-Meyer Motor Assessment Scale and Södring Motor Evaluation. Gait and walking can also be assessed quantitatively and qualitatively. Recently, the most popular is three-dimensional analysis of movement. This review article presents the current possibilities of motor assessment in Parkinson`s disease.

Visual short-term memory deficits in REM sleep behaviour disorder mirror those in Parkinson's disease.

PubMed

Rolinski, Michal; Zokaei, Nahid; Baig, Fahd; Giehl, Kathrin; Quinnell, Timothy; Zaiwalla, Zenobia; Mackay, Clare E; Husain, Masud; Hu, Michele T M

2016-01-01

Individuals with REM sleep behaviour disorder are at significantly higher risk of developing Parkinson's disease. Here we examined visual short-term memory deficits--long associated with Parkinson's disease--in patients with REM sleep behaviour disorder without Parkinson's disease using a novel task that measures recall precision. Visual short-term memory for sequentially presented coloured bars of different orientation was assessed in 21 patients with polysomnography-proven idiopathic REM sleep behaviour disorder, 26 cases with early Parkinson's disease and 26 healthy controls. Three tasks using the same stimuli controlled for attentional filtering ability, sensorimotor and temporal decay factors. Both patients with REM sleep behaviour disorder and Parkinson's disease demonstrated a deficit in visual short-term memory, with recall precision significantly worse than in healthy controls with no deficit observed in any of the control tasks. Importantly, the pattern of memory deficit in both patient groups was specifically explained by an increase in random responses. These results demonstrate that it is possible to detect the signature of memory impairment associated with Parkinson's disease in individuals with REM sleep behaviour disorder, a condition associated with a high risk of developing Parkinson's disease. The pattern of visual short-term memory deficit potentially provides a cognitive marker of 'prodromal' Parkinson's disease that might be useful in tracking disease progression and for disease-modifying intervention trials. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.

Personality, depression, and premorbid lifestyle in twin pairs discordant for Parkinson's disease

PubMed Central

Heberlein, I.; Ludin, H.; Scholz, J.; Vieregge, P.

1998-01-01

Present personality traits (Freiburg personality inventory, FPI-R), depression (von Zerssen's depression scale), and self assessed state of health were evaluated in 15 twin pairs (six monozygotic and nine dizygotic; mean age 62.5 years) discordant for idiopathic Parkinson's disease and in 17 unrelated healthy control subjects. The twins had additional questionnaire based interviews on premorbid lifestyle.
For disability, twins with Parkinson's disease scored lower on FPI-R than controls in "achievement orientation" and "extraversion", higher in "inhibitedness", "somatic complaints", and "emotionality". They scored higher for depression and for state of health than unaffected twins and controls. For zygosity, monozygotic twins scored lower than dizygotic twins in "achievement orientation", "aggressiveness", and "strain". Monozygotic twins had less "achievement orientation" and "extraversion" and more "somatic complaints" than controls. Monozygotic twins had a lower within pair difference than dizygotic twins in "social orientation". During premorbid times the affected twin with later Parkinson's disease was estimated to have been "less often the leader" in the twin pair.
Although small in sample size, this twin study indicates a genetic impact for some personality features beyond the Parkinson's disease motor syndrome.

 PMID:9489545

Clinical utility of FDG PET in Parkinson's disease and atypical parkinsonism associated with dementia.

PubMed

Walker, Zuzana; Gandolfo, Federica; Orini, Stefania; Garibotto, Valentina; Agosta, Federica; Arbizu, Javier; Bouwman, Femke; Drzezga, Alexander; Nestor, Peter; Boccardi, Marina; Altomare, Daniele; Festari, Cristina; Nobili, Flavio

2018-05-19

There are no comprehensive guidelines for the use of FDG PET in the following three clinical scenarios: (1) diagnostic work-up of patients with idiopathic Parkinson's disease (PD) at risk of future cognitive decline, (2) discriminating idiopathic PD from progressive supranuclear palsy, and (3) identifying the underlying neuropathology in corticobasal syndrome. We therefore performed three literature searches and evaluated the selected studies for quality of design, risk of bias, inconsistency, imprecision, indirectness and effect size. Critical outcomes were the sensitivity, specificity, accuracy, positive/negative predictive value, area under the receiving operating characteristic curve, and positive/negative likelihood ratio of FDG PET in detecting the target condition. Using the Delphi method, a panel of seven experts voted for or against the use of FDG PET based on published evidence and expert opinion. Of 91 studies selected from the three literature searches, only four included an adequate quantitative assessment of the performance of FDG PET. The majority of studies lacked robust methodology due to lack of critical outcomes, inadequate gold standard and no head-to-head comparison with an appropriate reference standard. The panel recommended the use of FDG PET for all three clinical scenarios based on nonquantitative evidence of clinical utility. Despite widespread use of FDG PET in clinical practice and extensive research, there is still very limited good quality evidence for the use of FDG PET. However, in the opinion of the majority of the panellists, FDG PET is a clinically useful imaging biomarker for idiopathic PD and atypical parkinsonism associated with dementia.

Increased Motor Activity During REM Sleep Is Linked with Dopamine Function in Idiopathic REM Sleep Behavior Disorder and Parkinson Disease.

PubMed

Zoetmulder, Marielle; Nikolic, Miki; Biernat, Heidi; Korbo, Lise; Friberg, Lars; Jennum, Poul

2016-06-15

Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by impaired motor inhibition during REM sleep, and dream-enacting behavior. RBD is especially associated with α-synucleinopathies, such as Parkinson disease (PD). Follow-up studies have shown that patients with idiopathic RBD (iRBD) have an increased risk of developing an α-synucleinopathy in later life. Although abundant studies have shown that degeneration of the nigrostriatal dopaminergic system is associated with daytime motor function in Parkinson disease, only few studies have investigated the relation between this system and electromyographic (EMG) activity during sleep. The objective of this study was to investigate the relationship between the nigrostriatal dopamine system and muscle activity during sleep in iRBD and PD. 10 iRBD patients, 10 PD patients with PD, 10 PD patients without RBD, and 10 healthy controls were included and assessed with (123)I-N-omega-fluoropropyl-2-beta-carboxymethoxy-3beta-(4-iodophenyl) nortropane ((123)I-FP-CIT) Single-photon emission computed tomography (SPECT) scanning ((123)I-FP-CIT SPECT), neurological examination, and polysomnography. iRBD patients and PD patients with RBD had increased EMG-activity compared to healthy controls. (123)I-FP-CIT uptake in the putamen-region was highest in controls, followed by iRBD patients, and lowest in PD patients. In iRBD patients, EMG-activity in the mentalis muscle was correlated to (123)I-FP-CIT uptake in the putamen. In PD patients, EMG-activity was correlated to anti-Parkinson medication. Our results support the hypothesis that increased EMG-activity during REM sleep is at least partly linked to the nigrostriatal dopamine system in iRBD, and with dopamine function in PD. © 2016 American Academy of Sleep Medicine.

Spine Topographical Distribution of Skin α-Synuclein Deposits in Idiopathic Parkinson Disease.

PubMed

Donadio, Vincenzo; Incensi, Alex; Rizzo, Giovanni; Scaglione, Cesa; Capellari, Sabina; Fileccia, Enrico; Avoni, Patrizia; Liguori, Rocco

2017-05-01

Phosphorylated α-synuclein (p-syn) in skin nerves mainly in the proximal sites is a promising neurodegenerative biomarker for idiopathic Parkinson disease (IPD). However, the p-syn spine distribution particularly in patients with unilateral motor dysfunctions remains undefined. This study aimed to investigate in IPD p-syn differences between left and right cervical spine sites in patients with prevalent unilateral motor symptoms, and cervical and thoracic spine sites in patients with bilateral motor symptoms. We enrolled 28 IPD patients fulfilling clinical diagnostic criteria associated with abnormal nigro-striatal DatScan and cardiac MIBG: 15 with prevalently unilateral motor symptoms demonstrated by DatScan; 13 with bilateral motor symptoms and DatScan abnormalities. Patients underwent skin biopsy searching for intraneural p-syn deposits: skin samples were taken from C7 paravertebral left and right sites in unilateral patients and from cervical (C7) and thoracic (Th12) paravertebral spine regions in bilateral patients. Unilateral patients displayed 20% of abnormal p-syn deposits in the affected motor site, 60% in both sites and 20% only in the non-affected site. P-syn was found in all patients in C7 but in only 62% of patients in Th12. Our data showed that cervical p-syn deposits displayed a uniform distribution between both sides not following the motor dysfunction in unilateral patients, and skin nerve p-syn deposits demonstrated a spine gradient with the cervical site expressing the highest positivity. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

Parkinson disease

MedlinePlus

... this page: //medlineplus.gov/ency/article/000755.htm Parkinson disease To use the sharing features on this page, please enable JavaScript. Parkinson disease results from certain brain cells dying. These cells ...

Risk for femoral fractures in Parkinson's disease patients with and without severe functional impairment.

PubMed

Benzinger, Petra; Rapp, Kilian; Maetzler, Walter; König, Hans-Helmut; Jaensch, Andrea; Klenk, Jochen; Büchele, Gisela

2014-01-01

Impaired balance is a major problem in patients with idiopathic Parkinson's disease (PD) resulting in an increased risk of falls and fall-related fractures. Most studies which analyzed the risk of femoral fractures in patients with idiopathic PD were performed either in specialized centers or excluded very frail patients. The current study used a large population-based dataset in order to analyze the risk of femoral fractures in patients with idiopathic PD. Data from more than 880.000 individuals aged 65 years or older and insured between 2004 and 2009 at a large German health insurance company were used for the analyses. Persons with idiopathic PD were identified by the dispensing of Parkinson-specific medication and by hospital diagnoses, if available. People without PD served as the reference group. Incident femoral fractures were obtained from hospital diagnoses. Analyses were stratified by gender and information on severe functional impairment (care need) as provided by reimbursement claims. Compared with the reference group, persons with idiopathic PD had a more than doubled risk to sustain a femoral fracture. The risk was higher in men (HR = 2.61; 95%-CI: 2.28-2.98) than in women (HR = 1.79; 95%-CI: 1.66-1.94). The increased risk was only observed in people without severe functional impairment. The sensitivity analysis using a refined definition of idiopathic PD patients yielded similar results. The findings confirm the increased risk of femoral fractures in patients with idiopathic PD. The relative risk is particularly high in male PD patients and in patients without severe functional impairment.

Changes to Articulatory Kinematics in Response to Loudness Cues in Individuals with Parkinson's Disease

ERIC Educational Resources Information Center

Darling, Meghan; Huber, Jessica E.

2011-01-01

Purpose: Individuals with Parkinson's disease (PD) exhibit differences in displacement and velocity of the articulators as compared with older adults. The purpose of the current study was to examine effects of 3 loudness cues on articulatory movement patterns in individuals with PD. Method: Nine individuals diagnosed with idiopathic PD and 9 age-…

Fatigue and excessive daytime sleepiness in idiopathic Parkinson's disease differently correlate with motor symptoms, depression and dopaminergic treatment.

PubMed

Valko, P O; Waldvogel, D; Weller, M; Bassetti, C L; Held, U; Baumann, C R

2010-12-01

A comprehensive study of both fatigue and excessive daytime sleepiness (EDS) in association with Parkinson's disease (PD)-related symptoms and treatment has not been performed yet. To assess the frequency and severity of fatigue and EDS in patients with idiopathic PD and to study their relation to motor and non-motor symptoms and dopaminergic treatment. We prospectively assessed Fatigue Severity Scale (FSS) scores, Epworth Sleepiness Scale (ESS) scores, Beck Depression Inventory (BDI) scores, severity (Unified PD Rating Scale, UPDRS, part III; Hoehn & Yahr staging) and duration of the disease, and the current dopaminergic treatment in 88 consecutive patients with idiopathic PD. Fatigue was found in 52 (59%), EDS in 42 (48%), and both complaints in 31 (35%) patients. Fatigued patients had higher UPDRS III scores (23.5 ± 11.1 vs. 18.6 ± 7.6, P = 0.03), higher Hoehn & Yahr staging (2.4 ± 0.9 vs. 2.1 ± 0.7, P = 0.03), and higher BDI scores (13.4 ± 7.1 vs. 9.1 ± 5.8, P = 0.004) than non-fatigued patients. In contrast, UPDRS III, Hoehn & Yahr, and BDI scores did not differ between patients with or without EDS. However, the type of dopaminergic treatment (levodopa monotherapy versus combination of levodopa/dopamine agonists) was associated with significant differences in ESS (8.5 ± 5.2 vs. 10.8 ± 4.3, P = 0.04), but not FSS scores (4.1 ± 1.5 vs. 4.3 ± 1.5, P = 0.55). Disease duration correlated with ESS scores (r = 0.32, P = 0.003), but not with FSS scores (r = -0.02, P = 0.82). In PD, there is a significant overlap of fatigue and EDS, but the two symptoms are differently correlated with the severity of motor symptoms, disease duration, depression, and dopaminergic treatment. © 2010 The Author(s). European Journal of Neurology © 2010 EFNS.

[King's Parkinson's disease pain scale : Intercultural adaptation in the German language].

PubMed

Jost, W H; Rizos, A; Odin, P; Löhle, M; Storch, A

2018-02-01

Pain is a frequent symptom of idiopathic Parkinson's disease and has a substantial impact on quality of life. The King's Parkinson's disease pain scale (KPPS) has become internationally established and is an English-language, standardized, reliable and valid scale for evaluation of pain in idiopathic Parkinson's disease. This article presents a validated version in German. The German translation was adapted interculturally and developed using an internationally recognized procedure in consultation with the authors of the original publication. The primary text was first translated by two bilingual neuroscientists independently of one another. Thereafter, the two versions were collated to generate a consensus version, which was accepted by the translators and preliminarily trialled with 10 patients. Hereafter, the German version was re-translated back into English by two other neurologists, again independently of one another, and a final consensus was agreed on using these versions. This English version was then compared with the original text by all of the translators, a process which entailed as many linguistic modifications to the German version as the translators considered necessary to generate a linguistically acceptable German version that was as similar as possible to the original English version. After this test text had been subsequently approved by the authors, the German text was applied to 50 patients in two hospitals, and reviewed as to its practicability and comprehensibility. This work led to the successful creation of an inter-culturally adapted and linguistically validated German version of the KPPS. The German version presented here is a useful scare for recording and quantifying pain in empirical studies, as well as in clinical practice.

The association between fear of falling and quality of life for balance impairments based on hip and ankle strategies in the drug On- and Off-phase of patients with idiopathic Parkinson' disease.

PubMed

Mehdizadeh, Maryam; Lajevardi, Laleh; Habibi, Seyed Amir Hassan; ArabBaniasad, Mina; Baghoori, Delaram; Daneshjoo, Fatemeh; Taghizadeh, Ghorban

2016-01-01

Background: Despite the negative effect of fear of falling during functioning and social participation of patients with Parkinson' disease, so far, only few studies have investigated its effect on the quality of life in these patients. We aimed to investigate the association between fear of falling and quality of life controlling for balance impairments based on hip and ankle strategy in drug On- and Off-phase of patients with idiopathic Parkinson' disease. Methods: In this non-experimental cross-sectional study, 139 patients with idiopathic Parkinson' disease (100 male, 39 female) by mean± SD age of 60.2±12.27 years, mean±SD time since diagnosis of 6.7±5.53 years and mean±SD Hoehn and Yahr stage of 2.8±1.49 were selected by a simple non-probability method. Balance function was measured by a functional reach test with hip and ankle strategy. The Persian version of the selfcompleted Fall Efficacy Scale-International and Parkinson's disease quality of life questionnaire was used to evaluate fear of falling and quality of life, respectively. Results: The results showed that the score of all dimensions of quality of life (i.e., mobility, activities of daily living, emotional wellbeing, stigma, social support, cognition, communication and bodily discomfort) were significantly affected by the intensity of fear of falling. Multiple regression analysis indicated a significant association between fear of falling and quality of life in a way that fear of falling explained 11% to 47% and 12% to 43% of variance in drug On-phase, as well as 8% to 45% and 9% to 48% of variance in the drug Off-phase in dimensions of quality of life after controlling for balance function based on hip and ankle strategy, respectively. In the drug On-phase, the strongest association (R=0.85, p<0.001) was found between fear of falling and mobility dimension of quality of life. In the drug Off-phase, the strongest relation was observed between fear of falling and mobility (R=0.82, p<0.001) as

Normal CAG and CCG repeats in the Huntington`s disease genes of Parkinson`s disease patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rubinsztein, D.C.; Leggo, J.; Barton, D.E.

1995-04-24

The clinical features of Parkinson`s disease, particularly rigidity and bradykinesia and occasionally tremor, are seen in juvenile-onset Huntington`s disease. Therefore, the CAG and CCG repeats in the Huntington`s disease gene were investigated in 45 Parkinson`s disease patients and compared to 40 control individuals. All of the Parkinson`s disease chromosomes fell within the normal size ranges. In addition, the distributions of the two repeats in the Parkinson`s disease patients did not differ significantly from those of the control population. Therefore, abnormalities of these trinucleotide repeats in the Huntington`s disease gene are not likely to contribute to the pathogenesis of Parkinson`s disease.more » 12 refs., 2 figs.« less

Factors associated with fall-related fractures in Parkinson's disease.

PubMed

Cheng, Kuei-Yueh; Lin, Wei-Che; Chang, Wen-Neng; Lin, Tzu-Kong; Tsai, Nai-Wen; Huang, Chih-Cheng; Wang, Hung-Chen; Huang, Yung-Cheng; Chang, Hsueh-Wen; Lin, Yu-Jun; Lee, Lian-Hui; Cheng, Ben-Chung; Kung, Chia-Te; Chang, Ya-Ting; Su, Chih-Min; Chiang, Yi-Fang; Su, Yu-Jih; Lu, Cheng-Hsien

2014-01-01

Fall-related fracture is one of the most disabling features of idiopathic Parkinson's disease (PD). A better understanding of the associated factors is needed to predict PD patients who will require treatment. This prospective study enrolled 100 adult idiopathic PD patients. Stepwise logistic regressions were used to evaluate the relationships between clinical factors and fall-related fracture. Falls occurred in 56 PD patients, including 32 with fall-related fractures. The rate of falls in the study period was 2.2 ± 1.4 per 18 months. The percentage of osteoporosis was 34% (19/56) and 11% in PD patients with and without falls, respectively. Risk factors associated with fall-related fracture were sex, underlying knee osteoarthritis, mean Unified Parkinson's Disease Rating Scale score, mean Morse fall scale, mean Hoehn and Yahr stage, and exercise habit. By stepwise logistic regression, sex and mean Morse fall scale were independently associated with fall-related fracture. Females had an odds ratio of 3.8 compared to males and the cut-off value of the Morse fall scale for predicting fall-related fracture was 72.5 (sensitivity 72% and specificity 70%). Higher mean Morse fall scales (>72.5) and female sex are associated with higher risk of fall-related fractures. Preventing falls in the high-risk PD group is an important safety issue and highly relevant for their quality of life. Copyright © 2013 Elsevier Ltd. All rights reserved.

Quality of life in people with Parkinson's disease: the relevance of social relationships and communication.

PubMed

Takahashi, Kayoko; Kamide, Naoto; Suzuki, Makoto; Fukuda, Michinari

2016-01-01

[Purpose] Maintaining high quality of life is crucial for the rehabilitation of patients with Parkinson's disease. The quality of life scales currently in use do not assess all quality of life domains or their importance for each individual. Therefore, a new quality of life measure, the Schedule for the Evaluation of Individual Quality of Life-Direct Weighting, was used to investigate quality of life in people with Parkinson's disease. [Subjects and Methods] Fifteen people with idiopathic Parkinson's disaese (average age = 80.0 years, standard deviation = 10.3 years, Hoehn & Yahr stages 1-4) were interviewed using the Schedule for the Evaluation of Individual Quality of Life-Direct Weighting. Its quality of life constructs were tested by comparing them against disease-specific quality of life (39-items Parkinson's Disease Questionnaire), motor functioning (Unified Parkinson's Disease Rating Scale Part III), and activities of daily living (Barthel Index). [Results] Social connections such as "family" and "friends" were revealed as important constructs of life satisfaction. The Schedule for the Evaluation of Individual Quality of Life-Direct Weighting was not significantly correlated with the 39-items Parkinson's Disease Questionnaire, Unified Parkinson's Disease Rating Scale Part III, or Barthel Index but was significantly correlated with the "communication" dimension of the 39-items Parkinson's Disease Questionnaire. [Conclusion] The Schedule for the Evaluation of Individual Quality of Life-Direct Weighting detected various domains of quality of life, especially social relationships with family and friends. "Being heard" was also revealed as an essential component of life satisfaction, as it provides patients with a feeling of acceptance and assurance, possibly resulting in better quality of life.

There is no Parkinson disease.

PubMed

Weiner, William J

2008-06-01

The term Parkinson disease defines a specific clinical condition characterized by a typical history and characteristic signs. This review examines the historical evolution of the concept of Parkinson disease and how the misunderstanding of Parkinson disease may be hindering clinical research trials. It is proposed that this syndrome be called Parkinson diseases or parkinsonism type 1 through infinity.

The relationship between glucocerebrosidase mutations and Parkinson disease.

PubMed

Migdalska-Richards, Anna; Schapira, Anthony H V

2016-10-01

Parkinson disease (PD) is the second most common neurodegenerative disorder after Alzheimer disease, whereas Gaucher disease (GD) is the most frequent lysosomal storage disorder caused by homozygous mutations in the glucocerebrosidase (GBA1) gene. Increased risk of developing PD has been observed in both GD patients and carriers. It has been estimated that GBA1 mutations confer a 20- to 30-fold increased risk for the development of PD, and that at least 7-10% of PD patients have a GBA1 mutation. To date, mutations in the GBA1 gene constitute numerically the most important risk factor for PD. The type of PD associated with GBA1 mutations (PD-GBA1) is almost identical to idiopathic PD, except for a slightly younger age of onset and a tendency to more cognitive impairment. Importantly, the pathology of PD-GBA1 is identical to idiopathic PD, with nigral dopamine cell loss, Lewy bodies, and neurites containing alpha-synuclein. The mechanism by which GBA1 mutations increase the risk for PD is still unknown. However, given that clinical manifestation and pathological findings in PD-GBA1 patients are almost identical to those in idiopathic PD individuals, it is likely that, as in idiopathic PD, alpha-synuclein accumulation, mitochondrial dysfunction, autophagic impairment, oxidative and endoplasmic reticulum stress may contribute to the development and progression of PD-GBA1. Here, we review the GBA1 gene, its role in GD, and its link with PD. The impact of glucocerebrosidase 1 (GBA1) mutations on functioning of endoplasmic reticulum (ER), lysosomes, and mitochondria. GBA1 mutations resulting in production of misfolded glucocerebrosidase (GCase) significantly affect the ER functioning. Misfolded GCase trapped in the ER leads to both an increase in the ubiquitin-proteasome system (UPS) and the ER stress. The presence of ER stress triggers the unfolded protein response (UPR) and/or endoplasmic reticulum-associated degradation (ERAD). The prolonged activation of UPR and ERAD

Evaluation of extracranial blood flow in Parkinson disease.

PubMed

Haktanir, Alpay; Yaman, Mehmet; Acar, Murat; Gecici, Omer; Demirel, Reha; Albayrak, Ramazan; Demirkirkan, Kemal

2006-01-02

Decreased cerebral flow velocities in Parkinsonian patients were reported previously. Because of the limited data on vascular changes in Parkinson disease (PD), which may have a vascular etiology, we aimed to disclose any possible cerebral hemodynamic alteration in Parkinsonian patients. We prospectively evaluated 28 non-demented, idiopathic parkinsonian patients and 19 age and sex matched controls with Doppler sonography. Flow volumes, peak systolic flow velocities, and cross-sectional areas of vertebral and internal carotid arteries (ICA) were measured and compared between patients and controls. Correlation of patient age and disease duration with Doppler parameters was observed; and each Doppler parameter of patients within each Hoehn-Yahr scale was compared. There was no significant difference of measured parameters between groups. No correlation was found between disease duration and age with flow volume, cross-sectional area or peak systolic velocity. Hoehn-Yahr scale was not found having significant relation with Doppler parameters. Values of vertebral, internal carotid and cerebral blood flow volumes (CBF), peak systolic velocities, and cross-sectional areas were not significantly different between Parkinsonian patients and age and sex matched controls. Although regional blood flow decreases may be seen as reported previously, Parkinson disease is not associated with a flow volume or velocity alteration of extracranial cerebral arteries.

Quality of life in Parkinson`s Disease

PubMed Central

Opara, JA; Brola, W; Leonardi, M; Błaszczyk, B

2012-01-01

In this review report, current possibilities of evaluation of quality of life in Parkinson’s disease have been critically presented. Health Related Quality of Life (-HRQoL) comprises a wide spectrum of consequences of the disease. Measurement of quality of life has become increasingly relevant as an outcome parameter, especially in long-term trials. Most of the available QoL instruments depend on patient self-reports. The data can be collected by written questionnaires. There are universal questionnaires of QoL – for many diseases and the specific ones – specially created for one disease. Among universal questionnaires, the Sickness Impact Profile (SIP) and the Short-Form Health Status Survey (SF-36) are the most popular in Parkinson’s disease. As for specific questionnaires: the Parkinson`s Disease Questionnaire (PDQ-39) and the Parkinson`s Disease Quality of Life Questionnaire (PDQL) have been described. PMID:23346238

Parkinson disease - resources

MedlinePlus

Resources - Parkinson disease ... The following organizations are good resources for information on Parkinson disease : The Michael J. Fox Foundation -- www.michaeljfox.org National Institute of Neurological Disorders and Stroke -- www. ...

The Functional Dysphagia Scale Is a Useful Tool for Predicting Aspiration Pneumonia in Patients With Parkinson Disease.

PubMed

Lee, Jong Hwa; Lee, Kyeong Woo; Kim, Sang Beom; Lee, Sook Joung; Chun, Sang Myung; Jung, Sung Moon

2016-06-01

To describe the correlation between the functional dysphagia scale and aspiration pneumonia and which characteristics influence the occurrence of aspiration pneumonia in patients with idiopathic Parkinson disease. Fifty-three patients with idiopathic Parkinson disease were prospectively evaluated in this study. Disease severity and functional status were measured by modified Hoehn and Yahr (H&Y) staging, Schwab and England activities of daily living (S-E ADL) scale and Korean version of Mini-Mental State Examination (K-MMSE). Swallowing function was evaluated by the functional dysphagia scale (FDS) and the penetration-aspiration scale (PAS) based on a videofluoroscopic swallowing study. The patients were followed up for 3 months and divided into two groups according to the occurrence of aspiration pneumonia. The correlation between the variables and aspiration pneumonia was analyzed. Eight patients of the 53 patients were allocated to the aspiration pneumonia group and 45 patients to the non-aspiration pneumonia group. The patients in the aspiration pneumonia group had significantly higher H&Y staging, and scored lower on S-E ADL scale and K-MMSE. The patients in the aspiration pneumonia group had significantly higher scores on FDS and PAS. A multiple logistic regression analysis showed that the S-E ADL scale and the FDS were associated with the occurrence of aspiration pneumonia in the patients with Parkinson disease. Given that the FDS can quantitatively assess the functional problems associated with dysphagia, it can be clinically effective in predicting the occurrence of aspiration pneumonia, and the FDS and the S-E ADL scale could be predictive variables for aspiration pneumonia in patients with Parkinson disease.

Traditional chinese medicine improves activities of daily living in Parkinson's disease.

PubMed

Pan, Weidong; Kwak, Shin; Liu, Yun; Sun, Yan; Fang, Zhenglong; Qin, Baofeng; Yamamoto, Yoshiharu

2011-01-01

We evaluated the effects of a traditional Chinese medicine (TCM), named Zeng-xiao An-shen Zhi-chan 2 (ZAZ2), on patients with Parkinson's disease (PD). Among 115 patients with idiopathic PD enrolled (mean age, 64.7 ± 10.2 years old), 110 patients (M = 65, F = 45; mean age, 64.9 ± 10.7 years old) completed the study. Patients took either ZAZ2 (n = 59) or placebo granule (n = 56) in a blind manner for 13 weeks while maintaining other anti-Parkinson medications unchanged. All participants wore a motion logger, and we analyzed the power-law temporal autocorrelation of the motion logger records taken on 3 occasions (before, one week, and 13 weeks after the drug administration). Drug efficacy was evaluated with the conventional Unified Parkinson Disease Rating Scale (UPDRS), as well as the power-law exponent α, which corresponds to the level of physical activity of the patients. ZAZ2 but not placebo granule improved the awake-sleep rhythm, the UPDRS Part II, Part II + III, and Part IV scores, and the α values. The results indicate that ZAZ2 improved activities of daily living (ADL) of parkinsonism and, thus, is a potentially suitable drug for long-term use.

Traditional Chinese Medicine Improves Activities of Daily Living in Parkinson's Disease

PubMed Central

Pan, Weidong; Kwak, Shin; Liu, Yun; Sun, Yan; Fang, Zhenglong; Qin, Baofeng; Yamamoto, Yoshiharu

2011-01-01

We evaluated the effects of a traditional Chinese medicine (TCM), named Zeng-xiao An-shen Zhi-chan 2 (ZAZ2), on patients with Parkinson's disease (PD). Among 115 patients with idiopathic PD enrolled (mean age, 64.7 ± 10.2 years old), 110 patients (M = 65, F = 45; mean age, 64.9 ± 10.7 years old) completed the study. Patients took either ZAZ2 (n = 59) or placebo granule (n = 56) in a blind manner for 13 weeks while maintaining other anti-Parkinson medications unchanged. All participants wore a motion logger, and we analyzed the power-law temporal autocorrelation of the motion logger records taken on 3 occasions (before, one week, and 13 weeks after the drug administration). Drug efficacy was evaluated with the conventional Unified Parkinson Disease Rating Scale (UPDRS), as well as the power-law exponent α, which corresponds to the level of physical activity of the patients. ZAZ2 but not placebo granule improved the awake-sleep rhythm, the UPDRS Part II, Part II + III, and Part IV scores, and the α values. The results indicate that ZAZ2 improved activities of daily living (ADL) of parkinsonism and, thus, is a potentially suitable drug for long-term use. PMID:21687764

Manganese-Induced Parkinsonism and Parkinson’s Disease: Shared and Distinguishable Features

PubMed Central

Kwakye, Gunnar F.; Paoliello, Monica M.B.; Mukhopadhyay, Somshuvra; Bowman, Aaron B.; Aschner, Michael

2015-01-01

Manganese (Mn) is an essential trace element necessary for physiological processes that support development, growth and neuronal function. Secondary to elevated exposure or decreased excretion, Mn accumulates in the basal ganglia region of the brain and may cause a parkinsonian-like syndrome, referred to as manganism. The present review discusses the advances made in understanding the essentiality and neurotoxicity of Mn. We review occupational Mn-induced parkinsonism and the dynamic modes of Mn transport in biological systems, as well as the detection and pharmacokinetic modeling of Mn trafficking. In addition, we review some of the shared similarities, pathologic and clinical distinctions between Mn-induced parkinsonism and Parkinson’s disease. Where possible, we review the influence of Mn toxicity on dopamine, gamma aminobutyric acid (GABA), and glutamate neurotransmitter levels and function. We conclude with a survey of the preventive and treatment strategies for manganism and idiopathic Parkinson’s disease (PD). PMID:26154659

Diabetes mellitus and Parkinson disease.

PubMed

Pagano, Gennaro; Polychronis, Sotirios; Wilson, Heather; Giordano, Beniamino; Ferrara, Nicola; Niccolini, Flavia; Politis, Marios

2018-05-08

To investigate whether diabetes mellitus is associated with Parkinson-like pathology in people without Parkinson disease and to evaluate the effect of diabetes mellitus on markers of Parkinson pathology and clinical progression in drug-naive patients with early-stage Parkinson disease. We compared 25 patients with Parkinson disease and diabetes mellitus to 25 without diabetes mellitus, and 14 patients with diabetes mellitus and no Parkinson disease to 14 healthy controls (people with no diabetes mellitus or Parkinson disease). The clinical diagnosis of diabetes mellitus was confirmed by 2 consecutive fasting measurements of serum glucose levels >126 mL/dL. Over a 36-month follow-up period, we then investigated in the population with Parkinson disease whether the presence of diabetes mellitus was associated with faster motor progression or cognitive decline. The presence of diabetes mellitus was associated with higher motor scores ( p < 0.01), lower striatal dopamine transporter binding ( p < 0.05), and higher tau CSF levels ( p < 0.05) in patients with Parkinson disease. In patients with diabetes but without Parkinson disease, the presence of diabetes mellitus was associated with lower striatal dopamine transporter binding ( p < 0.05) and higher tau ( p < 0.05) and α-synuclein ( p < 0.05) CSF levels compared to healthy controls. At the Cox survival analysis in the population of patients with Parkinson disease, the presence of diabetes mellitus was associated with faster motor progression (hazard ratio = 4.521, 95% confidence interval = 1.468-13.926; p < 0.01) and cognitive decline (hazard ratio = 9.314, 95% confidence interval = 1.164-74.519; p < 0.05). Diabetes mellitus may predispose toward a Parkinson-like pathology, and when present in patients with Parkinson disease, can induce a more aggressive phenotype. © 2018 American Academy of Neurology.

Adolf Hitler's Parkinson's disease and an attempt to analyse his personality structure.

PubMed

Gerstenbrand, F; Karamat, E

1999-03-01

It has been proved that Adolf Hitler suffered from idiopathic Parkinson's disease. No indication for postencephalitic parkinsonism was found in the clinical symptoms or the case history. Professor Max de Crinis established his diagnosis of Parkinson's disease in Hitler early in 1945 and informed the SS leadership, who decided to initiate treatment with a specially prepared 'antiparkinsonian mixture' to be administered by a physician. However, Hitler never received the mixture, this implies that the SS intended to remove the severely diseased 'Leader'. Two different character traits can be analysed in Hitler's personality: on the one hand the typical premorbid personality of parkinsonian patients with uncorrectable mental rigidity, extreme inflexibility and insupportable pedantry. On the other an antisocial personality disorder with lack of ethical and social values, a deeply rooted tendency to betray others and to deceive himself and uncontrollable emotional reactions. This special combination in Hitler's personality resulted in the uncritical conviction of his mission and an enormous driving for recognition. The neuropsychiatric analysis of Hitler's personality could lead to a better explanation of the pathological traits of one of the most conspicuous historical personalities. Copyright 1999 Lippincott Williams & Wilkins.

Effects of an Extended Version of the Lee Silverman Voice Treatment on Voice and Speech in Parkinson's Disease

ERIC Educational Resources Information Center

Spielman, Jennifer; Ramig, Lorraine O.; Mahler, Leslie; Halpern, Angela; Gavin, William J.

2007-01-01

Purpose: The present study examined vocal SPL, voice handicap, and speech characteristics in Parkinson's disease (PD) following an extended version of the Lee Silverman Voice Treatment (LSVT), to help determine whether current treatment dosages can be altered without compromising clinical outcomes. Method: Twelve participants with idiopathic PD…

PDON: Parkinson's disease ontology for representation and modeling of the Parkinson's disease knowledge domain.

PubMed

Younesi, Erfan; Malhotra, Ashutosh; Gündel, Michaela; Scordis, Phil; Kodamullil, Alpha Tom; Page, Matt; Müller, Bernd; Springstubbe, Stephan; Wüllner, Ullrich; Scheller, Dieter; Hofmann-Apitius, Martin

2015-09-22

Despite the unprecedented and increasing amount of data, relatively little progress has been made in molecular characterization of mechanisms underlying Parkinson's disease. In the area of Parkinson's research, there is a pressing need to integrate various pieces of information into a meaningful context of presumed disease mechanism(s). Disease ontologies provide a novel means for organizing, integrating, and standardizing the knowledge domains specific to disease in a compact, formalized and computer-readable form and serve as a reference for knowledge exchange or systems modeling of disease mechanism. The Parkinson's disease ontology was built according to the life cycle of ontology building. Structural, functional, and expert evaluation of the ontology was performed to ensure the quality and usability of the ontology. A novelty metric has been introduced to measure the gain of new knowledge using the ontology. Finally, a cause-and-effect model was built around PINK1 and two gene expression studies from the Gene Expression Omnibus database were re-annotated to demonstrate the usability of the ontology. The Parkinson's disease ontology with a subclass-based taxonomic hierarchy covers the broad spectrum of major biomedical concepts from molecular to clinical features of the disease, and also reflects different views on disease features held by molecular biologists, clinicians and drug developers. The current version of the ontology contains 632 concepts, which are organized under nine views. The structural evaluation showed the balanced dispersion of concept classes throughout the ontology. The functional evaluation demonstrated that the ontology-driven literature search could gain novel knowledge not present in the reference Parkinson's knowledge map. The ontology was able to answer specific questions related to Parkinson's when evaluated by experts. Finally, the added value of the Parkinson's disease ontology is demonstrated by ontology-driven modeling of PINK1

Intensive Voice Treatment (LSVT[R]LOUD) for Parkinson's Disease Following Deep Brain Stimulation of the Subthalamic Nucleus

ERIC Educational Resources Information Center

Spielman, Jennifer; Mahler, Leslie; Halpern, Angela; Gilley, Phllip; Klepitskaya, Olga; Ramig, Lorraine

2011-01-01

Purpose: Intensive voice therapy (LSVT[R]LOUD) can effectively manage voice and speech symptoms associated with idiopathic Parkinson disease (PD). This small-group study evaluated voice and speech in individuals with and without deep brain stimulation of the subthalamic nucleus (STN-DBS) before and after LSVT LOUD, to determine whether outcomes…

Genetics in Parkinson disease: Mendelian versus non-Mendelian inheritance.

PubMed

Hernandez, Dena G; Reed, Xylena; Singleton, Andrew B

2016-10-01

Parkinson's disease is a common, progressive neurodegenerative disorder, affecting 3% of those older than 75 years of age. Clinically, Parkinson's disease (PD) is associated with resting tremor, postural instability, rigidity, bradykinesia, and a good response to levodopa therapy. Over the last 15 years, numerous studies have confirmed that genetic factors contribute to the complex pathogenesis of PD. Highly penetrant mutations producing rare, monogenic forms of the disease have been discovered in singular genes such as SNCA, Parkin, DJ-1, PINK 1, LRRK2, and VPS35. Unique variants with incomplete penetrance in LRRK2 and GBA have been shown to be strong risk factors for PD in certain populations. Additionally, over 20 common variants with small effect sizes are now recognized to modulate the risk for PD. Investigating Mendelian forms of PD has provided precious insight into the pathophysiology that underlies the more common idiopathic form of disease; however, no treatment methodologies have developed. Furthermore, for identified common risk alleles, the functional basis underlying risk principally remains unknown. The challenge over the next decade will be to strengthen the findings delivered through genetic discovery by assessing the direct, biological consequences of risk variants in tandem with additional high-content, integrated datasets. This review discusses monogenic risk factors and mechanisms of Mendelian inheritance of Parkinson disease. Highly penetrant mutations in SNCA, Parkin, DJ-1, PINK 1, LRRK2 and VPS35 produce rare, monogenic forms of the disease, while unique variants within LRRK2 and GBA show incomplete penetrance and are strong risk factors for PD. Additionally, over 20 common variants with small effect sizes modulate disease risk. The challenge over the next decade is to strengthen genetic findings by assessing direct, biological consequences of risk variants in tandem with high-content, integrated datasets. This article is part of a special

Phenotype, genotype, and worldwide genetic penetrance of LRRK2-associated Parkinson's disease: a case-control study

PubMed Central

Healy, Daniel G; Falchi, Mario; O'Sullivan, Sean S; Bonifati, Vincenzo; Durr, Alexandra; Bressman, Susan; Brice, Alexis; Aasly, Jan; Zabetian, Cyrus P; Goldwurm, Stefano; Ferreira, Joaquim J; Tolosa, Eduardo; Kay, Denise M; Klein, Christine; Williams, David R; Marras, Connie; Lang, Anthony E; Wszolek, Zbigniew K; Berciano, Jose; Schapira, Anthony HV; Lynch, Timothy; Bhatia, Kailash P; Gasser, Thomas; Lees, Andrew J; Wood, Nicholas W

2008-01-01

Summary Background Mutations in LRRK2, the gene that encodes leucine-rich repeat kinase 2, are a cause of Parkinson's disease (PD). The International LRRK2 Consortium was established to answer three key clinical questions: can LRRK2-associated PD be distinguished from idiopathic PD; which mutations in LRRK2 are pathogenic; and what is the age-specific cumulative risk of PD for individuals who inherit or are at risk of inheriting a deleterious mutation in LRRK2? Methods Researchers from 21 centres across the world collaborated on this study. The frequency of the common LRRK2 Gly2019Ser mutation was estimated on the basis of data from 24 populations worldwide, and the penetrance of the mutation was defined in 1045 people with mutations in LRRK2 from 133 families. The LRRK2 phenotype was defined on the basis of 59 motor and non-motor symptoms in 356 patients with LRRK2-associated PD and compared with the symptoms of 543 patients with pathologically proven idiopathic PD. Findings Six mutations met the consortium's criteria for being proven pathogenic. The frequency of the common LRRK2 Gly2019Ser mutation was 1% of patients with sporadic PD and 4% of patients with hereditary PD; the frequency was highest in the middle east and higher in southern Europe than in northern Europe. The risk of PD for a person who inherits the LRRK2 Gly2019Ser mutation was 28% at age 59 years, 51% at 69 years, and 74% at 79 years. The motor symptoms (eg, disease severity, rate of progression, occurrence of falls, and dyskinesia) and non-motor symptoms (eg, cognition and olfaction) of LRRK2-associated PD were more benign than those of idiopathic PD. Interpretation Mutations in LRRK2 are a clinically relevant cause of PD that merit testing in patients with hereditary PD and in subgroups of patients with PD. However, this knowledge should be applied with caution in the diagnosis and counselling of patients. Funding UK Medical Research Council; UK Parkinson's Disease Society; UK Brain Research

Genetics Home Reference: Parkinson disease

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Parkinson's Disease: Diagnosis and Treatment

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Parkinson disease.

PubMed

Poewe, Werner; Seppi, Klaus; Tanner, Caroline M; Halliday, Glenda M; Brundin, Patrik; Volkmann, Jens; Schrag, Anette-Eleonore; Lang, Anthony E

2017-03-23

Parkinson disease is the second-most common neurodegenerative disorder that affects 2-3% of the population ≥65 years of age. Neuronal loss in the substantia nigra, which causes striatal dopamine deficiency, and intracellular inclusions containing aggregates of α-synuclein are the neuropathological hallmarks of Parkinson disease. Multiple other cell types throughout the central and peripheral autonomic nervous system are also involved, probably from early disease onwards. Although clinical diagnosis relies on the presence of bradykinesia and other cardinal motor features, Parkinson disease is associated with many non-motor symptoms that add to overall disability. The underlying molecular pathogenesis involves multiple pathways and mechanisms: α-synuclein proteostasis, mitochondrial function, oxidative stress, calcium homeostasis, axonal transport and neuroinflammation. Recent research into diagnostic biomarkers has taken advantage of neuroimaging in which several modalities, including PET, single-photon emission CT (SPECT) and novel MRI techniques, have been shown to aid early and differential diagnosis. Treatment of Parkinson disease is anchored on pharmacological substitution of striatal dopamine, in addition to non-dopaminergic approaches to address both motor and non-motor symptoms and deep brain stimulation for those developing intractable L-DOPA-related motor complications. Experimental therapies have tried to restore striatal dopamine by gene-based and cell-based approaches, and most recently, aggregation and cellular transport of α-synuclein have become therapeutic targets. One of the greatest current challenges is to identify markers for prodromal disease stages, which would allow novel disease-modifying therapies to be started earlier.

A molecular analysis of the GBA gene in Caucasian South Africans with Parkinson's disease.

PubMed

Barkhuizen, Melinda; Anderson, David G; van der Westhuizen, Francois H; Grobler, Anne F

2017-03-01

The molecular basis of Parkinson's disease in South African population groups remains elusive. To date, substitutions in the GBA gene are the most common large-effect genetic risk factor for Parkinson's disease. The primary objective of this study was to determine the prevalence of GBA substitutions in South Africans with idiopathic Parkinson's disease. Participants were recruited from tertiary hospitals in the Gauteng Province in South Africa. All participants were screened for substitutions in GBA exon 8-11 and the full coding region was analysed in 20 participants. Peripheral β -glucocerebrosidase enzymatic activity of GBA -carriers was measured in mixed leukocytes. Of 105 Caucasian Parkinson's disease participants (82.7% Afrikaner) with an average age of disease onset of 61.9 ± 12.2 years and 40 controls (age 73.4 ± 12.4 years) were included. Heterozygous GBA substitutions were identified in 12.38% of affected participants (p.G35A, p.E326K, p.I368T, p.T369M, p.N370S, p.P387L and p.K441N) and 5.00% of controls (p.E326K and p.T369M). The substitutions ranged from predicted benign to moderately damaging; with p.E326K and p.T369M most prevalent, followed by the Afrikaner Gaucher disease substitution p.P387L. Severe Gaucher disease mutations, like p.L444P, were absent in this cohort. Enzyme activity analysis revealed a nonsignificant reduction in the GBA -Parkinson's disease individuals (14.49 ± 2.30 nmol/h/mg protein vs. 15.98 ± 3.06 nmol/h/mg in control samples). GBA substitutions occur in both young-onset and late-onset Parkinson's cases in the cohort. Mild GBA substitutions that may not cause Gaucher disease were a common risk factor for Parkinson's disease in the participant group.

Colonic Oxidative and Mitochondrial Function in Parkinson's Disease and Idiopathic REM Sleep Behavior Disorder.

PubMed

Morén, C; González-Casacuberta, Í; Navarro-Otano, J; Juárez-Flores, D; Vilas, D; Garrabou, G; Milisenda, J C; Pont-Sunyer, C; Catalán-García, M; Guitart-Mampel, M; Tobías, E; Cardellach, F; Valldeoriola, F; Iranzo, A; Tolosa, E

2017-01-01

To determine potential mitochondrial and oxidative alterations in colon biopsies from idiopathic REM sleep behavior disorder (iRBD) and Parkinson's disease (PD) subjects. Colonic biopsies from 7 iRBD subjects, 9 subjects with clinically diagnosed PD, and 9 healthy controls were homogenized in 5% w/v mannitol. Citrate synthase (CS) and complex I (CI) were analyzed spectrophotometrically. Oxidative damage was assessed either by lipid peroxidation, through malondialdehyde and hydroxyalkenal content by spectrophotometry, or through antioxidant enzyme levels of superoxide dismutase-2 (SOD2), glutathione peroxidase-1 (Gpx1), and catalase (CAT) by western blot. The presence of mitochondrial DNA (mtDNA) deletions was assessed by long PCR and electrophoresis. Nonsignificant trends to CI decrease in both iRBD (45.69 ± 18.15; 23% decrease) and PD patients (37.57 ± 12.41; 37% decrease) were found compared to controls (59.51 ± 12.52, p : NS). Lipid peroxidation was maintained among groups (iRBD: 27.46 ± 3.04, PD: 37.2 ± 3.92, and controls: 31.71 ± 3.94; p : NS). Antioxidant enzymes SOD2 (iRBD: 2.30 ± 0.92, PD: 1.48 ± 0.39, and controls: 1.09 ± 0.318) and Gpx1 (iRBD 0.29 ± 0.12, PD: 0.56 ± 0.33, and controls: 0.38 ± 0.16) did not show significant differences between groups. CAT was only detected in 2 controls and 1 iRBD subject. One iRBD patient presented a single mtDNA deletion.

Increased risk of parkinsonism associated with welding exposure

PubMed Central

Racette, Brad A.; Criswell, Susan R.; Lundin, Jessica I.; Hobson, Angela; Seixas, Noah; Kotzbauer, Paul T.; Evanoff, Bradley A.; Perlmutter, Joel S.; Zhang, Jing; Sheppard, Lianne; Checkoway, Harvey

2013-01-01

Objective Manganese (Mn), an established neurotoxicant, is a common component of welding fume. The neurological phenotype associated with welding exposures has not been well described. Prior epidemiologic evidence linking occupational welding to parkinsonism is mixed, and remains controversial. Methods This was a cross-sectional and nested case–control study to investigate the prevalence and phenotype of parkinsonism among 811 shipyard and fabrication welders recruited from trade unions. Two reference groups included 59 non-welder trade workers and 118 newly diagnosed, untreated idiopathic PD patients. Study subjects were examined by a movement disorders specialist using the Unified Parkinson Disease Rating Scale motor subsection 3 (UPDRS3). Parkinsonism cases were defined as welders with UPDRS3 score ≥15. Normal was defined as UPDRS3 < 6. Exposure was classified as intensity adjusted, cumulative years of welding. Adjusted prevalence ratios for parkinsonism were calculated in relation to quartiles of welding years. Results The overall prevalence estimate of parkinsonism was 15.6% in welding exposed workers compared to 0% in the reference group. Among welders, we observed a U-shaped dose–response relation between weighted welding exposure-years and parkinsonism. UPDRS3 scores for most domains were similar between welders and newly diagnosed idiopathic Parkinson disease (PD) patients, except for greater frequency of rest tremor and asymmetry in PD patients. Conclusion This work-site based study among welders demonstrates a high prevalence of parkinsonism compared to nonwelding-exposed workers and a clinical phenotype that overlaps substantially with PD. PMID:22975422

Identification of Balance Deficits in People with Parkinson Disease; is the Sensory Organization Test Enough?

PubMed

Gera, G; Freeman, D L; Blackinton, M T; Horak, F B; King, L

2016-02-01

Balance deficits in people with Parkinson's disease can affect any of the multiple systems encompassing balance control. Thus, identification of the specific deficit is crucial in customizing balance rehabilitation. The sensory organization test, a test of sensory integration for balance control, is sometimes used in isolation to identify balance deficits in people with Parkinson's disease. More recently, the Mini-Balance Evaluations Systems Test, a clinical scale that tests multiple domains of balance control, has begun to be used to assess balance in patients with Parkinson's disease. The purpose of our study was to compare the use of Sensory Organization Test and Mini-Balance Evaluations Systems Test in identifying balance deficits in people with Parkinson's disease. 45 participants (27M, 18F; 65.2 ± 8.2 years) with idiopathic Parkinson's disease participated in the cross-sectional study. Balance assessment was performed using the Sensory Organization Test and the Mini-Balance Evaluations Systems Test. People were classified into normal and abnormal balance based on the established cutoff scores (normal balance: Sensory Organization Test >69; Mini-Balance Evaluations Systems Test >73). More subjects were classified as having abnormal balance with the Mini-Balance Evaluations Systems Test (71% abnormal) than with the Sensory Organization Test (24% abnormal) in our cohort of people with Parkinson's disease. There were no subjects with a normal Mini-Balance Evaluations Systems Test score but abnormal Sensory Organization Test score. In contrast, there were 21 subjects who had an abnormal Mini-Balance Evaluations Systems Test score but normal Sensory Organization Test scores. Findings from this study suggest that investigation of sensory integration deficits, alone, may not be able to identify all types of balance deficits found in patients with Parkinson's disease. Thus, a comprehensive approach should be used to test of multiple balance systems to provide

Neurosurgical interventions in the treatment of idiopathic Parkinson disease: neurostimulation and neural implantation.

PubMed

Kupsch, A; Earl, C

1999-01-01

With the exception of thalamotomy for drug-refractory tremor, surgical therapy for Parkinson's disease has been almost abandoned as treatment for Parkinsonian symptoms between 1965 and 1985. Reasons for this development relate to inconsistent postoperative results, complications associated with stereotactic surgical techniques and, most importantly, the advent of levodopa, which is still considered to be the gold standard in pharmacotherapy for Parkinson's disease. However, both, the long-term experience with L-DOPA therapy on the one hand and the progress of advanced stereotactic techniques and fetal graft research on the other hand have lead to reconsideration of surgical therapy in Parkinson's disease for patients, who can not be treated satisfactorily with medication. Both lesions (via thermocoagulation) and/or neurostimulation (via chronic intracerebral implantation of electrodes) in thalamic nuclei (nucleus ventralis oralis posterior/intermedialis thalami; VOP/VIM) may alleviate rest tremor in PD patients. In principle neurostimulation has the significant advantage of reversibility with regard to side effects in comparison to lesion surgery. Furthermore ventro-posterior pallidotomy or chronic stimulation in this structures may ameliorate bradykinesia and levodopa-induced dyskinesias. Additionally, "switching-off" the subthalamic nucleus by neurostimulation has been reported to reduce rigidity, bradykinesia and levodopa-induced ON-OFF-fluctuations. On the other hand, neuronal transplantation of fetal nigral dopamine precursor cells aims at restoring the striatal dopamine deficit. Both animal and clinical experiments have shown that fetal grafts survive intrastriatal transplantation and may ensue moderate to satisfactory improvements, especially in regard to bradykinesia and ON-OFF-fluctuations. Further progress in the field of neuronal transplantation will largely depend on the development of alternative cell resources.

Cognition in Patients With a Clinical Diagnosis of Parkinson Disease and Scans Without Evidence of Dopaminergic Deficit (SWEDD): 2-Year Follow-Up.

PubMed

Wyman-Chick, Kathryn A; Martin, Phillip K; Minár, Michal; Schroeder, Ryan W

2016-12-01

More than 10% of patients clinically diagnosed with Parkinson disease demonstrate normal dopamine uptake on dopamine transporter single-photon emission computed tomography (DaTscan), but little is known about how cognitive function differs between patients with dopamine deficiency on DaTscan and patients with scans without evidence of dopaminergic deficit (SWEDD). We compared the cognitive function of these two groups of patients over 2 years. We retrospectively analyzed data obtained from the Parkinson's Progression Markers Initiative on 309 participants clinically diagnosed with idiopathic Parkinson disease who had scored in the normal range on the Montreal Cognitive Assessment at baseline and had completed 1- and 2-year follow-up visits. We compared the Montreal Cognitive Assessment scores at 1 and 2 years between the 42 participants with SWEDD and the 267 with dopamine deficiency. Mean cognitive scores did not differ significantly between groups at 1 year, but at 2 years the participants with SWEDD performed more poorly. At 2 years, 31% of the participants with SWEDD versus 15% of those with dopamine deficiency had statistically reliable cognitive impairment. This study provides evidence that some individuals clinically diagnosed with idiopathic Parkinson disease but with SWEDD demonstrate early cognitive decline. The results also suggest that recently diagnosed patients with SWEDD may be at even greater risk for cognitive decline than patients with DaTscan-confirmed early-stage Parkinson disease. While patients with SWEDD likely represent a heterogeneous group of etiologies, our results highlight the need to monitor these patients' cognitive function over time.

Lewy Body Dementias: Dementia With Lewy Bodies and Parkinson Disease Dementia

PubMed Central

Gomperts, Stephen N.

2016-01-01

ABSTRACT Purpose of Review: This article provides an overview of the clinical features, neuropathologic findings, diagnostic criteria, and management of dementia with Lewy bodies (DLB) and Parkinson disease dementia (PDD), together known as the Lewy body dementias. Recent Findings: DLB and PDD are common, clinically similar syndromes that share characteristic neuropathologic changes, including deposition of α-synuclein in Lewy bodies and neurites and loss of tegmental dopamine cell populations and basal forebrain cholinergic populations, often with a variable degree of coexisting Alzheimer pathology. The clinical constellations of DLB and PDD include progressive cognitive impairment associated with parkinsonism, visual hallucinations, and fluctuations of attention and wakefulness. Current clinical diagnostic criteria emphasize these features and also weigh evidence for dopamine cell loss measured with single-photon emission computed tomography (SPECT) imaging and for rapid eye movement (REM) sleep behavior disorder, a risk factor for the synucleinopathies. The timing of dementia relative to parkinsonism is the major clinical distinction between DLB and PDD, with dementia arising in the setting of well-established idiopathic Parkinson disease (after at least 1 year of motor symptoms) denoting PDD, while earlier cognitive impairment relative to parkinsonism denotes DLB. The distinction between these syndromes continues to be an active research question. Treatment for these illnesses remains symptomatic and relies on both pharmacologic and nonpharmacologic strategies. Summary: DLB and PDD are important and common dementia syndromes that overlap in their clinical features, neuropathology, and management. They are believed to exist on a spectrum of Lewy body disease, and some controversy persists in their differentiation. Given the need to optimize cognition, extrapyramidal function, and psychiatric health, management can be complex and should be systematic. PMID

Conjugal Parkinsonism and Parkinson Disease: A Case Series with Environmental Risk Factor Analysis

PubMed Central

Sterling, Callen; Racette, Brad A.

2009-01-01

PD occurring in married couples, “conjugal PD” represents a unique opportunity to study environmental risk factors for PD due to the shared environment. This retrospective study of non-related married individuals who both presented to the Washington University Movement Disorders Center between 1994 and 2005 investigated the clinical presentation, therapy response, and disease course in conjugal PD subjects. In addition, an occupational, residential, and environmental survey was administered to elucidate potential shared environmental risk factors. Eighteen married subjects had a clinical picture suggestive of idiopathic Parkinson disease. Average age of motor symptom onset was 66.1 (±6.22) years in women, 63.4 (±7.87) years in men. Subjects cohabitated an average of 39.9 years prior to motor symptom onset in the first affected spouse and an average of nine years elapsed prior to symptom onset in their partner. Disease course in conjugal pairs varied substantially. Seventeen out of eighteen subjects reported at least one environmental exposure of interest. Concordant exposures were residential, non-occupational pesticide and heavy metal exposure, each reported by 77.8% (7/9) of couples. Multiple exposures were reported by 88.9% (16/18) of subjects, most often residential agricultural chemical and heavy metal in combination. This case series of conjugal PD suggests that combined residential exposures may be important in the pathogenesis of idiopathic PD. Larger conjugal PD studies may permit stratification of concordant environmental exposures to determine dose responsiveness and relative contributions to PD risk. PMID:19818671

Real life evaluation of safinamide effectiveness in Parkinson's disease.

PubMed

Mancini, Francesca; Di Fonzo, Alessio; Lazzeri, Giulia; Borellini, Linda; Silani, Vincenzo; Lacerenza, Marco; Comi, Cristoforo

2018-04-01

In this retrospective study, we evaluated both efficacy and effectiveness of safinamide 50 and 100 mg in the treatment of motor fluctuations and disabling dyskinesias in a cohort of patients with idiopathic Parkinson's disease (PD). Ninety-one PD patients were evaluated during the first year of commercialization of the drug, both prior to starting safinamide and at the last available follow-up. Evaluations were based on the Unified Parkinson's Disease Scale part III (UPDRS III), Hoehn & Yahr (HY), Unified Dyskinesia Rating Scale (UDysRS) walking and balance item 9 score, daily time spent in OFF and in ON with disabling dyskinesias (1 week diary), mean daily dose of levodopa (LD), dopamine-agonists (DA), catechol-O-methyl transferase inhibitor (COMT-I), monoamine oxidase B inhibitor (MAOB-I), and their LD equivalent dose (LEDD). Eight patients withdrew safinamide within the first month for minor side effects. At the follow-up evaluation, after a mean time with safinamide of 7.5 months ± 3.4, all patients showed a significant improvement of all the scale scores, except for HY, and of the daily dosages of the drugs and the LEDD. The same results were shown by PD patients treated with safinamide 50 mg and patients who started safinamide without switching from a previous MAOBI. PD patients with safinamide 100 mg and patients who started safinamide switching from a previous MAOBI significantly improved in time spent in OFF and LEDD. In conclusion, safinamide is safe and effective in improving motor complications in patients with idiopathic PD and can be considered a useful levodopa sparing strategy.

A randomized controlled trial of movement strategies compared with exercise for people with Parkinson's disease.

PubMed

Morris, Meg E; Iansek, Robert; Kirkwood, Beth

2009-01-15

This randomized controlled clinical trial was conducted to compare the effects of movement rehabilitation strategies and exercise therapy in hospitalized patients with idiopathic Parkinson's disease. Participants were randomly assigned to a group that received movement strategy training or musculoskeletal exercises during 2 consecutive weeks of hospitalization. The primary outcome was disability as measured by the Unified Parkinson's Disease Rating Scale, UPDRS (motor and ADL components). Secondary outcomes were balance, walking speed, endurance, and quality of life. Assessments were carried out by blinded testers at baseline, after the 2 weeks of treatment and 3 months after discharge. The movement strategy group showed improvements on several outcome measures from admission to discharge, including the UPDRS, 10 m walk, 2 minute walk, balance, and PDQ39. However, from discharge to follow up there was significant regression in performance on the 2 minute walk and PDQ39. For the exercise group, quality of life improved significantly during inpatient hospitalization and this was retained at follow-up. Inpatient rehabilitation produces short term reductions in disability and improvements in quality of life in people with Parkinson's disease.

The coeruleus/subcoeruleus complex in idiopathic rapid eye movement sleep behaviour disorder.

PubMed

Ehrminger, Mickael; Latimier, Alice; Pyatigorskaya, Nadya; Garcia-Lorenzo, Daniel; Leu-Semenescu, Smaranda; Vidailhet, Marie; Lehericy, Stéphane; Arnulf, Isabelle

2016-04-01

Idiopathic rapid eye movement sleep behaviour disorder is characterized by nocturnal violence, increased muscle tone during rapid eye movement sleep and the lack of any other neurological disease. However, idiopathic rapid eye movement sleep behaviour disorder can precede parkinsonism and dementia by several years. Using 3 T magnetic resonance imaging and neuromelanin-sensitive sequences, we previously found that the signal intensity was reduced in the locus coeruleus/subcoeruleus area of patients with Parkinson's disease and rapid eye movement sleep behaviour disorder. Here, we studied the integrity of the locus coeruleus/subcoeruleus complex with neuromelanin-sensitive imaging in 21 patients with idiopathic rapid eye movement sleep behaviour disorder and compared the results with those from 21 age- and gender-matched healthy volunteers. All subjects underwent a clinical examination, motor, cognitive, autonomous, psychological, olfactory and colour vision tests, and rapid eye movement sleep characterization using video-polysomnography and 3 T magnetic resonance imaging. The patients more frequently had preclinical markers of alpha-synucleinopathies, including constipation, olfactory deficits, orthostatic hypotension, and subtle motor impairment. Using neuromelanin-sensitive imaging, reduced signal intensity was identified in the locus coeruleus/subcoeruleus complex of the patients with idiopathic rapid eye movement sleep behaviour. The mean sensitivity of the visual analyses of the signal performed by neuroradiologists who were blind to the clinical diagnoses was 82.5%, and the specificity was 81% for the identification of idiopathic rapid eye movement sleep behaviour. The results confirm that this complex is affected in idiopathic rapid eye movement sleep behaviour (to the same degree as it is affected in Parkinson's disease). Neuromelanin-sensitive imaging provides an early marker of non-dopaminergic alpha-synucleinopathy that can be detected on an individual

Hereditary Parkinson s Disease Natural History Protocol

ClinicalTrials.gov

2018-03-27

Parkinson Disease 6, Early-Onset; Parkinson Disease (Autosomal Recessive, Early Onset) 7, Human; Parkinson Disease Autosomal Recessive, Early Onset; Parkinson Disease, Autosomal Recessive Early-Onset, Digenic, Pink1/Dj1

Beyond factor analysis: Multidimensionality and the Parkinson's Disease Sleep Scale-Revised.

PubMed

Pushpanathan, Maria E; Loftus, Andrea M; Gasson, Natalie; Thomas, Meghan G; Timms, Caitlin F; Olaithe, Michelle; Bucks, Romola S

2018-01-01

Many studies have sought to describe the relationship between sleep disturbance and cognition in Parkinson's disease (PD). The Parkinson's Disease Sleep Scale (PDSS) and its variants (the Parkinson's disease Sleep Scale-Revised; PDSS-R, and the Parkinson's Disease Sleep Scale-2; PDSS-2) quantify a range of symptoms impacting sleep in only 15 items. However, data from these scales may be problematic as included items have considerable conceptual breadth, and there may be overlap in the constructs assessed. Multidimensional measurement models, accounting for the tendency for items to measure multiple constructs, may be useful more accurately to model variance than traditional confirmatory factor analysis. In the present study, we tested the hypothesis that a multidimensional model (a bifactor model) is more appropriate than traditional factor analysis for data generated by these types of scales, using data collected using the PDSS-R as an exemplar. 166 participants diagnosed with idiopathic PD participated in this study. Using PDSS-R data, we compared three models: a unidimensional model; a 3-factor model consisting of sub-factors measuring insomnia, motor symptoms and obstructive sleep apnoea (OSA) and REM sleep behaviour disorder (RBD) symptoms; and, a confirmatory bifactor model with both a general factor and the same three sub-factors. Only the confirmatory bifactor model achieved satisfactory model fit, suggesting that PDSS-R data are multidimensional. There were differential associations between factor scores and patient characteristics, suggesting that some PDSS-R items, but not others, are influenced by mood and personality in addition to sleep symptoms. Multidimensional measurement models may also be a helpful tool in the PDSS and the PDSS-2 scales and may improve the sensitivity of these instruments.

Voice quality outcomes of idiopathic Parkinson's disease medical treatment: A systematic review.

PubMed

Lechien, J R; Blecic, S; Huet, K; Delvaux, V; Piccaluga, M; Roland, V; Harmegnies, B; Saussez, S

2018-06-01

To investigate voice quality (VQ) impairments in idiopathic Parkinson's disease (IPD) and to explore the impact of medical treatments and L-Dopa challenge testing on voice. Relevant studies published between January 1980 and June 2017 describing VQ evaluations in IPD were retrieved using PubMed, Scopus, Biological Abstracts, BioMed Central and Cochrane databases. Issues of clinical relevance, including IPD treatment efficiency and voice quality outcomes, were evaluated for each study. The grade of recommendation for each publication was determined according to the Oxford Centre for Evidence-Based Medicine evidence levels. The database research yielded 106 relevant publications, of which 33 studies met the inclusion criteria, for a total of 964 patients with IPD. Data were extracted by 3 independent physicians who identified 21, 11 and 1 trials with IIIb, IIb and IIa evidence levels, respectively. The main VQ assessment tools used were acoustic testing (N = 27), aerodynamic testing (N = 10), subjective measurements (N = 8) and videolaryngostroboscopy (N = 3). The majority of trials (N = 32/33) identified subjective or objective VQ improvements after medical treatment (N = 10) or better VQ evaluations in healthy subjects compared to patients with IPD (N = 22). Especially, our analysis supports that VQ overall improves during the L-Dopa challenge testing, making the VQ evaluation an additional tool for the IPD diagnosis. The methodology used to assess subjective and objective VQ substantially varied from 1 study to another. All of the included studies took into consideration the patient's clinical profile in the VQ analysis. The majority of studies supported that VQ assessments remain useful as outcome measures of the effectiveness of medical treatment and could be helpful for the IPD diagnosis based on L-Dopa challenge testing. Further controlled studies using standardised and transparent methodology for measuring acoustic parameters are necessary to

Presymptomatic detection of Parkinson's disease.

PubMed

Jenner, P

1993-01-01

Presymptomatic detection of Parkinson's disease is necessary if neuroprotective therapies are to be utilized in its treatment. Various methods (PET, electrophysiology, enzyme assays, olfactory function) may be applicable but none has been rigorously evaluated. Other possible approaches are now considered. Plasma HVA levels (pHVA) in the presence of debrisoquine may reflect cerebral dopamine function. However, there are no detectable differences in pHVA between newly diagnosed and untreated parkinsonian patients and control subjects. Compensatory increases in dopamine turnover may mask a decrease in pHVA in the early stages of the disease. So, at present this technique could not be used as a diagnostic tool. Post-mortem studies of brain in Parkinson's disease may provide clues to biochemical markers indicative of nigral pathology. Mitochondrial complex I activity is reduced in substantia nigra in Parkinson's disease and it was reported also to be markedly reduced in blood platelets. However, subsequent studies suggest that the difference in platelet complex I activity is too small to be diagnostic of Parkinson's disease. There are also selective reductions in brain glutathione levels in Parkinson's disease restricted to substantia nigra, which do not occur in other neurodegenerative disorders and are not due to drug treatment. Importantly, in incidental Lewy body disease (preclinical Parkinson's disease) nigral glutathione levels are reduced to the same degree as in advanced Parkinson's disease. So, some peripheral index of altered glutathione function may be valuable in the early detection of the disease process.

Increased risk of parkinsonism associated with welding exposure.

PubMed

Racette, Brad A; Criswell, Susan R; Lundin, Jessica I; Hobson, Angela; Seixas, Noah; Kotzbauer, Paul T; Evanoff, Bradley A; Perlmutter, Joel S; Zhang, Jing; Sheppard, Lianne; Checkoway, Harvey

2012-10-01

Manganese (Mn), an established neurotoxicant, is a common component of welding fume. The neurological phenotype associated with welding exposures has not been well described. Prior epidemiologic evidence linking occupational welding to parkinsonism is mixed, and remains controversial. This was a cross-sectional and nested case-control study to investigate the prevalence and phenotype of parkinsonism among 811 shipyard and fabrication welders recruited from trade unions. Two reference groups included 59 non-welder trade workers and 118 newly diagnosed, untreated idiopathic PD patients. Study subjects were examined by a movement disorders specialist using the Unified Parkinson Disease Rating Scale motor subsection 3 (UPDRS3). Parkinsonism cases were defined as welders with UPDRS3 score ≥15. Normal was defined as UPDRS3<6. Exposure was classified as intensity adjusted, cumulative years of welding. Adjusted prevalence ratios for parkinsonism were calculated in relation to quartiles of welding years. The overall prevalence estimate of parkinsonism was 15.6% in welding exposed workers compared to 0% in the reference group. Among welders, we observed a U-shaped dose-response relation between weighted welding exposure-years and parkinsonism. UPDRS3 scores for most domains were similar between welders and newly diagnosed idiopathic Parkinson disease (PD) patients, except for greater frequency of rest tremor and asymmetry in PD patients. This work-site based study among welders demonstrates a high prevalence of parkinsonism compared to nonwelding-exposed workers and a clinical phenotype that overlaps substantially with PD. Copyright © 2012 Elsevier Inc. All rights reserved.

Astrocyte dysfunction following molybdenum-associated purine loading could initiate Parkinson's disease with dementia.

PubMed

Bourke, Christopher A

2018-01-01

Sporadic or idiopathic Parkinson's disease is a movement disorder with a worldwide distribution, a long pre-clinical latent period and a frequent association with dementia. The combination of molybdenum deficiency and purine ingestion could explain the movement disorder, the distribution, the latent period and the dementia association. Recent studies in sheep have shown that molybdenum deficiency enables some dietary purines to accumulate in the central nervous system. This causes astrocyte dysfunction, altered neuromodulation and eventually irreversible central nervous system disease. Humans and sheep share the ability to salvage purines and this ability places humans at risk when they ingest xanthosine, inosine, adenosine and guanosine. Adenosine ingestion in molybdenum-deficient humans will lead to adenosine loading and potentially a disturbance to the A2a adenosine receptors in the nigro-striatum. This could result in Parkinson's disease. Guanosine ingestion in molybdenum-deficient humans will lead to guanosine loading and potentially a disturbance to the guanosine receptors in the hippocampus, amygdala and ventral striatum. This could result in dementia. The molybdenum content of the average daily diet in the United States is 0.07 ppm and in the United Kingdom 0.04 ppm. Central nervous system disease occurs in sheep at <0.04 ppm. Consistent with the role proposed for molybdenum deficiency in Parkinson's disease is the observation that affected individuals have elevated sulfur amino acid levels, depressed sulfate levels, and depressed uric acid levels. Likewise the geographical distribution of Parkinson's dementia complex on Guam corresponds with the distribution of molybdenum-deficient soils hence molybdenum-deficient food gardens on that island.

Tremor analysis separates Parkinson's disease and dopamine receptor blockers induced parkinsonism.

PubMed

Shaikh, Aasef G

2017-05-01

Parkinson's disease, the most common cause of parkinsonism is often difficult to distinguish from its second most common etiology due to exposure to dopamine receptor blocking agents such as antiemetics and neuroleptics. Dual axis accelerometry was used to quantify tremor in 158 patients with parkinsonism; 62 had Parkinson's disease and 96 were clinically diagnosed with dopamine receptor blocking agent-induced parkinsonism. Tremor was measured while subjects rested arms (resting tremor), outstretched arms in front (postural tremor), and reached a target (kinetic tremor). Cycle-by-cycle analysis was performed to measure cycle duration, oscillation amplitude, and inter-cycle variations in the frequency. Patients with dopamine receptor blocker induced parkinsonism had lower resting and postural tremor amplitude. There was a substantial increase of kinetic tremor amplitude in both disorders. Postural and resting tremor in subjects with dopamine receptor blocking agent-induced parkinsonism was prominent in the abduction-adduction plane. In contrast, the Parkinson's disease tremor had equal amplitude in all three planes of motion. Tremor frequency was comparable in both groups. Remarkable variability in the width of the oscillatory cycles suggested irregularity in the oscillatory waveforms in both subtypes of parkinsonism. Quantitative tremor analysis can distinguish Parkinson's disease from dopamine receptor blocking agent-induced parkinsonism.

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Multiple Factors Are Involved in the Dysarthria Associated with Parkinson's Disease: A Review with Implications for Clinical Practice and Research

ERIC Educational Resources Information Center

Sapir, Shimon

2014-01-01

Purpose: Motor speech abnormalities are highly common and debilitating in individuals with idiopathic Parkinson's disease (IPD). These abnormalities, collectively termed hypokinetic dysarthria (HKD), have been traditionally attributed to hypokinesia and bradykinesia secondary to muscle rigidity and dopamine deficits. However, the role of…

Idiopathic Parkinson’s disease phenotype related to C9ORF72 repeat expansions: contribution of the neuropsychological assessment

PubMed Central

2013-01-01

Background Expanded GGGGCC hexanucleotide repeats in the non-coding region of the C9ORF72 gene was recently identified as being responsible for over 40% of the cases of amyotrophic lateral sclerosis associated with frontotemporal lobar degeneration, in various extrapyramidal syndromes including supranuclear gaze palsy and corticobasal degeneration, and in addition, has been found to be a rare genetic cause of isolated Parkinsonism. To our knowledge, there is no published data concerning the neuropsychological evaluation of patients diagnosed with idiopathic Parkinson’s disease related with C9ORF72 repeat expansions. Case presentation We report the results of the comprehensive neuropsychological evaluation in a newly described case in the literature (the sixth) of a patient presenting isolated idiopathic Parkinson’s disease associated with C9ORF72 repeat expansions. The decrease in the patient’s prefrontal functions resulted in a slight decrease in global efficiency. These abnormalities did not appear to be different, with respect to the deficit observed and the intensity of the cognitive impairment, from those classically observed in cases of sporadic idiopathic Parkinson’s disease. Our patient also exhibited a significant impairment in visual gnosis. Conclusions If confirmed in other patients, visuoperceptive deficits in idiopathic Parkinson’s disease could represent a red flag that should prompt the clinician to perform addition diagnostic procedures. A thorough neuropsychological assessment may prove to be useful for detecting idiopathic Parkinson’s disease in patients who are suspected of having repeat abnormalities of C9ORF72 expansions. PMID:23987827

Lower urinary tract symptoms in men with Parkinson disease.

PubMed

Robinson, Joanne P; Bradway, Christine W; Bunting-Perry, Lisette; Avi-Itzhak, Tamara; Mangino, Marie; Chittams, Jesse; Duda, John E

2013-12-01

The aim of this study was to examine the prevalence, presentation, and predictors of lower urinary tract symptoms (LUTS) in men with idiopathic Parkinson disease (PD). Guided by the Theory of Unpleasant Symptoms, this retrospective exploratory study used data abstracted from admission clinical records of 271 male patients with idiopathic PD enrolled in a movement disorders clinic at a large metropolitan Veterans Affairs Medical Center in the eastern region of the United States. Data from the admission questionnaire, Unified Parkinson's Disease Rating Scale, and Mini Mental State Examination were abstracted by trained research assistants. Interrater reliability for the abstraction process was 0.99 in a randomly selected 10% sample of records. Descriptive statistics were used to determine the prevalence of LUTS. Logistic regression was used to determine LUTS risk factors and predictors. At least one LUTS was reported by 40.2% of participants. Incontinence was the most prevalent symptom, affecting almost 25% of participants, followed by nocturia (14.8%) and frequency (13.7%). Of the 10 identified risk factors for LUTS, four significant predictors were discovered: number of non-PD medications (p < .05), PD duration (p < .05), number of comorbidities (p < .05), and history of a hernia diagnosis (p < .05). Assessment for LUTS should be a component of every evaluation of a patient with PD. Our findings offer a preliminary profile of the male PD patient with LUTS, which is an important step toward effective screening, detection, and access to care and treatment. Next steps in research include further work to identify predictors of LUTS in both male and female PD populations, explore patient perspectives, begin trials of interventions for LUTS in the PD population, and analyze the economic impact.

Electroconvulsive Therapy Intervention for Parkinson's Disease.

PubMed

Narang, Puneet; Glowacki, Anna; Lippmann, Steven

2015-01-01

Electroconvulsive therapy is an established means to improve function in a variety of psychiatric and neurologic conditions, particularly for patients who remain treatment-refractory. Parkinson's disease is a neurodegenerative disorder that sometimes does not respond well to conventional pharmacotherapies. Reports have indicated that electroconvulsive therapy may be an effective and safe treatment for those patients with Parkinson's disease who are not optimally responding to first-line treatments. Despite these reports, however, electroconvulsive therapy is not often used by clinicians in patients with treatment-resistant Parkinson's disease, perhaps due to stigma, lack of knowledge regarding its safety and efficacy, and/or inability to predict the duration of therapeutic benefit. Our objective was to determine if the available literature on ECT supports it as a safe and effective treatment option in patients with treatment-refractory Parkinson's disease. Motoric improvement induced by electroconvulsive therapy has been documented for decades in persons with Parkinson's disease. Efficacy and safety are reported following electroconvulsive therapy in people with Parkinson's disease who have sub-optimal response to medicines or experience the "on/off" phenomenon to L-dopa. Electroconvulsive therapy is an effective option for acute and maintenance treatment of Parkinson's disease in select patients. Inability to predict how long the beneficial effects of ECT therapy will last in patients with Parkinson's disease may be a reason why this treatment is underutilized by clinicians. More research is warranted to clarify parameters for application and duration of therapeutic benefit in individuals with difficult-to-treat Parkinson's disease.

Multi-Modal Hallucinations and Cognitive Function in Parkinson's Disease

PubMed Central

Katzen, Heather; Myerson, Connie; Papapetropoulos, Spiridon; Nahab, Fatta; Gallo, Bruno; Levin, Bonnie

2010-01-01

Background/Aims Hallucinations have been linked to a constellation of cognitive deficits in Parkinson's disease (PD), but it is not known whether multi-modal hallucinations are associated with greater neuropsychological dysfunction. Methods 152 idiopathic PD patients were categorized based on the presence or absence of hallucinations and then were further subdivided into visual-only (VHonly; n = 35) or multi-modal (VHplus; n = 12) hallucination groups. All participants underwent detailed neuropsychological assessment. Results Participants with hallucinations performed more poorly on select neuropsychological measures and exhibited more mood symptoms. There were no differences between VHonly and VHplus groups. Conclusions PD patients with multi-modal hallucinations are not at greater risk for neuropsychological impairment than those with single-modal hallucinations. PMID:20689283

Evaluation of dyskinesias in a pilot, randomized, placebo-controlled trial of remacemide in advanced Parkinson disease.

PubMed

2001-10-01

Long-term levodopa therapy for Parkinson disease commonly results in motor complications including "on-off" fluctuations and dyskinesias, but it is still unclear how best to assess treatment effects on dyskinesias in clinical trials. To compare several methods of rating levodopa-induced dyskinesias to evaluate the effect of remacemide hydrochloride treatment in patients with advanced Parkinson disease. Two-week multicenter randomized, double-blind, placebo-controlled, parallel-group study. Five academic sites of the Parkinson Study Group. Thirty-nine subjects at least 30 years old with idiopathic Parkinson disease and disabling dyskinesias. Randomly received daily doses of 150 mg, 300 mg, or 600 mg of remacemide hydrochloride or matching placebo for 2 weeks. The dyskinesia rating scales used were the Modified Goetz Dyskinesia Rating scale (MGDRS), a newly created Lang-Fahn Activities of Daily Living Dyskinesia scale (LFADLDS), and diary dyskinesia ratings. Patient and investigator diaries showed excellent agreement in dyskinesia ratings. The MGDRS score correlated with clinic diary ratings of the percentage of "on" time with dyskinesias, and the LFADLDS score correlated with home and clinic diary assessments of percentage of on time with severe dyskinesias. The MGDRS score did not correlate highly with the LFADLDS score. This pilot study also validated previous results demonstrating the safety and tolerability of remacemide treatment for advanced Parkinson disease but did not result in any demonstrable improvement or worsening in dyskinesia measures. Diaries may provide a valid means of evaluating dyskinesias in clinical trials for Parkinson disease, but there remain other aspects of dyskinesias, as assessed by the MGDRS and LFADLDS, that are not reflected in diary ratings.

Self-amplification of nigral degeneration in Parkinson's disease: a hypothesis.

PubMed

Ionov, Ilya D

2008-12-01

This review analyzes current evidence regarding possible mechanisms of nigral damage in idiopathic Parkinson's disease (iPD). In normal brain, a specific interplay among the blood-brain barrier (BBB), substantia nigra (SN), and locus coeruleus (LC) creates the condition for a self-accelerating damage to the SN. Three vicious circles involving SN-BBB, LC-SN-BBB, and histamine-BBB-SN interactions are described. In iPD, a self-accelerating loss of nigral cells can be triggered by brain hypoperfusion and by an increased blood histamine level. iPD-associated factors such as decreased CSF levels of substance P, somatostatin, and glutamate can aggravate the vicious-circle-induced damage to the SN.

Adolf Hitler and His Parkinsonism.

PubMed

Bhattacharyya, Kalyan B

2015-01-01

Research works have suggested almost incontrovertibly, that Adolf Hitler suffered from Parkinsonism. However, the precise nature of his illness had always been controversial and post-encephalitic and idiopathic varieties were the ones which were most commonly thought as the possible etiology. He displayed features like oculogyric crisis, palilalia, and autonomic symptoms which strongly implicate post-encephalitic etiology in the genesis of his illness. Others on the contrary, observed premorbid personality traits like non-flinching mental rigidity, extreme inflexibility, and awesome pedantry; which are often observed in idiopathic Parkinson's disease. Moreover, nonmotor symptoms like disturbed sleep, proneness to temper tantrums, phases of depression, suspiciousness, and lack of trust on colleagues have also been described by various authors. Additionally, he was prescribed methamphetamine by his personal doctor and that might have led to the development of some of the later traits in his personality.

Assessment of postural instability in patients with Parkinson's disease.

PubMed

Błaszczyk, J W; Orawiec, R; Duda-Kłodowska, D; Opala, G

2007-10-01

Postural instability is one of the most disabling features of idiopathic Parkinson's disease (PD). In this study, we focused on postural instability as the main factor predisposing parkinsonians to falls. For this purpose, changes in sway characteristics during quiet stance due to visual feedback exclusion were studied. We searched for postural sway measures that could be potential discriminators for an increased fall risk. A group of 110 subjects: 55 parkinsonians (Hoehn and Yahr: 1-3), and 55 age-matched healthy volunteers participated in the experiment. Their spontaneous sway characteristics while standing quiet with eyes open and eyes closed were analyzed. We found that an increased mediolateral sway and sway area while standing with eyes closed are characteristic of parkinsonian postural instability and may serve to quantify well a tendency to fall. These sway indices significantly correlated with disease severity rated both by the Hoehn and Yahr scale as well as by the Motor Section of the UPDRS. A forward shift of a mean COP position in parkinsonians which reflects their flexed posture was also significantly greater to compare with the elderly subjects and exhibited a high sensitivity to visual conditions. Both groups of postural sway abnormalities identified here may be used as accessible and reliable measures which allow for quantitative assessment of postural instability in Parkinson's disease.

Acute Modulation of Brain Connectivity in Parkinson Disease after Automatic Mechanical Peripheral Stimulation: A Pilot Study.

PubMed

Quattrocchi, Carlo Cosimo; de Pandis, Maria Francesca; Piervincenzi, Claudia; Galli, Manuela; Melgari, Jean Marc; Salomone, Gaetano; Sale, Patrizio; Mallio, Carlo Augusto; Carducci, Filippo; Stocchi, Fabrizio

2015-01-01

The present study shows the results of a double-blind sham-controlled pilot trial to test whether measurable stimulus-specific functional connectivity changes exist after Automatic Mechanical Peripheral Stimulation (AMPS) in patients with idiopathic Parkinson Disease. Eleven patients (6 women and 5 men) with idiopathic Parkinson Disease underwent brain fMRI immediately before and after sham or effective AMPS. Resting state Functional Connectivity (RSFC) was assessed using the seed-ROI based analysis. Seed ROIs were positioned on basal ganglia, on primary sensory-motor cortices, on the supplementary motor areas and on the cerebellum. Individual differences for pre- and post-effective AMPS and pre- and post-sham condition were obtained and first entered in respective one-sample t-test analyses, to evaluate the mean effect of condition. Effective AMPS, but not sham stimulation, induced increase of RSFC of the sensory motor cortex, nucleus striatum and cerebellum. Secondly, individual differences for both conditions were entered into paired group t-test analysis to rule out sub-threshold effects of sham stimulation, which showed stronger connectivity of the striatum nucleus with the right lateral occipital cortex and the cuneal cortex (max Z score 3.12) and with the right anterior temporal lobe (max Z score 3.42) and of the cerebellum with the right lateral occipital cortex and the right cerebellar cortex (max Z score 3.79). Our results suggest that effective AMPS acutely increases RSFC of brain regions involved in visuo-spatial and sensory-motor integration. This study provides Class II evidence that automatic mechanical peripheral stimulation is effective in modulating brain functional connectivity of patients with Parkinson Disease at rest. Clinical Trials.gov NCT01815281.

Insomnia, Sleep Quality, and Quality of Life in Mild to Moderate Parkinson's Disease.

PubMed

Shafazand, Shirin; Wallace, Douglas M; Arheart, Kristopher L; Vargas, Silvia; Luca, Corneliu C; Moore, Henry; Katzen, Heather; Levin, Bonnie; Singer, Carlos

2017-03-01

Sleep disorders are prevalent in Parkinson's disease but underreported in clinical settings. The contribution of sleep disorders to health-related quality of life (HRQOL) for patients with this degenerative neurological disease are not well known. To evaluate the impact of insomnia symptoms, obstructive sleep apnea (OSA), and poor sleep quality on HRQOL in a cohort of patients with idiopathic Parkinson's disease. We enrolled a convenience sample of 66 adults seen in the University of Miami Movement Disorders Clinic between July 2011 and June 2013. Participants completed validated questionnaires to determine insomnia symptoms, OSA risk, depression, anxiety, and HRQOL. All patients underwent unattended polysomnography to confirm OSA. Results were compared for those with and without insomnia symptoms. Principal component and regression analyses were performed to evaluate determinants of HRQOL. Participants were predominately Hispanic males with mild to moderate Parkinson's disease. Insomnia symptoms were reported for 46% of the study subjects. OSA (apnea-hypopnea index, ≥5) was noted in 47%, with a mean apnea-hypopnea index of 8.3 ± 11.0. Fairly bad to very bad sleep quality was reported by 21% of the participants. Insomnia (r = 0.71; P < 0.001), daytime sleepiness (r = 0.36; P = 0.003), depression symptoms (r =  0.44; P < 0.001), and anxiety symptoms (r = 0.33; P = 0.006) were significant correlates of poor sleep quality. OSA, severity of Parkinson's disease, and dopaminergic therapy were not. In the principal component analysis, sleep quality was a significant component of the "psychological factor" that in turn was a significant determinant of overall HRQOL. Insomnia symptoms, OSA, and subsequent poor sleep quality are prevalent in Parkinson's disease. In this single-center, exploratory study, we found that insomnia and poor sleep quality, but not OSA, play important roles in determining overall quality of life for patients

Atomoxetine restores the response inhibition network in Parkinson's disease.

PubMed

Rae, Charlotte L; Nombela, Cristina; Rodríguez, Patricia Vázquez; Ye, Zheng; Hughes, Laura E; Jones, P Simon; Ham, Timothy; Rittman, Timothy; Coyle-Gilchrist, Ian; Regenthal, Ralf; Sahakian, Barbara J; Barker, Roger A; Robbins, Trevor W; Rowe, James B

2016-08-01

Parkinson's disease impairs the inhibition of responses, and whilst impulsivity is mild for some patients, severe impulse control disorders affect ∼10% of cases. Based on preclinical models we proposed that noradrenergic denervation contributes to the impairment of response inhibition, via changes in the prefrontal cortex and its subcortical connections. Previous work in Parkinson's disease found that the selective noradrenaline reuptake inhibitor atomoxetine could improve response inhibition, gambling decisions and reflection impulsivity. Here we tested the hypotheses that atomoxetine can restore functional brain networks for response inhibition in Parkinson's disease, and that both structural and functional connectivity determine the behavioural effect. In a randomized, double-blind placebo-controlled crossover study, 19 patients with mild-to-moderate idiopathic Parkinson's disease underwent functional magnetic resonance imaging during a stop-signal task, while on their usual dopaminergic therapy. Patients received 40 mg atomoxetine or placebo, orally. This regimen anticipates that noradrenergic therapies for behavioural symptoms would be adjunctive to, not a replacement for, dopaminergic therapy. Twenty matched control participants provided normative data. Arterial spin labelling identified no significant changes in regional perfusion. We assessed functional interactions between key frontal and subcortical brain areas for response inhibition, by comparing 20 dynamic causal models of the response inhibition network, inverted to the functional magnetic resonance imaging data and compared using random effects model selection. We found that the normal interaction between pre-supplementary motor cortex and the inferior frontal gyrus was absent in Parkinson's disease patients on placebo (despite dopaminergic therapy), but this connection was restored by atomoxetine. The behavioural change in response inhibition (improvement indicated by reduced stop-signal reaction

Vaccination strategies for Parkinson disease

PubMed Central

Romero-Ramos, Marina; von Euler Chelpin, Marianne; Sanchez-Guajardo, Vanesa

2014-01-01

Parkinson disease is the second most common neurodegenerative disease in the world, but there is currently no available cure for it. Current treatments only alleviate some of the symptoms for a few years, but they become ineffective in the long run and do not stop the disease. Therefore it is of outmost importance to develop therapeutic strategies that can prevent, stop, or cure Parkinson disease. A very promising target for these therapies is the peripheral immune system due to its probable involvement in the disease and its potential as a tool to modulate neuroinflammation. But for such strategies to be successful, we need to understand the particular state of the peripheral immune system during Parkinson disease in order to avoid its weaknesses. In this review we examine the available data regarding how dopamine regulates the peripheral immune system and how this regulation is affected in Parkinson disease; the specific cytokine profiles observed during disease progression and the alterations documented to date in patients’ peripheral blood mononuclear cells. We also review the different strategies used in Parkinson disease animal models to modulate the adaptive immune response to salvage dopaminergic neurons from cell death. After analyzing the evidence, we hypothesize the need to prime the immune system to restore natural tolerance against α-synuclein in Parkinson disease, including at the same time B and T cells, so that T cells can reprogram microglia activation to a beneficial pattern and B cell/IgG can help neurons cope with the pathological forms of α-synuclein. PMID:24670306

Parkinson's Disease

MedlinePlus

Parkinson's disease (PD) is a type of movement disorder. It happens when nerve cells in the brain don't ... coordination As symptoms get worse, people with the disease may have trouble walking, talking, or doing simple ...

Quantitative assessment of driving performance in Parkinson's disease

PubMed Central

Wood, J; Worringham, C; Kerr, G; Mallon, K; Silburn, P

2005-01-01

Objectives: The primary aim of this study was to determine how Parkinson's disease (PD) affects driving performance. It also examined whether changes in driver safety were related to specific clinical disease markers or an individual's self rating of driving ability. Methods: The driving performance of 25 patients with idiopathic PD and 21 age matched controls was assessed on a standardised open road route by an occupational therapist and driving instructor, to provide overall safety ratings and specific driving error scores. Results: The drivers with PD were rated as significantly less safe (p<0.05) than controls, and more than half of the drivers with PD would not have passed a state based driving test. The driver safety ratings were more strongly related to disease duration (r = –0.60) than to their on time Unified Parkinson's Disease Rating Scale (r = –0.24). Drivers with PD made significantly more errors than the control group during manoeuvres that involved changing lanes and lane keeping, monitoring their blind spot, reversing, car parking, and traffic light controlled intersections. The driving instructor also had to intervene to avoid an incident significantly more often for drivers with PD than for controls. Interestingly, driver safety ratings were unrelated to an individual's rating of their own driving performance, and this was the case for all participants. Conclusions: As a group, drivers with PD are less safe to drive than age matched controls. Standard clinical markers cannot reliably predict driver safety. Further studies are required to ascertain whether the identified driving difficulties can be ameliorated. PMID:15654027

The motor and cognitive features of Parkinson's disease in patients with concurrent Gaucher disease over 2 years: a case series.

PubMed

Collins, Lucy M; Williams-Gray, Caroline H; Morris, Elizabeth; Deegan, Patrick; Cox, Timothy M; Barker, Roger A

2018-05-29

We report the cognitive features and progression of Parkinson's disease (PD) in five patients with concurrent Gaucher disease. The patients presented at an earlier age than patients with sporadic PD, as previously noted by others; but in contrast to many previous reports, our patients followed a variable clinical course. While two patients developed early cognitive deficits and dementia, three others remained cognitively intact over the follow-up period. Thus, in this small case series, PD in the context of GD more closely resembles idiopathic PD in terms of its clinical heterogeneity in contrast to PD associated with GBA heterozygote mutations.

[Sexual delinquency and Parkinson's disease].

PubMed

Berger, Ch; Mehrhoff, F W; Beier, K M; Meinck, H-M

2003-04-01

The risk of aberrant sexual behaviour such as hypersexuality, exhibitionism, or pederasty may be underestimated in Parkinson's disease and its therapy with high-dosage L-dopa or dopamine agonists. We describe two legal cases which are representative of the forensic assessment of these side effects. The first case brought to court was a 45-year-old man suffering for 20 years from Parkinson's disease who developed hypersexuality and exhibitionism under high-dose therapy with ropinirol. The second patient, a 57-year-old man with an 11-year history of Parkinson's disease, developed increased libido and pederasty under therapy with L-dopa and bromocriptine. We discuss the present literature concerning hypersexuality and sexually deviant behaviour in Parkinson's disease and dopaminergic therapy in the German legal context. Doctors treating Parkinson patients should be aware of increased sexual impulses or reduced behavioural control and ask specifically about them during anamnesis, and counteractive therapeutic strategies should be considered to prevent the occurrence of illegal sexually aberrant behavioural disorders.

Treatment of early Parkinson's disease.

PubMed

Pahwa, Rajesh; Lyons, Kelly E

2014-08-01

This review summarizes currently available treatment options and treatment strategies, investigational treatments, and the importance of exercise for early Parkinson's disease. The available treatment options for early Parkinson's disease have changed little in the past decade and include carbidopa/levodopa, dopamine agonists, and monoamine oxidase type B (MAO-B) inhibitors. However, we discuss changes in treatment strategies, including dosing and the use of combination therapy used in an attempt to reduce or delay the appearance of motor complications and other adverse events. We will also review several investigational treatments that have shown promise for the treatment of early Parkinson's disease, including a new extended release formulation of carbidopa/levodopa (IPX066), safinamide which inhibits MAO-B, dopamine uptake and glutamate and pardoprunox which is a 5HT-1A agonist and a partial dopamine agonist. Finally, we discuss recent studies focusing on exercise as an important component in the management of early Parkinson's disease. Advances in the management of early Parkinson's disease include evolving treatment strategies, new investigational treatments, and earlier implementation of various forms of exercise.

Long-term safety and tolerability of rotigotine transdermal system in patients with early-stage idiopathic Parkinson's disease: a prospective, open-label extension study.

PubMed

Elmer, Lawrence W; Surmann, Erwin; Boroojerdi, Babak; Jankovic, Joseph

2012-06-01

This prospective, open-label extension (SP702; NCT00594165) of a 6-month double-blind, randomized study investigated the long-term safety and tolerability of rotigotine transdermal system in early Parkinson's disease (PD). Patients with early-stage idiopathic PD received transdermal rotigotine for up to 6 years at optimal dose (up to 16 mg/24h). Adjunctive levodopa was allowed. Primary outcomes included adverse events (AEs) and extent of rotigotine exposure. Other outcomes included time to levodopa, incidence of dyskinesias, and efficacy using the Unified Parkinson's Disease Rating Scale (UPDRS) II+III total score. Of 217 patients entering the open-label study, 47% were still in the study upon closure; 24% withdrew because of AEs and 6% because of lack of efficacy. The median exposure to rotigotine was 1910 days (≈ 5 years, 3 months; range 1-2188 days). Most common AEs were somnolence (23% per patient-year), falls (17%), peripheral edema (14%), nausea (12%), and application site reactions (ASRs; 12%). 3% withdrew because of ASRs. 26% patients did not initiate levodopa; of those who did, fewer than half started levodopa in the first year. Dyskinesias were reported by 25% patients; the majority (83%) reported their first episode after initiating levodopa. Mean UPDRS II+III total scores remained below double-blind baseline for up to 2 years of open-label treatment. This is the longest interventional study of rotigotine conducted to date. Transdermal rotigotine was generally well tolerated for up to 6 years; AEs reported were similar to those observed in shorter studies and led to discontinuation in only 24% patients. Copyright © 2012 Elsevier Ltd. All rights reserved.

Dysphagia and sialorrhea: the relationship to Parkinson's disease.

PubMed

Nicaretta, Denise Hack; Rosso, Ana Lucia; Mattos, James Pitágoras de; Maliska, Carmelindo; Costa, Milton M B

2013-01-01

Dysphagia and sialorrhea in patients with Parkinson's disease are both automatically accepted as dependent on this neurological disease. The aim were to establish if these two complaints are a consequence or associated manifestations of Parkinson's disease. Two Parkinson's diseases groups from the same outpatients' population were studied. Patients in the first group, with dysphagia, were studied by videofluoroscopy. The second, with sialorrhea, were studied by the scintigraphic method, Videofluoroscopic examination of the oral, pharyngeal and esophageal phases of swallowing showed that 94% of Parkinson's diseases patients present, structural causes, not related to Parkinson's diseases, able to produce or intensify the observed disphagia. The scintigraphic examination of Parkinson's diseases patients with sialorrhea showed that there is no increase of serous saliva production. Nevertheless, showed a significantly higher velocity of saliva excretion in the Parkinson's diseases patients. Dysphagia can be due to the muscular rigidity often present in the Parkinson's diseases patient, or more usually by non Parkinson's disease associated causes. In Parkinson's diseases patients, sialorrhea is produced by saliva retention. Nevertheless, sialorrhea can produce discomfort in swallowing, although without a formal complaint of dysphagia. In this case, subclinical dysphagia must be considered. Sialorrhea is indicative of dysphagia or at least of subclinical dysphagia. As final conclusion, Parkinson's diseases can be an isolated cause of dysphagia and/or sialorrhea, but frequently, a factor unrelated to Parkinson's diseases is the main cause of or at least aggravates the dysphagia.

Impaired sense of smell and color discrimination in monogenic and idiopathic Parkinson's disease.

PubMed

Kertelge, Lena; Brüggemann, Norbert; Schmidt, Alexander; Tadic, Vera; Wisse, Claudia; Dankert, Sylwia; Drude, Laura; van der Vegt, Joyce; Siebner, Hartwig; Pawlack, Heike; Pramstaller, Peter P; Behrens, Maria Isabel; Ramirez, Alfredo; Reichel, Dirk; Buhmann, Carsten; Hagenah, Johann; Klein, Christine; Lohmann, Katja; Kasten, Meike

2010-11-15

Olfaction is typically impaired in idiopathic Parkinson's disease (IPD), but its role is uncertain in monogenic PD. Diminished color discrimination has been suggested as another early sign of dopaminergic dysfunction but not been systematically studied. Furthermore, it is unknown whether both deficits are linked. We examined 100 patients with IPD, 27 manifesting mutation carriers (MC), 20 nonmanifesting mutation carriers (NMC), and 110 controls. Participants underwent a standardized neurological examination, the University of Pennsylvania Smell Identification Test (UPSIT), the Farnsworth-Munsell (FM) color discrimination test, and mutation testing in known PD genes. The monogenic group consisted of 15 Parkin (6MC/9NMC), 17 PINK1 (10MC/7NMC), 8 LRRK2 (4MC/4NMC), 3 SNCA (MC), and 4 ATP13A2 (MC) carriers. Olfaction was most impaired in IPD (UPSIT percentiles 10.1 ± 13.5) compared with all other groups (MC 13.8 ± 11.9, NMC 19.6 ± 13.0, controls 33.8 ± 22.4). Within MC, carriers of two mutations in Parkin and PINK1 showed higher UPSIT percentiles than LRRK2 and SNCA carriers. Color discrimination was reduced in IPD (FM total error score 134.8 ± 92.7). In MC (122.4 ± 142.4), the reduction was most pronounced in LRRK2, NMC (80.0 ± 38.8) were comparable with controls (97.2 ± 61.1). UPSIT and FM scores were correlated in the control (r = -0.305; P = 0.002) and the IPD group (r = -0.303; P = 0.006) but not among mutation carriers. First, we confirmed olfaction and color discrimination to be impaired in IPD and suggest olfaction to be a premotor sign. Second, olfaction differed between carriers with one and two mutations in Parkin/PINK1-associated PD. Third, olfaction and color discrimination impairment do not necessarily evolve in parallel. © 2010 Movement Disorder Society.

Mitochondrial Dysfunction in Parkinson's Disease: Pathogenesis and Neuroprotection

PubMed Central

Mounsey, Ross B.; Teismann, Peter

2011-01-01

Mitochondria are vitally important organelles involved in an array of functions. The most notable is their prominent role in energy metabolism, where they generate over 90% of our cellular energy in the form of ATP through oxidative phosphorylation. Mitochondria are involved in various other processes including the regulation of calcium homeostasis and stress response. Mitochondrial complex I impairment and subsequent oxidative stress have been identified as modulators of cell death in experimental models of Parkinson's disease (PD). Identification of specific genes which are involved in the rare familial forms of PD has further augmented the understanding and elevated the role mitochondrial dysfunction is thought to have in disease pathogenesis. This paper provides a review of the role mitochondria may play in idiopathic PD through the study of experimental models and how genetic mutations influence mitochondrial activity. Recent attempts at providing neuroprotection by targeting mitochondria are described and their progress assessed. PMID:21234411

Pilot study assessing the feasibility of applying bilateral subthalamic nucleus deep brain stimulation in very early stage Parkinson's disease: study design and rationale.

PubMed

Charles, David; Tolleson, Christopher; Davis, Thomas L; Gill, Chandler E; Molinari, Anna L; Bliton, Mark J; Tramontana, Michael G; Salomon, Ronald M; Kao, Chris; Wang, Lily; Hedera, Peter; Phibbs, Fenna T; Neimat, Joseph S; Konrad, Peter E

2012-01-01

Deep brain stimulation provides significant symptomatic benefit for people with advanced Parkinson's disease whose symptoms are no longer adequately controlled with medication. Preliminary evidence suggests that subthalamic nucleus stimulation may also be efficacious in early Parkinson's disease, and results of animal studies suggest that it may spare dopaminergic neurons in the substantia nigra. We report the methodology and design of a novel Phase I clinical trial testing the safety and tolerability of deep brain stimulation in early Parkinson's disease and discuss previous failed attempts at neuroprotection. We recently conducted a prospective, randomized, parallel-group, single-blind pilot clinical trial of deep brain stimulation in early Parkinson's disease. Subjects were randomized to receive either optimal drug therapy or deep brain stimulation plus optimal drug therapy. Follow-up visits occurred every six months for a period of two years and included week-long therapy washouts. Thirty subjects with Hoehn & Yahr Stage II idiopathic Parkinson's disease were enrolled over a period of 32 months. Twenty-nine subjects completed all follow-up visits; one patient in the optimal drug therapy group withdrew from the study after baseline. Baseline characteristics for all thirty patients were not significantly different. This study demonstrates that it is possible to recruit and retain subjects in a clinical trial testing deep brain stimulation in early Parkinson's disease. The results of this trial will be used to support the design of a Phase III, multicenter trial investigating the efficacy of deep brain stimulation in early Parkinson's disease.

Parkinson's Disease: The Newest Advances

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Adolf Hitler and His Parkinsonism

PubMed Central

Bhattacharyya, Kalyan B.

2015-01-01

Research works have suggested almost incontrovertibly, that Adolf Hitler suffered from Parkinsonism. However, the precise nature of his illness had always been controversial and post-encephalitic and idiopathic varieties were the ones which were most commonly thought as the possible etiology. He displayed features like oculogyric crisis, palilalia, and autonomic symptoms which strongly implicate post-encephalitic etiology in the genesis of his illness. Others on the contrary, observed premorbid personality traits like non-flinching mental rigidity, extreme inflexibility, and awesome pedantry; which are often observed in idiopathic Parkinson's disease. Moreover, nonmotor symptoms like disturbed sleep, proneness to temper tantrums, phases of depression, suspiciousness, and lack of trust on colleagues have also been described by various authors. Additionally, he was prescribed methamphetamine by his personal doctor and that might have led to the development of some of the later traits in his personality. PMID:26713007

Parkinson's disease as a result of aging

PubMed Central

Rodriguez, Manuel; Rodriguez-Sabate, Clara; Morales, Ingrid; Sanchez, Alberto; Sabate, Magdalena

2015-01-01

It is generally considered that Parkinson's disease is induced by specific agents that degenerate a clearly defined population of dopaminergic neurons. Data commented in this review suggest that this assumption is not as clear as is often thought and that aging may be critical for Parkinson's disease. Neurons degenerating in Parkinson's disease also degenerate in normal aging, and the different agents involved in the etiology of this illness are also involved in aging. Senescence is a wider phenomenon affecting cells all over the body, whereas Parkinson's disease seems to be restricted to certain brain centers and cell populations. However, reviewed data suggest that Parkinson's disease may be a local expression of aging on cell populations which, by their characteristics (high number of synaptic terminals and mitochondria, unmyelinated axons, etc.), are highly vulnerable to the agents promoting aging. The development of new knowledge about Parkinson's disease could be accelerated if the research on aging and Parkinson's disease were planned together, and the perspective provided by gerontology gains relevance in this field. PMID:25677794

Tai Chi and Postural Stability in Patients with Parkinson's Disease

PubMed Central

Li, Fuzhong; Harmer, Peter; Fitzgerald, Kathleen; Eckstrom, Elizabeth; Stock, Ronald; Galver, Johnny; Maddalozzo, Gianni; Batya, Sara S.

2012-01-01

Background Patients with Parkinson's disease have substantially impaired balance, leading to diminished functional ability and an increased risk of falling. Although exercise is routinely encouraged by health care providers, few programs have been proven effective. Methods We conducted a randomized, controlled trial to determine whether a tailored tai chi program could improve postural control in patients with idiopathic Parkinson's disease. We randomly assigned 195 patients with stage 1 to 4 disease on the Hoehn and Yahr staging scale (which ranges from 1 to 5, with higher stages indicating more severe disease) to one of three groups: tai chi, resistance training, or stretching. The patients participated in 60-minute exercise sessions twice weekly for 24 weeks. The primary outcomes were changes from baseline in the limits-of-stability test (maximum excursion and directional control; range, 0 to 100%). Secondary outcomes included measures of gait and strength, scores on functional-reach and timed up-and-go tests, motor scores on the Unified Parkinson's Disease Rating Scale, and number of falls. Results The tai chi group performed consistently better than the resistance-training and stretching groups in maximum excursion (between-group difference in the change from baseline, 5.55 percentage points; 95% confidence interval [CI], 1.12 to 9.97; and 11.98 percentage points; 95% CI, 7.21 to 16.74, respectively) and in directional control (10.45 percentage points; 95% CI, 3.89 to 17.00; and 11.38 percentage points; 95% CI, 5.50 to 17.27, respectively). The tai chi group also performed better than the stretching group in all secondary outcomes and outperformed the resistance-training group in stride length and functional reach. Tai chi lowered the incidence of falls as compared with stretching but not as compared with resistance training. The effects of tai chi training were maintained at 3 months after the intervention. No serious adverse events were observed. Conclusions

Pragmatic communication is impaired in Parkinson disease.

PubMed

Hall, Deborah; Ouyang, Bichun; Lonnquist, Eryn; Newcombe, Jill

2011-05-01

The purpose of this study was to determine whether severity of disease, cognitive function, age, gender, or amount of social interaction were associated with pragmatic dysfunction in Parkinson disease. No studies have previously been done to investigate variables that may be associated with pragmatic dysfunction in Parkinson disease. A case-control study was conducted with 17 Parkinson disease patients and 17 convenience controls. Each Parkinson disease patient and a control were interviewed, and their pragmatic skills were evaluated using a scale of pragmatic communication skills. Correlation analysis was used to determine what factors were associated with pragmatic dysfunction in the Parkinson disease patients. Cases scored lower on the pragmatic scale with a mean of 29.7 compared with 38.9 in the controls (p < .001) out of 40 possible points. The score on the scale of pragmatic communication skills had moderate to strong correlations with the MMSE (r = .81, p = .002), Unified Parkinson's Disease Rating Scale score (r = -.71, p = .002), and duration of disease (r = -.53, p = .03). These results show that Parkinson disease patients have impaired pragmatic function compared with controls on both verbal and nonverbal sections, and this impairment correlates with mental state, duration, and severity of disease.

Acute Modulation of Brain Connectivity in Parkinson Disease after Automatic Mechanical Peripheral Stimulation: A Pilot Study

PubMed Central

Piervincenzi, Claudia; Galli, Manuela; Melgari, Jean Marc; Salomone, Gaetano; Sale, Patrizio; Mallio, Carlo Augusto; Carducci, Filippo; Stocchi, Fabrizio

2015-01-01

Objective The present study shows the results of a double-blind sham-controlled pilot trial to test whether measurable stimulus-specific functional connectivity changes exist after Automatic Mechanical Peripheral Stimulation (AMPS) in patients with idiopathic Parkinson Disease. Methods Eleven patients (6 women and 5 men) with idiopathic Parkinson Disease underwent brain fMRI immediately before and after sham or effective AMPS. Resting state Functional Connectivity (RSFC) was assessed using the seed-ROI based analysis. Seed ROIs were positioned on basal ganglia, on primary sensory-motor cortices, on the supplementary motor areas and on the cerebellum. Individual differences for pre- and post-effective AMPS and pre- and post-sham condition were obtained and first entered in respective one-sample t-test analyses, to evaluate the mean effect of condition. Results Effective AMPS, but not sham stimulation, induced increase of RSFC of the sensory motor cortex, nucleus striatum and cerebellum. Secondly, individual differences for both conditions were entered into paired group t-test analysis to rule out sub-threshold effects of sham stimulation, which showed stronger connectivity of the striatum nucleus with the right lateral occipital cortex and the cuneal cortex (max Z score 3.12) and with the right anterior temporal lobe (max Z score 3.42) and of the cerebellum with the right lateral occipital cortex and the right cerebellar cortex (max Z score 3.79). Conclusions Our results suggest that effective AMPS acutely increases RSFC of brain regions involved in visuo-spatial and sensory-motor integration. Classification of Evidence This study provides Class II evidence that automatic mechanical peripheral stimulation is effective in modulating brain functional connectivity of patients with Parkinson Disease at rest. Trial Registration Clinical Trials.gov NCT01815281 PMID:26469868

Deficits in the Mimicry of Facial Expressions in Parkinson's Disease

PubMed Central

Livingstone, Steven R.; Vezer, Esztella; McGarry, Lucy M.; Lang, Anthony E.; Russo, Frank A.

2016-01-01

Background: Humans spontaneously mimic the facial expressions of others, facilitating social interaction. This mimicking behavior may be impaired in individuals with Parkinson's disease, for whom the loss of facial movements is a clinical feature. Objective: To assess the presence of facial mimicry in patients with Parkinson's disease. Method: Twenty-seven non-depressed patients with idiopathic Parkinson's disease and 28 age-matched controls had their facial muscles recorded with electromyography while they observed presentations of calm, happy, sad, angry, and fearful emotions. Results: Patients exhibited reduced amplitude and delayed onset in the zygomaticus major muscle region (smiling response) following happy presentations (patients M = 0.02, 95% confidence interval [CI] −0.15 to 0.18, controls M = 0.26, CI 0.14 to 0.37, ANOVA, effect size [ES] = 0.18, p < 0.001). Although patients exhibited activation of the corrugator supercilii and medial frontalis (frowning response) following sad and fearful presentations, the frontalis response to sad presentations was attenuated relative to controls (patients M = 0.05, CI −0.08 to 0.18, controls M = 0.21, CI 0.09 to 0.34, ANOVA, ES = 0.07, p = 0.017). The amplitude of patients' zygomaticus activity in response to positive emotions was found to be negatively correlated with response times for ratings of emotional identification, suggesting a motor-behavioral link (r = –0.45, p = 0.02, two-tailed). Conclusions: Patients showed decreased mimicry overall, mimicking other peoples' frowns to some extent, but presenting with profoundly weakened and delayed smiles. These findings open a new avenue of inquiry into the “masked face” syndrome of PD. PMID:27375505

Familial Hemiplegic Migraine Type 1 Associated with Parkinsonism: A Case Report

PubMed Central

Bruun, Marie; Hjermind, Lena Elisabeth; Thomsen, Carsten; Danielsen, Else; Thomsen, Lise Lykke; Pinborg, Lars Hageman; Khabbazbavani, Nastaran; Nielsen, Joergen Erik

2015-01-01

Familial hemiplegic migraine type 1 (FHM1), episodic ataxia type 2 (EA2) and spinocerebellar ataxia type 6 (SCA6) are allelic disorders caused by mutations in the CACNA1A gene on chromosome 19p13. It is well described that FHM1 can present with cerebellar signs, but parkinsonism has not previously been reported in FHM1 or EA2 even though parkinsonism has been described in SCA6. We report a 63-year-old woman with FHM1 caused by an R583Q mutation in the CACNA1A gene, clinically presenting with migraine and permanent cerebellar ataxia. Since the age of 60 years, the patient also developed parkinsonism with rigidity, bradykinesia and a resting tremor. An MRI showed a normal substantia nigra, but a bilateral loss of substance in the basal ganglia, which is in contrast to the typically normal MRI in idiopathic Parkinson's disease. Dopamine transporter (DAT) imaging with single-photon emission computed tomography demonstrated a decreased DAT-binding potential in the putamen. We wish to draw attention to FHM1 associated with parkinsonism; however, whether the reported case is a consequence of FHM1 being allelic to SCA6, unknown modifiers to the specific R583Q CACNA1A mutation or idiopathic Parkinson's disease remains unanswered. PMID:25969684

Cardiac abnormalities in Parkinson's disease and Parkinsonism.

PubMed

Scorza, Fulvio A; Fiorini, Ana C; Scorza, Carla A; Finsterer, Josef

2018-07-01

Though there is increasing evidence for primary cardiac disease in Parkinson's disease (PD) and Parkinsonism (PS), this evidence is hardly included in the general management of these patients. Literature review. PD is one of the most common age-related neurodegenerative disorders. Epidemiological studies have shown that PD is accompanied by high rates of premature death compared with the general population. In general, death in PD/PS is usually caused by determinant factors such as pneumonia, cerebrovascular, and cardiovascular disease. There is a significant body of literature demonstrating involvement of the heart in PD/PS. Cardiac involvement in PD/PS includes cardiac autonomic dysfunction, cardiomyopathy, coronary heart disease, arrhythmias, conduction defects, and sudden cardiac death (SCD), and sudden unexpected death in Parkinson's disease (SUDPAR). Cardiac abnormalities found in PD/PS are manifold but the most prominent is cardiac autonomic dysfunction. The frequency of coronary heart disease in PD is a matter of debate. Only rarely reported in PD/PS are cardiomyopathies, arrhythmias, and sudden cardiac death, and SUDPAR. It is particularly recommended that PD/PS patients are more intensively investigated cardiologically as soon as the diagnosis is established. Early recognition of cardiac involvement is important for preventing SCD and SUDPAR. Copyright © 2018 Elsevier Ltd. All rights reserved.

Sleep disorders and Parkinson disease; lessons from genetics.

PubMed

Gan-Or, Ziv; Alcalay, Roy N; Rouleau, Guy A; Postuma, Ronald B

2018-01-31

Parkinson disease is a common, age-related neurodegenerative disorder, projected to afflict millions of individuals in the near future. Understanding its etiology and identifying clinical, genetic or biological markers for Parkinson disease onset and progression is therefore of major importance. Various sleep-related disorders are the most common group of non-motor symptoms in advanced Parkinson disease, but they can also occur during its prodromal phase. However, with the exception of REM sleep behavior disorder, it is unclear whether they are part of the early pathological process of Parkinson disease, or if they develop as Parkinson disease advances because of treatments and neurodegeneration progression. The advancements in genetic studies in the past two decades have generated a wealth of information, and recent genetic studies offer new insight on the association of sleep-related disorders with Parkinson disease. More specifically, comparing genetic data between Parkinson disease and sleep-related disorders can clarify their association, which may assist in determining whether they can serve as clinical markers for Parkinson disease risk or progression. In this review, we discuss the current knowledge on the genetics of sleep-related disorders in Parkinson disease context, and the potential implications on research, diagnosis, counseling and treatment. Copyright © 2018 Elsevier Ltd. All rights reserved.

Pesticides exposure as etiological factors of Parkinson's disease and other neurodegenerative diseases--a mechanistic approach.

PubMed

Baltazar, Maria Teresa; Dinis-Oliveira, Ricardo Jorge; de Lourdes Bastos, Maria; Tsatsakis, Aristidis M; Duarte, José Alberto; Carvalho, Félix

2014-10-15

The etiology of most neurodegenerative disorders is multifactorial and consists of an interaction between environmental factors and genetic predisposition. The role of pesticide exposure in neurodegenerative disease has long been suspected, but the specific causative agents and the mechanisms underlying are not fully understood. For the main neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis there are evidences linking their etiology with long-term/low-dose exposure to pesticides such as paraquat, maneb, dieldrin, pyrethroids and organophosphates. Most of these pesticides share common features, namely the ability to induce oxidative stress, mitochondrial dysfunction, α-synuclein fibrillization and neuronal cell loss. This review aims to clarify the role of pesticides as environmental risk factors in genesis of idiopathic PD and other neurological syndromes. For this purpose, the most relevant epidemiological and experimental data is highlighted in order to discuss the molecular mechanisms involved in neurodegeneration. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Abnormal sexuality in Parkinson's disease: fact or fancy?

PubMed

Ferrucci, Roberta; Panzeri, Marta; Ronconi, Lucia; Ardolino, Gianluca; Cogiamanian, Filippo; Barbieri, Sergio; Barone, Paolo; Bertolasi, Laura; Padovani, Alessandro; Priori, Alberto

2016-10-15

Patients with Parkinson's disease (PD) variably report sexual dysfunctions. We assessed sexuality in PD by comparing sexual function between a large group of patients with idiopathic PD and a group of subjects without PD. We recruited 121 patients with mild-to-moderate PD (aged 40-80years) from four Italian Movement Disorder Clinics and 123 non-Parkinsonian controls (NPC) (aged 40-80years). Sexual function was assessed with four scales: the Brief Index of Sexual Functioning (BISF-M for men; BISF-W for women), the International Index of Erectile Function (IIEF), and the Female Sexual Function Index (FSFI). Both groups also underwent assessment with the Beck Depression Inventory (BDI) and the Mini Mental State Examination (MMSE), and patients were assessed with the Parkinson's Disease Questionnaire-8 (PDQ-8). No differences in total score were found between PD and NPC for any sexual function scale (BISF-M, BISF-W, IIEF, FSFI: p>0.05). However, the Orgasm/Pleasure Domain (BISF, D5) was significantly lower in male patients than in controls. Our findings fail to confirm previous findings that PD is associated with a significant sexual impairment. NPC and patients with PD have comparable sexual function in both sexes. Thus, rather than dismissing sexual dysfunction as a normal parkinsonian symptom, physicians should refer patients to sexual medicine specialists who can investigate and discuss problems fully, diagnose possible comorbidities, and suggest appropriate treatments. Copyright © 2016. Published by Elsevier B.V.

Pilot Study Assessing the Feasibility of Applying Bilateral Subthalamic Nucleus Deep Brain Stimulation in Very Early Stage Parkinson's Disease: Study design and rationale

PubMed Central

Charles, David; Tolleson, Christopher; Davis, Thomas L.; Gill, Chandler E.; Molinari, Anna L.; Bliton, Mark J.; Tramontana, Michael G.; Salomon, Ronald M.; Kao, Chris; Wang, Lily; Hedera, Peter; Phibbs, Fenna T.; Neimat, Joseph S.; Konrad, Peter E.

2014-01-01

Background Deep brain stimulation provides significant symptomatic benefit for people with advanced Parkinson's disease whose symptoms are no longer adequately controlled with medication. Preliminary evidence suggests that subthalamic nucleus stimulation may also be efficacious in early Parkinson's disease, and results of animal studies suggest that it may spare dopaminergic neurons in the substantia nigra. Objective We report the methodology and design of a novel Phase I clinical trial testing the safety and tolerability of deep brain stimulation in early Parkinson's disease and discuss previous failed attempts at neuroprotection. Methods We recently conducted a prospective, randomized, parallel-group, single-blind pilot clinical trial of deep brain stimulation in early Parkinson's disease. Subjects were randomized to receive either optimal drug therapy or deep brain stimulation plus optimal drug therapy. Follow-up visits occurred every six months for a period of two years and included week-long therapy washouts. Results Thirty subjects with Hoehn & Yahr Stage II idiopathic Parkinson's disease were enrolled over a period of 32 months. Twenty-nine subjects completed all follow-up visits; one patient in the optimal drug therapy group withdrew from the study after baseline. Baseline characteristics for all thirty patients were not significantly different. Conclusions This study demonstrates that it is possible to recruit and retain subjects in a clinical trial testing deep brain stimulation in early Parkinson's disease. The results of this trial will be used to support the design of a Phase III, multicenter trial investigating the efficacy of deep brain stimulation in early Parkinson's disease. PMID:23938229

Recent developments in biomarkers in Parkinson disease

PubMed Central

Schapira, Anthony H.V.

2013-01-01

Purpose of review Parkinson disease is the second most common neurodegenerative disease after Alzheimer disease, and current demographic trends indicate a life-time risk approaching 4% and predict a doubling of prevalence by 2030. Strategies are being developed to apply recent advances in our understanding of the cause of Parkinson disease to the development of biomarkers that will enable the identification of at-risk individuals, enable early diagnosis and reflect the progression of disease. The latter will be particularly important for the testing of disease-modifying therapies. This review summarizes recent advances in Parkinson disease biomarker development. Recent findings Recent reports continue to reflect the application of a variety of clinical, imaging or biochemical measurements, alone or in combination, to general Parkinson disease populations. Probably the most promising is the assay of alpha-synuclein in the diagnosis and evolution of Parkinson disease. At present, detection techniques are still being refined, but once accurate and reproducible assays are available, it will be important to define the relationship of these to early diagnosis and progression. Alpha-synuclein concentrations may also be modulated by certain disease-modifying agents in development and so may represent a measure of their efficacy. It has to be accepted that no single measure currently fulfils all the necessary criteria for a biomarker in Parkinson disease, but combinations of measures are more likely to deliver benefit. Summary The Parkinson disease biomarker field is approaching a stage when certain combinations of clinical, imaging and biochemical measures may identify a proportion of individuals at risk for developing the disease. However, their general applicability may be limited. Attention is now turning to stratification of Parkinson disease into certain at-risk groups defined by genotype. The application of multimodal screening to these populations may be more

Early diagnosis of Parkinson's disease.

PubMed

Becker, Georg; Müller, Antje; Braune, Stefan; Büttner, Thomas; Benecke, Reiner; Greulich, Wolfgang; Klein, Wolfgang; Mark, Günter; Rieke, Jürgen; Thümler, Reiner

2002-10-01

In idiopathic Parkinson's disease (IPD) approximately 60 % of the nigrostriatal neurons of the substantia nigra (SN) are degenerated before neurologists can establish the diagnosis according to the widely accepted clinical diagnostic criteria. It is conceivable that neuroprotective therapy starting at such an 'advanced stage' of the disease will fail to stop the degenerative process. Therefore, the identification of patients at risk and at earlier stages of the disease appears to be essential for any successful neuroprotection. The discovery of several genetic mutations associated with IPD raises the possibility that these, or other biomarkers, of the disease may help to identify persons at risk of IPD. Transcranial ultrasound have shown susceptibility factors for IPD related to an increased iron load of the substantia nigra. In the early clinical phase, a number of motor and particularly non-motor signs emerge, which can be identified by the patients and physicians years before the diagnosis is made, notably olfactory dysfunction, depression, or 'soft' motor signs such as changes in handwriting, speech or reduced ambulatory arm motion. These signs of the early, prediagnostic phase of IPD can be detected by inexpensive and easy-to-administer tests. As one single instrument will not be sensitive enough, a battery of tests has to be composed measuring independent parameters of the incipient disease. Subjects with abnormal findings in this test battery should than be submitted to nuclear medicine examinations to quantify the extent of dopaminergic injury and to reach the goal of a reliable, early diagnosis.

Compensatory postural adjustments in Parkinson's disease assessed via a virtual reality environment.

PubMed

Yelshyna, Darya; Gago, Miguel F; Bicho, Estela; Fernandes, Vítor; Gago, Nuno F; Costa, Luís; Silva, Hélder; Rodrigues, Maria Lurdes; Rocha, Luís; Sousa, Nuno

2016-01-01

Postural control is a complex dynamic mechanism, which integrates information from visual, vestibular and somatosensory systems. Idiopathic Parkinson's disease (IPD) patients are unable to produce appropriate reflexive responses to changing environmental conditions. Still, it is controversial what is due to voluntary or involuntary postural control, even less what is the effect of levodopa. We aimed to evaluate compensatory postural adjustments (CPA), with kinematic and time-frequency analyzes, and further understand the role of dopaminergic medication on these processes. 19 healthy subjects (Controls) and 15 idiopathic Parkinson's disease (IPD) patients in the OFF and ON medication states, wearing IMUs, were submitted to a virtual reality scenario with visual downward displacements on a staircase. We also hypothesized if CPA would involve mechanisms occurring in distinct time scales. We subsequently analyzed postural adjustments on two frequency bands: low components between 0.3 and 1.5 Hz (LB), and high components between 1.5 and 3.5 Hz (HB). Vertical acceleration demonstrated a greater power for discriminating IPD patients from healthy subjects. Visual perturbation significantly increased the power of the HB in all groups, being particularly more evident in the OFF state. Levodopa significantly increased their basal power taking place on the LB. However, controls and IPD patients in the ON state revealed a similar trend of the control mechanism. Results indicate an improvement in muscular stiffness provided by levodopa. They also suggest the role of different compensatory postural adjustment patterns, with LB being related to inertial properties of the oscillating mass and HB representing reactions to the ongoing visual input-changing scenario. Copyright © 2015 Elsevier B.V. All rights reserved.

Transcranial direct current stimulation (tDCS) for idiopathic Parkinson's disease.

PubMed

Elsner, Bernhard; Kugler, Joachim; Pohl, Marcus; Mehrholz, Jan

2016-07-18

Idiopathic Parkinson's disease (IPD) is a neurodegenerative disorder, with the severity of the disability usually increasing with disease duration. IPD affects patients' health-related quality of life, disability, and impairment. Current rehabilitation approaches have limited effectiveness in improving outcomes in patients with IPD, but a possible adjunct to rehabilitation might be non-invasive brain stimulation by transcranial direct current stimulation (tDCS) to modulate cortical excitability, and hence to improve these outcomes in IPD. To assess the effectiveness of tDCS in improving motor and non-motor symptoms in people with IPD. We searched the following databases (until February 2016): the Cochrane Central Register of Controlled Trials (CENTRAL; the Cochrane Library ; 2016 , Issue 2), MEDLINE, EMBASE, CINAHL, AMED, Science Citation Index, the Physiotherapy Evidence Database (PEDro), Rehabdata, and Inspec. In an effort to identify further published, unpublished, and ongoing trials, we searched trial registers and reference lists, handsearched conference proceedings, and contacted authors and equipment manufacturers. We included only randomised controlled trials (RCTs) and randomised controlled cross-over trials that compared tDCS versus control in patients with IPD for improving health-related quality of life , disability, and impairment. Two review authors independently assessed trial quality (JM and MP) and extracted data (BE and JM). If necessary, we contacted study authors to ask for additional information. We collected information on dropouts and adverse events from the trial reports. We included six trials with a total of 137 participants. We found two studies with 45 participants examining the effects of tDCS compared to control (sham tDCS) on our primary outcome measure, impairment, as measured by the Unified Parkinson's Disease Rating Scale (UPDRS). There was very low quality evidence for no effect of tDCS on change in global UPDRS score ( mean

Adolf Hitler had post-encephalitic Parkinsonism.

PubMed

Lieberman, A

1996-04-01

Adolf Hitler had Parkinson symptoms in 1934, at age 45 years. He may have had transient symptoms in 1923, at age 34 years. Young-onset parkinsonism, during the 1920s, favored a diagnosis of post-encephalitic rather than idiopathic parkinsonism. Hitler had oculogyric crises, phenomena only associated with post-encephalitic parkinsonism. In addition, he had dystonic facial spasms, palilalia and a sleep disorder, phenomena more likely to be associated with post-encephalitic than idiopathic parkinsonism. In November 1918, at age 29 years, Hitler may have had von Economo's encephalitis, while he was a patient in a hospital, recovering from poison gas. This paper looks at the possible relationship of von Economo's encephalitis to Hitler's asocial behavior; his obsessions and compulsions, his cruelty and rages. The influence of Hitler's parkinsonism on his conduct during World War II is discussed.

Pharmacotherapy for Parkinson's disease.

PubMed

Chen, Jack J; Swope, David M

2007-12-01

The available pharmacotherapies for Parkinson's disease address symptomatology because no agent has been demonstrated to provide definite neuroprotection against the disease. Choice of pharmacotherapy must include consideration of short-term benefits as well as long-term consequences. Patients with mild Parkinson's disease often function adequately without symptomatic treatment. However, recent data suggest that initiation of treatment with a well-tolerated agent (e.g., the monoamine oxidase [MAO]-B inhibitor rasagiline) in the absence of functional impairment is associated with improved long-term outcomes. Consideration should also be given to many patient-specific factors, including patient expectations, level of disability, employment status, functional as well as chronologic age, expected efficacy and tolerability of drugs, and response to previous Parkinson's disease therapies. Increasingly, initial monotherapy begins with a nondopaminergic agent or, if the patient is considered functionally young, a dopamine agonist. Since Parkinson's disease is a progressive disorder, adjustments to pharmacotherapy must be expected over time. When greater symptomatic relief is desired, or in the more frail elderly patient, levodopa therapy should be considered. If motor fluctuations develop, addition of a catechol-O-methyltransferase inhibitor or MAO-B inhibitor should be considered. For management of levodopa-induced dyskinesias, addition of amantadine is an option. Surgery may be considered when patients need additional symptomatic control or are experiencing severe motor complications despite pharmacologically optimized therapy.

Parkinson's disease dementia: a neural networks perspective.

PubMed

Gratwicke, James; Jahanshahi, Marjan; Foltynie, Thomas

2015-06-01

In the long-term, with progression of the illness, Parkinson's disease dementia affects up to 90% of patients with Parkinson's disease. With increasing life expectancy in western countries, Parkinson's disease dementia is set to become even more prevalent in the future. However, current treatments only give modest symptomatic benefit at best. New treatments are slow in development because unlike the pathological processes underlying the motor deficits of Parkinson's disease, the neural mechanisms underlying the dementing process and its associated cognitive deficits are still poorly understood. Recent insights from neuroscience research have begun to unravel the heterogeneous involvement of several distinct neural networks underlying the cognitive deficits in Parkinson's disease dementia, and their modulation by both dopaminergic and non-dopaminergic transmitter systems in the brain. In this review we collate emerging evidence regarding these distinct brain networks to give a novel perspective on the pathological mechanisms underlying Parkinson's disease dementia, and discuss how this may offer new therapeutic opportunities. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.

[The experimental models of Parkinson's disease in animals].

PubMed

Grigor'ian, G A; Bazian, A S

2007-01-01

The current review describes the modem Parkinson's disease models in animals, their advantages, limitations and disadvantages. It was noted that the most widespread up-to-date models based on etiology of the Parkinson's disease. Although toxins mostly produce the Parkinson's disease, a study of involved genes allows investigating not only inherited but also sporadic (not inherited) forms of disease since the same genes are involved in both cases. Mutations of genes lead to formation of "mutant" toxic proteins, which produce a death of the specialized neurons of the nigrostriatal dopaminergic system and the development of Parkinson's disease. A significant place in the review takes adescription of characteristics of the toxic models produced by 6-OHDA, MPTP and rotenone, their similarities and differences in pathogenetic mechanisms of the Parkinson's disease development. On the basis of the considered experimental models of Parkinson's disease a conclusion has been done that none of these models may in full and adequate scale imitate the entire clinical, pathophysiological, morphological, biochemical and other aspects of the Parkinson's disease development.

Advanced Parkinson's or "complex phase" Parkinson's disease? Re-evaluation is needed.

PubMed

Titova, Nataliya; Martinez-Martin, Pablo; Katunina, Elena; Chaudhuri, K Ray

2017-12-01

Holistic management of Parkinson's disease, now recognised as a combined motor and nonmotor disorder, remains a key unmet need. Such management needs relatively accurate definition of the various stages of Parkinson's from early untreated to late palliative as each stage calls for personalised therapies. Management also needs to have a robust knowledge of the progression pattern and clinical heterogeneity of the presentation of Parkinson's which may manifest in a motor dominant or nonmotor dominant manner. The "advanced" stages of Parkinson's disease qualify for advanced treatments such as with continuous infusion or stereotactic surgery yet the concept of "advanced Parkinson's disease" (APD) remains controversial in spite of growing knowledge of the natural history of the motor syndrome of PD. Advanced PD is currently largely defined on the basis of consensus opinion and thus with several caveats. Nonmotor aspects of PD may also reflect advancing course of the disorder, so far not reflected in usual scale based assessments which are largely focussed on motor symptoms. In this paper, we discuss the problems with current definitions of "advanced" PD and also propose the term "complex phase" Parkinson's disease as an alternative which takes into account a multimodal symptoms and biomarker based approach in addition to patient preference.

Slower saccadic reading in Parkinson's disease.

PubMed

Jehangir, Naz; Yu, Caroline Yizhu; Song, Jeehey; Shariati, Mohammad Ali; Binder, Steven; Beyer, Jill; Santini, Veronica; Poston, Kathleen; Liao, Yaping Joyce

2018-01-01

Idiopathic Parkinson's Disease (PD) is characterized by degeneration of dopaminergic and other neurons, leading to motor and non-motor deficits. Abnormal eye movements in PD, including fixations, saccades, and convergence, are well described. However, saccadic reading, which requires serial and alternating saccades and fixations, is not well studied, despite its obvious impact on the quality of life. In this study, we assessed saccadic reading using variations of the King-Devick (KD) test, a rapid single digit number naming test, as a way to assess the ability to make serial left-to-right ocular motor movements necessary for reading. We recruited 42 treated PD patients and 80 age-matched controls and compared their reading times with a variety of measures, including age, duration of disease, Unified Parkinson's Disease Rating Scale (UPDRS), the National Eye Institute 25-Item Visual Functioning Questionnaire 25 (VFQ-25), and Montreal Cognitive assessment (MoCA) test. The subjects performed 4 trials of reading 120 single digit numbers aloud as fast as possible without making errors. In each trial, they read 3 pages (KD1, KD2, and KD3), and each page contained 40 numbers per page in 8 lines with 5 numbers/line. We found that PD patients read about 20% slower than controls on all tests (KD1, 2, and 3 tests) (p < 0.02), and both groups read irregularly spaced numbers slower than regularly spaced numbers. Having lines between numbers to guide reading (KD1 tests) did not impact reading time in both PD and controls, but increased visual crowding as a result of decreased spacing between numbers (KD3 tests) was associated with significantly slower reading times in both PD and control groups. Our study revealed that saccadic reading is slower in PD, but controls and PD patients are both impacted by visuospatial planning challenges posed by increased visual crowding and irregularity of number spacing. Reading time did not correlate with UPDRS or MoCA scores in PD patients but

Curcumin's Neuroprotective Efficacy in Drosophila Model of Idiopathic Parkinson's Disease Is Phase Specific: Implication of its Therapeutic Effectiveness

PubMed Central

Phom, Limamanen; Achumi, Bovito; Alone, Debasmita P.; Muralidhara

2014-01-01

Abstract Selective degeneration of dopaminergic neurons in the substantia nigra underlies the basic motor impairments of Parkinson's disease (PD). Curcumin has been used for centuries in traditional medicines in India. Our aim is to understand the efficacy of genotropic drug curcumin as a neuroprotective agent in PD. Analysis of different developmental stages in model organisms revealed that they are characterized by different patterns of gene expression which is similar to that of developmental stages of human. Genotropic drugs would be effective only during those life cycle stages for which their target molecules are available. Hence there exists a possibility that targets of genotropic compounds such as curcumin may not be present in all life stages. However, no reports are available in PD models illustrating the efficacy of curcumin in later phases of adult life. This is important because this is the period during which late-onset disorders such as idiopathic PD set in. To understand this paradigm, we tested the protective efficacy of curcumin in different growth stages (early, late health stage, and transition phase) in adult Drosophila flies. Results showed that it can rescue the motor defects during early stages of life but is ineffective at later phases. This observation was substantiated with the finding that curcumin treatment could replenish depleted brain dopamine levels in the PD model only during early stages of life cycle, clearly suggesting its limitation as a therapeutic agent in late-onset neurodegenerative disorders such as PD. PMID:25238331

Immediate effects of thermal-tactile stimulation on timing of swallow in idiopathic Parkinson's disease.

PubMed

Regan, Julie; Walshe, Margaret; Tobin, W Oliver

2010-09-01

Oropharyngeal dysphagia frequently presents in people with idiopathic Parkinson's disease (IPD). Clinical sequelae of dysphagia in this group include weight loss and aspiration pneumonia, the latter of which is the leading cause of hospital admissions and death in IPD. Thermal-tactile stimulation (TTS) is a sensory technique whereby stimulation is provided to the anterior faucial pillars to speed up the pharyngeal swallow. The effects of TTS on swallowing have not yet been investigated in IPD. The aim of this study was to investigate the immediate effects of TTS on the timing of swallow in a cohort of people with IPD and known oropharyngeal dysphagia. Thirteen participants with IPD and known dysphagia attended for videofluoroscopy during which standardised volumes of liquid barium and barium paste were administered preceding and immediately subsequent to TTS. The immediate effects of TTS on swallowing were examined using oral, pharyngeal, and total transit times and pharyngeal delay times as outcome measures. TTS significantly reduced median pharyngeal transit time on fluids (0.20 s, 95% CI = 0.12-0.28, p = 0.004) and on paste (0.3 s, 95% CI = 0.08-0.66, p = 0.01). Median total transit time was also reduced on fluids (0.48 s, 95% CI = 0.00-1.17, p = 0.049) and on paste (0.52 s, 95% CI = 0.08-1.46, p = 0.033). Median pharyngeal delay time was reduced on fluids (0.20 s, 95% CI = 0.12-0.34, p = 0.002). TTS did not significantly alter median oral transit time on either fluid or paste consistency. TTS significantly reduced temporal measures of the pharyngeal phase of swallowing in the IPD population. Significant results may be attributed to the role of sensory stimulation in improving motor function in IPD, with emphasis on the impaired glossopharyngeal and vagus nerves in this population. It is still unclear whether these findings will translate into a clinically beneficial effect.

Water-based vs. non-water-based physiotherapy for rehabilitation of postural deformities in Parkinson's disease: a randomized controlled pilot study.

PubMed

Volpe, Daniele; Giantin, Maria Giulia; Manuela, Pilleri; Filippetto, Consuelo; Pelosin, Elisa; Abbruzzese, Giovanni; Antonini, Angelo

2017-08-01

To compare the efficacy of two physiotherapy protocols (water-based vs. non-water-based) on postural deformities of patients with Parkinson's disease. A single blind, randomized controlled pilot study. Inpatient (Rehabilitative Department). A total of 30 patients with idiopathic Parkinson's disease. Participants were randomly assigned to one of two eight-week treatment groups: Water-based ( n = 15) or non-water-based physiotherapy exercises ( n = 15). Changes in the degree of cervical and dorsal flexion and in the angle of lateral inclination of the trunk (evaluated by means of a posturographic system) were used as primary outcomes. Unified Parkinson Disease Rating Scale section III, Time Up and Go Test, Berg Balance Scale, Activities-specific Balance Confidence, Falls Efficacy Scale and the Parkinson's disease quality of life questionnaire (39 items) were the secondary outcomes. All outcomes were assessed at baseline, at the end of training and eight weeks after treatment. Patients were always tested at the time of their optimal antiparkinsonian medication ('on' phase). After the treatment, only Parkinson's disease subjects randomized to water-based treatment showed a significant improvement of trunk posture with a significant reduction of cervical flexion (water-based group: -65.2°; non-water-based group: +1.7°) and dorsal flexion (water-based group: -22.5°; non-water-based group: -6.5°) and lateral inclination of the trunk (water-based group: -2.3°; non-water-based group: +0.3°). Both groups presented significant improvements in the secondary clinical outcomes without between-group differences. Our results show that water-based physiotherapy was effective for improving postural deformities in patients with Parkinson's disease.

A tangled web - tau and sporadic Parkinson's disease.

PubMed

Wray, Selina; Lewis, Patrick A

2010-01-01

Parkinson's disease (PD) represents a major challenge for health care systems around the world: it is the most common degenerative movement disorder of old age, affecting over 100,000 people in the UK alone (Schrag et al., 2000). Despite the remarkable success of treatments directed at potentiating or replacing dopamine within the brain, which can relieve symptoms for over a decade, PD remains an incurable and invariably fatal disorder. As such, efforts to understand the processes that lead to cell death in the brains of patients with PD are a priority for neurodegenerative researchers. A great deal of progress has been made in this regard by taking advantage of advances in genetics, initially by the identification of genes responsible for rare Mendelian forms of PD (outlined in Table 1), and more recently by applying genome wide association studies (GWAS) to the sporadic form of the disease (Hardy et al., 2009). Several such GWAS have now been carried out, with a meta-analysis currently under way. Using over 6000 cases and 10,000 controls, two of these studies have identified variation at a number of loci as being associated with an increased risk of disease (Satake et al., 2009; Simon-Sanchez et al., 2009). Three genes stand out as candidates from these studies - the SNCA gene, coding for α-synuclein, the LRRK2 gene, coding for leucine rich repeat kinase 2, and MAPT, coding for the microtubule-associated protein tau. Mutations at all three of these loci have been associated with Mendelian forms of disease presenting with the clinical syndrome of Parkinsonism, however only SNCA and LRRK2 have been previously associated with pathologically defined PD (Hardy et al., 2009). Point mutations in α-synuclein, along with gene multiplication events, result in autosomal dominant PD, often with a significant dementia component. In addition to this, α-synuclein is the principle component of the main pathological hallmark of idiopathic PD, the Lewy body, making it an

The Expression of DJ-1 (PARK7) in Normal Human CNS and Idiopathic Parkinson's Disease

ERIC Educational Resources Information Center

Bandopadhyay, Rina; Kingsbury, Ann E.; Cookson, Mark R.; Reid, Andrew R.; Evans, Ian M.; Hope, Andrew D.; Pittman, Alan M.; Lashley, Tammaryn; Canet-Aviles, Rosa; Miller, David W.; McLendon, Chris; Strand, Catherine; Leonard, Andrew J.; Abou-Sleiman, Patrick M.; Healy, Daniel G.; Ariga, Hiroyashi; Wood, Nicholas W.; de Silva, Rohan; Revesz, Tamas; Hardy, John A.; Lees, Andrew J.

2004-01-01

Two mutations in the DJ-1 gene on chromosome1p36 have been identified recently to cause early-onset, autosomal recessive Parkinson's disease. As no information is available regarding the distribution of DJ-1 protein in the human brain, in this study we used a monoclonal antibody for DJ-1 to map its distribution in frontal cortex and substantia…

[Drug treatment of early-stage (de novo and "honeymoon") Parkinson disease].

PubMed

Cesaro, P; Defebvre, L

2014-04-01

In this article, we discuss the management of motor symptoms during the early phases of Parkinson's disease, excluding that of any other clinical manifestation. We relied primarily upon recently published data and do not describe older publications relating to anticholinergic drugs or amantadine. The initial pharmacological treatment of idiopathic Parkinson's disease (IPD) is symptomatic and remains based upon dopaminergic drugs. However, the development of new drugs has broadened the range of strategic options and improved overall patient management. Announcing the diagnosis is a critical moment, as pointed out by patients' associations. Patients should be advised to maintain personal, professional, social and physical activities as long as possible. The potential benefit of early pharmacological treatment should be explained, focusing on the possible disease-modifying effect of drugs such as rasagiline. According to current guidelines, L-Dopa is preferred in patients above 65years of age, while those below 65 should be treated with dopamine agonists. Like monoamine oxidase inhibitors B (MAOI-B), synthetic dopamine agonists exhibit several advantages: easy-to-use treatment with a once-daily administration, delayed L-Dopa initiation, significant efficacy on motor symptoms (although lower than that of L-Dopa). MOAI can be prescribed in association with L-Dopa or dopamine agonists. Rasagiline also delays L-Dopa initiation, and consequently motor complications. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Dream Robber: Living with Parkinson's disease

MedlinePlus

... Current Issue Past Issues Dream Robber: Living with Parkinson's disease Past Issues / Summer 2006 Table of Contents For ... Now 65, he has been permanently grounded by Parkinson's disease, unable, due to the loss of motor control ...

Mild Cognitive Impairment in Parkinson's Disease-What Is It?

PubMed

Weil, Rimona S; Costantini, Alyssa A; Schrag, Anette E

2018-03-10

Mild cognitive impairment is a common feature of Parkinson's disease, even at the earliest disease stages, but there is variation in the nature and severity of cognitive involvement and in the risk of conversion to Parkinson's disease dementia. This review aims to summarise current understanding of mild cognitive impairment in Parkinson's disease. We consider the presentation, rate of conversion to dementia, underlying pathophysiology and potential biomarkers of mild cognitive impairment in Parkinson's disease. Finally, we discuss challenges and controversies of mild cognitive impairment in Parkinson's disease. Large-scale longitudinal studies have shown that cognitive involvement is important and common in Parkinson's disease and can present early in the disease course. Recent criteria for mild cognitive impairment in Parkinson's provide the basis for further study of cognitive decline and for the progression of different cognitive phenotypes and risk of conversion to dementia. Improved understanding of the underlying pathology and progression of cognitive change are likely to lead to opportunities for early intervention for this important aspect of Parkinson's disease.

Complete genomic screen in Parkinson disease: evidence for multiple genes.

PubMed

Scott, W K; Nance, M A; Watts, R L; Hubble, J P; Koller, W C; Lyons, K; Pahwa, R; Stern, M B; Colcher, A; Hiner, B C; Jankovic, J; Ondo, W G; Allen, F H; Goetz, C G; Small, G W; Masterman, D; Mastaglia, F; Laing, N G; Stajich, J M; Slotterbeck, B; Booze, M W; Ribble, R C; Rampersaud, E; West, S G; Gibson, R A; Middleton, L T; Roses, A D; Haines, J L; Scott, B L; Vance, J M; Pericak-Vance, M A

2001-11-14

The relative contribution of genes vs environment in idiopathic Parkinson disease (PD) is controversial. Although genetic studies have identified 2 genes in which mutations cause rare single-gene variants of PD and observational studies have suggested a genetic component, twin studies have suggested that little genetic contribution exists in the common forms of PD. To identify genetic risk factors for idiopathic PD. Genetic linkage study conducted 1995-2000 in which a complete genomic screen (n = 344 markers) was performed in 174 families with multiple individuals diagnosed as having idiopathic PD, identified through probands in 13 clinic populations in the continental United States and Australia. A total of 870 family members were studied: 378 diagnosed as having PD, 379 unaffected by PD, and 113 with unclear status. Logarithm of odds (lod) scores generated from parametric and nonparametric genetic linkage analysis. Two-point parametric maximum parametric lod score (MLOD) and multipoint nonparametric lod score (LOD) linkage analysis detected significant evidence for linkage to 5 distinct chromosomal regions: chromosome 6 in the parkin gene (MLOD = 5.07; LOD = 5.47) in families with at least 1 individual with PD onset at younger than 40 years, chromosomes 17q (MLOD = 2.28; LOD = 2.62), 8p (MLOD = 2.01; LOD = 2.22), and 5q (MLOD = 2.39; LOD = 1.50) overall and in families with late-onset PD, and chromosome 9q (MLOD = 1.52; LOD = 2.59) in families with both levodopa-responsive and levodopa-nonresponsive patients. Our data suggest that the parkin gene is important in early-onset PD and that multiple genetic factors may be important in the development of idiopathic late-onset PD.

Parkinson's Disease, Diabetes and Cognitive Impairment.

PubMed

Ashraghi, Mohammad R; Pagano, Gennaro; Polychronis, Sotirios; Niccolini, Flavia; Politis, Marios

2016-01-01

Parkinson's disease is a chronic neurodegenerative disorder characterized by a progressive loss of dopaminergic neurons. The pathophysiological mechanisms underlying Parkinson's are still unknown. Mitochondrial dysfunction, abnormal protein aggregation, increased neuroinflammation and impairment of brain glucose metabolism are shared processes among insulinresistance, diabetes and neurodegeneration and have been suggested as key mechanisms in development of Parkinson's and cognitive impairment. To review experimental and clinical evidence of underlying Parkinson's pathophysiology in common with diabetes and cognitive impairment. Anti-diabetic agents and recent patents for insulin-resistance that might be repositioned in the treatment of Parkinson's also have been included in this review. A narrative review using MEDLINE database. Common antidiabetic treatments such as DPP4 inhibitors, GLP-1 agonists and metformin have shown promise in the treatment of Parkinson's disease and cognitive impairment in animals and humans. Study of the pathophysiology of neurodegeneration common between diabetes and Parkinson's disease has given rise to new treatment possibilities. Patents published in the last 5 years could be used in novel approaches to Parkinson's treatment by targeting specific pathophysiology proteins, such as Nurr1, PINK1 and NrF2, while patents to improve penetration of the blood brain barrier could allow improved efficacy of existing treatments. Further studies using GLP-1 agonists and DPP-4 inhibitors to treat PD are warranted as they have shown promise.

Perceptive rehabilitation and trunk posture alignment in patients with Parkinson disease: a single blind randomized controlled trial.

PubMed

Morrone, Michelangelo; Miccinilli, Sandra; Bravi, Marco; Paolucci, Teresa; Melgari, Jean M; Salomone, Gaetano; Picelli, Alessandro; Spadini, Ennio; Ranavolo, Alberto; Saraceni, Vincenzo M; DI Lazzaro, Vincenzo; Sterzi, Silvia

2016-12-01

Recent studies aimed to evaluate the potential effects of perceptive rehabilitation in Parkinson Disease reporting promising preliminary results for postural balance and pain symptoms. To date, no randomized controlled trial was carried out to compare the effects of perceptive rehabilitation and conventional treatment in patients with Parkinson Disease. To evaluate whether a perceptive rehabilitation treatment could be more effective than a conventional physical therapy program in improving postural control and gait pattern in patients with Parkinson Disease. Single blind, randomized controlled trial. Department of Physical and Rehabilitation Medicine of a University Hospital. Twenty outpatients affected by idiopathic Parkinson Disease at Hoehn and Yahr stage ≤3. Recruited patients were divided into two groups: the first one underwent individual treatment with Surfaces for Perceptive Rehabilitation (Su-Per), consisting of rigid wood surfaces supporting deformable latex cones of various dimensions, and the second one received conventional group physical therapy treatment. Each patient underwent a training program consisting of ten, 45-minute sessions, three days a week for 4 consecutive weeks. Each subject was evaluated before treatment, immediately after treatment and at one month of follow-up, by an optoelectronic stereophotogrammetric system for gait and posture analysis, and by a computerized platform for stabilometric assessment. Kyphosis angle decreased after ten sessions of perceptive rehabilitation, thus showing a substantial difference with respect to the control group. No significant differences were found as for gait parameters (cadence, gait speed and stride length) within Su-Per group and between groups. Parameters of static and dynamic evaluation on stabilometric platform failed to demonstrate any statistically relevant difference both within-groups and between-groups. Perceptive training may help patients affected by Parkinson Disease into restoring

Association of Parkinsonism or Parkinson Disease with Polypharmacy in the Year Preceding Diagnosis: A Nested Case-Control Study in South Korea.

PubMed

Park, Hae-Young; Park, Ji-Won; Sohn, Hyun Soon; Kwon, Jin-Won

2017-11-01

Published studies on the association between polypharmacy and parkinsonism or Parkinson disease are very limited. The objective of this study was to investigate whether polypharmacy is associated with parkinsonism or Parkinson disease in elderly patients. From a South Korean national health insurance sample cohort database for 2002-2013, we matched parkinsonism cases (defined by diagnosis codes for parkinsonism/Parkinson disease) and Parkinson disease cases (patients who had records for both Parkinson disease diagnosis and anti-Parkinson disease drug prescriptions) with controls. Logistic regression analysis evaluated the associations of parkinsonism/Parkinson disease with polypharmacy (i.e., five or more prescribed daily drugs) during the year preceding parkinsonism/Parkinson disease diagnosis, medications potentially associated with parkinsonism, and comorbidity status (using the Charlson Comorbidity Index score and hospitalization records). The study population included 6209 cases and 24,836 controls for parkinsonism and 1331 cases and 5324 controls for Parkinson disease. In univariate logistic regression, odds ratios for parkinsonism/Parkinson disease increased significantly with increased polypharmacy, medications potentially associated with parkinsonism, Charlson Comorbidity Index score, or prior hospitalizations. In multiple logistic regression, odds ratios for parkinsonism/Parkinson disease (adjusted for medications potentially associated with parkinsonism and comorbidities) also increased with increased polypharmacy. Odds ratios (95% confidence interval) for Parkinson disease were higher than those for parkinsonism with stronger statistical significance: 1.41 (1.28-1.55) and 2.17 (1.84-2.57) for parkinsonism and 2.87 (2.30-3.58) and 4.75 (3.39-6.66) for Parkinson disease for between five and ten prescribed daily drugs and ten or more drugs, respectively. Polypharmacy in the year preceding diagnosis may be associated with an increased risk for parkinsonism/Parkinson

Combined Diffusion Tensor Imaging and Apparent Transverse Relaxation Rate Differentiate Parkinson Disease and Atypical Parkinsonism.

PubMed

Du, G; Lewis, M M; Kanekar, S; Sterling, N W; He, L; Kong, L; Li, R; Huang, X

2017-05-01

Both diffusion tensor imaging and the apparent transverse relaxation rate have shown promise in differentiating Parkinson disease from atypical parkinsonism (particularly multiple system atrophy and progressive supranuclear palsy). The objective of the study was to assess the ability of DTI, the apparent transverse relaxation rate, and their combination for differentiating Parkinson disease, multiple system atrophy, progressive supranuclear palsy, and controls. A total of 106 subjects (36 controls, 35 patients with Parkinson disease, 16 with multiple system atrophy, and 19 with progressive supranuclear palsy) were included. DTI and the apparent transverse relaxation rate measures from the striatal, midbrain, limbic, and cerebellar regions were obtained and compared among groups. The discrimination performance of DTI and the apparent transverse relaxation rate among groups was assessed by using Elastic-Net machine learning and receiver operating characteristic curve analysis. Compared with controls, patients with Parkinson disease showed significant apparent transverse relaxation rate differences in the red nucleus. Compared to those with Parkinson disease, patients with both multiple system atrophy and progressive supranuclear palsy showed more widespread changes, extending from the midbrain to striatal and cerebellar structures. The pattern of changes, however, was different between the 2 groups. For instance, patients with multiple system atrophy showed decreased fractional anisotropy and an increased apparent transverse relaxation rate in the subthalamic nucleus, whereas patients with progressive supranuclear palsy showed an increased mean diffusivity in the hippocampus. Combined, DTI and the apparent transverse relaxation rate were significantly better than DTI or the apparent transverse relaxation rate alone in separating controls from those with Parkinson disease/multiple system atrophy/progressive supranuclear palsy; controls from those with Parkinson

Gene Therapy for Parkinson's Disease

PubMed Central

Denyer, Rachel; Douglas, Michael R.

2012-01-01

Current pharmacological and surgical treatments for Parkinson's disease offer symptomatic improvements to those suffering from this incurable degenerative neurological disorder, but none of these has convincingly shown effects on disease progression. Novel approaches based on gene therapy have several potential advantages over conventional treatment modalities. These could be used to provide more consistent dopamine supplementation, potentially providing superior symptomatic relief with fewer side effects. More radically, gene therapy could be used to correct the imbalances in basal ganglia circuitry associated with the symptoms of Parkinson's disease, or to preserve or restore dopaminergic neurons lost during the disease process itself. The latter neuroprotective approach is the most exciting, as it could theoretically be disease modifying rather than simply symptom alleviating. Gene therapy agents using these approaches are currently making the transition from the laboratory to the bedside. This paper summarises the theoretical approaches to gene therapy for Parkinson's disease and the findings of clinical trials in this rapidly changing field. PMID:22619738

Gene therapy for Parkinson's disease.

PubMed

Denyer, Rachel; Douglas, Michael R

2012-01-01

Current pharmacological and surgical treatments for Parkinson's disease offer symptomatic improvements to those suffering from this incurable degenerative neurological disorder, but none of these has convincingly shown effects on disease progression. Novel approaches based on gene therapy have several potential advantages over conventional treatment modalities. These could be used to provide more consistent dopamine supplementation, potentially providing superior symptomatic relief with fewer side effects. More radically, gene therapy could be used to correct the imbalances in basal ganglia circuitry associated with the symptoms of Parkinson's disease, or to preserve or restore dopaminergic neurons lost during the disease process itself. The latter neuroprotective approach is the most exciting, as it could theoretically be disease modifying rather than simply symptom alleviating. Gene therapy agents using these approaches are currently making the transition from the laboratory to the bedside. This paper summarises the theoretical approaches to gene therapy for Parkinson's disease and the findings of clinical trials in this rapidly changing field.

Longitudinal Study of Gray Matter Changes in Parkinson Disease.

PubMed

Jia, X; Liang, P; Li, Y; Shi, L; Wang, D; Li, K

2015-12-01

The pathology of Parkinson disease leads to morphological brain volume changes. So far, the progressive gray matter volume change across time specific to patients with Parkinson disease compared controls remains unclear. Our aim was to investigate the pattern of gray matter changes in patients with Parkinson disease and to explore the progressive gray matter volume change specific to patients with Parkinson disease with disease progression by using voxel-based morphometry analysis. Longitudinal cognitive assessment and structural MR imaging of 89 patients with Parkinson disease (62 men) and 55 healthy controls (33 men) were from the Parkinson's Progression Markers Initiative data base, including the initial baseline and 12-month follow-up data. Two-way analysis of covariance was performed with covariates of age, sex, years of education, imaging data from multiple centers, and total intracranial volume by using Diffeomorphic Anatomical Registration Through Exponentiated Lie Algebra tool from SPM8 software. Gray matter volume changes for patients with Parkinson disease were detected with decreased gray matter volume in the frontotemporoparietal areas and the bilateral caudate, with increased gray matter volume in the bilateral limbic/paralimbic areas, medial globus pallidus/putamen, and the right occipital cortex compared with healthy controls. Progressive gray matter volume decrease in the bilateral caudate was found for both patients with Parkinson disease and healthy controls, and this caudate volume was positively associated with cognitive ability for both groups. The progressive gray matter volume increase specific to the patients with Parkinson disease was identified close to the left ventral lateral nucleus of thalamus, and a positive relationship was found between the thalamic volume and the tremor scores in a subgroup with tremor-dominant patients with Parkinson disease. The observed progressive changes in gray matter volume in Parkinson disease may provide

The frequency of buccopalpebral reflex in Parkinson disease.

PubMed

Eser, Hülya; Ünal, Yasemin; Kutlu, Gülnihal; Öcal, Ruhsen; İnan, Levent Ertuğrul

2016-11-17

This study aimed to define the frequency of a primitive reflex, the buccopalpebral reflex (BPR), and its association with the clinical situation in patients with Parkinson disease. Between May 2010 and May 2011, 222 patients, 115 with Parkinson disease and 107 patients without any sign of neurodegenerative disease, were included in the study. All included patients were examined for BPR and snout reflex and were also evaluated with the Mini Mental State Examination. All patients with Parkinson disease were classified with the Unified Parkinson's Disease Rating Scale (UPDRS) and the Hoehn and Yahr Score to determine their clinical severity. Sixteen patients with Parkinson disease (13.9%) had a BPR (+) and 4 patients in the control group (3.7%) (P < 0.001). The UPDRS score, UPDRS daily life activities score, and UPDRS motor system score were all higher in the group with BPR (+). All patients with a BPR also had a positive snout reflex. BPR is more frequent in patients with Parkinson disease than in patients without a neurodegenerative disease.

Parkinson's disease and α-synuclein expression.

PubMed

Devine, Michael J; Gwinn, Katrina; Singleton, Andrew; Hardy, John

2011-10-01

Genetic studies of Parkinson's disease over the last decade or more have revolutionized our understanding of this condition. α-Synuclein was the first gene to be linked to Parkinson's disease, and is arguably the most important: the protein is the principal constituent of Lewy bodies, and variation at its locus is the major genetic risk factor for sporadic disease. Intriguingly, duplications and triplications of the locus, as well as point mutations, cause familial disease. Therefore, subtle alterations of α-synuclein expression can manifest with a dramatic phenotype. We outline the clinical impact of α-synuclein locus multiplications, and the implications that this has for Parkinson's disease pathogenesis. Finally, we discuss potential strategies for disease-modifying therapies for this currently incurable disorder. Copyright © 2011 Movement Disorder Society.

Stimulus Timing by People with Parkinson's Disease

ERIC Educational Resources Information Center

Wearden, J. H.; Smith-Spark, J. H.; Cousins, Rosanna; Edelstyn, N. M. J.; Cody, F. W. J.; O'Boyle, D. J.

2008-01-01

Previous literature suggests that Parkinson's disease is marked by deficits in timed behaviour. However, the majority of studies of central timing mechanisms in patients with Parkinson's disease have used timing tasks with a motor component. Since the motor abnormalities are a defining feature of the condition, the status of timing in Parkinson's…

Protein Kinases and Parkinson's Disease.

PubMed

Mehdi, Syed Jafar; Rosas-Hernandez, Hector; Cuevas, Elvis; Lantz, Susan M; Barger, Steven W; Sarkar, Sumit; Paule, Merle G; Ali, Syed F; Imam, Syed Z

2016-09-20

Currently, the lack of new drug candidates for the treatment of major neurological disorders such as Parkinson's disease has intensified the search for drugs that can be repurposed or repositioned for such treatment. Typically, the search focuses on drugs that have been approved and are used clinically for other indications. Kinase inhibitors represent a family of popular molecules for the treatment and prevention of various cancers, and have emerged as strong candidates for such repurposing because numerous serine/threonine and tyrosine kinases have been implicated in the pathobiology of Parkinson's disease. This review focuses on various kinase-dependent pathways associated with the expression of Parkinson's disease pathology, and evaluates how inhibitors of these pathways might play a major role as effective therapeutic molecules.

Parkinson's Disease

MedlinePlus

... in sexual desire or performance. Prevention Because the cause of Parkinson's is unknown, proven ways to prevent the disease also remain a mystery. However, some research has shown that caffeine — which is found in coffee, tea and cola — ...

Risk Factors for Neurodegeneration in Idiopathic REM sleep Behavior Disorder: A Multicenter Study

PubMed Central

Postuma, RB; Iranzo, A; Hogl, B; Arnulf, I; Ferini-Strambi, L; Manni, R; Miyamoto, T.; Oertel, W; Dauvilliers, Y; Ju, Y; Puligheddu, M; Sonka, K; Pelletier, A; Santamaria, J; Frauscher, B; Leu-Semenescu, S; Zucconi, M; Terzaghi, M; Miyamoto, M.; Unger, MM; Carlander, B; Fantini, ML; Montplaisir, JY

2018-01-01

Objective To assess whether risk factors for Parkinson’s disease and Dementia with Lewy bodies increase rate of defined neurodegenerative disease in idiopathic REM sleep behavior disorder Methods 12 centers administered a detailed questionnaire assessing risk factors for neurodegenerative synucleinopathy to patients with idiopathic REM sleep behavior disorder. Variables included demographics, lifestyle factors, pesticide exposures, occupation, co-morbid conditions, medication use, family history, and autonomic/motor symptoms. After 4-years follow-up, patients were assessed for dementia or parkinsonism. Disease risk was assessed with Kaplan-Meier analysis, and epidemiologic variables were compared between convertors and those still idiopathic using logistic regression. Results Of 305 patients, follow-up information was available for 279, of whom 93 (33.3%) developed defined neurodegenerative disease. Disease risk was 25% at 3 years, and 41% after 5 years. Patients who converted were older (difference=4.5 years, p<0.001), with similar sex distribution. Neither caffeine, smoking, nor alcohol exposure predicted conversion. Although occupation was similar between groups, those who converted had a lower likelihood of pesticide exposure (occupational insecticide=2.3% vs. 9.0%). Convertors were more likely to report family history of dementia (OR=2.09), without significant differences in Parkinson’s disease or sleep disorders. Medication exposures and medical history were similar between groups. Autonomic and motor symptoms were more common among those who converted. Risk factors for primary dementia and parkinsonism were generally similar, except for a notably higher clonazepam use in dementia convertors (OR=2.6). Interpretation Patients with idiopathic RBD are at very high risk of neurodegenerative synucleinopathy. Risk factor profiles between convertors and non-convertors have both important commonalities and differences. PMID:25767079

Personality and reported quality of life in Parkinson's disease.

PubMed

Pontone, Gregory M; Mari, Zoltan; Perepezko, Kate; Weiss, Howard D; Bassett, Susan S

2017-03-01

Personality affects an individual's ability to cope with the burden of chronic disease. However, the impact of personality on quality of life (QoL) in Parkinson's disease (PD) is not well characterized. The goal of this study is to determine the effect of personality on QoL in PD. The study included 92 patients with idiopathic PD from Baltimore-Washington area movement disorder neurology clinics. QoL was assessed using the 37-item Parkinson's disease Quality of Life Questionnaire (PDQL) total score, and the Neuroticism-Extraversion-Openness Inventory was used to determine personality traits. Step-wise regression models examined the contribution of personality, depression, demographic, and PD variables on PDQL-assessed QoL. Neuroticism, conscientiousness, years of education, and depression explained 42% of the variance in the PDQL total score after adjusting for other disease variables. High neuroticism (β = -0.727, 95% confidence interval (CI) -1.125, -0.328, p < 0.0001) and depression (β = -9.058, 95%CI -17.46, -0.657, p = 0.035) negatively affected the PDQL, while high conscientiousness (β = 0.468, 95%CI 0.078, 0.858, p = 0.019), and years of education (β = 1.441, 95%CI 0.371, 2.510, p = 0.009) were positive factors. Personality can have a positive or negative influence on QoL in PD. PD patients with otherwise similar disease burdens and depressive symptoms may experience different levels of QoL depending on the level of neurotic or conscientious personality traits. Therefore, when interpreting patient responses on the PDQL, it is important to understand whether they reflect aspects of PD, that is, motor impairment and depression, which are amenable to treatment or whether they reflect personality traits. Copyright © 2016 John Wiley & Sons, Ltd.

Comparison of CSF Distribution between Idiopathic Normal Pressure Hydrocephalus and Alzheimer Disease.

PubMed

Yamada, S; Ishikawa, M; Yamamoto, K

2016-07-01

CSF volumes in the basal cistern and Sylvian fissure are increased in both idiopathic normal pressure hydrocephalus and Alzheimer disease, though the differences in these volumes in idiopathic normal pressure hydrocephalus and Alzheimer disease have not been well-described. Using CSF segmentation and volume quantification, we compared the distribution of CSF in idiopathic normal pressure hydrocephalus and Alzheimer disease. CSF volumes were extracted from T2-weighted 3D spin-echo sequences on 3T MR imaging and quantified semi-automatically. We compared the volumes and ratios of the ventricles and subarachnoid spaces after classification in 30 patients diagnosed with idiopathic normal pressure hydrocephalus, 10 with concurrent idiopathic normal pressure hydrocephalus and Alzheimer disease, 18 with Alzheimer disease, and 26 control subjects 60 years of age or older. Brain to ventricle ratios at the anterior and posterior commissure levels and 3D volumetric convexity cistern to ventricle ratios were useful indices for the differential diagnosis of idiopathic normal pressure hydrocephalus or idiopathic normal pressure hydrocephalus with Alzheimer disease from Alzheimer disease, similar to the z-Evans index and callosal angle. The most distinctive characteristics of the CSF distribution in idiopathic normal pressure hydrocephalus were small convexity subarachnoid spaces and the large volume of the basal cistern and Sylvian fissure. The distribution of the subarachnoid spaces in the idiopathic normal pressure hydrocephalus with Alzheimer disease group was the most deformed among these 3 groups, though the mean ventricular volume of the idiopathic normal pressure hydrocephalus with Alzheimer disease group was intermediate between that of the idiopathic normal pressure hydrocephalus and Alzheimer disease groups. The z-axial expansion of the lateral ventricle and compression of the brain just above the ventricle were the common findings in the parameters for differentiating

Vocal tract characteristics in Parkinson's disease.

PubMed

Gillivan-Murphy, Patricia; Carding, Paul; Miller, Nick

2016-06-01

Voice tremor is strongly linked to the Parkinson's disease speech-voice symptom complex. Little is known about the underlying anatomic source(s) of voice tremor when it occurs. We review recent literature addressing this issue. Additionally we report findings from a study we conducted employing rating of vocal tract structures viewed using nasolaryngoscopy during vocal and nonspeech tasks. In Parkinson's disease, using laryngeal electromyography, tremor has not been identified in muscles in the vocal folds even when perceived auditorily. Preliminary findings using nasolaryngoscopy suggest that Parkinson's disease voice tremor is not associated with the vocal folds and may involve the palate, the global larynx, and the arytenoids. Tremor in the vertical larynx on /a/, and tremor in the arytenoid cartilages on /s/ differentiated patients with Parkinson's disease from neurologically healthy controls. Visual reliable detection of tremor when it is absent or borderline present, is challenging. Parkinson's disease voice tremor is likely to be related to oscillatory movement in structures across the vocal tract rather than just the vocal folds. To progress clinical practice, more refined tools for the visual rating of tremor would be beneficial. How far voice tremor represents a functionally significant factor for speakers would also add to the literature.

Parkinson's Disease Subtypes in the Oxford Parkinson Disease Centre (OPDC) Discovery Cohort.

PubMed

Lawton, Michael; Baig, Fahd; Rolinski, Michal; Ruffman, Claudio; Nithi, Kannan; May, Margaret T; Ben-Shlomo, Yoav; Hu, Michele T M

2015-01-01

Within Parkinson's there is a spectrum of clinical features at presentation which may represent sub-types of the disease. However there is no widely accepted consensus of how best to group patients. Use a data-driven approach to unravel any heterogeneity in the Parkinson's phenotype in a well-characterised, population-based incidence cohort. 769 consecutive patients, with mean disease duration of 1.3 years, were assessed using a broad range of motor, cognitive and non-motor metrics. Multiple imputation was carried out using the chained equations approach to deal with missing data. We used an exploratory and then a confirmatory factor analysis to determine suitable domains to include within our cluster analysis. K-means cluster analysis of the factor scores and all the variables not loading into a factor was used to determine phenotypic subgroups. Our factor analysis found three important factors that were characterised by: psychological well-being features; non-tremor motor features, such as posture and rigidity; and cognitive features. Our subsequent five cluster model identified groups characterised by (1) mild motor and non-motor disease (25.4%), (2) poor posture and cognition (23.3%), (3) severe tremor (20.8%), (4) poor psychological well-being, RBD and sleep (18.9%), and (5) severe motor and non-motor disease with poor psychological well-being (11.7%). Our approach identified several Parkinson's phenotypic sub-groups driven by largely dopaminergic-resistant features (RBD, impaired cognition and posture, poor psychological well-being) that, in addition to dopaminergic-responsive motor features may be important for studying the aetiology, progression, and medication response of early Parkinson's.

Laughter Yoga, Adults Living With Parkinson׳s Disease, and Caregivers: A Pilot Study.

PubMed

DeCaro, Debra Swedberg; Constantine Brown, Jodi L

2016-01-01

This study explored outcomes of Laughter Yoga in adults with Parkinson׳s disease (PD) and their caregivers. Laughter has been shown to generally improve mood in physically healthy adults, and specifically in adults with heart disease or cancer, but little research exists regarding the impact of laughter in adults with Parkinson׳s disease. Low mood is frequently a co-morbid condition for adults with Parkinson׳s disease, and can negatively affect their caregivers. Pre-experimental (O1 × O2) pretest-posttest design. Data collection occurred at six unique PD support groups in Southern California. Participants (N = 85) comprised a convenience sample of adults diagnosed with Parkinson׳s disease (n = 47) and accompanying caregivers (n = 38). Subjects participated in a 45-min Laughter Yoga (LY) session conducted by a Certified Laughter Yoga Teacher. This study utilized the Laughter Yoga "How Do You Feel?" (HDYF) form. The form consists of a series of 10 scales labeled "well-being" measures including enthusiasm, energy level, mood, optimism, stress level, level of friendship with group members, level of awareness about breathing, level of muscle relaxation, level of mental relaxation, and ability to laugh without a reason. Paired sample t-tests reveal statistically significant improvements in well-being for adults with PD and their caregivers after attending an LY session. Therapists and other clinicians should consider utilizing this unique technique with adults with PD to address co-morbid low-mood conditions and include caregivers in the LY sessions for support and their own benefit. Copyright © 2016 Elsevier Inc. All rights reserved.

Boxing training for patients with Parkinson disease: a case series.

PubMed

Combs, Stephanie A; Diehl, M Dyer; Staples, William H; Conn, Lindsay; Davis, Kendra; Lewis, Nicole; Schaneman, Katie

2011-01-01

A nontraditional form of exercise recently applied for patients with Parkinson disease (PD) is boxing training. The primary purpose of this case series is to describe the effects of disease severity and duration of boxing training (short term and long term) on changes in balance, mobility, and quality of life for patients with mild or moderate to severe PD. The feasibility and safety of the boxing training program also were assessed. Six patients with idiopathic PD attended 24 to 36 boxing training sessions for 12 weeks, with the option of continuing the training for an additional 24 weeks (a seventh patient attended sessions for only 4 weeks). The 90-minute sessions included boxing drills and traditional stretching, strengthening, and endurance exercises. Outcomes were tested at the baseline and after 12, 24, and 36 weeks of boxing sessions (12-, 24-, and 36-week tests). The outcome measures were the Functional Reach Test, Berg Balance Scale, Activities-specific Balance Confidence Scale, Timed "Up & Go" Test, Six-Minute Walk Test, gait speed, cadence, stride length, step width, activities of daily living and motor examination subscales of the Unified Parkinson Disease Rating Scale, and Parkinson Disease Quality of Life Scale. Six patients completed all phases of the case series, showed improvements on at least 5 of the 12 outcome measures over the baseline at the 12-week test, and showed continued improvements at the 24- and 36-week tests. Patients with mild PD typically showed improvements earlier than those with moderate to severe PD. Despite the progressive nature of PD, the patients in this case series showed short-term and long-term improvements in balance, gait, activities of daily living, and quality of life after the boxing training program. A longer duration of training was necessary for patients with moderate to severe PD to show maximal training outcomes. The boxing training program was feasible and safe for these patients with PD.

Understanding Parkinson Disease: A Complex and Multifaceted Illness.

PubMed

Gopalakrishna, Apoorva; Alexander, Sheila A

2015-12-01

Parkinson disease is an incredibly complex and multifaceted illness affecting millions of people in the United States. Parkinson disease is characterized by progressive dopaminergic neuronal dysfunction and loss, leading to debilitating motor, cognitive, and behavioral symptoms. Parkinson disease is an enigmatic illness that is still extensively researched today to search for a better understanding of the disease, develop therapeutic interventions to halt or slow progression of the disease, and optimize patient outcomes. This article aims to examine in detail the normal function of the basal ganglia and dopaminergic neurons in the central nervous system, the etiology and pathophysiology of Parkinson disease, related signs and symptoms, current treatment, and finally, the profound impact of understanding the disease on nursing care.

[Advance of the study on LRRK2 gene in Parkinson's disease].

PubMed

Zhang, Yu; Chen, Shengdi

2008-12-01

The leucine-rich repeat kinase2 (LRRK2) has been identified to be the gene causing autosomal dominant inherited Parkinson's disease(PD)8. The clinical features of this type of PD are similar to those of idiopathic PD, but the pathological changes are diverse. The mutation types and frequencies of the LRRK2 distribute unevenly in different populations. LRRK2 is a large complex protein with multiple functions and expresses widely in human body. Sequence alignment shows that LRRK2 might be a multiple function kinase for substrate phosphorylation and might also act as a scaffolding protein. Further study on the physiological function and pathogenic mechanism of LRRK2 will help to find out the possible pathogenesis and new treatment for PD.

Home-based virtual reality balance training and conventional balance training in Parkinson's disease: A randomized controlled trial.

PubMed

Yang, Wen-Chieh; Wang, Hsing-Kuo; Wu, Ruey-Meei; Lo, Chien-Shun; Lin, Kwan-Hwa

2016-09-01

Virtual reality has the advantage to provide rich sensory feedbacks for training balance function. This study tested if the home-based virtual reality balance training is more effective than the conventional home balance training in improving balance, walking, and quality of life in patients with Parkinson's disease (PD). Twenty-three patients with idiopathic PD were recruited and underwent twelve 50-minute training sessions during the 6-week training period. The experimental group (n = 11) was trained with a custom-made virtual reality balance training system, and the control group (n = 12) was trained by a licensed physical therapist. Outcomes were measured at Week 0 (pretest), Week 6 (posttest), and Week 8 (follow-up). The primary outcome was the Berg Balance Scale. The secondary outcomes included the Dynamic Gait Index, timed Up-and-Go test, Parkinson's Disease Questionnaire, and the motor score of the Unified Parkinson's Disease Rating Scale. The experimental and control groups were comparable at pretest. After training, both groups performed better in the Berg Balance Scale, Dynamic Gait Index, timed Up-and-Go test, and Parkinson's Disease Questionnaire at posttest and follow-up than at pretest. However, no significant differences were found between these two groups at posttest and follow-up. This study did not find any difference between the effects of the home-based virtual reality balance training and conventional home balance training. The two training options were equally effective in improving balance, walking, and quality of life among community-dwelling patients with PD. Copyright © 2015. Published by Elsevier B.V.

Association of single-nucleotide polymorphisms of the tau gene with late-onset Parkinson disease.

PubMed

Martin, E R; Scott, W K; Nance, M A; Watts, R L; Hubble, J P; Koller, W C; Lyons, K; Pahwa, R; Stern, M B; Colcher, A; Hiner, B C; Jankovic, J; Ondo, W G; Allen, F H; Goetz, C G; Small, G W; Masterman, D; Mastaglia, F; Laing, N G; Stajich, J M; Ribble, R C; Booze, M W; Rogala, A; Hauser, M A; Zhang, F; Gibson, R A; Middleton, L T; Roses, A D; Haines, J L; Scott, B L; Pericak-Vance, M A; Vance, J M

2001-11-14

The human tau gene, which promotes assembly of neuronal microtubules, has been associated with several rare neurologic diseases that clinically include parkinsonian features. We recently observed linkage in idiopathic Parkinson disease (PD) to a region on chromosome 17q21 that contains the tau gene. These factors make tau a good candidate for investigation as a susceptibility gene for idiopathic PD, the most common form of the disease. To investigate whether the tau gene is involved in idiopathic PD. Among a sample of 1056 individuals from 235 families selected from 13 clinical centers in the United States and Australia and from a family ascertainment core center, we tested 5 single-nucleotide polymorphisms (SNPs) within the tau gene for association with PD, using family-based tests of association. Both affected (n = 426) and unaffected (n = 579) family members were included; 51 individuals had unclear PD status. Analyses were conducted to test individual SNPs and SNP haplotypes within the tau gene. Family-based tests of association, calculated using asymptotic distributions. Analysis of association between the SNPs and PD yielded significant evidence of association for 3 of the 5 SNPs tested: SNP 3, P =.03; SNP 9i, P =.04; and SNP 11, P =.04. The 2 other SNPs did not show evidence of significant association (SNP 9ii, P =.11, and SNP 9iii, P =.87). Strong evidence of association was found with haplotype analysis, with a positive association with one haplotype (P =.009) and a negative association with another haplotype (P =.007). Substantial linkage disequilibrium (P<.001) was detected between 4 of the 5 SNPs (SNPs 3, 9i, 9ii, and 11). This integrated approach of genetic linkage and positional association analyses implicates tau as a susceptibility gene for idiopathic PD.

Association of Single-Nucleotide Polymorphisms of the Tau Gene With Late-Onset Parkinson Disease

PubMed Central

Martin, Eden R.; Scott, William K.; Nance, Martha A.; Watts, Ray L.; Hubble, Jean P.; Koller, William C.; Lyons, Kelly; Pahwa, Rajesh; Stern, Matthew B.; Colcher, Amy; Hiner, Bradley C.; Jankovic, Joseph; Ondo, William G.; Allen, Fred H.; Goetz, Christopher G.; Small, Gary W.; Masterman, Donna; Mastaglia, Frank; Laing, Nigel G.; Stajich, Jeffrey M.; Ribble, Robert C.; Booze, Michael W.; Rogala, Allison; Hauser, Michael A.; Zhang, Fengyu; Gibson, Rachel A.; Middleton, Lefkos T.; Roses, Allen D.; Haines, Jonathan L.; Scott, Burton L.; Pericak-Vance, Margaret A.; Vance, Jeffery M.

2013-01-01

Context The human tau gene, which promotes assembly of neuronal microtubules, has been associated with several rare neurologic diseases that clinically include parkinsonian features. We recently observed linkage in idiopathic Parkinson disease (PD) to a region on chromosome 17q21 that contains the tau gene. These factors make tau a good candidate for investigation as a susceptibility gene for idiopathic PD, the most common form of the disease. Objective To investigate whether the tau gene is involved in idiopathic PD. Design, Setting, and Participants Among a sample of 1056 individuals from 235 families selected from 13 clinical centers in the United States and Australia and from a family ascertainment core center, we tested 5 single-nucleotide polymorphisms (SNPs) within the tau gene for association with PD, using family-based tests of association. Both affected (n = 426) and unaffected (n = 579) family members were included; 51 individuals had unclear PD status. Analyses were conducted to test individual SNPs and SNP haplotypes within the tau gene. Main Outcome Measure Family-based tests of association, calculated using asymptotic distributions. Results Analysis of association between the SNPs and PD yielded significant evidence of association for 3 of the 5 SNPs tested: SNP 3, P = .03; SNP 9i, P = .04; and SNP 11, P = .04. The 2 other SNPs did not show evidence of significant association (SNP 9ii, P = .11, and SNP 9iii, P = .87). Strong evidence of association was found with haplotype analysis, with a positive association with one haplotype (P = .009) and a negative association with another haplotype (P = .007). Substantial linkage disequilibrium (P<.001) was detected between 4 of the 5 SNPs (SNPs 3,9i, 9ii, and 11). Conclusions This integrated approach of genetic linkage and positional association analyses implicates tau as a susceptibility gene for idiopathic PD. PMID:11710889

Progressive resistance training in Parkinson's disease: a systematic review and meta-analysis

PubMed Central

Saltychev, Mikhail; Bärlund, Esa; Paltamaa, Jaana; Katajapuu, Niina; Laimi, Katri

2016-01-01

Objectives To investigate if there is evidence on effectiveness of progressive resistance training in rehabilitation of Parkinson disease. Design Systematic review and meta-analysis. Data sources: Central, Medline, Embase, Cinahl, Web of Science, Pedro until May 2014. Randomised controlled or controlled clinical trials. The methodological quality of studies was assessed according to the Cochrane Collaboration's domain-based evaluation framework. Data synthesis: random effects meta-analysis with test for heterogeneity using the I² and pooled estimate as the raw mean difference. Participants Adults with primary/idiopathic Parkinson's disease of any severity, excluding other concurrent neurological condition. Interventions Progressive resistance training defined as training consisting of a small number of repetitions until fatigue, allowing sufficient rest between exercises for recovery, and increasing the resistance as the ability to generate force improves. Comparison Progressive resistance training versus no treatment, placebo or other treatment in randomised controlled or controlled clinical trials. Primary and secondary outcome measures Any outcome. Results Of 516 records, 12 were considered relevant. Nine of them had low risk of bias. All studies were randomised controlled trials conducted on small samples with none or 1 month follow-up after the end of intervention. Of them, six were included in quantitative analysis. Pooled effect sizes of meta-analyses on fast and comfortable walking speed, the 6 min walking test, Timed Up and Go test and maximal oxygen consumption were below the level of minimal clinical significance. Conclusions There is so far no evidence on the superiority of progressive resistance training compared with other physical training to support the use of this technique in rehabilitation of Parkinson's disease. Systematic review registration number PROSPERO 2014:CRD42014009844. PMID:26743698

Parkinson's disease - the story of an eponym.

PubMed

Goedert, Michel; Compston, Alastair

2018-01-01

One of the most prevalent neurodegenerative diseases worldwide is still referred to as 'Parkinson's disease'. The condition is named after James Parkinson who, in 1817, described the shaking palsy (paralysis agitans). In the bicentennial year of this publication, we trace when and why the shaking palsy became Parkinson's disease. The term was coined by William Rutherford Sanders of Edinburgh in 1865 and later entered general usage through the influence of Jean-Martin Charcot and the school that he nurtured at the Salpêtrière Hospital in Paris. Despite a move towards more mechanism-based nosology for many medical conditions in recent years, the Parkinson's disease eponym remains in place, celebrating the life and work of this doctor, palaeontologist and political activist.

No allelic association between Parkinson`s disease and dopamine D2, D3, and D4 receptor gene polymorphisms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nanko, S.; Hattori, M.; Dai, X.Y.

1994-12-15

Parkinson`s disease is thought to be caused by a combination of unknown environmental, genetic, and degenerative factors. Evidence from necropsy brain samples and pharmacokinetics suggests involvement of dopamine receptors in the pathogenesis or pathophysiology of Parkinson`s disease. Genetic association studies between Parkinson`s disease and dopamine D2, D3 and D4 receptor gene polymorphisms were conducted. The polymorphism was examined in 71 patients with Parkinson`s disease and 90 controls. There were no significant differences between two groups in allele frequencies at the D2, D3, and D4 dopamine receptor loci. Our findings do not support the hypothesis that susceptibility to Parkinson`s disease ismore » associated with the dopamine receptor polymorphisms examined. 35 refs., 2 tabs.« less

A Tangled Web – Tau and Sporadic Parkinson's Disease

PubMed Central

Wray, Selina; Lewis, Patrick A.

2010-01-01

Parkinson's disease (PD) represents a major challenge for health care systems around the world: it is the most common degenerative movement disorder of old age, affecting over 100,000 people in the UK alone (Schrag et al., 2000). Despite the remarkable success of treatments directed at potentiating or replacing dopamine within the brain, which can relieve symptoms for over a decade, PD remains an incurable and invariably fatal disorder. As such, efforts to understand the processes that lead to cell death in the brains of patients with PD are a priority for neurodegenerative researchers. A great deal of progress has been made in this regard by taking advantage of advances in genetics, initially by the identification of genes responsible for rare Mendelian forms of PD (outlined in Table 1), and more recently by applying genome wide association studies (GWAS) to the sporadic form of the disease (Hardy et al., 2009). Several such GWAS have now been carried out, with a meta-analysis currently under way. Using over 6000 cases and 10,000 controls, two of these studies have identified variation at a number of loci as being associated with an increased risk of disease (Satake et al., 2009; Simon-Sanchez et al., 2009). Three genes stand out as candidates from these studies – the SNCA gene, coding for α-synuclein, the LRRK2 gene, coding for leucine rich repeat kinase 2, and MAPT, coding for the microtubule-associated protein tau. Mutations at all three of these loci have been associated with Mendelian forms of disease presenting with the clinical syndrome of Parkinsonism, however only SNCA and LRRK2 have been previously associated with pathologically defined PD (Hardy et al., 2009). Point mutations in α-synuclein, along with gene multiplication events, result in autosomal dominant PD, often with a significant dementia component. In addition to this, α-synuclein is the principle component of the main pathological hallmark of idiopathic PD, the Lewy body, making it an

Motivational modes and learning in Parkinson's disease.

PubMed

Foerde, Karin; Braun, Erin Kendall; Higgins, E Tory; Shohamy, Daphna

2015-08-01

Learning and motivation are intrinsically related, and both have been linked to dopamine. Parkinson's disease results from a progressive loss of dopaminergic inputs to the striatum and leads to impairments in motivation and learning from feedback. However, the link between motivation and learning in Parkinson's disease is not well understood. To address this gap, we leverage a well-established psychological theory of motivation, regulatory mode theory, which distinguishes between two functionally independent motivational concerns in regulating behavior: a concern with having an effect by initiating and maintaining movement (Locomotion) and a concern with establishing what is correct by critically evaluating goal pursuit means and outcomes (Assessment). We examined Locomotion and Assessment in patients with Parkinson's disease and age-matched controls. Parkinson's disease patients demonstrated a selective decrease in Assessment motivation but no change in Locomotion motivation, suggesting that Parkinson's disease leads to a reduced tendency to evaluate and monitor outcomes. Moreover, weaker Assessment motivation was correlated with poorer performance on a feedback-based learning task previously shown to depend on the striatum. Together, these findings link a questionnaire-based personality inventory with performance on a well-characterized experimental task, advancing our understanding of how Parkinson's disease affects motivation with implications for well-being and treatment outcomes. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Neuromuscular rate of force development deficit in Parkinson disease.

PubMed

Hammond, Kelley G; Pfeiffer, Ronald F; LeDoux, Mark S; Schilling, Brian K

2017-06-01

Bradykinesia and reduced neuromuscular force exist in Parkinson disease. The interpolated twitch technique has been used to evaluate central versus peripheral manifestations of neuromuscular strength in healthy, aging, and athletic populations, as well as moderate to advanced Parkinson disease, but this method has not been used in mild Parkinson disease. This study aimed to evaluate quadriceps femoris rate of force development and quantify potential central and peripheral activation deficits in individuals with Parkinson disease. Nine persons with mild Parkinson Disease (Hoehn & Yahr≤2, Unified Parkinson Disease Rating Scale total score=mean 19.1 (SD 5.0)) and eight age-matched controls were recruited in a cross-sectional investigation. Quadriceps femoris voluntary and stimulated maximal force and rate of force development were evaluated using the interpolated twitch technique. Thirteen participants satisfactorily completed the protocol. Individuals with early Parkinson disease (n=7) had significantly slower voluntary rate of force development (p=0.008; d=1.97) and rate of force development ratio (p=0.004; d=2.18) than controls (n=6). No significant differences were found between groups for all other variables. Persons with mild-to-moderate Parkinson disease display disparities in rate of force development, even without deficits in maximal force. The inability to produce force at a rate comparable to controls is likely a downstream effect of central dysfunction of the motor pathway in Parkinson disease. Copyright © 2017. Published by Elsevier Ltd.

Methamphetamine and Parkinson's Disease

PubMed Central

Granado, Noelia; Ares-Santos, Sara; Moratalla, Rosario

2013-01-01

Parkinson's disease (PD) is a neurodegenerative disorder predominantly affecting the elderly. The aetiology of the disease is not known, but age and environmental factors play an important role. Although more than a dozen gene mutations associated with familial forms of Parkinson's disease have been described, fewer than 10% of all cases can be explained by genetic abnormalities. The molecular basis of Parkinson's disease is the loss of dopamine in the basal ganglia (caudate/putamen) due to the degeneration of dopaminergic neurons in the substantia nigra, which leads to the motor impairment characteristic of the disease. Methamphetamine is the second most widely used illicit drug in the world. In rodents, methamphetamine exposure damages dopaminergic neurons in the substantia nigra, resulting in a significant loss of dopamine in the striatum. Biochemical and neuroimaging studies in human methamphetamine users have shown decreased levels of dopamine and dopamine transporter as well as prominent microglial activation in the striatum and other areas of the brain, changes similar to those observed in PD patients. Consistent with these similarities, recent epidemiological studies have shown that methamphetamine users are almost twice as likely as non-users to develop PD, despite the fact that methamphetamine abuse and PD have distinct symptomatic profiles. PMID:23476887

Thiazolidinediones and Parkinson Disease: A Cohort Study.

PubMed

Connolly, John G; Bykov, Katsiaryna; Gagne, Joshua J

2015-12-01

Thiazolidinediones, a class of medications indicated for the treatment of type 2 diabetes mellitus, reduce inflammation and have been shown to provide a therapeutic benefit in animal models of Parkinson disease. We examined the association between treatment with thiazolidinediones and the onset of Parkinson disease in older individuals. We performed a cohort study of 29,397 Medicare patients enrolled in state pharmaceutical benefits programs who initiated treatment with thiazolidinediones or sulfonylureas during the years 1997 through 2005 and had no prior diagnosis of Parkinson disease. New users of thiazolidinediones were propensity score matched to new users of sulfonylureas and followed to determine whether they were diagnosed with Parkinson disease. We used Cox proportional hazards models to compare time to diagnosis of Parkinson disease in the propensity score-matched populations. To assess the association with duration of use, we performed several analyses that required longer continuous use of medications. In the primary analysis, thiazolidinedione users had a hazard ratio for a diagnosis of Parkinson disease of 1.09 (95% confidence interval: 0.71, 1.66) when compared with sulfonylurea users. Increasing the duration-of-use requirements to 10 months did not substantially change the association; the hazard ratios ranged from 1.00 (95% confidence interval: 0.49, 2.05) to 1.17 (95% confidence interval: 0.60, 2.25). Thiazolidinedione use was not associated with a longer time to diagnosis of Parkinson disease than was sulfonylurea use, regardless of duration of exposure. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Prodromal Parkinson's disease--using REM sleep behavior disorder as a window.

PubMed

Postuma, Ronald B

2014-01-01

REM sleep behavior disorder (RBD) is characterized by loss of REM atonia of sleep, such that patients act out the contents of their dreams. Perhaps the most important facet of idiopathic RBD is that it is a powerful prodromal marker of Parkinson's disease (PD) and other synucleinopathies. Several prospective studies have now established that patients with idiopathic RBD have up to an 80% risk of developing a defined neurodegenerative synucleinopathy. This has profound implications for understanding and treating early disease. First, the extremely high risk and long latency/time to intervene make RBD patients the ideal candidates for neuroprotective therapy against synucleinopathy. Second, RBD patients can be used as a 'test lab' to assess other potential prodromal predictors of PD, which could be applied to the general population in future large-scale screening programs. Third, assessing epidemiology of RBD allows us to study the epidemiology of PD and dementia with Lewy bodies 10-15 years earlier, reducing bias and opening new hypotheses as to the mechanism of action of selected risk factors. Finally, by prospectively observing RBD patients as they transition to full neurodegenerative synucleinopathy, one has an unprecedented window in which to directly observe evolution of PD from its prodromal stages. The evidence for RBD as a marker of prodromal PD and all these implications will be discussed. Copyright © 2013 Elsevier Ltd. All rights reserved.

Quantifying gait patterns in Parkinson's disease

NASA Astrophysics Data System (ADS)

Romero, Mónica; Atehortúa, Angélica; Romero, Eduardo

2017-11-01

Parkinson's disease (PD) is constituted by a set of motor symptoms, namely tremor, rigidity, and bradykinesia, which are usually described but not quantified. This work proposes an objective characterization of PD gait patterns by approximating the single stance phase a single grounded pendulum. This model estimates the force generated by the gait during the single support from gait data. This force describes the motion pattern for different stages of the disease. The model was validated using recorded videos of 8 young control subjects, 10 old control subjects and 10 subjects with Parkinson's disease in different stages. The estimated force showed differences among stages of Parkinson disease, observing a decrease of the estimated force for the advanced stages of this illness.

Parkinson's disease and periodontitis - the missing link? A review.

PubMed

Kaur, Tejaswani; Uppoor, Ashita; Naik, Dilip

2016-12-01

In this article an attempt has been made to postulate a possible link between Parkinson's disease and periodontal disease. Various systemic diseases such as cardiac disease, diabetes, renal diseases, low birth weight and Alzheimer's disease have been proposed to be linked with periodontal disease on the basis of systemic inflammation. Parkinson's disease is a chronic progressive neurodegenerative disorder with multifactorial aetiology. Until now, periodontal disease and Parkinson's disease has been linked only on the basis of poor motor and cognitive control in Parkinson's patient which leads to poor oral health maintenance. Evidence now suggests that chronic neuroinflammation is consistently associated with the pathophysiology of Parkinson's disease. Also, recently, systemic inflammation has been suggested as one of the contributing factors for neurodegeneration. Dental and medical literature especially those dealing with neurosciences were selected which highlighted the link between systemic inflammation and infection. So far there is no direct evidence implicating an effect of periodontitis in the pathogenesis of Parkinson's disease. To clarify this link, studies on population based case-control or cohort design are needed. This would be especially significant in the present era where there is paucity for preventive measures as far as a cognitive disorder such as Parkinson's disease is concerned. We cannot cure Parkinson's disease, but if in future this missing link is established, an attempt can be made to prevent it by tackling one of its possible contributors (periodontitis) for systemic inflammation by simple preventive oral hygiene measures. © 2015 John Wiley & Sons A/S and The Gerodontology Association. Published by John Wiley & Sons Ltd.

Nicotinic receptors as CNS targets for Parkinson's disease.

PubMed

Quik, Maryka; Bordia, Tanuja; O'Leary, Kathryn

2007-10-15

Parkinson's disease is a debilitating neurodegenerative movement disorder characterized by damage to the nigrostriatal dopaminergic system. Current therapies are symptomatic only and may be accompanied by serious side effects. There is therefore a continual search for novel compounds for the treatment of Parkinson's disease symptoms, as well as to reduce or halt disease progression. Nicotine administration has been reported to improve motor deficits that arise with nigrostriatal damage in parkinsonian animals and in Parkinson's disease. In addition, nicotine protects against nigrostriatal damage in experimental models, findings that have led to the suggestion that the reduced incidence of Parkinson's disease in smokers may be due to the nicotine in tobacco. Altogether, these observations suggest that nicotine treatment may be beneficial in Parkinson's disease. Nicotine interacts with multiple nicotinic receptor (nAChR) subtypes in the peripheral and central nervous system, as well as in skeletal muscle. Work to identify the subtypes affected in Parkinson's disease is therefore critical for the development of targeted therapies. Results show that striatal alpha6beta2-containing nAChRs are particularly susceptible to nigrostriatal damage, with a decline in receptor levels that closely parallels losses in striatal dopamine. In contrast, alpha4beta2-containing nAChRs are decreased to a much smaller extent under the same conditions. These observations suggest that development of nAChR agonists or antagonists targeted to alpha6beta2-containing nAChRs may represent a particularly relevant target for Parkinson's disease therapeutics.

Haplotypes and gene expression implicate the MAPT region for Parkinson disease

PubMed Central

Tobin, J.E.; Latourelle, J.C.; Lew, M.F.; Klein, C.; Suchowersky, O.; Shill, H.A.; Golbe, L.I.; Mark, M.H.; Growdon, J.H.; Wooten, G.F.; Racette, B.A.; Perlmutter, J.S.; Watts, R.; Guttman, M.; Baker, K.B.; Goldwurm, S.; Pezzoli, G.; Singer, C.; Saint-Hilaire, M.H.; Hendricks, A.E.; Williamson, S.; Nagle, M.W.; Wilk, J.B.; Massood, T.; Laramie, J.M.; DeStefano, A.L.; Litvan, I.; Nicholson, G.; Corbett, A.; Isaacson, S.; Burn, D.J.; Chinnery, P.F.; Pramstaller, P.P.; Sherman, S.; Al-hinti, J.; Drasby, E.; Nance, M.; Moller, A.T.; Ostergaard, K.; Roxburgh, R.; Snow, B.; Slevin, J.T.; Cambi, F.; Gusella, J.F.; Myers, R.H.

2009-01-01

Background Microtubule-associated protein tau (MAPT) has been associated with several neurodegenerative disorders including forms of parkinsonism and Parkinson disease (PD). We evaluated the association of the MAPT region with PD in a large cohort of familial PD cases recruited by the GenePD Study. In addition, postmortem brain samples from patients with PD and neurologically normal controls were used to evaluate whether the expression of the 3-repeat and 4-repeat isoforms of MAPT, and neighboring genes Saitohin (STH) and KIAA1267, are altered in PD cerebellum. Methods Twenty-one single-nucleotide polymorphisms (SNPs) in the region of MAPT on chromosome 17q21 were genotyped in the GenePD Study. Single SNPs and haplotypes, including the H1 haplotype, were evaluated for association to PD. Relative quantification of gene expression was performed using real-time RT-PCR. Results After adjusting for multiple comparisons, SNP rs1800547 was significantly associated with PD affection. While the H1 haplotype was associated with a significantly increased risk for PD, a novel H1 subhaplotype was identified that predicted a greater increased risk for PD. The expression of 4-repeat MAPT, STH, and KIAA1267 was significantly increased in PD brains relative to controls. No difference in expression was observed for 3-repeat MAPT. Conclusions This study supports a role for MAPT in the pathogenesis of familial and idiopathic Parkinson disease (PD). Interestingly, the results of the gene expression studies suggest that other genes in the vicinity of MAPT, specifically STH and KIAA1267, may also have a role in PD and suggest complex effects for the genes in this region on PD risk. PMID:18509094

Parkinson disease. Unravelling the nonmotor mysteries of Parkinson disease.

PubMed

Chaudhuri, K Ray; Sauerbier, Anna

2016-01-01

Parkinson disease (PD) is now regarded as a mixed motor, nonmotor and multiorgan disorder rather than a pure movement disorder. Nonmotor symptoms (NMS) have underpinned this conceptual change, and new criteria for clinical and prodromal diagnosis of PD, incorporating a range of NMS, have recently been published.

Ability to Consent to Parkinson Disease Research

MedlinePlus

... Steven Karceski, MD The ability to consent to Parkinson disease research Eran Klein, MD, PhD WHAT IS THIS ... 1 on giving consent to be part of Parkinson disease (PD) research. People with PD often want to ...

Reduced Rapid Eye Movement Density in Parkinson Disease: A Polysomnography-Based Case-Control Study.

PubMed

Schroeder, Lynn A; Rufra, Olivier; Sauvageot, Nicolas; Fays, François; Pieri, Vannina; Diederich, Nico J

2016-12-01

To explore rapid eye movement density (RD) in patients with idiopathic Parkinson disease (IPD) and to investigate its usefulness as surrogate marker of excessive daytime sleepiness, a frequent complaint in IPD patients. Retrospective polysomnography study on 81 subjects without dementia: 29 patients with early stage IPD (disease duration ≤ 3 y), 21 patients with middle- stage IPD (disease duration > 3 and < 8 y) and 31 healthy controls (HC). Rapid eye movement (REM) sleep was defined as any REM episode with > 3 min of continuous REM sleep. RD was defined as number of ocular movements per minute of REM sleep. Patients with early stage IPD and HC fulfilled the PD-specific sleepiness questionnaires Parkinson's Disease Sleep Scale (PDSS) and the Nonmotor Symptoms Questionnaire for Parkinson's disease (NMSQuest). RD was lower in patients with IPD than in HC. The difference was most significant between patients with middle stage IPD and HC (P = 0.001), and most prominent for the third REM episode, again when comparing patients with middle stage IPD and HC (P = 0.03). RD was independent from sex, age, and other sleep parameters. In early stage IPD, RD correlated with the PDSS score (r = -0.63, P = 0.001) and the sleep-related questions of the NMSQuest score (r = 0.48, P = 0.017). REM density is reduced in patients with IPD and correlates with subjective scores on sleep impairment. As an indicator of persistent high sleep pressure, reduced RD in IPD is eligible as a biomarker of excessive daytime sleepiness in IPD. It possibly reflects direct involvement of the brainstem REM generation sites by the disease process. RD is a promising new tool for sleep research in IPD. © 2016 Associated Professional Sleep Societies, LLC.

Speech and swallowing disorders in Parkinson disease.

PubMed

Sapir, Shimon; Ramig, Lorraine; Fox, Cynthia

2008-06-01

To review recent research and clinical studies pertaining to the nature, diagnosis, and treatment of speech and swallowing disorders in Parkinson disease. Although some studies indicate improvement in voice and speech with dopamine therapy and deep brain stimulation of the subthalamic nucleus, others show minimal or adverse effects. Repetitive transcranial magnetic stimulation of the mouth motor cortex and injection of collagen in the vocal folds have preliminary data supporting improvement in phonation in people with Parkinson disease. Treatments focusing on vocal loudness, specifically LSVT LOUD (Lee Silverman Voice Treatment), have been effective for the treatment of speech disorders in Parkinson disease. Changes in brain activity due to LSVT LOUD provide preliminary evidence for neural plasticity. Computer-based technology makes the Lee Silverman Voice Treatment available to a large number of users. A rat model for studying neuropharmacologic effects on vocalization in Parkinson disease has been developed. New diagnostic methods of speech and swallowing are also available as the result of recent studies. Speech rehabilitation with the LSVT LOUD is highly efficacious and scientifically tested. There is a need for more studies to improve understanding, diagnosis, prevention, and treatment of speech and swallowing disorders in Parkinson disease.

Old and new challenges in Parkinson's disease therapeutics.

PubMed

Pires, Ana O; Teixeira, F G; Mendes-Pinheiro, B; Serra, Sofia C; Sousa, Nuno; Salgado, António J

2017-09-01

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons and/or loss od neuronal projections, in several dopaminergic networks. Current treatments for idiopathic PD rely mainly on the use of pharmacologic agents to improve motor symptomatology of PD patients. Nevertheless, so far PD remains an incurable disease. Therefore, it is of utmost importance to establish new therapeutic strategies for PD treatment. Over the last 20 years, several molecular, gene and cell/stem-cell therapeutic approaches have been developed with the aim of counteracting or retarding PD progression. The scope of this review is to provide an overview of PD related therapies and major breakthroughs achieved within this field. In order to do so, this review will start by focusing on PD characterization and current treatment options covering thereafter molecular, gene and cell/stem cell-based therapies that are currently being studied in animal models of PD or have recently been tested in clinical trials. Among stem cell-based therapies, those using MSCs as possible disease modifying agents for PD therapy and, specifically, the MSCs secretome contribution to meet the clinical challenge of counteracting or retarding PD progression, will be more deeply explored. Copyright © 2017 Elsevier Ltd. All rights reserved.

Computer assisted CT-guided stereotactic transplantation of foetal ventral mesencephalon to the caudate nucleus and putamen in Parkinson's disease.

PubMed

Molina, H; Quiñones, R; Ortega, I; Alvarez, L; Muñoz, J; Gonzalez, C; Suárez, C

1993-01-01

We report our preliminary results related to CT-guided stereotactic transplantation of foetal ventral mesencephalic cell suspension into the striatum of five patients with idiopathic Parkinson's disease. The mean age was 51 years, the evolution time of the disease ranged from 7 to 14 years, and all of them had motor complications associated with chronic L-dopa therapy. The patients were evaluated according to the Core Assessment Program for Intracerebral Transplantations (CAPIT) for one year before and three months after surgery. The postoperative clinical assessment demonstrated significant improvement of neurological symptoms and reduction of daily L-dopa dosage.

[Regional cerebral blood flow changes in Parkinson's disease: correlation with disease duration].

PubMed

Kapitán, M; Ferrando, R; Diéguez, E; de Medina, O; Aljanati, R; Ventura, R; Amorin, I; Salinas, D; Langhain, M; Gioia, A; Cardoso, A; Lago, G; Buzó, R

2009-01-01

Changes in regional cerebral blood flow (rCBF) have been reported in idiopathic Parkinson's disease (PD). Nonetheless, their typical pattern still remains controversial regarding some features, such as basal ganglia involvement and the main cortical regions affected. Functional neuroimaging makes it possible to identify the brain dysfunctions of the neural circuits underlying the disease. Voxel-based analysis methods make it possible to increase the reliability of the results. To assess the rCBF changes in patients with PD and their relation with disease duration. Thirty PD adult patients without dementia underwent evaluation with (99m)Tc-ECD SPECT. SPM5 was used for statistical comparison with 25 normal controls of similar ages. The disease course duration in years was added as a covariate. Additionally, patients with a 6-year evolution or less and those with more than 6 years were compared separately with normal controls. Significant hypoperfusion was detected in bilateral premotor and posterior parietal cortex and increase of perfusion was present in the cerebellum. These changes correlated with the years of evolution of the illness. Patients with longer evolution also presented thalamic, subthalamic and basal ganglia hypoperfusion. We describe rCBF changes in PD in neural circuits related with control of movements. These changes are more manifest in patients with a longer duration of the disease.

Parkinson's disease biomarkers: perspective from the NINDS Parkinson's Disease Biomarkers Program

PubMed Central

Gwinn, Katrina; David, Karen K; Swanson-Fischer, Christine; Albin, Roger; Hillaire-Clarke, Coryse St; Sieber, Beth-Anne; Lungu, Codrin; Bowman, F DuBois; Alcalay, Roy N; Babcock, Debra; Dawson, Ted M; Dewey, Richard B; Foroud, Tatiana; German, Dwight; Huang, Xuemei; Petyuk, Vlad; Potashkin, Judith A; Saunders-Pullman, Rachel; Sutherland, Margaret; Walt, David R; West, Andrew B; Zhang, Jing; Chen-Plotkin, Alice; Scherzer, Clemens R; Vaillancourt, David E; Rosenthal, Liana S

2017-01-01

Biomarkers for Parkinson's disease (PD) diagnosis, prognostication and clinical trial cohort selection are an urgent need. While many promising markers have been discovered through the National Institute of Neurological Disorders and Stroke Parkinson's Disease Biomarker Program (PDBP) and other mechanisms, no single PD marker or set of markers are ready for clinical use. Here we discuss the current state of biomarker discovery for platforms relevant to PDBP. We discuss the role of the PDBP in PD biomarker identification and present guidelines to facilitate their development. These guidelines include: harmonizing procedures for biofluid acquisition and clinical assessments, replication of the most promising biomarkers, support and encouragement of publications that report negative findings, longitudinal follow-up of current cohorts including the PDBP, testing of wearable technologies to capture readouts between study visits and development of recently diagnosed (de novo) cohorts to foster identification of the earliest markers of disease onset. PMID:28644039

Brain SPECT can differentiate between essential tremor and early-stage tremor-dominant Parkinson's disease.

PubMed

Song, In-Uk; Park, Jeong-Wook; Chung, Sung-Woo; Chung, Yong-An

2014-09-01

There are no confirmatory or diagnostic tests or tools to differentiate between essential tremor (ET) and tremor in idiopathic Parkinson's disease (PD). Although a number of imaging studies have indicated that there are differences between ET and PD, the functional imaging study findings are controversial. Therefore, we analyzed regional cerebral blood flow (CBF) by perfusion brain single-photon emission computed tomography (SPECT) to identify differences between ET and tremor-dominant Parkinson's disease (TPD). We recruited 33 patients with TPD, 16 patients with ET, and 33 healthy controls. We compared the severity of tremor symptoms by comparing the Fahn-Tolosa-Marin rating scale (FTM) score and the tremor score from Unified Parkinson's Disease Rating Scale (UPDRS) between TPD and ET patients. Subjects were evaluated by neuropsychological assessments, MRI and perfusion SPECT of the brain. Total FTM score was significantly higher in ET patients than TPD patients. However, there was no significant difference in FTM Part A scores between the two patient groups, while the scores for FTM Part B and C were significantly higher in ET patients than TPD patients. Brain SPECT analysis of the TPD group demonstrated significant hypoperfusion of both the lentiform nucleus and thalamus compared to the ET group. Brain perfusion SPECT may be a useful clinical method to differentiate between TPD and ET even during early-phase PD, because the lentiform nucleus and thalamus show differences in regional perfusion between these two groups during this time period. Additionally, we found evidence of cerebellar dysfunction in both TPT and ET. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effect of three cueing devices for people with Parkinson's disease with gait initiation difficulties.

PubMed

McCandless, Paula J; Evans, Brenda J; Janssen, Jessie; Selfe, James; Churchill, Andrew; Richards, Jim

2016-02-01

Freezing of gait (FOG) remains one of the most common debilitating aspects of Parkinson's disease and has been linked to injuries, falls and reduced quality of life. Although commercially available portable cueing devices exist claiming to assist with overcoming freezing; their immediate effectiveness in overcoming gait initiation failure is currently unknown. This study investigated the effects of three different types of cueing device in people with Parkinson's disease who experience freezing. Twenty participants with idiopathic Parkinson's disease who experienced freezing during gait but who were able to walk short distances indoors independently were recruited. At least three attempts at gait initiation were recorded using a 10 camera Qualisys motion analysis system and four force platforms. Test conditions were; Laser Cane, sound metronome, vibrating metronome, walking stick and no intervention. During testing 12 of the 20 participants had freezing episodes, from these participants 100 freezing and 91 non-freezing trials were recorded. Clear differences in the movement patterns were seen between freezing and non-freezing episodes. The Laser Cane was most effective cueing device at improving the forwards/backwards and side to side movement and had the least number of freezing episodes. The walking stick also showed significant improvements compared to the other conditions. The vibration metronome appeared to disrupt movement compared to the sound metronome at the same beat frequency. This study identified differences in the movement patterns between freezing episodes and non-freezing episodes, and identified immediate improvements during gait initiation when using the Laser Cane over the other interventions. Copyright © 2015. Published by Elsevier B.V.

Rotigotine transdermal patch in combination therapy for Parkinson's disease--observations in routine clinical practice.

PubMed

Ceballos-Baumann, Andres; Häck, Hermann-Josef

2011-10-01

The dopamine agonist rotigotine has shown efficacy and safety for the treatment of early and advanced Parkinson's disease (PD) in controlled clinical trials. This observational study evaluated rotigotine administration in combination with other antiparkinsonian medication in routine clinical practice. Data were collected by 688 German practice-based neurologists, initiating rotigotine treatment in patients with idiopathic Parkinson's disease. Assessments included rotigotine maintenance dose, changes in concomitant PD medication, changes in sleep quality, and rotigotine tolerability over an observation period of 12-16 weeks. The median rotigotine maintenance dose was 6 mg/24 h (n = 969, full analysis set). The proportion of all other prescribed PD medications declined over the observation period; combination therapy decreased by 18.7%. Daily levodopa intake was markedly reduced by 87 mg (18.9%) in 47.6% of the patients with levodopa documentation; 7% no longer required levodopa after 12-16 weeks. Mean overall sleep quality (PD Sleep Scale item 1) improved by 21.4 points, the occurrence of nocturias (PDSS item 8) by 13.4 points, and 'turning in bed' (Unified Parkinson's Disease Rating Scale part II) by 0.6 points. Drug-related adverse events were reported for 7.9% of all patients (n = 1152, safety population). Application site reactions were the most common adverse events (2.2%) resulting in early discontinuation in 1.4% of patients. In routine clinical practice, treatment initiation with rotigotine transdermal patch was associated with a reduction of other prescribed PD medications and with an improvement of self-reported sleep quality.

Idiopathic orthostatic hypotension treated with levodopa and MAO inhibitor: a preliminary report

PubMed Central

Sharpe, J.; Marquez-Julio, A.; Ashby, P.

1972-01-01

The clinical and pathophysiological features of a case of idiopathic orthostatic hypotension (Shy-Drager syndrome) are presented. Recent reports on the pathological findings in this condition indicate that there may be a defect in catecholamine synthesis in the pigmented brain stem nuclei and sympathetic ganglia similar to that in idiopathic parkinsonism. On this basis a new form of therapy using levodopa combined with MAO inhibition is derived. The results of a trial of this therapy, which produced improvements in both the hypotension and in the extrapyramidal features of the disease, are reported. PMID:5056115

NIH Research: Advances in Parkinson's Disease Research

MedlinePlus

... of this page please turn JavaScript on. NIH Research: Advances in Parkinson's Disease Research Past Issues / Winter 2014 Table of Contents Story ... Photo courtesy of NIH Advances in Parkinson's Disease Research Story Landis, Ph.D., has been Director of ...

Mortalin inhibition in experimental Parkinson's disease.

PubMed

Chiasserini, Davide; Tozzi, Alessandro; de Iure, Antonio; Tantucci, Michela; Susta, Federica; Orvietani, Pier Luigi; Koya, Keizo; Binaglia, Luciano; Calabresi, Paolo

2011-08-01

Among heat shock proteins, mortalin has been linked to the pathogenesis of Parkinson's disease. In the present work a rat model of Parkinson's disease was used to analyze the expression of striatal proteins and, more specifically, mortalin expression. The possible involvement of mortalin in Parkinson's disease pathogenesis was further investigated by utilizing an electrophysiological approach and pharmacological inhibition of mortalin in both the physiological and the parkinsonian states. Proteomic analysis was used to investigate changes in striatal protein expression in the 6-hydroxydopamine rat model of Parkinson's disease. The electrophysiological effects of MKT-077, a rhodamine-123 analogue acting as an inhibitor of mortalin, were measured by field potential recordings from corticostriatal brain slices obtained from control, sham-operated, and 6-hydroxydopamine-denervated animals. Slices in the presence of rotenone, an inhibitor of mitochondrial complex I, were also analyzed. Proteomic analysis revealed downregulation of mortalin in the striata of 6-hydroxydopamine-treated rats in comparison with sham-operated animals. MKT-077 reduced corticostriatal field potential amplitude in physiological conditions, inducing membrane depolarization and inward current in striatal medium spiny neurons. In addition, we observed that concentrations of MKT-077 not inducing any electrophysiological effect in physiological conditions caused significant changes in striatal slices from parkinsonian animals as well as in slices treated with a submaximal concentration of rotenone. These findings suggest a critical link between mortalin function and mitochondrial activity in both physiological and pathological conditions mimicking Parkinson's disease. Copyright © 2011 Movement Disorder Society.

Analysis of Nucleotide Variations in Genes of Iron Management in Patients of Parkinson's Disease and Other Movement Disorders

PubMed Central

Castiglioni, Emanuela; Finazzi, Dario; Goldwurm, Stefano; Pezzoli, Gianni; Forni, Gianluca; Girelli, Domenico; Maccarinelli, Federica; Poli, Maura; Ferrari, Maurizio; Cremonesi, Laura; Arosio, Paolo

2011-01-01

The capacity to act as an electron donor and acceptor makes iron an essential cofactor of many vital processes. Its balance in the body has to be tightly regulated since its excess can be harmful by favouring oxidative damage, while its deficiency can impair fundamental activities like erythropoiesis. In the brain, an accumulation of iron or an increase in its availability has been associated with the development and/or progression of different degenerative processes, including Parkinson's disease, while iron paucity seems to be associated with cognitive deficits, motor dysfunction, and restless legs syndrome. In the search of DNA sequence variations affecting the individual predisposition to develop movement disorders, we scanned by DHPLC the exons and intronic boundary regions of ceruloplasmin, iron regulatory protein 2, hemopexin, hepcidin and hemojuvelin genes in cohorts of subjects affected by Parkinson's disease and idiopathic neurodegeneration with brain iron accumulation (NBIA). Both novel and known sequence variations were identified in most of the genes, but none of them seemed to be significantly associated to the movement diseases of interest. PMID:20981230

[Sleep disturbances in Parkinson's disease: characteristics, evaluation and therapeutic approaches].

PubMed

Faludi, Béla; Janszky, József; Komoly, Sámuel; Kovács, Norbert

2015-07-05

Parkinson's disease is a well known representent of the movement disorder group of neurological disorders. The diagnosis of Parkinson's disease is based on specific symptoms and signs of movement abnormalities. In addition to classic motor symptoms, Parkinson's disease has characteristic non-motor features, and some of these emerges the classic signs. The authors discuss characteristics and therapeutic interventions in Parkinson's disease related sleep disturbances. The authors reviewed and summarised literature data on sleep disorders in Parkinson's disease published in the PubMed database up to January 2015. Sleep problems are important non-motor complains (insomnia, hypersomnia, REM behaviour disorder, sleep apnea and restless legs syndrome). The neurodegenerative process of the brain-stem, the effect of symptoms of Parkinson's disease on sleep and concomitant sleep disorders constitute the background of the patient's complains. Appropriate diagnosis and therapy of the consequential or concomitant sleep disorders in Parkinson's disease will help to improve the patient's quality of life.

Physical therapy and occupational therapy in Parkinson's disease.

PubMed

Radder, Danique L M; Sturkenboom, Ingrid H; van Nimwegen, Marlies; Keus, Samyra H; Bloem, Bastiaan R; de Vries, Nienke M

2017-10-01

Current medical management is only partially effective in controlling the symptoms of Parkinson's disease. As part of comprehensive multidisciplinary care, physical therapy and occupational therapy aim to support people with Parkinson's disease in dealing with the consequences of their disease in daily activities. In this narrative review, we address the limitations that people with Parkinson's disease may encounter despite optimal medical management, and we clarify both the unique and shared approaches that physical therapists and occupational therapists can apply in treating these limitations.

Idiopathic inflammatory myopathies overlapping with systemic diseases

PubMed Central

Lepreux, Sébastien; Hainfellner, Johannes A.; Vital, Anne

2018-01-01

A muscle biopsy is currently requested to assess the diagnosis of an idiopathic inflammatory myopathy overlapping with a systemic disease. During the past few years, the classification of inflammatory myopathy subtypes has been revisited progressively on the basis of correlations between clinical phenotypes, autoantibodies and histological data. Several syndromic entities are now more clearly defined, and the aim of the present review is to clarify the contribution of muscle biopsy in a setting of idiopathic inflammatory myopathies overlapping with systemic diseases. PMID:29154752

Genetic influences on cognitive decline in Parkinson's disease

PubMed Central

Morley, J.F.; Xie, S.X.; Hurtig, H.I.; Stern, M.B.; Colcher, A.; Horn, S.; Dahodwala, N.; Duda, J.E.; Weintraub, D.; Chen-Plotkin, A.S.; Van Deerlin, V.; Falcone, D.; Siderowf, A.

2012-01-01

Background The role of genetic factors in cognitive decline associated with Parkinson's disease is unclear. We examined whether variations in apolipoprotein E, microtubule-associated protein tau or catechol-O-methytransferase genotypes are associated with cognitive decline in Parkinson's disease. Methods We performed a prospective cohort study of 212 patients with a clinical diagnosis of Parkinson's disease. The primary outcome was change in Mattis Dementia Rating Scale version 2 score. Linear mixed-effects models and survival analysis were used to test for associations between genotypes and change in cognitive function over time. Results The ε4 allele of apoliporotein E was associated with more rapid decline (loss of 2.9 (95% CI, 1.7–4.1) more points/year, p<0.001) in total score and an increased risk of a ≥10 pointdrop during the follow-up period (HR 2.8, 95% CI 1.4–5.4, p=0.003). Microtubule-associated protein tau haplotype and catechol-O-methytransferase genotype were associated with measures of memory and attention, respectively, over the entire followup period but not with the overall rate of cognitive decline. Conclusion These results confirm and extend previously described genetic associations with cognitive decline in Parkinson's disease and imply that individual genes may exert effects on specific cognitive domains or at different disease stages. Carrying at least one apolipoprotein E ε4 allele is associated with more rapid cognitive decline in Parkinson's disease, supporting the idea of a component of shared etiology between Parkinson's disease dementia and Alzheimer disease. Clinically, these results suggest genotyping can provide information about the risk of future cognitive decline for Parkinson's disease patients. PMID:22344634

Decreased β-phenylethylamine in CSF in Parkinson's disease

PubMed Central

Zhou, G.; Shoji, H.; Yamada, S.; Matsuishi, T.

1997-01-01

OBJECTIVE—To determine the concentrations of β-phenylethylamine (PEA) in CSF in patients with Parkinson's disease, and to evaluate the relation between concentration of PEA in CSF and severity of Parkinson's disease.
METHODS—Using gas chromatography-chemical ionisation mass spectrometry, CSF concentrations of PEA were measured in 23 patients with Parkinson's disease (mean age, 64.0 (SD 8.2) years), of whom three were at Hoehn and Yahr stage II, 11 were at stage III, and nine were at stage IV. Comparison was made with eight patients with neuropathy (mean age, 57.0 (SD 19.2) years) and 12 controls without neurological disease (mean age, 57.6 (SD 4.8) years).
RESULTS—Concentrations of PEA in CSF in Parkinson's disease were significantly lower (mean 205 (SD 131) pg/ml) than in patients with peripheral neuropathy (433 (SD 254) pg/ml) and controls (387 (SD 194) pg/ml). The concentrations of PEA in CSF correlated negatively with Hoehn and Yahr stage (P<0.01).
CONCLUSIONS—There are decreased CSF concentrations of PEA in patients with Parkinson's disease.

 PMID:9416810

Unilateral pedunculopontine stimulation improves falls in Parkinson's disease.

PubMed

Moro, Elena; Hamani, Clement; Poon, Yu-Yan; Al-Khairallah, Thamar; Dostrovsky, Jonathan O; Hutchison, William D; Lozano, Andres M

2010-01-01

Postural instability and falls are a major source of disability in patients with advanced Parkinson's disease. These problems are currently not well addressed by either pharmacotherapy nor by subthalamic nucleus deep-brain stimulation surgery. The neuroanatomical substrates of posture and gait are poorly understood but a number of important observations suggest a major role for the pedunculopontine nucleus and adjacent areas in the brainstem. We conducted a double-blinded evaluation of unilateral pedunculopontine nucleus deep-brain stimulation in a pilot study in six advanced Parkinson's disease patients with significant gait and postural abnormalities. There was no significant difference in the double-blinded on versus off stimulation Unified Parkinson's Disease Rating Scale motor scores after 3 or 12 months of continuous stimulation and no improvements in the Unified Parkinson's Disease Rating Scale part III scores compared to baseline. In contrast, patients reported a significant reduction in falls in the on and off medication states both at 3 and 12 months after pedunculopontine nucleus deep-brain stimulation as captured in the Unified Parkinson's Disease Rating Scale part II scores. Our results suggest that pedunculopontine nucleus deep-brain stimulation may be effective in preventing falls in patients with advanced Parkinson's disease but that further evaluation of this procedure is required.

Idiopathic intracranial hypertension and sickle cell disease: two case reports.

PubMed

Segal, Laura; Discepola, Marino

2005-12-01

Two patients with sickle cell disease presented with headaches and visual disturbances, typical complaints of this disorder. However, prompt diagnosis of idiopathic intracranial hypertension and initiation of medical therapy lead to improved symptoms and restored vision. Ophthalmologists should consider sickle cell disease to be an independent risk factor for idiopathic intracranial hypertension when a patient is being assessed for visual disturbances. Although a rare condition, idiopathic intracranial hypertension has several key signs useful in establishing a diagnosis. It is critical to recognize the warning signs and symptoms to prevent devastating ophthalmologic complications. We report the first cases of idiopathic intracranial hypertension in patients with the novel Quebec-Chori beta-chain variant of sickle cell disease.

Actigraphy monitoring of symptoms in patients with Parkinson's disease.

PubMed

Pan, Weidong; Kwak, Shin; Li, Fuzhong; Wu, Chunlan; Chen, Yiyun; Yamamoto, Yoshiharu; Cai, Dingfang

2013-07-02

Although the Unified Parkinson's Disease Rating Scale (UPDRS) is the "gold-standard" tool in assessing the severity of symptoms in patients with Parkinson's disease (PD), not all activity-related disease symptoms can be accurately captured by the well-established clinical rating scale. Using an alternative approach, this study examined the level of physical activity measured by actigraphy over time and whether change in physical activity was associated with disease severity assessed by UPDRS. We used a longitudinal design in which physical activity and disease severity were assessed repeatedly during a 4-month interval, over a 3-year observational period, in a sample of 61 patients with idiopathic PD and a control group of 32 neurologically intact individuals. Physical activity data during awake-time were analyzed using the power-law exponent (PLE) method. Correlational relationships between changes in maxima values of PLE and scores of total UPDRS, UPDRS-part II (Activities of Daily Living), and UPDRS-part III (Motor Examination) in patients with PD were examined. Results show an increase in maxima values of PLE and the UPDRS total score in PD patients and that there is a positive association between changes in maxima values and total UPDRS score (r=0.746, p=0.032), UPDRS-part II score (r=0.687, p=0.027), and UPDRS-part III score (r=0.893, p=0.018). There was no significant change in the level of physical activity over time for the controls. Findings from this study indicate that change in physical activity, as captured by actigraphy, is associated with increased severity in patients' clinical symptoms of PD over time. Thus, these data suggest that, when used in conjunction with the conventional UPDRS measure, an actigraphic measure of physical activity may provide clinicians an adjunct measurement approach to monitor patients' activity-based disease progression or responses to treatment in outpatient clinic settings. Copyright © 2013 The Authors. Published by

Parkinson Disease and Dementia.

PubMed

Garcia-Ptacek, Sara; Kramberger, Milica G

2016-09-01

Dementia is a frequent complication of Parkinson disease (PD) with a yearly incidence of around 10% of patients with PD. Lewy body pathology is the most important factor in the development of Parkinson disease dementia (PDD) and there is evidence for a synergistic effect with β-amyloid. The clinical phenotype in PDD extends beyond the dysexecutive syndrome that is often present in early PD and encompasses deficits in recognition memory, attention, and visual perception. Sleep disturbances, hallucinations, neuroleptic sensitivity, and fluctuations are often present. This review provides an update on current knowledge of PDD including aspects of epidemiology, pathology, clinical presentation, management, and prognosis. © The Author(s) 2016.

Serum lipid alterations in GBA-associated Parkinson's disease.

PubMed

Guedes, Leonor Correia; Chan, Robin Barry; Gomes, Marcos António; Conceição, Vasco A; Machado, Raquel Bouça; Soares, Tiago; Xu, Yimeng; Gaspar, Paulo; Carriço, Joao André; Alcalay, Roy N; Ferreira, Joaquim J; Outeiro, Tiago Fleming; Miltenberger-Miltenyi, Gabriel

2017-11-01

Mutations in the GBA gene, encoding for the lysosomal enzyme glucocerebrosidase, are associated with Gaucher disease. Alterations in plasma sphingolipids have been reported in Gaucher, and similarly in brain extracts in Lewy body disease. As GBA mutations are prevalent risk factors for Parkinson's disease and overlap of molecular pathways are presumable, here we assessed the lipid profiles in Parkinson's patients with and without GBA mutations. We sequenced all GBA exons in 415 Parkinson's patients, previously genotyped for LRRK2. 64 patients (29 GBA positive vs. 35 non-GBA-carriers including 18 LRRK2 positive and 17 non-mutated) were analyzed for chitotriosidase activity and for the concentration of 40 lipid classes using HPLC-MS. 29/415 patients (6.9%) carried 8 different GBA mutations associated with Gaucher or Parkinson's, including one novel mutation. Chitotriosidase activity was similar across the genetic groups, while the levels of key lipids were altered in GBA mutation carriers: Monohexosylceramide, Ceramide and Sphingomyelin were elevated; while Phosphatidic acid (PA), Phosphatidylethanolamine (PE), Plasmalogen phosphatidylethanolamine (PEp) and Acyl Phosphatidylglycerol (AcylPG) were decreased. The results suggest an important role for these lipids in GBA mediated Parkinson's disease and assist in the identification of common pathways between Gaucher and Parkinson's. Ultimately, our findings may lead to the identification of novel biomarkers for individuals at increased risk of developing Parkinson's disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

Parkinson's Disease Research at NIH | NIH MedlinePlus the Magazine

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... turn JavaScript on. Feature: Parkinson's Disease Parkinson's Disease Research at NIH Past Issues / Winter 2014 Table of ... Disorders/All-Disorders/Parkinsons-Disease-Information-Page What Research Is Being Done? The National Institute of Neurological ...

Learning about Parkinson's Disease

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... having genetic testing can learn more about their risk for Parkinson's disease and the availability and accuracy of genetic testing for this disease by setting up an appointment with a genetics health professional. Genetic professionals work as members of health ...

The effects of augmented visual feedback during balance training in Parkinson's disease: study design of a randomized clinical trial.

PubMed

van den Heuvel, Maarten R C; van Wegen, Erwin E H; de Goede, Cees J T; Burgers-Bots, Ingrid A L; Beek, Peter J; Daffertshofer, Andreas; Kwakkel, Gert

2013-10-04

Patients with Parkinson's disease often suffer from reduced mobility due to impaired postural control. Balance exercises form an integral part of rehabilitative therapy but the effectiveness of existing interventions is limited. Recent technological advances allow for providing enhanced visual feedback in the context of computer games, which provide an attractive alternative to conventional therapy. The objective of this randomized clinical trial is to investigate whether a training program capitalizing on virtual-reality-based visual feedback is more effective than an equally-dosed conventional training in improving standing balance performance in patients with Parkinson's disease. Patients with idiopathic Parkinson's disease will participate in a five-week balance training program comprising ten treatment sessions of 60 minutes each. Participants will be randomly allocated to (1) an experimental group that will receive balance training using augmented visual feedback, or (2) a control group that will receive balance training in accordance with current physical therapy guidelines for Parkinson's disease patients. Training sessions consist of task-specific exercises that are organized as a series of workstations. Assessments will take place before training, at six weeks, and at twelve weeks follow-up. The functional reach test will serve as the primary outcome measure supplemented by comprehensive assessments of functional balance, posturography, and electroencephalography. We hypothesize that balance training based on visual feedback will show greater improvements on standing balance performance than conventional balance training. In addition, we expect that learning new control strategies will be visible in the co-registered posturographic recordings but also through changes in functional connectivity.

Copper and Copper Proteins in Parkinson's Disease

PubMed Central

Rivera-Mancia, Susana; Diaz-Ruiz, Araceli; Tristan-Lopez, Luis; Rios, Camilo

2014-01-01

Copper is a transition metal that has been linked to pathological and beneficial effects in neurodegenerative diseases. In Parkinson's disease, free copper is related to increased oxidative stress, alpha-synuclein oligomerization, and Lewy body formation. Decreased copper along with increased iron has been found in substantia nigra and caudate nucleus of Parkinson's disease patients. Copper influences iron content in the brain through ferroxidase ceruloplasmin activity; therefore decreased protein-bound copper in brain may enhance iron accumulation and the associated oxidative stress. The function of other copper-binding proteins such as Cu/Zn-SOD and metallothioneins is also beneficial to prevent neurodegeneration. Copper may regulate neurotransmission since it is released after neuronal stimulus and the metal is able to modulate the function of NMDA and GABA A receptors. Some of the proteins involved in copper transport are the transporters CTR1, ATP7A, and ATP7B and the chaperone ATOX1. There is limited information about the role of those biomolecules in the pathophysiology of Parkinson's disease; for instance, it is known that CTR1 is decreased in substantia nigra pars compacta in Parkinson's disease and that a mutation in ATP7B could be associated with Parkinson's disease. Regarding copper-related therapies, copper supplementation can represent a plausible alternative, while copper chelation may even aggravate the pathology. PMID:24672633

The History of Parkinson's Disease: Early Clinical Descriptions and Neurological Therapies

PubMed Central

Goetz, Christopher G.

2011-01-01

Although components of possible Parkinson's disease can be found in very early documents, the first clear medical description was written in 1817 by James Parkinson. In the mid-1800s, Jean-Martin Charcot was particularly influential in refining and expanding this early description and in disseminating information internationally about Parkinson's disease. He separated Parkinson's disease from multiple sclerosis and other disorders characterized by tremor, and he recognized cases that later would likely be classified among the Parkinsonism-plus syndromes. Early treatments of Parkinson's disease were based on empirical observation, and anticholinergic drugs were used as early as the nineteenth century. The discovery of dopaminergic deficits in Parkinson's disease and the synthetic pathway of dopamine led to the first human trials of levodopa. Further historically important anatomical, biochemical, and physiological studies identified additional pharmacological and neurosurgical targets for Parkinson's disease and allow modern clinicians to offer an array of therapies aimed at improving function in this still incurable disease. PMID:22229124

[Physical therapy for parkinson's disease].

PubMed

Hubert, M

2011-09-01

Parkinson's disease is a complex neurologic and progressive incapacitating disease. Parkinson's disease severely threatens the quality of live and the number of patients worldwide is expected to rise considerably in the coming decade due to aging of the population. Even with optimal medical management using drugs or neurosurgery, patients are faced with progressively increasing impairments (e.g. in speech, mental and movement related functions), and restrictions in participation (e.g. domestic life and social activities). Physical therapy is often prescribed next to medical treatment but there is a lack of uniform treatment. A systematic literature search for guidelines, systematic reviews, trials, and expert opinions lead to a better understanding. The key question: Is physiotherapy able to optimally treat the Parkinson's disease symptoms? In which way, how and on which scientific bases can the physiotherapist participate to improve autonomy and to help them living independently and avoid, as long as possible, institutionalization? This article has integrated clinical research findings to provide clinicians with an overview to physical therapist management of disorders in people with Parkinson's disease. An Evidence-Based Physical Therapy Guideline providing practice recommendations was developed by the Royal Dutch Society for Physical Therapy (KNGF). Evidence from research was supplemented with clinical expertise and patients values. Randomized clinical trials reflect specific core areas of physical therapy, that is, transfer, posture, balance, reaching and grasping, gait and physical condition. Another aspect is that of educating patients (as well as their partners and family) about the disease process and the benefits of exercise therapy. Alternative therapies can be helpful like Tai Chi, virtual games, dancing, yoga, ball games for example.

Update in therapeutic strategies for Parkinson's disease.

PubMed

Kulisevsky, Jaime; Oliveira, Lais; Fox, Susan H

2018-05-08

To review recent advances in therapeutics for motor and nonmotor symptoms of Parkinson's disease. Neuroprotection remains a large area of investigation with preliminary safety data on alpha synuclein immunotherapy and glucagon-like peptide-1 agonists. Novel Monoamine Oxidase B and Caetchol-O-methyltransferase-inhibitors for motor fluctuations have shown benefit and are recently approved for clinical use. Long-acting amantadine has also been approved to reduce dyskinesia. Alternative delivery strategies (sublingual, inhaled) dopaminergics may prove useful for rapid reversal of Parkinson's disease motor symptoms. Advanced therapies (surgery and infusional therapies) continue to be useful in subgroups of patients for motor complications with improved safety and also benefit on some nonmotor symptoms, including neuropsychiatric issues. Specific therapeutics for cognition, swallowing, sleep, and mood disorders had moderate to limited benefits. Exercise-based therapy appears beneficial at all stages of Parkinson's disease. The motor symptoms of Parkinson's disease can be reasonably treated and managed. However, therapies to slow or prevent disease progression remain a focus of research. Despite increased studies, treating nonmotor symptoms remains a challenge and an ongoing priority.

Four Cases of Parkinson Disease Diagnosed During the Postpartum Period.

PubMed

Maltête, David; Grangeon, Lou; Le Goff, Floriane; Ozel, Gulden; Fetter, Damien; Ahtoy, Patrick; Temgoua, Olivier; Rouillé, Audrey; Lefaucheur, Romain

2017-07-01

There is little experience with the effect of pregnancy on Parkinson disease because the number of women with Parkinson disease who are of childbearing age is small. We report four cases beginning during the postpartum period and discuss the potential contribution of different factors that may influence the occurrence of Parkinson disease in this time period. Four women aged 29-35 years developed arm tremor, shoulder pain, dizziness, or decreased dexterity of the hand in the first few days or months after childbirth. They were initially diagnosed with postpartum depression or psychogenic parkinsonism. Finally, dopamine transporter imaging confirmed the diagnosis of young-onset Parkinson disease. Early-onset Parkinson disease may present in postpartum women. In women with atypical motor symptoms in addition to depression, this diagnosis should be considered.

Autobiographical memory in Parkinson's disease: a retrieval deficit.

PubMed

Souchay, Celine; Smith, Sarah Jane

2013-09-01

This study examined the effects of providing cues to facilitate autobiographical memory retrieval in Parkinson's disease. Previous findings have shown that individuals with Parkinson's disease retrieve fewer specific autobiographical memories than older adult controls. These findings are clinically significant since the quality of autobiographical memory is linked to identity and sense of self. In the current study, 16 older adults with Parkinson's disease without dementia and 16 matched older adult controls were given 3 min in which to recall autobiographical memories associated with five different time periods and to give each memory a short title. Participants were later asked to retrieve the memories in three phases: firstly in a free recall phase; secondly in response to general cues (time periods) and finally in response to specific cues (the short titles previously given). The number of memories and the quality of the memory (general or specific) was recorded in each condition. Compared with matched older adult controls, the Parkinson's disease group was impaired in retrieving the memories that they had previously given in the free recall phase and in response to general cues. The performance of the group with Parkinson's disease was only equivalent to the older adults when they retrieved memories in response to self-generated cues. The findings are discussed in relation to theories of autobiographical memory and the neuropsychology of Parkinson's disease. © 2013 The British Psychological Society.

Association between polychlorinated biphenyls and Parkinson's disease neuropathology.

PubMed

Hatcher-Martin, Jaime M; Gearing, Marla; Steenland, Kyle; Levey, Allan I; Miller, Gary W; Pennell, Kurt D

2012-10-01

Polychlorinated biphenyls (PCBs) are synthetic chemicals primarily used as coolants and insulators in electrical equipment. Although banned for several decades, PCBs continue to exist in the environment because of their long half-life, continued presence in items produced before the ban, and poor disposal practices. Epidemiological and experimental studies have identified exposure to PCBs as a potential risk factor for Parkinson's disease, perhaps more so in females. The objective of this work was to examine the association between PCB levels in post-mortem human brain tissue and the diagnosis of Parkinson's disease, as well as the degree of nigral depigmentation. We also sought to determine if this association was more significant when patients were stratified by sex. Post-mortem brain samples from control patients and those diagnosed with Parkinson's disease were obtained from the Emory University Brain Bank and from the Nun Study. Concentrations of eight prevalent PCB congeners were extracted from post-mortem brain tissue and analyzed using gas chromatography-mass spectrometry. PCB congeners 153 and 180 were significantly elevated in the brains of Parkinson's disease patients. When stratified by sex, the female Parkinson's disease group demonstrated significantly elevated concentrations of total PCBs and specifically congeners 138, 153, and 180 compared to controls, whereas PCB concentrations in males were not significantly different between control and Parkinson's disease groups. In a separate population of women (Nun Study) who had no clinical signs or symptoms of PD, elevated concentrations total PCB and congeners 138, 153 and 180 were also observed in post-mortem brain tissue exhibiting moderate nigral depigmentation compared to subjects with mild or no depigmentation. These quantitative data demonstrate an association between brain PCB levels and Parkinson's disease-related pathology. Furthermore, these data support epidemiological and laboratory studies

Wireless Monitoring for Patients with Cardiovascular Diseases and Parkinson's Disease.

PubMed

Kefaliakos, Antonios; Pliakos, Ioannis; Charalampidou, Martha; Diomidous, Marianna

2016-01-01

The use of applications for mobile devices and wireless sensors is common for the sector of telemedicine. Recently various studies and systems were developed in order to help patients suffering from severe diseases such as cardiovascular diseases and Parkinson's disease. They present a challenge for the sector because such systems demand the flow of accurate data in real time and the use of specialized sensors. In this review will be presented some very interesting applications developed for patients with cardiovascular diseases and Parkinson's disease.

Daytime Napping, Nighttime Sleeping, and Parkinson Disease

PubMed Central

Gao, Jianjun; Huang, Xuemei; Park, Yikyung; Hollenbeck, Albert; Blair, Aaron; Schatzkin, Arthur; Chen, Honglei

2011-01-01

Preliminary evidence suggests that daytime sleepiness may predate clinical diagnosis of Parkinson disease. The authors examined daytime napping and nighttime sleeping durations, reported in 1996–1997 by 220,934 US NIH-AARP Diet and Health Study participants, in relation to Parkinson disease diagnoses at 3 clinical stages: established (cases diagnosed before 1995, n = 267), recent (1995–1999, n = 396), and prediagnostic (2000 and after, n = 770). Odds ratios and 95% confidence intervals were derived from multivariate logistic regression models. Longer daytime napping was associated with higher odds of Parkinson disease at all 3 clinical stages: the odds ratios comparing long nappers (>1 hour/day) with nonnappers were 3.9 (95% confidence interval: 2.8, 5.6) for established cases, 2.2 (95% confidence interval: 1.7, 3.0) for recent cases, and 1.5 (95% confidence interval: 1.2, 1.9) for prediagnostic cases. Further control for health status or nighttime sleeping duration attenuated the association for established cases but made little difference for recent or prediagnostic cases. In the nighttime sleeping analysis, a clear U-shaped association with Parkinson disease was observed for established cases; however, this association was attenuated markedly for recent cases and disappeared for prediagnostic cases. This study supports the notion that daytime sleepiness, but not nighttime sleeping duration, is one of the early nonmotor symptoms of Parkinson disease. PMID:21402730

Parkinson Disease: Treating Symptoms Unrelated to Muscle Movement

MedlinePlus

... Evidence-based Guideline for PATIENTS and their FAMILIES PARKINSON DISEASE: TREATING SYMPTOMS UNRELATED TO MUSCLE MOVEMENT This fact sheet may help you understand which therapies help Parkinson disease (PD) symptoms unrelated to muscle movement. Neurologists from ...

[Parkinson's disease in literature, cinema and television].

PubMed

Collado-Vázquez, Susana; Cano-de-la-Cuerda, Roberto; Carrillo, Jesús M

2014-02-01

INTRODUCTION. Since James Parkinson published what can be considered the first treaty on the disease that bears his name in 1817, the scientific literature on this pathology has not ceased to grow. But the illness has also been represented in literature, the cinema and on television, where the symptoms, treatment and socio-familial context of the disease have often been examined very closely. AIM. To address the cases in which Parkinson's disease appears in literature, cinema and television, as well as to reflect on the image of the condition presented in those contexts. DEVELOPMENT. We reviewed some of the most important works in the literature dealing with Parkinson's disease from any period of history and many of them were found to offer very faithful portrayals of the disease. Likewise, we also reviewed major films and TV series that sometimes offer the general public a close look at the vision and the impact of the disease on patients or their relatives. CONCLUSIONS. Literature, cinema and television have helped provide a realistic view of both Parkinson's disease and the related healthcare professionals, and there are many examples that portray the actual experiences of the patients themselves, while also highlighting the importance of healthcare and socio-familial care.

Current management of Parkinson's disease.

PubMed

Salawu, F; Olokoba, A; Danburam, A

2010-01-01

Although Parkinson's disease (PD) is still incurable, a large number of different treatments have become available to improve the quality of life and physical and psychological morbidity, and its early treatment is of prime importance. This article reviews the current situation of PD. This review was based on a search of Medline, the Cochrane Database of Systemic Reviews, and citation lists of relevant publications. The subject headings and keywords used were Parkinson's disease and therapeutic advances. Only articles written in English were included.The management of PD has evolved rapidly over the last 10 years with the advent of new drugs and new classes of drugs, but the currently available treatment methods are all symptomatic ones. However, some of these may have marginal disease-modifying effects. Progress in manufacture of newer drugs has markedly improved the treatment of early PD; however, the management of advanced Parkinson's symptoms remains a challenge. Currently no treatment has been proven to slow the progression of PD. Although symptomatic therapy can provide benefit for many years, PD will eventually result in significant morbidity.

Swallowing disorders in Parkinson's disease.

PubMed

Mamolar Andrés, Sandra; Santamarina Rabanal, María Liliana; Granda Membiela, Carla María; Fernández Gutiérrez, María José; Sirgo Rodríguez, Paloma; Álvarez Marcos, César

Parkinson's disease is a type of chronic neurodegenerative pathology with a typical movement pattern, as well as different, less studied symptoms such as dysphagia. Disease-related disorders in efficacy or safety in the process of swallowing usually lead to malnutrition, dehydration or pneumonias. The aim of this study was identifying and analyzing swallowing disorders in Parkinson's disease. The initial sample consisted of 52 subjects with Parkinson's disease to whom the specific test for dysphagia SDQ was applied. Nineteen participants (36.5%) with some degree of dysphagia in the SDQ test were selected to be evaluated by volume-viscosity clinical exploration method and fiberoptic endoscopic evaluation of swallowing. Disorders in swallowing efficiency and safety were detected in 94.7% of the selected sample. With regards to efficiency, disorders were found in food transport (89.5%), insufficient labial closing (68.4%) and oral residues (47.4%), relating to duration of ingestion. Alterations in security were also observed: pharynx residues (52.7%), coughing (47.4%), penetration (31.64%), aspiration and decrease of SaO 2 (5.3%), relating to the diagnosis of respiratory pathology in the previous year. The SDQ test detected swallowing disorders in 36.5% of the subjects with Parkinson's disease. Disorders in swallowing efficiency and safety were demonstrated in 94.7% of this subset. Disorders of efficiency were more frequent than those of safety, establishing a relationship with greater time in ingestion and the appearance of respiratory pathology and pneumonias. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. All rights reserved.

Rasagiline in the pharmacotherapy of Parkinson's disease--a review.

PubMed

Rascol, Olivier

2005-10-01

Despite the current efficacious symptomatic approaches, the search is on for new therapies for Parkinson's disease that can control the cardinal symptoms of the disease (tremor, rigidity and bradykinesia), control/prevent motor complications induced by long-term levodopa, act on non-motor disease symptoms (dementia, dysautonomia, pain, insomnia, falls) and halt disease progression. Rasagiline is a monoamine oxidase-B inhibitor that has demonstrated efficacy against the cardinal symptoms of Parkinson's disease when used as monotherapy in early Parkinson's disease, and as an adjunct to levodopa in advanced disease stages. It reduces the duration and severity of poor symptom response episodes in fluctuating patients. Preliminary results allow discussion of putative effects of rasagiline on some non-motor signs and disease progression. This article outlines the evidence surrounding the efficacy and safety of rasagiline, and discusses its potential to address some of the currently unmet needs of Parkinson's disease therapy.

Rasagiline. Parkinson's disease: a simple me-too.

PubMed

2006-12-01

In Parkinson's disease, rasagiline, either alone (in early stage disease) or combined with levodopa, provides nothing new in terms of efficacy or tolerability. It is better to continue using one of the many anti-parkinson drugs with which we have more experience rather than expose patients to a new drug which offers no advantages.

Association between physical fitness, cardiovascular risk factors, and Parkinson's disease.

PubMed

Müller, Jan; Myers, Jonathan

2018-01-01

Objective Exercise is a cornerstone of therapy for Parkinson's disease. This study addressed the association between physical fitness and the onset of Parkinson's disease and association with cardiovascular risk factors. Patients and methods Male veterans ( N = 7347, 59.0 ± 11.2 years) from the Veterans Exercise Testing Study cohort were evaluated. Physical fitness was measured objectively by maximal exercise testing. Onset of Parkinson's disease was abstracted from the Veterans Affairs computerized patient records system. Results After a mean follow-up of 12.5 ± 6.3 years, a total of 94 (1.3%) developed Parkinson's disease. Incidence was 86 cases per 100,000 person-years. The strongest multivariate factors associated with incidence of Parkinson's disease were higher age (hazard ratio: 1.067, 95% confidence interval (CI): 1.043-1.093, p < .001), current smoking (hazard ratio: 0.511, 95% CI: 0.274-0.953, p = .035) and physical fitness (high vs. low: hazard ratio: 0.239, 95% CI: 0.079-0.725, p = .011). Compared with patients with no or only one of these risk factors, patients with two risk factors had a 3.7-fold ( p < .001) increased risk for incidence of Parkinson's disease; those with all three risk factors had a 7.8-fold ( p < .001) higher risk. Conclusions High physical fitness, current smoking and younger age were associated with a lower incidence of Parkinson's disease. These findings parallel those of several epidemiological studies focusing on physical activity and the onset of Parkinson's disease. Together, these observations provide strong support for recommending physical activity to diminish risk of Parkinson's disease.

Applying chaperones to protein-misfolding disorders: molecular chaperones against α-synuclein in Parkinson's disease.

PubMed

Chaari, Ali; Hoarau-Véchot, Jessica; Ladjimi, Moncef

2013-09-01

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the accumulation of a protein called α-synuclein (α-syn) into inclusions known as lewy bodies (LB) within neurons. This accumulation is also due to insufficient formation and activity of dopamine produced in certain neurons within the substantia nigra. Lewy bodies are the pathological hallmark of the idiopathic disorder and the cascade that allows α-synuclein to misfold, aggregate and form these inclusions has been the subject of intensive research. Targeting these early steps of oligomerization is one of the main therapeutic approaches in order to develop neurodegenerative-modifying agents. Because the folding and refolding of alpha synuclein is the key point of this cascade, we are interested in this review to summarize the role of some molecular chaperones proteins such as Hsp70, Hsp90 and small heat shock proteins (sHsp) and Hsp 104. Hsp70 and its co-chaperone, Hsp70 and small heat shock proteins can prevent neurodegeneration by preventing α-syn misfolding, oligomerization and aggregation in vitro and in Parkinson disease animal models. Hsp104 is able to resolve disordered protein aggregates and cross beta amyloid conformers. Together, these chaperones have a complementary effect and can be a target for therapeutic intervention in PD. Published by Elsevier B.V.

Is PIGD a legitimate motor subtype in Parkinson disease?

PubMed

Kotagal, Vikas

2016-06-01

Parkinson disease is a chronic progressive syndrome with a broad array of clinical features. Different investigators have suggested the heterogeneous motor manifestations of early Parkinson disease can be conceptualized through a taxonomy of clinical subtypes including tremor-predominant and postural instability and gait difficulty-predominant subtypes. Although it is theoretically valuable to distinguish subtypes of Parkinson disease, the reality is that few patients fit these discrete categories well and many transition from exhibiting elements of one subtype to elements of another. In the time since the initial description of the postural instability and gait difficulty-predominant subtype, Parkinson disease clinical research has blossomed in many ways - including an increased emphasis on the role of medical comorbidities and extranigral pathologies in Parkinson disease as markers of prognostic significance. By conceptualizing the pathogenesis of an expansive disease process in the limited terms of categorical motor subtypes, we run the risk of overlooking or misclassifying clinically significant pathogenic risk factors that lead to the development of motor milestones such as falls and related axial motor disability. Given its critical influence on quality of life and overall prognosis, we are in need of a model of postural instability and gait difficulty-predominant features in Parkinson disease that emphasizes the overlooked pathological influence of aging and medical comorbidities on the development of axial motor burden and postural instability and gait difficulty-predominant features. This Point of View proposes thinking of postural instability and gait difficulties in Parkinson disease not as a discrete subtype, but rather as multidimensional continuum influenced by several overlapping age-related pathologies.

Association of restless legs syndrome, pain, and mood disorders in Parkinson's disease.

PubMed

Rana, Abdul Qayyum; Qureshi, Abdul Rehman M; Rahman, Labiba; Jesudasan, Ajantha; Hafez, Kevin K; Rana, Mohammad A

2016-01-01

The objectives of the study were to analyze the association between Parkinson's disease and restless legs syndrome, and to explore the relationship between mood disorder comorbidity (anxiety and depression), pain, and restless legs syndrome. This study included 123 Parkinson's disease patients and 123 non-Parkinson's disease patients matched for age and gender, and evaluated for anxiety severity, depression severity, pain severity, pain interference, pain disability, and restless legs syndrome prevalence. This was performed using semi-structured interviews and a neurological examination through the restless legs syndrome diagnostic criteria and the following inventories; Hospital Anxiety and Depression Scale, Brief Pain Inventory, and Pain Disability Index. Parkinson's disease patients had significantly greater anxiety severity, depression severity, pain severity, pain interference, pain disability, and restless legs syndrome prevalence in comparison to controls. In addition, Parkinson's disease patients' comorbid for anxiety and depression had significantly greater pain severity, pain interference, and pain disability, but not RLS prevalence, in comparison to Parkinson's disease only, Parkinson's disease anxiety, and Parkinson's disease depression patients. Pain interference, pain severity, and pain disability is greater among Parkinson's disease patients with anxiety and depression, in comparison to Parkinson's disease patients without anxiety and depression. On the contrary, the prevalence of restless legs syndrome was not found to be relevant.

Parkinson's disease in China.

PubMed

Tian, You-yong; Tang, Cui-ju; Wu, Jie; Zhou, Jun-shan

2011-02-01

Paralysis agitans was first documented in 1817 by James Parkinson, and therefore the syndrome was named Parkinson's disease (PD). In fact, as early as more than 2000 years ago, the clinical manifestations of this disease have been described in Chinese medicine classics, such as the "Huangdi Neijing (Yellow Emperor's Internal Classic)" and "Zhong Zang Jing (Hua's Zhong Zang Classic)." In recent years, especially in the past 30 years after reform and opening-up, PD has drawn a lot of attention by Chinese scholars. Although great progress in the studies of PD has been made in recent years, the gap between China and western countries still exists. In this review, we concentrate on the main progress made in epidemic characteristics, etiology, diagnosis and management of PD in China.

Validation of the Bulgarian version of Scales for Outcomes in Parkinson's Disease - Autonomic (SCOPA-AUT-BG).

PubMed

Mantarova, Stefka G; Velcheva, Irena V; Georgieva, Spaska O; Stambolieva, Katerina I

2013-01-01

The last twenty years have witnessed a surge of interest in the autonomic symptoms in Parkinson's disease (PD) and the possibilities to diagnose and treat them. The specialized questionnaire assessing the autonomic symptoms in Parkinson's disease (SCOPA-AUT) has been validated and available in English, Dutch and Spanish. In this study we aim at evaluating the validity, reliability and applicability of the Bulgarian version of SCOPA-AUT (SCOPA-AUT-BG). The study included 55 patients with idiopathic PD (mean age 64.4 +/- 8.9 yrs), and 40 healthy controls (mean age 58.5 +/- 9.4 yrs). Clinical severity and disease stage were assessed by United Parkinson's disease rating scale (UPRDS) and Hoen and Yahr (H&Y). Thirty-two of the PD patients completed SCOPA-AUT-BG again after a 7-day interval. Questionnaire reliability was analyzed by determining the internal consistency, homogeneity, discriminatory and construct validity and test-retest reliability. Analyses showed good internal consistency of the summary evaluation of SCOPA-AUT-BG (coefficient alpha of Cronbach = 0.79), which indicates the high reliability of the questionnaire. The lowest Cronbach's alpha coefficient (0.53) was found for the subscale "cardiovascular functions". A dominant role belongs to the subscales for gastrointestinal and urinary functions (Cronbach's Alpha > 0.7), where a significantly high correlation of PD with the UPDRS scale was observed. We found high test-retest reliability based on the responses associated with dysfunction of the gastrointestinal, urinary, thermoregulatory and pupillary autonomic systems. The correlation of the results of SCOPA-AUT-BG with UPDRS is higher than that with H&Y, and the construct validity is high except for the cardiovascular and pupillomotor functions subscales. The results of this study show that SCOPA-AUT-BG is a valid and reliable specialized questionnaire to evaluate autonomic function in patients with Parkinson's disease. Using it allows for more detailed

Metabolic Imaging in Parkinson Disease.

PubMed

Meles, Sanne K; Teune, Laura K; de Jong, Bauke M; Dierckx, Rudi A; Leenders, Klaus L

2017-01-01

This review focuses on recent human 18 F-FDG PET studies in Parkinson disease. First, an overview is given of the current analytic approaches to metabolic brain imaging data. Next, we discuss how 18 F-FDG PET studies have advanced understanding of the relation between distinct brain regions and associated symptoms in Parkinson disease, including cognitive decline. In addition, the value of 18 F-FDG PET studies in differential diagnosis, identifying prodromal patients, and the evaluation of treatment effects are reviewed. Finally, anticipated developments in the field are addressed. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Excessive daytime sleepiness in Parkinson disease: a SPECT study.

PubMed

Matsui, Hideaki; Nishinaka, Kazuto; Oda, Masaya; Hara, Narihiro; Komatsu, Kenichi; Kubori, Tamotsu; Udaka, Fukashi

2006-07-01

The underlying pathologic mechanism of excessive daytime sleepiness (EDS) in Parkinson disease and the relative contributions of brain function to this process are poorly understood. We compared brain perfusion images between patients with Parkinson disease and EDS and those without EDS using n-isopropyl-p-1231 iodoamphetamine single photon emission computed tomography. Clinical study. Sumitomo Hospital. Thirteen patients with Parkinson disease with EDS (EDS group) and 27 patients with Parkinson disease without EDS (no-EDS group) were studied. Whether or not each case had EDS was determined according to the response to the Epworth Sleepiness Scale: patients with an Epworth Sleepiness Scale score > or = 10 were included in the EDS group, and patients with an Epworth Sleepiness Scale score < or = 9 were included in the no-EDS group. There were significant hypoperfusions in the left parietal and temporal association cortex in the EDS group. In the multivariable logistic regression model, attention and decreased regional cerebral blood flow of the left parietal association cortex and right caudate and increased regional cerebral blood flow of the right thalamus were the independent and significant factors. The cortical hypofunction relative to hyperfunction of the brain stem may relate to EDS in Parkinson disease. This is the first imaging study about EDS in Parkinson disease, and further studies are required.

Experience of care home residents with Parkinson's disease: Reason for admission and service use.

PubMed

Walker, Richard W; Palmer, Jessica; Stancliffe, Jonathan; Wood, Brian H; Hand, Annette; Gray, William K

2014-10-01

The care needs of people with Parkinson's disease (PD) are poorly understood. We aimed to investigate the factors that precipitate entry to institutional care, and on-going care needs once in care, within a representative cohort of community-dwelling people with PD. All people with idiopathic PD, Parkinson's plus syndromes and vascular parkinsonism under the care of the Northumbria Healthcare NHS Foundation Trust PD service who were living in care homes on 1 January 2013 were included. Disease severity (Hoehn and Yahr stage) and demographic data were collected. Admissions to hospital over the previous 2 years and in the year before institutional care admission were documented. A total of 90 patients (51 females) with a mean age of 81.3 years were included. During care home stay, the median number of emergency department attendances, the median number of hospital admissions and the median length of stay for those admitted per year were significantly lower than before care home admission. Both before care home admission and during care home stay, falls were the most common diagnoses in people attending emergency departments, with 32 of 65 (49.2%) admissions before and 34 of 59 (57.6%) admissions during care home stay having falls recorded as a cause of attendance. Hospital attendances and admissions were relatively common, even after institutional care home placement. Events precipitating admission, such as falls, might be preventable. PD nurse specialists could be an effective way to help train staff in homes where someone is known to have PD. © 2013 Japan Geriatrics Society.

Blood dendritic cell frequency declines in idiopathic Parkinson's disease and is associated with motor symptom severity.

PubMed

Ciaramella, Antonio; Salani, Francesca; Bizzoni, Federica; Pontieri, Francesco E; Stefani, Alessandro; Pierantozzi, Mariangela; Assogna, Francesca; Caltagirone, Carlo; Spalletta, Gianfranco; Bossù, Paola

2013-01-01

The role of inflammation in Parkinson's Disease (PD) is well appreciated, but its underlying mechanisms are still unclear. Our objective was to determine whether dendritic cells (DC), a unique type of migratory immune cells that regulate immunological response and inflammation have an impact on PD. In a case-control study including 80 PD patients and 80 age- and gender-matched healthy control subjects, the two main blood subsets of plasmacytoid and myeloid DC were defined by flow cytometry analysis. Clinical evaluation of subjects consisting of cognition and depression assessment was performed using the Mini Mental State Examination and the Beck Depression Inventory. The severity of motor symptoms was measured using the Unified Parkinson's Disease Rating Scale-Part III. Comparison between patient and control DC measures and their relationships with clinical assessments were evaluated.The following main results were obtained: 1) the level of circulating DC (mainly the myeloid subset) was significantly reduced in PD patients in comparison with healthy controls; 2) after controlling for depressive and cognitive characteristics, the frequency of myeloid DC was confirmed as one of the independent determinants of PD; 3) the number of both myeloid and plasmacytoid DC was negatively associated with motor symptom severity. Overall, the decline of blood DC, perhaps due to the recruitment of immune cells to the site of disease-specific lesions, can be considered a clue of the immune alteration that characterizes PD, suggesting innovative exploitations of DC monitoring as a clinically significant tool for PD treatment. Indeed, this study suggests that reduced peripheral blood DC are a pathologically-relevant factor of PD and also displays the urgency to better understand DC role in PD for unraveling the immune system contribution to disease progression and thus favoring the development of innovative therapies ideally based on immunomodulation.

Retinal nerve fiber layer thinning: a window into rapid eye movement sleep behavior disorders in Parkinson's disease.

PubMed

Yang, Zi-Jiao; Wei, Jing; Mao, Cheng-Jie; Zhang, Jin-Ru; Chen, Jing; Ji, Xiao-Yan; Liu, Jun-Yi; Shen, Yun; Xiong, Kang-Ping; Huang, Jun-Ying; Yang, Ya-Ping; Liu, Chun-Feng

2016-12-01

Retinal nerve fiber layer (RNFL) thinning occurs in Parkinson's disease (PD) and other neurodegenerative diseases. Idiopathic RBD (iRBD) is a well-established prodromal hallmark of synucleinopathies and occurs secondary to many neurodegenerative diseases, including PD. The aim of this study is to determine whether or not retinal structures are altered with the onset of rapid eye movement (REM) sleep behavior disorders (RBD). In all, a total of 63 patients with PD, 14 patients with idiopathic RBD, and 26 sex- and age-matched healthy controls were enrolled and underwent optical coherence tomography measurements (HD-OCT (Zeiss) ) for the average and every quadrant of RNFL thickness. The REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) was used to classify PD patients with clinically probable RBD (PD + pRBD) or without probable RBD (PD - pRBD). Patients with iRBD were identified by polysomnography. For patients with RBD (idiopathic or secondary to PD), we found a significant decrease in RNFL thickness compared with groups without RBD (PD - pRBD and healthy controls) (all p < 0.05). Average RNFL thickness in patients with iRBD is significantly thinner than in healthy controls (p < 0.05). In PD, the average RNFL thickness was dramatically thinner in the PD + pRBD group than the PD - pRBD group (p < 0.005). Compared with healthy controls, RNFL thickness was slightly thinner in the drug-naive PD group but not the PD group with drug treatment. Multiple linear regression analysis showed that RBDSQ score was negatively associated with average and inferior RNFL variation in PD (all p < 0.005). The findings show that RNFL was slightly but significantly thinner in idiopathic RBD. In PD, RNFL thickness may vary depending on the presence of RBD.

Involvement of Gaucher Disease Mutations in Parkinson Disease.

PubMed

Vilageliu, Lluisa; Grinberg, Daniel

2017-01-01

Gaucher disease is an autosomal recessive lysosomal storage disorder, caused by mutations in the GBA gene. The frequency of Gaucher disease patients and heterozygote carriers that developed Parkinson disease has been found to be above that of the control population. This fact suggests that mutations in the GBA gene can be involved in Parkison's etiology. Analysis of large cohorts of patients with Parkinson disease has shown that there are significantly more cases bearing GBA mutations than those found among healthy individuals. Functional studies have proven an interaction between α-synuclein and GBA, the levels of which presented an inverse correlation. Mutant GBA proteins cause increases in α-synuclein levels, while an inhibition of GBA by α-synuclein has been also demonstrated. Saposin C, a coactivator of GBA, has been shown to protect GBA from this inhibition. Among the GBA variants associated with Parkinson disease, E326K seems to be one of the most prevalent. Interestingly, it is involved in Gaucher disease only when it forms part of a double-mutant allele, usually with the L444P mutation. Structural analyses have revealed that both residues (E326 and L444) interact with Saposin C and, probably, also with α-synuclein. This could explain the antagonistic role of these two proteins in relation to GBA. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Risk Factor Profile in Parkinson's Disease Subtype with REM Sleep Behavior Disorder.

PubMed

Jacobs, Marie L; Dauvilliers, Yves; St Louis, Erik K; McCarter, Stuart J; Romenets, Silvia Rios; Pelletier, Amélie; Cherif, Mahmoud; Gagnon, Jean-François; Postuma, Ronald B

2016-01-01

Numerous large-scale studies have found diverse risk factors for Parkinson's disease (PD), including caffeine non-use, non-smoking, head injury, pesticide exposure, and family history. These studies assessed risk factors for PD overall; however, PD is a heterogeneous condition. One of the strongest identifiers of prognosis and disease subtype is the co-occurrence of rapid eye movement sleep behavior disorder (RBD).In previous studies, idiopathic RBD was associated with a different risk factor profile from PD and dementia with Lewy bodies, suggesting that the PD-RBD subtype may also have a different risk factor profile. To define risk factors for PD in patients with or without associated RBD. In a questionnaire, we assessed risk factors for PD, including demographic, medical, environmental, and lifestyle variables of 189 PD patients with or without associated polysomnography-confirmed RBD. The risk profile of patients with vs. without RBD was assessed with logistic regression, adjusting for age, sex, and disease duration. PD-RBD patients were more likely to have been a welder (OR = 3.11 (1.05-9.223), and to have been regular smokers (OR = 1.96 (1.04-3.68)). There were no differences in use of caffeine or alcohol, other occupations, pesticide exposure, rural living, or well water use. Patients with RBD had a higher prevalence of the combined family history of both dementia and parkinsonism (13.3% vs. 5.5% , OR = 3.28 (1.07-10.0). The RBD-specific subtype of PD may also have a different risk factor profile.

Pathological α-synuclein in gastrointestinal tissues from prodromal Parkinson disease patients.

PubMed

Stokholm, Morten Gersel; Danielsen, Erik Hvid; Hamilton-Dutoit, Stephen Jacques; Borghammer, Per

2016-06-01

It has been hypothesized that Lewy pathology initiates in the enteric nervous system years prior to debut of clinical motor symptoms in Parkinson disease patients. This study investigates whether Lewy pathology is present in various gastrointestinal tract tissues from Parkinson disease patients in the prodromal phase. We used the Danish National Pathology Registry to identify archived paraffin-embedded tissue blocks from 57 Parkinson disease patients (98 blocks) and 90 control subjects (98 blocks). We employed 2 different immunohistochemistry techniques visualizing aggregated α-synuclein and phosphorylated α-synuclein. Thirty-nine Parkinson disease patients contributed tissues obtained in the prodromal disease phase, whereas 18 Parkinson disease patients contributed tissues obtained solely after Parkinson diagnosis. Prodromal tissues were obtained on average 7.0 years prior to diagnosis (range = 20 years to 4 months), and postdiagnosis tissue on average 2.8 years after diagnosis (range = 2 days to 18 years). Phosphorylated α-synuclein positivity was seen in 22 of 39 (56%) prodromal Parkinson disease subjects and 30 of 67 (45%) prodromal tissue blocks. These fractions were significantly higher compared to control subjects (p = 0.0001 and p = 0.0032, respectively). In contrast, no significant difference was seen in the positivity rate between prodromal Parkinson disease patients and controls when using the aggregated α-synuclein immunohistochemistry technique. We detected Lewy pathology in the gastrointestinal tract of patients up to 20 years prior to their Parkinson disease diagnosis. These findings are in accordance with a hypothesized prodromal disease phase spanning 10 to 20 years. Ann Neurol 2016;79:940-949. © 2016 American Neurological Association.

Predicting beneficial effects of atomoxetine and citalopram on response inhibition in Parkinson's disease with clinical and neuroimaging measures

PubMed Central

Ye, Zheng; Rae, Charlotte L.; Nombela, Cristina; Ham, Timothy; Rittman, Timothy; Jones, Peter Simon; Rodríguez, Patricia Vázquez; Coyle‐Gilchrist, Ian; Regenthal, Ralf; Altena, Ellemarije; Housden, Charlotte R.; Maxwell, Helen; Sahakian, Barbara J.; Barker, Roger A.; Robbins, Trevor W.

2016-01-01

Abstract Recent studies indicate that selective noradrenergic (atomoxetine) and serotonergic (citalopram) reuptake inhibitors may improve response inhibition in selected patients with Parkinson's disease, restoring behavioral performance and brain activity. We reassessed the behavioral efficacy of these drugs in a larger cohort and developed predictive models to identify patient responders. We used a double‐blind randomized three‐way crossover design to investigate stopping efficiency in 34 patients with idiopathic Parkinson's disease after 40 mg atomoxetine, 30 mg citalopram, or placebo. Diffusion‐weighted and functional imaging measured microstructural properties and regional brain activations, respectively. We confirmed that Parkinson's disease impairs response inhibition. Overall, drug effects on response inhibition varied substantially across patients at both behavioral and brain activity levels. We therefore built binary classifiers with leave‐one‐out cross‐validation (LOOCV) to predict patients’ responses in terms of improved stopping efficiency. We identified two optimal models: (1) a “clinical” model that predicted the response of an individual patient with 77–79% accuracy for atomoxetine and citalopram, using clinically available information including age, cognitive status, and levodopa equivalent dose, and a simple diffusion‐weighted imaging scan; and (2) a “mechanistic” model that explained the behavioral response with 85% accuracy for each drug, using drug‐induced changes of brain activations in the striatum and presupplementary motor area from functional imaging. These data support growing evidence for the role of noradrenaline and serotonin in inhibitory control. Although noradrenergic and serotonergic drugs have highly variable effects in patients with Parkinson's disease, the individual patient's response to each drug can be predicted using a pattern of clinical and neuroimaging features. Hum Brain Mapp 37:1026–1037

Abnormal Bidirectional Plasticity-Like Effects in Parkinson's Disease

ERIC Educational Resources Information Center

Huang, Ying-Zu; Rothwell, John C.; Lu, Chin-Song; Chuang, Wen-Li; Chen, Rou-Shayn

2011-01-01

Levodopa-induced dyskinesia is a major complication of long-term dopamine replacement therapy for Parkinson's disease that becomes increasingly problematic in advanced Parkinson's disease. Although the cause of levodopa-induced dyskinesias is still unclear, recent work in animal models of the corticostriatal system has suggested that…

Dancing for Parkinson Disease: A Randomized Trial of Irish Set Dancing Compared With Usual Care.

PubMed

Shanahan, Joanne; Morris, Meg E; Bhriain, Orfhlaith Ni; Volpe, Daniele; Lynch, Tim; Clifford, Amanda M

2017-09-01

To examine the feasibility of a randomized controlled study design and to explore the benefits of a set dancing intervention compared with usual care. Randomized controlled design, with participants randomized to Irish set dance classes or a usual care group. Community based. Individuals with idiopathic Parkinson disease (PD) (N=90). The dance group attended a 1.5-hour dancing class each week for 10 weeks and undertook a home dance program for 20 minutes, 3 times per week. The usual care group continued with their usual care and daily activities. The primary outcome was feasibility, determined by recruitment rates, success of randomization and allocation procedures, attrition, adherence, safety, willingness of participants to be randomized, resource availability, and cost. Secondary outcomes were motor function (motor section of the Unified Parkinson's Disease Rating Scale), quality of life (Parkinson's Disease Questionnaire-39), functional endurance (6-min walk test), and balance (mini-BESTest). Ninety participants were randomized (45 per group). There were no adverse effects or resource constraints. Although adherence to the dancing program was 93.5%, there was >40% attrition in each group. Postintervention, the dance group had greater nonsignificant gains in quality of life than the usual care group. There was a meaningful deterioration in endurance in the usual care group. There were no meaningful changes in other outcomes. The exit questionnaire showed participants enjoyed the classes and would like to continue participation. For people with mild to moderately severe PD, set dancing is feasible and enjoyable and may improve quality of life. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Prying into the Prion Hypothesis for Parkinson's Disease.

PubMed

Brundin, Patrik; Melki, Ronald

2017-10-11

In Parkinson's disease, intracellular α-synuclein inclusions form in neurons. We suggest that prion-like behavior of α-synuclein is a key component in Parkinson's disease pathogenesis. Although multiple molecular changes are involved in the triggering of the disease process, we propose that neuron-to-neuron transfer is a crucial event that is essential for Lewy pathology to spread from one brain region to another. In this review, we describe key findings in human postmortem brains, cultured cells, and animal models of disease that support the idea that α-synuclein can act as a prion. We consider potential triggers of the α-synuclein misfolding and why the aggregates escape cellular degradation under disease conditions. We also discuss whether different strains of α-synuclein fibrils can underlie differences in cellular and regional distribution of aggregates in different synucleinopathies. Our conclusion is that α-synuclein probably acts as a prion in human diseases, and a deeper understanding of this step in the pathogenesis of Parkinson's disease can facilitate the development of disease-modifying therapies in the future. Dual Perspectives Companion Paper: Parkinson's Disease Is Not Simply a Prion Disorder, by D. James Surmeier, José A. Obeso, and Glenda M. Halliday. Copyright © 2017 the authors 0270-6474/17/379808-11$15.00/0.

Safinamide for symptoms of Parkinson's disease.

PubMed

Müller, T

2015-11-01

Chronic and slow progression of neuronal death in Parkinson's disease is responsible for an altered neurotransmission of various biogenic amines, such as dopamine. Therefore, an individually different pronounced heterogeneity of motor and nonmotor symptoms characterizes each Parkinson's disease patient. Ideal candidates for the balance of these neurotransmitter deficits are compounds like safinamide with broad mechanisms of action such as reversible monoamine oxidase type B inhibition, blockage of voltage-dependent sodium channels, modulation of calcium channels and of glutamate release. Safinamide is administered one time daily with oral doses ranging from 50 to 100 mg. Safinamide was well tolerated and safe, ameliorated motor symptoms when combined with dopamine agonist only or additional levodopa in clinical trials. Safinamide is a novel instrument for the drug therapy of Parkinson's disease with better safety and tolerability particularly concerning diarrhea than inhibitors of catechol-O-methyltransferase, like entacapone, according to an indirect comparison within a meta-analysis with entacapone. Copyright 2015 Prous Science, S.A.U. or its licensors. All rights reserved.

Comorbid Normal Pressure Hydrocephalus with Parkinsonism: A Clinical Challenge and Call for Awareness.

PubMed

Cucca, A; Biagioni, M C; Sharma, K; Golomb, J; Gilbert, R M; Di Rocco, A; Fleisher, J E

2018-01-01

Idiopathic normal pressure hydrocephalus (iNPH) is the most common cause of hydrocephalus in adults. The diagnosis may be challenging, requiring collaborative efforts between different specialists. According to the International Society for Hydrocephalus and Cerebrospinal Fluid Disorders, iNPH should be considered in the differential of any unexplained gait failure with insidious onset. Recognizing iNPH can be even more difficult in the presence of comorbid neurologic disorders. Among these, idiopathic Parkinson's disease (PD) is one of the major neurologic causes of gait dysfunction in the elderly. Both conditions have their peak prevalence between the 6th and the 7th decade. Importantly, postural instability and gait dysfunction are core clinical features in both iNPH and PD. Therefore, diagnosing iNPH where diagnostic criteria of PD have been met represents an additional clinical challenge. Here, we report a patient with parkinsonism initially consistent with PD who subsequently displayed rapidly progressive postural instability and gait dysfunction leading to the diagnosis of concomitant iNPH. In the following sections, we will review the clinical features of iNPH, as well as the overlapping and discriminating features when degenerative parkinsonism is in the differential diagnosis. Understanding and recognizing the potential for concomitant disease are critical when treating both conditions.

Data protection in biomaterial banks for Parkinson's disease research: the model of GEPARD (Gene Bank Parkinson's Disease Germany).

PubMed

Eggert, Karla; Wüllner, Ullrich; Antony, Gisela; Gasser, Thomas; Janetzky, Bernd; Klein, Christine; Schöls, Ludger; Oertel, Wolfgang

2007-04-15

Parkinson's disease (PD) is the second most common neurodegenerative disease. Although 10 gene loci have been identified to cause a Parkinsonian syndrome, these loci account only for a minority of PD patients. Large, systematic research programs are required to collect, store, and analyze DNA samples and clinical information to support further discovery of additional genetic components of PD or other movement disorders. Such programs facilitate research into the relationship between genotype and phenotype. The German Competence Network on Parkinson's disease (CNP) initiated the Gene Bank Parkinson's Disease Germany (GEPARD), providing an administrative and scientific infrastructure for the storage of DNA and clinical data that are electronically accessible and protective of patient rights. In this article, we offer guidance on how to establish a framework for a clinical genetic data and DNA bank, and describe GEPARD as a model that may be useful to other local, national, and international research groups developing similar programs.

Proteome analysis of human substantia nigra in Parkinson's disease

PubMed Central

Werner, Cornelius J; Heyny-von Haussen, Roland; Mall, Gerhard; Wolf, Sabine

2008-01-01

previously thought. The results point towards a heterogeneous aetiopathogenesis of the disease, including alterations of GSH-related proteins as well as alterations of proteins involved in retinoid metabolism, and they indicate that proteins involved in familial PD may not be differentially regulated in idiopathic Parkinson's disease. PMID:18275612

Tai Chi Exercise to Improve Non-Motor Symptoms of Parkinson's Disease.

PubMed

Nocera, Joe R; Amano, Shinichi; Vallabhajosula, Srikant; Hass, Chris J

2013-08-20

A substantial number of individuals with Parkinson's disease exhibit debilitating non-motor symptoms that decrease quality of life. To date, few treatment options exist for the non-motor symptomatology related to Parkinson's disease. The goal of this pilot investigation was to determine the effects of Tai Chi exercise on the non-motor symptomology in Parkinson's disease. Twenty-one individuals with Parkinson's disease were enrolled in a Tai Chi intervention (n=15) or a noncontact control group (n=6). Participants assigned to Tai Chi participated in 60-minute Tai Chi sessions three times per week, for 16 weeks. Pre and post measures included indices of cognitive-executive function including visuomotor tracking and attention, selective attention, working memory, inhibition, processing speed and task switching. Additionally, all participants were evaluated on the Parkinson's disease Questionnaire-39 and Tinetti's Falls Efficacy Scale. Results indicated that the Tai Chi training group had significantly better scores following the intervention than the control group on the Parkinson's disease Questionnaire-39 total score as well as the emotional well-being sub score. Trends for improvement were noted for the Tai Chi group on Digits Backwards, Tinetti's Falls Efficacy Scale, and the activities of daily living and communication sub scores of the Parkinson's disease Questionnaire-39. This research provides initial data that supports future studies to definitively establish efficacy of Tai Chi to improve non-motor features of Parkinson's disease.

Imaging Amyloidopathy in Parkinson Disease and Parkinsonian Dementia Syndromes.

PubMed

Frey, Kirk A; Petrou, Myria

2015-02-01

Dementia arising in patients with Parkinson disease or parkinsonian neurodegeneration comprises a heterogeneous neuropathology. Clinical labeling of patients with both dementia and Parkinson disease is dichotomous, depending on the temporal development of cognitive impairment and motor parkinsonism. Patients with dementia arising first (or within the first year of PD) are classified as dementia with Lewy bodies; patients with PD for more than one year before cognitive decline are classified as Parkinson disease with dementia. Despite this differential clinical classification, autopsy studies demonstrate variable admixtures of cortical synuicleinopathy, Aβ-amyloidopathy and tau neurofibrillary tangle deposition. There are no routine clinical diagnostic measures that accurately distinguish the underlying neuropathologies in individual patients. In the present paper, we review the published literature describing characteristics of fibrillary Aβ-amyloid deposition on the basis of PET radiotracer imaging in patients with Parkinson disease and in parkinsonian dementia syndromes. Although individual reports often include only small-to-modest subject numbers, there is overall suggestion that PD patients have a lower incidence of Aβ-amyloid deposition than seen amongst elderly normal subjects, and that Parkinson disease with dementia patients have a lower incidence of Aβ-amyloid deposition than do patients with dementia with Lewy bodies. These apparent features contrast the findings of Aβ-amyloid-PET imaging in normal aging and the development of Alzheimer disease, where Aβ-amyloid deposition arises asymptomatically and apparently many years before development of signs or symptoms of dementia. It is proposed that focused, prospective studies are needed to further address and understand the complex role(s) of Aβ-amyloid pathology in Parkinson disease, and that this understanding will be critical to the development of targeted disease-modifying therapy for dementia in

Preprohypocretin polymorphisms in Parkinson disease patients reporting "sleep attacks".

PubMed

Rissling, Ida; Körner, Yvonne; Geller, Frank; Stiasny-Kolster, Karin; Oertel, Wolfgang H; Möller, J Carsten

2005-07-01

Previously, we found a significant association between the dopamine D2 receptor gene polymorphism Taq IA and sudden onset of sleep in patients with Parkinson disease. Here we evaluated the association between the preprohypocretin (-909T/C), (-22C/T), and (-20C/A) polymorphisms and sudden onset of sleep in the same population of patients with Parkinson disease. We conducted an association study analyzing the distribution of preprohypocretin polymorphisms in Germanic, caucasian Parkinson disease patients with and without sudden onset of sleep, matched according to drug therapy, disease duration, sex, and age. Movement disorders section at a university hospital. 132 Parkinson disease patients with sudden onset of sleep and 132 Parkinson disease patients without sudden onset of sleep. Blood samples were taken from each participant and used for DNA extraction. Polymorphisms were analyzed by established polymerase chain reaction protocols or direct sequencing. The variant allele T of the (-909T/C) preprohypocretin polymorphism was more commonly found in Parkinson disease patients with sudden onset of sleep. Statistical analysis showed that there were significant differences in the genotype (P = .024) and allele (P = .018) distribution between both groups. For heterozygous and homozygous carriers of allele T, the genotype relative-risk estimates for the presence of sudden onset of sleep were 2.01 (95% confidence interval: 0.76-5.34) and 2.81 (95% confidence interval: 1.09-7.25), respectively. Our results show a significant association between the (-909T/C) preprohypocretin polymorphism and sudden onset of sleep in Parkinson disease. However, we could not demonstrate any interaction between the Taq IA and (-909T/C) polymorphisms with respect to the occurrence of sudden onset of sleep, suggesting that multiple genetic factors may contribute to the pathogenesis of this phenomenon.

Elective Thoracolumbar Spine Fusion Surgery in Patients with Parkinson Disease.

PubMed

Puvanesarajah, Varun; Jain, Amit; Qureshi, Rabia; Carstensen, S Evan; Tyger, Rosemarie; Hassanzadeh, Hamid

2016-12-01

Few data are available concerning clinical outcomes in patients with Parkinson disease who undergo elective thoracolumbar spine fusion surgery. The goal of this study is to elucidate complication and revision rates after posterior thoracolumbar fusion surgery in patients with Parkinson disease, with a focus on how Parkinson disease modifies these rates. The PearlDiver database (2005-2012) was queried for patients who underwent posterior approach thoracolumbar fusion from 2006 to 2011. Cohorts of patients with a previous diagnosis of Parkinson disease (n = 4816) and without (n = 280,702) were compared. Multivariate analysis that included various comorbidities and demographics was used to calculate effects of Parkinson disease on development of postoperative infection and major medical complications within 90 days and revision surgery within 1 year. For analyses, significance was set at P < 0.001. Major medical complications were observed in 545 patients (11.3%) for 90 days after the index procedure. Postoperative infection was noted in 91 patients (1.9%) within 90 days, and revision surgeries were performed in 250 patients (5.2%) within 1 year. Multivariate analysis showed that Parkinson disease was significantly associated with an increased risk for medical complications (adjusted odds ratio, 1.22; 95% confidence interval, 1.11-1.34; P < 0.001) and revision surgery (adjusted odds ratio, 1.70; 95% confidence interval, 1.49-1.93; P < 0.001), but not postoperative infection (P = 0.02). Patients with Parkinson disease are more likely to require revision surgery and have higher rates of adverse medical events postoperatively. Patients with Parkinson disease should be appropriately selected to ensure favorable clinical outcomes. Copyright © 2016. Published by Elsevier Inc.

Consistent abnormalities in metabolic network activity in idiopathic rapid eye movement sleep behaviour disorder.

PubMed

Wu, Ping; Yu, Huan; Peng, Shichun; Dauvilliers, Yves; Wang, Jian; Ge, Jingjie; Zhang, Huiwei; Eidelberg, David; Ma, Yilong; Zuo, Chuantao

2014-12-01

Rapid eye movement sleep behaviour disorder has been evaluated using Parkinson's disease-related metabolic network. It is unknown whether this disorder is itself associated with a unique metabolic network. 18F-fluorodeoxyglucose positron emission tomography was performed in 21 patients (age 65.0±5.6 years) with idiopathic rapid eye movement sleep behaviour disorder and 21 age/gender-matched healthy control subjects (age 62.5±7.5 years) to identify a disease-related pattern and examine its evolution in 21 hemi-parkinsonian patients (age 62.6±5.0 years) and 16 moderate parkinsonian patients (age 56.9±12.2 years). We identified a rapid eye movement sleep behaviour disorder-related metabolic network characterized by increased activity in pons, thalamus, medial frontal and sensorimotor areas, hippocampus, supramarginal and inferior temporal gyri, and posterior cerebellum, with decreased activity in occipital and superior temporal regions. Compared to the healthy control subjects, network expressions were elevated (P<0.0001) in the patients with this disorder and in the parkinsonian cohorts but decreased with disease progression. Parkinson's disease-related network activity was also elevated (P<0.0001) in the patients with rapid eye movement sleep behaviour disorder but lower than in the hemi-parkinsonian cohort. Abnormal metabolic networks may provide markers of idiopathic rapid eye movement sleep behaviour disorder to identify those at higher risk to develop neurodegenerative parkinsonism. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Hypokinesia without decrement distinguishes progressive supranuclear palsy from Parkinson's disease

PubMed Central

Massey, Luke A.; Lees, Andrew J.; Brown, Peter; Day, Brian L.

2012-01-01

Repetitive finger tapping is commonly used to assess bradykinesia in Parkinson's disease. The Queen Square Brain Bank diagnostic criterion of Parkinson's disease defines bradykinesia as ‘slowness of initiation with progressive reduction in speed and amplitude of repetitive action’. Although progressive supranuclear palsy is considered an atypical parkinsonian syndrome, it is not known whether patients with progressive supranuclear palsy have criteria-defined bradykinesia. This study objectively assessed repetitive finger tap performance and handwriting in patients with Parkinson's disease (n = 15), progressive supranuclear palsy (n = 9) and healthy age- and gender-matched controls (n = 16). The motion of the hand and digits was recorded in 3D during 15-s repetitive index finger-to-thumb tapping trials. The main finding was hypokinesia without decrement in patients with progressive supranuclear palsy, which differed from the finger tap pattern in Parkinson's disease. Average finger separation amplitude in progressive supranuclear palsy was less than half of that in controls and Parkinson's disease (P < 0.001 in both cases). Change in tap amplitude over consecutive taps was computed by linear regression. The average amplitude slope in progressive supranuclear palsy was nearly zero (0.01°/cycle) indicating a lack of decrement, which differed from the negative slope in patients with Parkinson's disease OFF levodopa (−0.20°/cycle, P = 0.002). ‘Hypokinesia’, defined as <50% of control group's mean amplitude, combined with ‘absence of decrement’, defined as mean positive amplitude slope, were identified in 87% of finger tap trials in the progressive supranuclear palsy group and only 12% in the Parkinson's disease OFF levodopa group. In progressive supranuclear palsy, the mean amplitude was not correlated with disease duration or other clinimetric scores. In Parkinson's disease, finger tap pattern was compatible with criteria

Reduced glucocerebrosidase is associated with increased α-synuclein in sporadic Parkinson's disease.

PubMed

Murphy, Karen E; Gysbers, Amanda M; Abbott, Sarah K; Tayebi, Nahid; Kim, Woojin S; Sidransky, Ellen; Cooper, Antony; Garner, Brett; Halliday, Glenda M

2014-03-01

Heterozygous mutations in GBA1, the gene encoding lysosomal glucocerebrosidase, are the most frequent known genetic risk factor for Parkinson's disease. Reduced glucocerebrosidase and α-synuclein accumulation are directly related in cell models of Parkinson's disease. We investigated relationships between Parkinson's disease-specific glucocerebrosidase deficits, glucocerebrosidase-related pathways, and α-synuclein levels in brain tissue from subjects with sporadic Parkinson's disease without GBA1 mutations. Brain regions with and without a Parkinson's disease-related increase in α-synuclein levels were assessed in autopsy samples from subjects with sporadic Parkinson's disease (n = 19) and age- and post-mortem delay-matched controls (n = 10). Levels of glucocerebrosidase, α-synuclein and related lysosomal and autophagic proteins were assessed by western blotting. Glucocerebrosidase enzyme activity was measured using a fluorimetric assay, and glucocerebrosidase and α-synuclein messenger RNA expression determined by quantitative polymerase chain reaction. Related sphingolipids were analysed by mass spectrometry. Multivariate statistical analyses were performed to identify differences between disease groups and regions, with non-parametric correlations used to identify relationships between variables. Glucocerebrosidase protein levels and enzyme activity were selectively reduced in the early stages of Parkinson's disease in regions with increased α-synuclein levels although limited inclusion formation, whereas GBA1 messenger RNA expression was non-selectively reduced in Parkinson's disease. The selective loss of lysosomal glucocerebrosidase was directly related to reduced lysosomal chaperone-mediated autophagy, increased α-synuclein and decreased ceramide. Glucocerebrosidase deficits in sporadic Parkinson's disease are related to the abnormal accumulation of α-synuclein and are associated with substantial alterations in lysosomal chaperone-mediated autophagy

Doppler sonography characteristics of vertebrobasilar circulation in patients with Parkinson's disease.

PubMed

Vidović, Mirjana; Sinanović, Osman; Smajlović, Dzevdet; Burina, Adnan; Hudić, Josip

2008-08-01

The objective of the study was to analyze the doppler sonography findings of vertebrobasilar circulation (VB) in patients with Parkinson's disease. 40 patients were analyzed (25 men's and 15 women) with Parkinson's disease, average age was 61.9 years (SD=11.43), treated at the Clinic for Neurology in Tuzla. Device for doppler sonography was Multidop x 4. Doppler sonography findings of VB circulation were analyzed in order to computerized tomography (CT) findings of the brain (with or without ischemic lacunar lesions) and in order to presence of postural disturbances as one of dominant Parkinson's disease symptoms during actual hospitalization. Our results suggest that vertebrobasilar insufficiency is more frequent in patients with Parkinson's disease (no matter of type) and postural disturbances as a dominant symptom comparing to group of Parkinson's disease patients without postural disturbances. These results implicate the importance of doppler sonography findings of vertebrobasilar circulation in patients with Parkinson's disease and possibility of considering role of vertebrobasilar insufficiency in development of postural disturbances.

The longitudinal impact of depression on disability in Parkinson disease.

PubMed

Pontone, Gregory M; Bakker, Catherine C; Chen, Shaojie; Mari, Zoltan; Marsh, Laura; Rabins, Peter V; Williams, James R; Bassett, Susan S

2016-05-01

Depression in Parkinson disease (PD) is a common problem that worsens quality of life and causes disability. However, little is known about the longitudinal impact of depression on disability in PD. This study examined the association between disability and DSM-IV-TR depression status across six years. Longitudinal cohort study with assessments at study entry, year two, four, and six conducted in the Morris K. Udall Parkinson Disease Research Center. Recruitment totaled 137 adult men and women with idiopathic PD in which up to six years of data on demographic, motor, and non-motor variables was collected. Movement disorder specialists used the structured interview for DSM-IV-TR depressive disorders and the Northwestern Disability Scale to assess depression and disability. A generalized linear mixed model was fitted with Northwestern Disability Scale score as the dependent variable to determine the effect of baseline depression status on disability. A total of 43 participants were depressed at baseline compared to 94 without depression. Depressed participants were more likely to be female, were less educated, were less likely to take dopamine agonists, and more likely to have motor fluctuations. Controlling for these variables, symptomatic depression predicted greater disability compared to both never depressed (p = 0.0133) and remitted depression (p = 0.0009). Disability associated with symptomatic depression at baseline was greater over the entire six-year period compared to participants with remitted depressive episodes or who were never depressed. Persisting depression is associated with a long-term adverse impact on daily functioning in PD. Adequate treatment or spontaneous remission of depression improves ADL function. Copyright © 2015 John Wiley & Sons, Ltd.

[A core deficit in Parkinson disease?].

PubMed

Benítez-Burraco, A; Herrera, E; Cuetos, F

2016-05-01

Parkinson disease is a neurodegenerative condition involving motor, cognitive, and linguistic deficits. It is important to know why all these different deficits co-occur in the affected people. This paper aims to clarify whether these comorbid deficits result from the selective impairment of a computational primitive, namely, a context-sensitive computational ability according to Chomsky's Hierarchy (a well-established research tool in comparative neuroscience). A total of 15 medicated subjects with Parkinson disease and 15 controls were selected. They were matched in age and education. A battery of tasks was designed to test 3 different domains (motor capacities, cognition, and language) and 2 different computational abilities (context-free and context-sensitive operations). Significant differences between groups were observed only regarding the linguistic task involving context-sensitive computations (correferences). The observed deficits in our patients with Parkinson disease cannot be explained in terms of the selective impairment of one only unspecific, low-level computational process. At the same time, differences between patients and controls are expected to be greater if the former are not medicated. Moreover, we should pursue in the search of (this kind of) computational primitives than can be selectively impaired in people with Parkinson disease, because they may help to achieve an earlier diagnosis of this condition. Copyright © 2014 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

The emerging science of precision medicine and pharmacogenomics for Parkinson's disease.

PubMed

Payami, Haydeh

2017-08-01

Current therapies for Parkinson's disease are problematic because they are symptomatic and have adverse effects. New drugs have failed in clinical trials because of inadequate efficacy. At the core of the problem is trying to make one drug work for all Parkinson's disease patients, when we know this premise is wrong because (1) Parkinson's disease is not a single disease, and (2) no two individuals have the same biological makeup. Precision medicine is the goal to strive for, but we are only at the beginning stages of building the infrastructure for one of the most complex projects in the history of science, and it will be a long time before Parkinson's disease reaps the benefits. Pharmacogenomics, a cornerstone of precision medicine, has already proven successful for many conditions and could also propel drug discovery and improve treatment for Parkinson's disease. To make progress in the pharmacogenomics of Parkinson's disease, we need to change course from small inconclusive candidate gene studies to large-scale rigorously planned genome-wide studies that capture the nuclear genome and the microbiome. Pharmacogenomic studies must use homogenous subtypes of Parkinson's disease or apply the brute force of statistical power to overcome heterogeneity, which will require large sample sizes achievable only via internet-based methods and electronic databases. Large-scale pharmacogenomic studies, together with biomarker discovery efforts, will yield the knowledge necessary to design clinical trials with precision to alleviate confounding by disease heterogeneity and interindividual variability in drug response, two of the major impediments to successful drug discovery and effective treatment. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

Visual short-term memory deficits associated with GBA mutation and Parkinson's disease.

PubMed

Zokaei, Nahid; McNeill, Alisdair; Proukakis, Christos; Beavan, Michelle; Jarman, Paul; Korlipara, Prasad; Hughes, Derralynn; Mehta, Atul; Hu, Michele T M; Schapira, Anthony H V; Husain, Masud

2014-08-01

Individuals with mutation in the lysosomal enzyme glucocerebrosidase (GBA) gene are at significantly high risk of developing Parkinson's disease with cognitive deficit. We examined whether visual short-term memory impairments, long associated with patients with Parkinson's disease, are also present in GBA-positive individuals-both with and without Parkinson's disease. Precision of visual working memory was measured using a serial order task in which participants observed four bars, each of a different colour and orientation, presented sequentially at screen centre. Afterwards, they were asked to adjust a coloured probe bar's orientation to match the orientation of the bar of the same colour in the sequence. An additional attentional 'filtering' condition tested patients' ability to selectively encode one of the four bars while ignoring the others. A sensorimotor task using the same stimuli controlled for perceptual and motor factors. There was a significant deficit in memory precision in GBA-positive individuals-with or without Parkinson's disease-as well as GBA-negative patients with Parkinson's disease, compared to healthy controls. Worst recall was observed in GBA-positive cases with Parkinson's disease. Although all groups were impaired in visual short-term memory, there was a double dissociation between sources of error associated with GBA mutation and Parkinson's disease. The deficit observed in GBA-positive individuals, regardless of whether they had Parkinson's disease, was explained by a systematic increase in interference from features of other items in memory: misbinding errors. In contrast, impairments in patients with Parkinson's disease, regardless of GBA status, was explained by increased random responses. Individuals who were GBA-positive and also had Parkinson's disease suffered from both types of error, demonstrating the worst performance. These findings provide evidence for dissociable signature deficits within the domain of visual short

Mitochondrial dysfunction of immortalized human adipose tissue-derived mesenchymal stromal cells from patients with Parkinson's disease.

PubMed

Moon, Hyo Eun; Yoon, Seung Hee; Hur, Yong Suk; Park, Hyung Woo; Ha, Ji Young; Kim, Kyung-Hee; Shim, Jung Hee; Yoo, Seung Hyun; Son, Jin H; Paek, Seung Leal; Kim, In Keyoung; Hwang, Jae Ha; Kim, Dong Gyu; Kim, Han-Joon; Jeon, Beom Seok; Park, Sung Sup; Paek, Sun Ha

2013-12-01

Mitochondrial dysfunction in dopaminergic neurons of patients with idiopathic and familial Parkinson's disease (PD) is well known although the underlying mechanism is not clear. We established a homogeneous population of human adipose tissue-derived mesenchymal stromal cells (hAD-MSCs) from human adult patients with early-onset hereditary familial Parkin-defect PD as well as late-onset idiopathic PD by immortalizing cells with the hTERT gene to better understand the underlying mechanism of PD. The hAD-MSCs from patients with idiopathic PD were designated as "PD", from patients with Parkin-defect PD as "Parkin" and from patients with pituitary adenomas as "non-PD" in short. The pGRN145 plasmid containing hTERT was introduced to establish telomerase immortalized cells. The established hTERT-immortalized cell lines showed chromosomal aneuploidy sustained stably over two-years. The morphological study of mitochondria in the primary and immortalized hAD-MSCs showed that the mitochondria of the non-PD were normal; however, those of the PD and Parkin were gradually damaged. A striking decrease in mitochondrial complex I, II, and IV activities was observed in the hTERT-immortalized cells from the patients with idiopathic and Parkin-defect PD. Comparative Western blot analyses were performed to investigate the expressions of PD specific marker proteins in the hTERT-immortalized cell lines. This study suggests that the hTERT-immortalized hAD-MSC cell lines established from patients with idiopathic and familial Parkin-defect PD could be good cellular models to evaluate mitochondrial dysfunction to better understand the pathogenesis of PD and to develop early diagnostic markers and effective therapy targets for the treatment of PD.

Mitochondrial Dysfunction of Immortalized Human Adipose Tissue-Derived Mesenchymal Stromal Cells from Patients with Parkinson's Disease

PubMed Central

Moon, Hyo Eun; Yoon, Seung Hee; Hur, Yong Suk; Park, Hyung Woo; Ha, Ji Young; Kim, Kyung-Hee; Shim, Jung Hee; Yoo, Seung Hyun; Son, Jin H.; Paek, Seung Leal; Kim, In Keyoung; Hwang, Jae Ha; Kim, Dong Gyu; Kim, Han-Joon; Jeon, Beom Seok; Park, Sung Sup

2013-01-01

Mitochondrial dysfunction in dopaminergic neurons of patients with idiopathic and familial Parkinson's disease (PD) is well known although the underlying mechanism is not clear. We established a homogeneous population of human adipose tissue-derived mesenchymal stromal cells (hAD-MSCs) from human adult patients with early-onset hereditary familial Parkin-defect PD as well as late-onset idiopathic PD by immortalizing cells with the hTERT gene to better understand the underlying mechanism of PD. The hAD-MSCs from patients with idiopathic PD were designated as "PD", from patients with Parkin-defect PD as "Parkin" and from patients with pituitary adenomas as "non-PD" in short. The pGRN145 plasmid containing hTERT was introduced to establish telomerase immortalized cells. The established hTERT-immortalized cell lines showed chromosomal aneuploidy sustained stably over two-years. The morphological study of mitochondria in the primary and immortalized hAD-MSCs showed that the mitochondria of the non-PD were normal; however, those of the PD and Parkin were gradually damaged. A striking decrease in mitochondrial complex I, II, and IV activities was observed in the hTERT-immortalized cells from the patients with idiopathic and Parkin-defect PD. Comparative Western blot analyses were performed to investigate the expressions of PD specific marker proteins in the hTERT-immortalized cell lines. This study suggests that the hTERT-immortalized hAD-MSC cell lines established from patients with idiopathic and familial Parkin-defect PD could be good cellular models to evaluate mitochondrial dysfunction to better understand the pathogenesis of PD and to develop early diagnostic markers and effective therapy targets for the treatment of PD. PMID:24465144

Molecular chaperones in Parkinson's disease--present and future.

PubMed

Ebrahimi-Fakhari, Darius; Wahlster, Lara; McLean, Pamela J

2011-01-01

Parkinson's disease, like many other neurodegenerative disorders, is characterized by the progressive accumulation of pathogenic protein species and the formation of intracellular inclusion bodies. The cascade by which the small synaptic protein α-synuclein misfolds to form distinctive protein aggregates, termed Lewy bodies and Lewy neurites, has been the subject of intensive research for more than a decade. Genetic and pathological studies in Parkinson's disease patients as well as experimental studies in disease models have clearly established altered protein metabolism as a key element in the pathogenesis of Parkinson's disease. Alterations in protein metabolism include misfolding and aggregation, post-translational modification and dysfunctional degradation of cytotoxic protein species. Protein folding and re-folding are both mediated by a highly conserved network of molecules, called molecular chaperones and co-chaperones. In addition to the regulatory role in protein folding, molecular chaperone function is intimately associated with pathways of protein degradation, such as the ubiquitin-proteasome system and the autophagy-lysosomal pathway, to effectively remove irreversibly misfolded proteins. Because of the central role of molecular chaperones in maintaining protein homeostasis, we herein review our current knowledge on the involvement of molecular chaperones and co-chaperones in Parkinson's disease. We further discuss the capacity of molecular chaperones to prevent or modulate neurodegeneration, an important concept for future neuroprotective strategies and summarize the current progress in preclinical studies in models of Parkinson's disease and other neurodegenerative disorders. Finally we include a discussion on the future potential of using molecular chaperones as a disease modifying therapy.

Predictive risk factors for chronic low back pain in Parkinson's disease.

PubMed

Ozturk, Erhan Arif; Kocer, Bilge Gonenli

2018-01-01

Although previous studies have reported that the prevalence of low back pain in Parkinson's disease was over 50% and low back pain was often classified as chronic, risk factors of chronic low back pain have not been previously investigated. The aim of this study was to determine the predictive risk factors of chronic low back pain in Parkinson's disease. One hundred and sixty-eight patients with Parkinson's disease and 179 controls were consecutively included in the study. Demographic data of the two groups and disease characteristics of Parkinson's disease patient group were recorded. Low back pain lasting for ≥3 months was evaluated as chronic. Firstly, the bivariate correlations were calculated between chronic low back pain and all possible risk factors. Then, a multivariate regression was used to evaluate the impact of the predictors of chronic low back pain. The frequency of chronic low back pain in Parkinson's disease patients and controls were 48.2% and 26.7%, respectively (p < 0.001). The predictive risk factors of chronic low back pain in Parkinson's disease were general factors including age (odds ratio = 1.053, p = 0.032) and Hospital Anxiety and Depression Scale - Depression subscore (odds ratio = 1.218, p = 0.001), and Parkinson's disease-related factors including rigidity (odds ratio = 5.109, p = 0.002) and posture item scores (odds ratio = 5.019, p = 0.0001). The chronic low back pain affects approximately half of the patients with Parkinson's disease. Prevention of depression or treatment recommendations for managing depression, close monitoring of anti- parkinsonian medication to keep motor symptoms under control, and attempts to prevent, correct or reduce abnormal posture may help reduce the frequency of chronic low back pain in Parkinson's disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Great shakes: famous people with Parkinson disease.

PubMed

Jones, Jeffrey M

2004-12-01

James Parkinson is credited with the first complete clinical description of the syndrome attributed to his name, Parkinson disease. It is recognized as the first syndrome defined after neurology became a specialty. Descriptions of Parkinson features are rare in antiquity, and famous people with this disorder have not been found before the 1800s. During the 20th century, more and more famous people appear to be afflicted with Parkinson, and this article reviews some of those who have withstood the "test of Time magazine," and examines some of the reasons why the syndrome is a relatively recent disorder.

Diagnostic Value of the Impairment of Olfaction in Parkinson's Disease

PubMed Central

Casjens, Swaantje; Eckert, Angelika; Woitalla, Dirk; Ellrichmann, Gisa; Turewicz, Michael; Stephan, Christian; Eisenacher, Martin; May, Caroline; Meyer, Helmut E.; Brüning, Thomas; Pesch, Beate

2013-01-01

Background Olfactory impairment is increasingly recognized as an early symptom in the development of Parkinson's disease. Testing olfactory function is a non-invasive method but can be time-consuming which restricts its application in clinical settings and epidemiological studies. Here, we investigate odor identification as a supportive diagnostic tool for Parkinson's disease and estimate the performance of odor subsets to allow a more rapid testing of olfactory impairment. Methodology/Principal Findings Odor identification was assessed with 16 Sniffin' sticks in 148 Parkinson patients and 148 healthy controls. Risks of olfactory impairment were estimated with proportional odds models. Random forests were applied to classify Parkinson and non-Parkinson patients. Parkinson patients were rarely normosmic (identification of more than 12 odors; 16.8%) and identified on average seven odors whereas the reference group identified 12 odors and showed a higher prevalence of normosmy (31.1%). Parkinson patients with rigidity dominance had a twofold greater prevalence of olfactory impairment. Disease severity was associated with impairment of odor identification (per score point of the Hoehn and Yahr rating OR 1.87, 95% CI 1.26–2.77). Age-related impairment of olfaction showed a steeper gradient in Parkinson patients. Coffee, peppermint, and anise showed the largest difference in odor identification between Parkinson patients and controls. Random forests estimated a misclassification rate of 22.4% when comparing Parkinson patients with healthy controls using all 16 odors. A similar rate (23.8%) was observed when only the three aforementioned odors were applied. Conclusions/Significance Our findings indicate that testing odor identification can be a supportive diagnostic tool for Parkinson's disease. The application of only three odors performed well in discriminating Parkinson patients from controls, which can facilitate a wider application of this method as a point

Diagnostic accuracy of Parkinson's disease and atypical parkinsonism in nursing homes.

PubMed

Weerkamp, N J; Tissingh, G; Poels, P J E; Zuidema, S U; Munneke, M; Koopmans, R T C M; Bloem, B R

2014-11-01

Management of Parkinson's disease (PD) and atypical parkinsonism in nursing homes depends on a timely and accurate diagnosis. However, little is known about the diagnostic accuracy of these parkinsonian syndromes in nursing homes. We examined this issue in a large group of Dutch nursing home residents. Twelve large nursing home organizations in the Netherlands accounting for 100 nursing homes with a total population of 5480 residents participated. Residents with PD or atypical parkinsonism were identified according to their nursing home medical chart diagnosis. Additionally, local pharmacists provided a list of all residents using antiparkinson medication. We compared the admission diagnosis to a clinical diagnosis made in the study, based upon interview and detailed neurological examination by movement disorders experts. Diagnoses were based on accepted clinical criteria for PD and atypical parkinsonism. In the total population of 5480 residents, 258 had previously been diagnosed with a form of parkinsonism according to their medical record. In 53 of these residents (20.5%) we changed or rejected the diagnosis. Specifically, we found no parkinsonism in 22 of these 53 residents (8.5% of all patients with suspected parkinsonism). In the remaining 31 residents (12%), we established a new diagnosis within the parkinsonian spectrum. In a large population of Dutch nursing home residents, 20% of diagnoses within the parkinsonian spectrum were inaccurate. Almost 9% of residents had inadvertently received a diagnosis of parkinsonism. Better recognition of parkinsonism in nursing homes is important, because of the consequences for management and prognosis. Copyright © 2014. Published by Elsevier Ltd.

Parkinson's disease: a population-based investigation of life satisfaction and employment.

PubMed

Gustafsson, Helena; Nordström, Peter; Stråhle, Stefan; Nordström, Anna

2015-01-01

To investigate relationships between individuals' socioeconomic situations and quality of life in working-aged subjects with Parkinson's disease. A population-based cohort comprising 1,432 people with Parkinson's disease and 1,135 matched controls, who responded to a questionnaire. Logistic regression analysis was performed to identify factors associated with life satisfaction and likelihood of employment. In multivariate analyses, Parkinson's disease was associated with an increased risk of dissatisfaction with life (odds ratio (OR) = 5.4, 95% confidence interval (95% CI) = 4.2-7.1) and reduced likelihood of employment (OR = 0.30, 95% CI = 0.25-0.37). Employers' support was associated with greater likelihood of employment (p < 0.001). Twenty-four percent of people with Parkinson's disease for ≥ 10 years remained employed and 6% worked full-time. People with Parkinson's disease also more frequently experienced work demands that exceeded their capacity; this factor and unemployment independently correlated with greater risk of dissatisfaction with life (both p < 0.05). People with Parkinson's disease have an increased risk of dissatisfaction with life. Employment situation is important for general life satisfaction among working-aged individuals. People with Parkinson's disease appear to find it difficult to meet the challenge of achieving a balanced employment situation.

Retrospective assessment of movement disorder society criteria for mild cognitive impairment in Parkinson's disease.

PubMed

Loftus, Andrea M; Bucks, Romola S; Thomas, Meghan; Kane, Robert; Timms, Caitlin; Barker, Roger A; Gasson, Natalie

2015-02-01

A Movement Disorder Society (MDS) taskforce recently proposed diagnostic criteria for Parkinson's disease with features of mild cognitive impairment (PD-MCI). This study first examined the prevalence and nature of PD-MCI in a non-demented cohort using the MDS criteria. Using the generic Monte Carlo simulation method developed by Crawford and colleagues (2007), this study then estimated the base rate of the representative population who would demonstrate PD-MCI due to chance alone. A total of 104 participants with idiopathic PD underwent extensive motor and neuropsychological testing at baseline and 2 years later. The Unified Parkinson's Disease Rating Scale (UPDRS) was used to assess motor symptoms of PD and a range of established neuropsychological tests was used to assess PD-MCI in accord with MDS criteria. In accord with MDS criteria, 38% of this cohort demonstrated PD-MCI at baseline and 48% at follow-up. Of the 36 participants in the multiple-domain PD-MCI subtype at time-1, 9 (25%) demonstrated no PD-MCI at follow up. Analysis revealed that approximately 13% of the representative population would demonstrate abnormally low scores for 2 of the 9 tests used, thereby meeting MDS criteria for PD-MCI. Clinicians and researchers need to approach a single diagnosis (i.e., based on one assessment) of PD-MCI with considerable caution.

Lumbar Spine Surgery in Patients with Parkinson Disease.

PubMed

Schroeder, Joshua E; Hughes, Alexander; Sama, Andrew; Weinstein, Joseph; Kaplan, Leon; Cammisa, Frank P; Girardi, Federico P

2015-10-21

Parkinson disease is the second most common neurodegenerative condition. The literature on patients with Parkinson disease and spine surgery is limited, but increased complications have been reported. All patients with Parkinson disease undergoing lumbar spine surgery between 2002 and 2012 were identified. Patients' charts, radiographs, and outcome questionnaires were reviewed. Parkinson disease severity was assessed with use of the modified Hoehn and Yahr staging scale. Complications and subsequent surgeries were analyzed. Risk for reoperation was assessed. Ninety-six patients underwent lumbar spine surgery. The mean patient age was 63.0 years. The mean follow-up duration was 30.1 months. The Parkinson disease severity stage was <2 in thirteen patients, 2 in thirty patients, 2.5 in twenty-three patients, and ≥3 in thirty patients. The primary indication for surgery was spinal stenosis in seventy-two patients, spondylolisthesis in seventeen patients, and coronal and/or sagittal deformity in seven patients. There were nineteen early complications, including postoperative infections requiring surgical irrigation and debridement and long-term antibiotics in ten patients. The visual analog scale for back pain improved from 7.4 cm preoperatively to 1.8 cm postoperatively (p < 0.001). The visual analog scale for lower-limb pain improved from 7.7 cm preoperatively to 2.3 cm postoperatively (p < 0.001). The Oswestry Disability Index score dropped from 54.1 points to 17.7 points at the time of the latest follow-up (p < 0.001). The Short Form-12 Physical Component Summary score improved from 26.6 points preoperatively to 30.5 points postoperatively (p < 0.05). Twenty patients required revision surgery. Risks for further surgery included a Parkinson disease severity stage of ≥3 (p < 0.05), a history of diabetes mellitus, treatment for osteoporosis, and a combined anterior and posterior approach. Despite a higher rate of complications than in the general population, the

Extended "Timed Up and Go" assessment as a clinical indicator of cognitive state in Parkinson's disease.

PubMed

Evans, Tess; Jefferson, Alexa; Byrnes, Michelle; Walters, Sue; Ghosh, Soumya; Mastaglia, Frank L; Power, Brian; Anderton, Ryan S

2017-04-15

To evaluate a modified extended Timed Up and Go (extended-TUG) assessment against a panel of validated clinical assessments, as an indicator of Parkinson's disease (PD) severity and cognitive impairment. Eighty-seven participants with idiopathic PD were sequentially recruited from a Movement Disorders Clinic. An extended-TUG assessment was employed which required participants to stand from a seated position, walk in a straight line for 7m, turn 180° and then return to the start, in a seated position. The extended-TUG assessment duration was correlated to a panel of clinical assessments, including the Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Quality of Life (PDQ-39), Scales for Outcomes in Parkinson's Disease (SCOPA-Cog), revised Addenbrooke's Cognitive Index (ACE-R) and Barratt's Impulsivity Scale 11 (BIS-11). Extended-TUG time was significantly correlated to MDS-UPDRS III score and to SCOPA-Cog, ACE-R (p<0.001) and PDQ-39 scores (p<0.01). Generalized linear models determined the extended-TUG to be a sole variable in predicting ACE-R or SCOPA-Cog scores. Patients in the fastest extended-TUG tertile were predicted to perform 8.3 and 13.4 points better in the SCOPA-Cog and ACE-R assessments, respectively, than the slowest group. Patients who exceeded the dementia cut-off scores with these instruments exhibited significantly longer extended-TUG times. Extended-TUG performance appears to be a useful indicator of cognition as well as motor function and quality of life in PD, and warrants further evaluation as a first line assessment tool to monitor disease severity and response to treatment. Poor extended-TUG performance may identify patients without overt cognitive impairment form whom cognitive assessment is needed. Copyright © 2017 Elsevier B.V. All rights reserved.

Downward finger displacement distinguishes Parkinson disease dementia from Alzheimer disease.

PubMed

Lieberman, Abraham; Deep, Aman; Shi, Jiong; Dhall, Rohit; Shafer, Saulena; Moguel-Cobos, Guillermo; Dhillon, Ravneet; Frames, Christopher W; McCauley, Margaret

2018-02-01

Purpose/Aim of the study: To study finger displacement in patients with Parkinson disease dementia (PDD) and in patients with Alzheimer disease (AD). We examined 56 patients with PDD and 35 with AD. Patients were examined during their regular outpatient clinic visit. Finger displacement was measured by observers not actively involved in the study using a creative grid ruler for all PDD and AD patients. Finger displacement was examined by asking patients to point their index fingers toward the grid ruler with the nails facing upward. Patients were asked to maintain the pointing position for 15 s. After 15 s, patients were asked to close their eyes for another 15 s while maintaining the same position. A positive result was downward index finger displacement of ≥5 cm within the 15-second time window with eyes closed. Of the 56 PDD patients, 53 had bilateral finger displacement of >5 cm. In comparison, of the 35 AD patients, only 1 patient had minimal displacement. Results of the non-invasive finger displacement test may provide insight, on an outpatient basis, of the integrity of subcortical-cortical circuits. Downward finger displacement, especially bilateral downward displacement, may signal the extensive disruption of subcortical-cortical circuits that occurs in PDD patients. AChE: acetylcholinesterase; AD: Alzheimer disease; DLB: dementia with Lewy bodies; ET: essential tremor; MDS-UPDRS: Movement Disorder Society-sponsored Unified Parkinson's Disease Rating Scale; MMSE: Mini-Mental State Examination; PD: Parkinson disease; PDD: Parkinson disease dementia.

Evidence for adaptive cortical changes in swallowing in Parkinson's disease.

PubMed

Suntrup, Sonja; Teismann, Inga; Bejer, Joke; Suttrup, Inga; Winkels, Martin; Mehler, David; Pantev, Christo; Dziewas, Rainer; Warnecke, Tobias

2013-03-01

Dysphagia is a relevant symptom in Parkinson's disease, whose pathophysiology is poorly understood. It is mainly attributed to degeneration of brainstem nuclei. However, alterations in the cortical contribution to deglutition control in the course of Parkinson's disease have not been investigated. Here, we sought to determine the patterns of cortical swallowing processing in patients with Parkinson's disease with and without dysphagia. Swallowing function in patients was objectively assessed with fiberoptic endoscopic evaluation. Swallow-related cortical activation was measured using whole-head magnetoencephalography in 10 dysphagic and 10 non-dysphagic patients with Parkinson's disease and a healthy control group during self-paced swallowing. Data were analysed applying synthetic aperture magnetometry, and group analyses were done using a permutation test. Compared with healthy subjects, a strong decrease of cortical swallowing activation was found in all patients. It was most prominent in participants with manifest dysphagia. Non-dysphagic patients with Parkinson's disease showed a pronounced shift of peak activation towards lateral parts of the premotor, motor and inferolateral parietal cortex with reduced activation of the supplementary motor area. This pattern was not found in dysphagic patients with Parkinson's disease. We conclude that in Parkinson's disease, not only brainstem and basal ganglia circuits, but also cortical areas modulate swallowing function in a clinically relevant way. Our results point towards adaptive cerebral changes in swallowing to compensate for deficient motor pathways. Recruitment of better preserved parallel motor loops driven by sensory afferent input seems to maintain swallowing function until progressing neurodegeneration exceeds beyond the means of this adaptive strategy, resulting in manifestation of dysphagia.

[Metronome therapy in patients with Parkinson disease].

PubMed

Enzensberger, W; Oberländer, U; Stecker, K

1997-12-01

We studied 10 patients with Parkinson's disease and 12 patients with Parkinson-plus-syndrome, trying to improve patients' gait by application of various external rhythmic stimuli, including metronome stimulation (96 beats per minute = middle andante). The test course of the patients was 4 x 10 meters and 3 U-turns. The patients' gait quality under stimulation was compared with their free walk (velocity, number of steps, number of freezing episodes). Metronome stimulation significantly reduced the time and number of steps needed for the test course and also diminished the number of freezing episodes. March music stimulation was less effective and tactile stimulation (rhythmically tapping on the patient's shoulder) even produced negative results. The positive effect of metronome stimulation was also found, when the tests were not performed inside the hospital building, but outside in the hospital parc. Metronome stimulation was comparably effective in both patient sub-groups examined in this study (M. Parkinson, Parkinson-plus-syndrome) and seems to be an important additional help in the treatment of these patients. Electronical metronomes are not expensive, easy in handling, and portable. A theoretical explanation of metronome stimulation effectivity in patients with Parkinson's disease still needs to be elucidated.

Parkinson's: a syndrome rather than a disease?

PubMed

Titova, Nataliya; Padmakumar, C; Lewis, Simon J G; Chaudhuri, K Ray

2017-08-01

Emerging concepts suggest that a multitude of pathology ranging from misfolding of alpha-synuclein to neuroinflammation, mitochondrial dysfunction, and neurotransmitter driven alteration of brain neuronal networks lead to a syndrome that is commonly known as Parkinson's disease. The complex underlying pathology which may involve degeneration of non-dopaminergic pathways leads to the expression of a range of non-motor symptoms from the prodromal stage of Parkinson's to the palliative stage. Non-motor clinical subtypes, cognitive and non-cognitive, have now been proposed paving the way for possible subtype specific and non-motor treatments, a key unmet need currently. Natural history of these subtypes remains unclear and need to be defined. In addition to in vivo biomarkers which suggest variable involvement of the cholinergic and noradrenergic patterns of the Parkinson syndrome, abnormal alpha-synuclein accumulation have now been demonstrated in the gut, pancreas, heart, salivary glands, and skin suggesting that Parkinson's is a multi-organ disorder. The Parkinson's phenotype is thus not just a dopaminergic motor syndrome, but a dysfunctional multi-neurotransmitter pathway driven central and peripheral nervous system disorder that possibly ought to be considered a syndrome and not a disease.

Calcium Channel Antagonists as Disease-Modifying Therapy for Parkinson's Disease: Therapeutic Rationale and Current Status.

PubMed

Swart, Tara; Hurley, Michael J

2016-12-01

Parkinson's disease is a disabling hypokinetic neurological movement disorder in which the aetiology is unknown in the majority of cases. Current pharmacological treatments, though effective at restoring movement, are only symptomatic and do nothing to slow disease progression. Electrophysiological, epidemiological and neuropathological studies have implicated Ca V 1.3 subtype calcium channels in the pathogenesis of the disorder, and drugs with some selectivity for this ion channel (brain-penetrant dihydropyridine calcium channel blockers) are neuroprotective in animal models of the disease. Dihydropyridines have been safely used for decades to treat hypertension and other cardiovascular disorders. A phase II clinical trial found that isradipine was safely tolerated by patients with Parkinson's disease, and a phase III trial is currently underway to determine whether treatment with isradipine is neuroprotective and therefore able to slow the progression of Parkinson's disease. This manuscript reviews the current information about the use of dihydropyridines as therapy for Parkinson's disease and discusses the possible mechanism of action of these drugs, highlighting Ca V 1.3 calcium channels as a potential therapeutic target for neuroprotection in Parkinson's disease.

Prognosis of Parkinson disease: risk of dementia and mortality: the Rotterdam Study.

PubMed

de Lau, Lonneke M L; Schipper, C Maarten A; Hofman, Albert; Koudstaal, Peter J; Breteler, Monique M B

2005-08-01

Most prognostic studies on Parkinson disease have been hospital based or have applied register-based case-finding methods. Potential under-representation of mild cases may have given biased results. To evaluate whether Parkinson disease is associated with an increased risk of dementia and death. Population-based cohort study. Parkinson disease and dementia were assessed through in-person examination at baseline (1990-1993) and 2 follow-up visits (1993-1994 and 1997-1999). Computerized linkage to medical and municipality records provided additional information on disease outcomes and mortality. General population. A total of 6969 participants, including 99 prevalent and 67 incident cases of Parkinson disease. Incident dementia and death. Adjusted hazard ratios were calculated through Cox proportional hazards regression analysis. Patients with Parkinson disease had an increased risk of dementia (hazard ratio, 2.8; 95% confidence interval, 1.8-4.4), which was especially pronounced in participants carrying at least 1 apolipoprotein E gene (APOE) epsilon2 allele (13.5; 4.5-40.6). Parkinson disease was associated with an increased mortality risk (1.8; 1.5-2.3). The association consistently diminished when analyses were sequentially restricted to patients with shorter disease duration and after adjustment for the occurrence of dementia. Especially patients with Parkinson disease who carry an APOE epsilon2 allele have an increased risk of developing dementia. Increased mortality risk in Parkinson disease is dependent on disease duration and is only modest in the absence of dementia.

Drooling in Parkinson's Disease: Evidence of a Role for Divided Attention.

PubMed

Reynolds, Hannah; Miller, Nick; Walker, Richard

2018-05-21

Drooling is a frequently reported symptom in Parkinson's Disease (PD) with significant psychosocial impact and negative health consequences including silent aspiration of saliva with the associated risk of respiratory infections. It is suggested that in PD drooling is associated with inefficient oropharyngeal swallowing which reduces the effective clearance of saliva rather than hyper-salivation. This is compounded by unintended mouth opening and flexed posture increasing anterior loss of saliva. It is reported to occur most frequently during cognitively distracting concurrent tasks suggesting an impact from divided attention in a dual-task situation. However, this supposition has not been systematically examined. This study assessed whether frequency of saliva swallows reduced, and drooling severity and frequency increased, when people with PD engaged in a cognitively distracting task. 18 patients with idiopathic PD reporting daytime drooling on the Unified Parkinson's Disease Rating Scale (UPDRS) were recruited. They completed the Radboud Oral Motor Inventory for PD saliva questionnaire and the Montreal Cognitive Assessment. UPDRS drooling score, disease stage, duration, gender, and age were recorded. Swallow frequency and drooling severity and frequency were measured at rest and during a distracting computer-based language task. There was no significant difference between drooling severity at rest and during distraction (Wilcoxon signed rank test z = - 1.724, p = 0.085). There was a significant difference between at rest and distraction conditions for both drooling frequency (Wilcoxon signed rank test z = - 2.041, p = 0.041) and swallow frequency (Wilcoxon signed rank test z = - 3.054, p = 0.002). Participants swallowed less frequently and drooled more often during the distraction task. The frequency of saliva swallows and drooling are affected by divided attention in a dual-task paradigm. Further studies are needed to explore the

Management of Parkinson׳s disease: Current and future pharmacotherapy.

PubMed

Kakkar, Ashish Kumar; Dahiya, Neha

2015-03-05

Parkinson׳s disease (PD) is chronic progressive neurodegenerative disorder characterized by profound loss of dopaminergic neurons in the nigrostriatal pathway. It is recognized by the cardinal clinical features of bradykinesia, rigidity, tremor and postural instability. Current therapeutic options are primarily dopamine replacement strategies that only provide symptomatic improvement without affecting progressive neuronal loss. These treatments often fail to provide sustained clinical benefit and most patients develop motor fluctuations and dyskinesias as the disease progresses. Additionally, non-motor symptoms such as autonomic disturbances, sensory alterations, olfactory dysfunction, mood disorders, sleep disturbances and cognitive impairment cause considerable functional disability in these patients and these features often fail to respond to standard dopaminergic treatments. This mini review outlines the current pharmacotherapeutic options for PD and highlights the emerging experimental therapies in various phases of clinical development. Copyright © 2015 Elsevier B.V. All rights reserved.

Toxoplasma gondii exposure and Parkinson's disease: a case–control study

PubMed Central

Alvarado-Esquivel, Cosme; Méndez-Hernández, Edna Madai; Salas-Pacheco, José Manuel; Ruano-Calderón, Luis Ángel; Hernández-Tinoco, Jesús; Arias-Carrión, Oscar; Sánchez-Anguiano, Luis Francisco; Castellanos-Juárez, Francisco Xavier; Sandoval-Carrillo, Ada Agustina; Liesenfeld, Oliver; Ramos-Nevárez, Agar

2017-01-01

Objectives To determine the association between Toxoplasma gondii infection and Parkinson's disease and to investigate whether T. gondii seropositivity is associated with the general characteristics of patients with Parkinson's disease. Design Case–control study. Setting Cases and controls were enrolled in Durango City, Mexico. Participants 65 patients with Parkinson's disease and 195 age- and gender-matched control subjects without Parkinson's disease. Primary and secondary outcome measures Serum samples of participants were analysed for anti-T. gondii IgG and IgM antibodies by commercially available enzyme-linked immunoassays. Prevalence of T. gondii DNA was determined in seropositive subjects using PCR. The association between clinical data and infection was examined by bivariate analysis. Results Anti-T. gondii IgG antibodies were found in 6/65 cases (9.2%) and in 21/195 controls (10.8%) (OR 0.84; 95% CI 0.32 to 2.18; p=0.81). The frequency of high (>150 IU/mL) antibody levels was similar among cases and controls (p=0.34). None of the anti-T. gondii IgG positive cases and four of the anti-T. gondii IgG positive controls had anti-T. gondii IgM antibodies (p=0.54). The prevalence of T. gondii DNA was comparable in seropositive cases and controls (16.7% and 25%, respectively; p=1.0). Seroprevalence of T. gondii infection was associated with a young age onset of disease (p=0.03), high Unified Parkinson Disease Rating Scale scores (p=0.04) and depression (p=0.02). Seropositivity to T. gondii infection was lower in patients treated with pramipexole than in patients without this treatment (p=0.01). However, none of the associations remained significant after Bonferroni correction. Conclusions The results do not support an association between T. gondii infection and Parkinson's disease. However, T. gondii infection might have an influence on certain symptoms of Parkinson's disease. Further research to elucidate the role of T. gondii exposure on Parkinson's disease

Apathy and noradrenaline: silent partners to mild cognitive impairment in Parkinson's disease?

PubMed

Loued-Khenissi, Leyla; Preuschoff, Kerstin

2015-08-01

Mild cognitive impairment (MCI) is a comorbid factor in Parkinson's disease. The aim of this review is to examine the recent neuroimaging findings in the search for Parkinson's disease MCI (PD-MCI) biomarkers to gain insight on whether MCI and specific cognitive deficits in Parkinson's disease implicate striatal dopamine or another system. The evidence implicates a diffuse pathophysiology in PD-MCI rather than acute dopaminergic involvement. On the one hand, performance in specific cognitive domains, notably in set-shifting and learning, appears to vary with dopaminergic status. On the other hand, motivational states in Parkinson's disease along with their behavioral and physiological indices suggest a noradrenergic contribution to cognitive deficits in Parkinson's disease. Finally, Parkinson's disease's pattern of neurodegeneration offers an avenue for continued research in nigrostriatal dopamine's role in distinct behaviors, as well as the specification of dorsal and ventral striatal functions. The search for PD-MCI biomarkers has employed an array of neuroimaging techniques, but still yields divergent findings. This may be due in part to MCI's broad definition, encompassing heterogeneous cognitive domains, only some of which are affected in Parkinson's disease. Most domains falling under the MCI umbrella include fronto-dependent executive functions, whereas others, notably learning, rely on the basal ganglia. Given the deterioration of the nigrostriatal dopaminergic system in Parkinson's disease, it has been the prime target of PD-MCI investigation. By testing well defined cognitive deficits in Parkinson's disease, distinct functions can be attributed to specific neural systems, overcoming conflicting results on PD-MCI. Apart from dopamine, other systems such as the neurovascular or noradrenergic systems are affected in Parkinson's disease. These factors may be at the basis of specific facets of PD-MCI for which dopaminergic involvement has not been conclusive

Gait bradykinesia in Parkinson's disease: a change in the motor program which controls the synergy of gait.

PubMed

Warabi, Tateo; Furuyama, Hiroyasu; Sugai, Eri; Kato, Masamichi; Yanagisawa, Nobuo

2018-01-01

This study examined how gait bradykinesia is changed by the motor programming in Parkinson's disease. Thirty-five idiopathic Parkinson's disease patients and nine age-matched healthy subjects participated in this study. After the patients fixated on a visual-fixation target (conditioning-stimulus), the voluntary-gait was triggered by a visual on-stimulus. While the subject walked on a level floor, soleus, tibialis anterior EMG latencies, and the y-axis-vector of the sole-floor reaction force were examined. Three paradigms were used to distinguish between the off-/on-latencies. The gap-task: the visual-fixation target was turned off; 200 ms before the on-stimulus was engaged (resulting in a 200 ms-gap). EMG latency was not influenced by the visual-fixation target. The overlap-task: the on-stimulus was turned on during the visual-fixation target presentation (200 ms-overlap). The no-gap-task: the fixation target was turned off and the on-stimulus was turned on simultaneously. The onset of EMG pause following the tonic soleus EMG was defined as the off-latency of posture (termination). The onset of the tibialis anterior EMG burst was defined as the on-latency of gait (initiation). In the gap-task, the on-latency was unchanged in all of the subjects. In Parkinson's disease, the visual-fixation target prolonged both the off-/on-latencies in the overlap-task. In all tasks, the off-latency was prolonged and the off-/on-latencies were unsynchronized, which changed the synergic movement to a slow, short-step-gait. The synergy of gait was regulated by two independent sensory-motor programs of the off- and on-latency levels. In Parkinson's disease, the delayed gait initiation was due to the difficulty in terminating the sensory-motor program which controls the subject's fixation. The dynamic gait bradykinesia was involved in the difficulty (long off-latency) in terminating the motor program of the prior posture/movement.

Excessive burden of lysosomal storage disorder gene variants in Parkinson's disease.

PubMed

Robak, Laurie A; Jansen, Iris E; van Rooij, Jeroen; Uitterlinden, André G; Kraaij, Robert; Jankovic, Joseph; Heutink, Peter; Shulman, Joshua M

2017-12-01

Mutations in the glucocerebrosidase gene (GBA), which cause Gaucher disease, are also potent risk factors for Parkinson's disease. We examined whether a genetic burden of variants in other lysosomal storage disorder genes is more broadly associated with Parkinson's disease susceptibility. The sequence kernel association test was used to interrogate variant burden among 54 lysosomal storage disorder genes, leveraging whole exome sequencing data from 1156 Parkinson's disease cases and 1679 control subjects. We discovered a significant burden of rare, likely damaging lysosomal storage disorder gene variants in association with Parkinson's disease risk. The association signal was robust to the exclusion of GBA, and consistent results were obtained in two independent replication cohorts, including 436 cases and 169 controls with whole exome sequencing and an additional 6713 cases and 5964 controls with exome-wide genotyping. In secondary analyses designed to highlight the specific genes driving the aggregate signal, we confirmed associations at the GBA and SMPD1 loci and newly implicate CTSD, SLC17A5, and ASAH1 as candidate Parkinson's disease susceptibility genes. In our discovery cohort, the majority of Parkinson's disease cases (56%) have at least one putative damaging variant in a lysosomal storage disorder gene, and 21% carry multiple alleles. Our results highlight several promising new susceptibility loci and reinforce the importance of lysosomal mechanisms in Parkinson's disease pathogenesis. We suggest that multiple genetic hits may act in combination to degrade lysosomal function, enhancing Parkinson's disease susceptibility. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Bisphenol A glucuronidation in patients with Parkinson's disease.

PubMed

Landolfi, Annamaria; Troisi, Jacopo; Savanelli, Maria Cristina; Vitale, Carmine; Barone, Paolo; Amboni, Marianna

2017-12-01

Bisphenol A (BPA) is a widely distributed estrogen-mimetic molecule, with well-established effects on the dopaminergic system. It can be found in canned food, dental sealants, thermal paper, etc. BPA undergoes liver conjugation with glucuronic acid and is subsequently excreted in the urine. In the present study we quantified the concentration of free and conjugated Bisphenol A in blood of patients affected by Parkinson Disease, using their spouses as controls. An interview was performed to determine possible confounders in BPA exposure. Free and conjugated BPA were quantified by gas chromatography coupled with mass spectrometry. Parkinson's Disease patients carried a statistically significant lower amount of conjugated Bisphenol A compared to controls. The two populations were mostly homogeneous in terms of exposure to possible Bisphenol A sources. The only exceptions were exposure to canned tuna and canned tomatoes PD patients consumed significantly more of both (p<0.05). Moreover, no difference in Bisphenol A glucuronidation was found after stratification by typology of anti-Parkinson's drug taken and after conversion to the Levodopa Equivalent Daily Dose. BPA glucuronidation was decreased in patients with Parkinson disease. The possible unique mechanisms underlying Bisphenol A metabolism in PD patients deserve further elucidation. Moreover, further study is needed to assess a possible BPA role in Parkinson's Disease pathogenesis, due to its documented dopaminergic toxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

Intact emotion recognition and experience but dysfunctional emotion regulation in idiopathic Parkinson's disease.

PubMed

Ille, Rottraut; Wabnegger, Albert; Schwingenschuh, Petra; Katschnig-Winter, Petra; Kögl-Wallner, Mariella; Wenzel, Karoline; Schienle, Anne

2016-02-15

A specific non-motor impairment in Parkinson's disease (PD) concerns difficulties to accurately identify facial emotions. Findings are numerous but very inconsistent, ranging from general discrimination deficits to problems for specific emotions up to no impairment at all. By contrast, only a few studies exist about emotion experience, altered affective traits and states in PD. To investigate the decoding capacity for affective facial expressions, affective experience of emotion-eliciting images and affective personality traits in PD. The study sample included 25 patients with mild to moderate symptom intensity and 25 healthy controls (HC) of both sexes. The participants were shown pictures of facial expressions depicting disgust, fear, and anger as well as disgusting and fear-relevant scenes. Additionally, they answered self-report scales for the assessment of affective traits. PD patients had more problems in controlling anger and disgust feelings than HC. Higher disgust sensitivity in PD was associated with lower functioning in everyday life and lower capacity to recognize angry faces. Furthermore, patients reported less disgust towards poor hygiene and spoiled food and they stated elevated anxiety. However, the clinical group displayed intact facial emotion decoding and emotion experience. Everyday life functionality was lowered in PD and decreased with stronger motor impairment. Furthermore, disease duration was negatively associated to correct classification of angry faces. Our data indicate that problems with emotion regulation may appear already in earlier disease stages of PD. By contrast, PD patients showed appropriate emotion recognition and experience. However, data also point to a deterioration of emotion recognition capacity with the course of the disease. Compensatory mechanisms in PD patients with less advanced disease are discussed. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Evaluation of Parkinson disease and Alzheimer disease with the use of neuromelanin MR imaging and (123)I-metaiodobenzylguanidine scintigraphy.

PubMed

Miyoshi, F; Ogawa, T; Kitao, S-i; Kitayama, M; Shinohara, Y; Takasugi, M; Fujii, S; Kaminou, T

2013-01-01

Progressive changes in the substantia nigra pars compacta and locus ceruleus of patients with Parkinson disease and Alzheimer disease visualized by neuromelanin MRI and cardiac postganglionic sympathetic nerve function on (123)I-metaiodobenzylguanidine scintigraphy have not been fully evaluated. We compared the diagnostic value of these modalities among patients with early Parkinson disease, late Parkinson disease, and Alzheimer disease. We compared contrast ratios of signal intensity in medial and lateral regions of the substantia nigra pars compacta and locus ceruleus with those of the tegmentum of the midbrain and the pons, respectively, by use of neuromelanin MRI in patients with early Parkinson disease (n = 13), late Parkinson disease (n = 31), Alzheimer disease (n = 6), and age-matched healthy control subjects (n = 20). We calculated heart-to-mediastinum ratios on (123)I-metaiodobenzylguanidine scintigrams after setting regions of interest on the left cardiac ventricle and upper mediastinum. The signal intensity of the lateral substantia nigra pars compacta on neuromelanin MRI was significantly reduced in early and late Parkinson disease, and that of the medial substantia nigra pars compacta was gradually and stage-dependently reduced in Parkinson disease. The signal intensity of the locus ceruleus was obviously reduced in late Parkinson disease. Signal reduction was not significant in the substantia nigra pars compacta and locus ceruleus of patients with Alzheimer disease. The heart-to-mediastinum ratio on (123)I-metaiodobenzylguanidine scintigrams was stage-dependently reduced in Parkinson disease and normal in Alzheimer disease. The signal intensity ratios in substantia nigra pars compacta and locus ceruleus on neuromelanin MRI positively correlated with the heart-to-mediastinum ratio on (123)I-metaiodobenzylguanidine scintigrams. Both neuromelanin MRI and (123)I-metaiodobenzylguanidine scintigraphy can help to evaluate disease progression in Parkinson

Idiopathic orbital inflammatory disease successfully treated with rituximab.

PubMed

Schafranski, Marcelo Derbli

2009-02-01

We report a case of a 66-year-old Caucasian female with a diagnosis of idiopathic orbital inflammatory disease (OID) refractory to azathioprine therapy. The coexistence of diabetes mellitus represented a relative contraindication to chronic prednisone use. After two infusions of rituximab, a chimeric anti-CD20+ antibody, ophthalmic signs and symptoms remarkably improved. To our knowledge, this is the first case of idiopathic OID successfully treated with rituximab.

Pramipexole in the treatment of Parkinson's disease: new developments.

PubMed

Möller, J Carsten; Oertel, Wolfgang H

2005-09-01

The nonergot dopamine agonist pramipexole is an efficient and safe drug for the treatment of Parkinson's disease. Clinicians may favor pramipexole over other dopamine agonists because of its suggested higher tolerability with respect to peripheral dopaminergic side effects. Importantly, nonergot dopamine agonists such as pramipexole may not cause restrictive valvular heart disease and may therefore represent the first choice in patients with valvular lesions under treatment with ergot dopamine agonists. However, particular caution has to be exercised in younger Parkinson's disease patients with a shorter disease duration regarding the occurrence of sudden onset of sleep. In light of cost-effectiveness and quality-of-life issues, its final significance for the initial treatment of patients with early Parkinson's disease remains to be determined.

Virtual house calls for Parkinson disease (Connect.Parkinson): study protocol for a randomized, controlled trial.

PubMed

Achey, Meredith A; Beck, Christopher A; Beran, Denise B; Boyd, Cynthia M; Schmidt, Peter N; Willis, Allison W; Riggare, Sara S; Simone, Richard B; Biglan, Kevin M; Dorsey, E Ray

2014-11-27

Interest in improving care for the growing number of individuals with chronic conditions is rising. However, access to care is limited by distance, disability, and distribution of doctors. Small-scale studies in Parkinson disease, a prototypical chronic condition, have suggested that delivering care using video house calls is feasible, offers similar clinical outcomes to in-person care, and reduces travel burden. We are conducting a randomized comparative effectiveness study (Connect.Parkinson) comparing usual care in the community to usual care augmented by virtual house calls with a Parkinson disease specialist. Recruitment is completed centrally using online advertisements and emails and by contacting physicians, support groups, and allied health professionals. Efforts target areas with a high proportion of individuals not receiving care from neurologists. Approximately 200 individuals with Parkinson disease and their care partners will be enrolled at 20 centers throughout the United States and followed for one year. Participants receive educational materials, then are randomized in a 1:1 ratio to continue their usual care (control arm) or usual care and specialty care delivered virtually (intervention arm). Care partners are surveyed about their time and travel burden and their perceived caregiver burden. Participants are evaluated via electronic survey forms and videoconferencing with a blinded independent rater at baseline and at 12 months. All study activities are completed remotely.The primary outcomes are: (1) feasibility, as measured by the proportion of visits completed, and (2) quality of life, as measured by the 39-item Parkinson's Disease Questionnaire. Secondary outcomes include measures of clinical benefit, quality of care, time and travel burden, and caregiver burden. Connect.Parkinson will evaluate the feasibility and effectiveness of using technology to deliver care into the homes of individuals with Parkinson disease. The trial may serve as a

Counterfactual cognitive deficit in persons with Parkinson's disease

PubMed Central

McNamara, P; Durso, R; Brown, A; Lynch, A

2003-01-01

Background: Counterfactuals are mental representations of alternatives to past events. Recent research has shown them to be important for other cognitive processes, such as planning, causal reasoning, problem solving, and decision making—all processes independently linked to the frontal lobes. Objective: To test the hypothesis that counterfactual thinking is impaired in some patients with Parkinson's disease and is linked to frontal dysfunction in these patients. Methods. Measures of counterfactual processing and frontal lobe functioning were administered to 24 persons with Parkinson's disease and 15 age matched healthy controls. Results. Patients with Parkinson's disease spontaneously generated significantly fewer counterfactuals than controls despite showing no differences from controls on a semantic fluency test; they also performed at chance levels on a counterfactual inference test, while age matched controls performed above chance levels on this test. Performance on both the counterfactual generation and inference tests correlated significantly with performance on two tests traditionally linked to frontal lobe functioning (Stroop colour–word interference and Tower of London planning tasks) and one test of pragmatic social communication skills. Conclusions: Counterfactual thinking is impaired in Parkinson's disease. This impairment may be related to frontal lobe dysfunction. PMID:12876235

Emerging (and converging) pathways in Parkinson's disease: keeping mitochondrial wellness

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cieri, Domenico; Brini, Marisa; Calì, Tito

The selective cell loss in the ventral component of the substantia nigra pars compacta and the presence of alpha-synuclein (α-syn)-rich intraneuronal inclusions called Lewy bodies are the pathological hallmarks of Parkinson's disease (PD), the most common motor system disorder whose aetiology remains largely elusive. Although most cases of PD are idiopathic, there are rare familial forms of the disease that can be traced to single gene mutations that follow Mendelian inheritance pattern. The study of several nuclear encoded proteins whose mutations are linked to the development of autosomal recessive and dominant forms of familial PD enhanced our understanding of biochemicalmore » and cellular mechanisms contributing to the disease and suggested that many signs of neurodegeneration result from compromised mitochondrial function. Here we present an overview of the current understanding of PD-related mitochondrial dysfunction including defects in bioenergetics and Ca{sup 2+} homeostasis, mitochondrial DNA mutations, altered mitochondrial dynamics and autophagy. We emphasize, in particular, the convergence of many “apparently” different pathways towards a common route involving mitochondria. Understanding whether mitochondrial dysfunction in PD represents the cause or the consequence of the disease is challenging and will help to define the pathogenic processes at the basis of the PD onset and progression. - Highlights: • Mitochondrial dysfunctions are a common feature of neurodegenerative diseases. • Many familial PD related proteins ensure mitochondrial function. • Mutations in PD genes differently affect mitochondria related activities.« less

PARK10 is a major locus for sporadic neuropathologically confirmed Parkinson disease.

PubMed

Beecham, Gary W; Dickson, Dennis W; Scott, William K; Martin, Eden R; Schellenberg, Gerard; Nuytemans, Karen; Larson, Eric B; Buxbaum, Joseph D; Trojanowski, John Q; Van Deerlin, Vivianna M; Hurtig, Howard I; Mash, Deborah C; Beach, Thomas G; Troncoso, Juan C; Pletnikova, Olga; Frosch, Matthew P; Ghetti, Bernardino; Foroud, Tatiana M; Honig, Lawrence S; Marder, Karen; Vonsattel, Jean Paul; Goldman, Samuel M; Vinters, Harry V; Ross, Owen A; Wszolek, Zbigniew K; Wang, Liyong; Dykxhoorn, Derek M; Pericak-Vance, Margaret A; Montine, Thomas J; Leverenz, James B; Dawson, Ted M; Vance, Jeffery M

2015-03-10

To minimize pathologic heterogeneity in genetic studies of Parkinson disease (PD), the Autopsy-Confirmed Parkinson Disease Genetics Consortium conducted a genome-wide association study using both patients with neuropathologically confirmed PD and controls. Four hundred eighty-four cases and 1,145 controls met neuropathologic diagnostic criteria, were genotyped, and then imputed to 3,922,209 variants for genome-wide association study analysis. A small region on chromosome 1 was strongly associated with PD (rs10788972; p = 6.2 × 10(-8)). The association peak lies within and very close to the maximum linkage peaks of 2 prior positive linkage studies defining the PARK10 locus. We demonstrate that rs10788972 is in strong linkage disequilibrium with rs914722, the single nucleotide polymorphism defining the PARK10 haplotype previously shown to be significantly associated with age at onset in PD. The region containing the PARK10 locus was significantly reduced from 10.6 megabases to 100 kilobases and contains 4 known genes: TCEANC2, TMEM59, miR-4781, and LDLRAD1. We confirm the association of a PARK10 haplotype with the risk of developing idiopathic PD. Furthermore, we significantly reduce the size of the PARK10 region. None of the candidate genes in the new PARK10 region have been previously implicated in the biology of PD, suggesting new areas of potential research. This study strongly suggests that reducing pathologic heterogeneity may enhance the application of genetic association studies to PD. © 2015 American Academy of Neurology.

PARK10 is a major locus for sporadic neuropathologically confirmed Parkinson disease

PubMed Central

Beecham, Gary W.; Dickson, Dennis W.; Scott, William K.; Martin, Eden R.; Schellenberg, Gerard; Nuytemans, Karen; Larson, Eric B.; Buxbaum, Joseph D.; Trojanowski, John Q.; Van Deerlin, Vivianna M.; Hurtig, Howard I.; Mash, Deborah C.; Beach, Thomas G.; Troncoso, Juan C.; Pletnikova, Olga; Frosch, Matthew P.; Ghetti, Bernardino; Foroud, Tatiana M.; Honig, Lawrence S.; Marder, Karen; Vonsattel, Jean Paul; Goldman, Samuel M.; Vinters, Harry V.; Ross, Owen A.; Wszolek, Zbigniew K.; Wang, Liyong; Dykxhoorn, Derek M.; Pericak-Vance, Margaret A.; Montine, Thomas J.; Leverenz, James B.; Dawson, Ted M.

2015-01-01

Objective: To minimize pathologic heterogeneity in genetic studies of Parkinson disease (PD), the Autopsy-Confirmed Parkinson Disease Genetics Consortium conducted a genome-wide association study using both patients with neuropathologically confirmed PD and controls. Methods: Four hundred eighty-four cases and 1,145 controls met neuropathologic diagnostic criteria, were genotyped, and then imputed to 3,922,209 variants for genome-wide association study analysis. Results: A small region on chromosome 1 was strongly associated with PD (rs10788972; p = 6.2 × 10−8). The association peak lies within and very close to the maximum linkage peaks of 2 prior positive linkage studies defining the PARK10 locus. We demonstrate that rs10788972 is in strong linkage disequilibrium with rs914722, the single nucleotide polymorphism defining the PARK10 haplotype previously shown to be significantly associated with age at onset in PD. The region containing the PARK10 locus was significantly reduced from 10.6 megabases to 100 kilobases and contains 4 known genes: TCEANC2, TMEM59, miR-4781, and LDLRAD1. Conclusions: We confirm the association of a PARK10 haplotype with the risk of developing idiopathic PD. Furthermore, we significantly reduce the size of the PARK10 region. None of the candidate genes in the new PARK10 region have been previously implicated in the biology of PD, suggesting new areas of potential research. This study strongly suggests that reducing pathologic heterogeneity may enhance the application of genetic association studies to PD. PMID:25663231

Michael J. Fox and his Parkinson's disease.

PubMed

Kempster, Peter A

2004-01-01

Michael J. Fox was a popular and successful film and television comic actor who developed Parkinson's disease at the age of 29 years. His recently published book, Lucky Man, structured around the story of his Parkinson's disease, is an amusing, briskly paced yet introspective memoir that covers the first 40 years of his life. Although quite anecdotal, it contains interesting observations on the preclinical phase of the disorder, evolution of motor fluctuations, and tactics for pharmacological treatment. Copyright 2003 Movement Disorder Society

Altered moral decision-making in patients with idiopathic Parkinson's disease.

PubMed

Rosen, Jan B; Rott, Elisa; Ebersbach, Georg; Kalbe, Elke

2015-10-01

Moral decision-making essentially contributes to social conduct. Although patients with Parkinson's disease (PD) show deficits in (non-moral) decision making and related neuropsychological functions, i.e. executive functions, theory of mind (ToM), and empathy, moral decision-making has rarely been examined in PD patients. We examined possible alterations of moral decision-making and associated functions in PD. Twenty non-demented PD patients and 23 age- and education-matched healthy control participants were examined with tests that assess reasoning, executive functions (set-shifting and planning), ToM and empathy, decision-making under risk, and moral intuitions. Moral decision-making was assessed with a close-to-everyday moral dilemma paradigm that opposes socially oriented "altruistic" choices to self-beneficial "egoistic" choices in 20 moral dilemma short stories (10 high and 10 low emotional). Concurrently, electrodermal activity was recorded. PD patients made more egoistic moral decisions than healthy controls. Remarkably, while reasoning, planning and empathy correlated with moral decision-making in the control group, in the PD group neuropsychological functions and dopaminergic medication did not correlate with moral decisions. No evidence for reduced skin conductance responses in PD patients and no relationships between skin conductance responses and moral decisions were observed. This study provides evidence for moral decision-making dysfunctions in PD patients who made more egoistic moral decisions. As a possible underlying mechanism, reduced exercise of attentional control due to a dysfunctional interplay between the prefrontal cortex and the basal ganglia is discussed. Future research will have to determine the impact of PD patients' moral decision-making dysfunctions on everyday life and further determine correlates of the deficits. Copyright © 2015 Elsevier Ltd. All rights reserved.

Parkinson's disease as a system-level disorder.

PubMed

Caligiore, Daniele; Helmich, Rick C; Hallett, Mark; Moustafa, Ahmed A; Timmermann, Lars; Toni, Ivan; Baldassarre, Gianluca

2016-01-01

Traditionally, the basal ganglia have been considered the main brain region implicated in Parkinson's disease. This single area perspective gives a restricted clinical picture and limits therapeutic approaches because it ignores the influence of altered interactions between the basal ganglia and other cerebral components on Parkinsonian symptoms. In particular, the basal ganglia work closely in concert with cortex and cerebellum to support motor and cognitive functions. This article proposes a theoretical framework for understanding Parkinson's disease as caused by the dysfunction of the entire basal ganglia-cortex-cerebellum system rather than by the basal ganglia in isolation. In particular, building on recent evidence, we propose that the three key symptoms of tremor, freezing, and impairments in action sequencing may be explained by considering partially overlapping neural circuits including basal ganglia, cortical and cerebellar areas. Studying the involvement of this system in Parkinson's disease is a crucial step for devising innovative therapeutic approaches targeting it rather than only the basal ganglia. Possible future therapies based on this different view of the disease are discussed.

Clear Speech Variants: An Acoustic Study in Parkinson's Disease

ERIC Educational Resources Information Center

Lam, Jennifer; Tjaden, Kris

2016-01-01

Purpose: The authors investigated how different variants of clear speech affect segmental and suprasegmental acoustic measures of speech in speakers with Parkinson's disease and a healthy control group. Method: A total of 14 participants with Parkinson's disease and 14 control participants served as speakers. Each speaker produced 18 different…

Deductive and inductive reasoning in Parkinson's disease patients and normal controls: review and experimental evidence.

PubMed

Natsopoulos, D; Katsarou, Z; Alevriadou, A; Grouios, G; Bostantzopoulou, S; Mentenopoulos, G

1997-09-01

In the present study, fifty-four subjects were tested; twenty-seven with idiopathic Parkinson's disease and twenty-seven normal controls matched in age, education, verbal ability, level of depression, sex and socio-economic status. The subjects were tested on eight tasks. Five of the tasks were the classic deductive reasoning syllogisms, modus ponens, modus tollendo tollens, affirming the consequent, denying the antecedent and three-term series problems phrased in a factual context (brief scripts). Three of the tasks were inductive reasoning, including logical inferences, metaphors and similes. All tasks were presented to subjects in a multiple choice format. The results, overall, have shown nonsignificant differences between the two groups in deductive and inductive reasoning, an ability traditionally associated with frontal lobes involvement. Of the comparisons performed between subgroups of the patients and normal controls concerning disease duration, disease onset and predominant involvement of the left and/or right hemisphere, significant differences were found between patients with earlier disease onset and normal controls and between bilaterally affected patients and normal controls, demonstrating an additive effect of lateralization to reasoning ability.

Ambroxol improves lysosomal biochemistry in glucocerebrosidase mutation-linked Parkinson disease cells.

PubMed

McNeill, Alisdair; Magalhaes, Joana; Shen, Chengguo; Chau, Kai-Yin; Hughes, Derralyn; Mehta, Atul; Foltynie, Tom; Cooper, J Mark; Abramov, Andrey Y; Gegg, Matthew; Schapira, Anthony H V

2014-05-01

Gaucher disease is caused by mutations in the glucocerebrosidase gene, which encodes the lysosomal hydrolase glucosylceramidase. Patients with Gaucher disease and heterozygous glucocerebrosidase mutation carriers are at increased risk of developing Parkinson's disease. Indeed, glucocerebrosidase mutations are the most frequent risk factor for Parkinson's disease in the general population. Therefore there is an urgent need to understand the mechanisms by which glucocerebrosidase mutations predispose to neurodegeneration to facilitate development of novel treatments. To study this we generated fibroblast lines from skin biopsies of five patients with Gaucher disease and six heterozygous glucocerebrosidase mutation carriers with and without Parkinson's disease. Glucosylceramidase protein and enzyme activity levels were assayed. Oxidative stress was assayed by single cell imaging of dihydroethidium. Glucosylceramidase enzyme activity was significantly reduced in fibroblasts from patients with Gaucher disease (median 5% of controls, P = 0.0001) and heterozygous mutation carriers with (median 59% of controls, P = 0.001) and without (56% of controls, P = 0.001) Parkinson's disease compared with controls. Glucosylceramidase protein levels, assessed by western blot, were significantly reduced in fibroblasts from Gaucher disease (median glucosylceramidase levels 42% of control, P < 0.001) and heterozygous mutation carriers with (median 59% of control, P < 0.001) and without (median 68% of control, P < 0.001) Parkinson's disease. Single cell imaging of dihydroethidium demonstrated increased production of cytosolic reactive oxygen species in fibroblasts from patients with Gaucher disease (dihydroethidium oxidation rate increased by a median of 62% compared to controls, P < 0.001) and heterozygous mutation carriers with (dihydroethidium oxidation rate increased by a median of 68% compared with controls, P < 0.001) and without (dihydroethidium oxidation rate increased by a

The intrinsic resting state voice network in Parkinson's disease

PubMed Central

New, Anneliese B.; Parkinson, Amy L.; Eickhoff, Claudia R.; Reetz, Kathrin; Hoffstaedter, Felix; Mathys, Christian; Sudmeyer, Martin; Michely, Jochen; Caspers, Julian; Grefkes, Christian; Larson, Charles R.; Ramig, Loraine O.; Fox, Peter T.; Eickhoff, Simon B.

2015-01-01

Abstract Over 90 percent of patients with Parkinson's disease experience speech‐motor impairment, namely, hypokinetic dysarthria characterized by reduced pitch and loudness. Resting‐state functional connectivity analysis of blood oxygen level‐dependent functional magnetic resonance imaging is a useful measure of intrinsic neural functioning. We utilized resting‐state functional connectivity modeling to analyze the intrinsic connectivity in patients with Parkinson's disease within a vocalization network defined by a previous meta‐analysis of speech (Brown et al., 2009). Functional connectivity of this network was assessed in 56 patients with Parkinson's disease and 56 gender‐, age‐, and movement‐matched healthy controls. We also had item 5 and 18 of the UPDRS, and the PDQ‐39 Communication subscale available for correlation with the voice network connectivity strength in patients. The within‐group analyses of connectivity patterns demonstrated a lack of subcortical–cortical connectivity in patients with Parkinson's disease. At the cortical level, we found robust (homotopic) interhemispheric connectivity but only inconsistent evidence for many intrahemispheric connections. When directly contrasted to the control group, we found a significant reduction of connections between the left thalamus and putamen, and cortical motor areas, as well as reduced right superior temporal gyrus connectivity. Furthermore, most symptom measures correlated with right putamen, left cerebellum, left superior temporal gyrus, right premotor, and left Rolandic operculum connectivity in the voice network. The results reflect the importance of (right) subcortical nodes and the superior temporal gyrus in Parkinson's disease, enhancing our understanding of the neurobiological underpinnings of vocalization impairment in Parkinson's disease. Hum Brain Mapp 36:1951–1962, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.. PMID:25627959

Parkin in Parkinson's Disease and Cancer: a Double-Edged Sword.

PubMed

Wahabi, Khushnuma; Perwez, Ahmad; Rizvi, Moshahid A

2018-01-18

Parkin for more than a decade has been portrayed as a neuroprotector gene is now increasingly emerging as a multifaceted gene that can exert entirely opposite effects i.e., both cell proliferation and apoptosis. Parkinson's disease, a neurological disease, progresses due to excess in cell death, while, in case of cancer, cell death normally fails to occur. Parkin, an E3 ubiquitin ligase, was first identified as a gene implicated in autosomal recessive juvenile Parkinsonism, but several evidences indicate that Parkin is a tumor suppressor gene, involved in a variety of cancers. It is hard to imagine that two entirely different classes of disease, like cancer and Parkinson's disease, can converge at a critical point attributable to a single gene, Parkin. This mysterious and hidden connection may prove a boon in disguise and has raised hopes that studying the biology of one disease may help to identify novel targets of therapy for the other. In this Parkinson's disease-cancer story, if the detail of Parkin pathway is unraveled and gaps in the storyline are properly filled up, we may end getting an entirely new therapeutic option. This review mainly highlights the recent literature which suggests how Parkin gene regulates the various hallmarks of both the Parkinson's disease and cancer.

[Juvenile Parkinson's disease and recurring prematurity. Case report].

PubMed

Ha, D-E; Legendre, G; Colau, J-C

2007-03-01

The association of Parkinson's disease and pregnancy is very rare. Some thirty cases are found in the literature. We report the case of a pregnancy in a 30-year-old patient with juvenile Parkinson's disease. During this pregnancy treated by levodopa and bromocriptine, no aggravation of the symptoms was been observed. However, the pregnancy was complicated by a premature delivery at 31 weeks of amenorrhoea.

[Morphochemical changes in the substantia nigra cellular structures in Parkinson's disease].

PubMed

Salkov, V N; Khudoerkov, R M; Voronkov, D N; Sobolev, V B; Kutukova, K A

to clarify the features of morphochemical changes in the substantia nigra cellular structures in Parkinson's disease. The structural characteristics of the substantia nigra were studied microscopically and quantified using computer morphometric methods at brain autopsies of individuals with Parkinson's disease who had died from intercurrent diseases and those who had no evidence of neurological disorders in their history (a control group). This investigation could clarify the features of morphochemical changes in both the neural network structures and the glial populations of the substantia nigra in Parkinson's disease. The number of neurons containing tyrosine hydroxylase (a marker of dopamine neurons) in the compact part of the substantia nigra (a ventral region) was smaller and the density distribution of Lewy bodies was higher in the patients with Parkinson's disease than in the control group. The accumulation of iron (II) compounds in the cellular elements and neuropile and the increased expression of glial fibrillary acidic protein in Parkinson's disease were more pronounced than those in the controls. Postmortem diagnosis in Parkinson's disease should be based on a full description of a set of neuronal and glial morphochemical and structural changes in the substantia nigra rather than on the identification of cellular markers for the neurodegenerative process.

Stereotaxical Infusion of Rotenone: A Reliable Rodent Model for Parkinson's Disease

PubMed Central

Xiong, Nian; Huang, Jinsha; Zhang, Zhentao; Zhang, Zhaowen; Xiong, Jing; Liu, Xingyuan; Jia, Min; Wang, Fang; Chen, Chunnuan; Cao, Xuebing; Liang, Zhihou; Sun, Shenggang; Lin, Zhicheng; Wang, Tao

2009-01-01

A clinically-related animal model of Parkinson's disease (PD) may enable the elucidation of the etiology of the disease and assist the development of medications. However, none of the current neurotoxin-based models recapitulates the main clinical features of the disease or the pathological hallmarks, such as dopamine (DA) neuron specificity of degeneration and Lewy body formation, which limits the use of these models in PD research. To overcome these limitations, we developed a rat model by stereotaxically (ST) infusing small doses of the mitochondrial complex-I inhibitor, rotenone, into two brain sites: the right ventral tegmental area and the substantia nigra. Four weeks after ST rotenone administration, tyrosine hydroxylase (TH) immunoreactivity in the infusion side decreased by 43.7%, in contrast to a 75.8% decrease observed in rats treated systemically with rotenone (SYS). The rotenone infusion also reduced the DA content, the glutathione and superoxide dismutase activities, and induced alpha-synuclein expression, when compared to the contralateral side. This ST model displays neither peripheral toxicity or mortality and has a high success rate. This rotenone-based ST model thus recapitulates the slow and specific loss of DA neurons and better mimics the clinical features of idiopathic PD, representing a reliable and more clinically-related model for PD research. PMID:19924288

McArdle's disease: A differential diagnosis of idiopathic toe walking.

PubMed

Pomarino, David; Martin, Stephan; Pomarino, Andrea; Morigeau, Stefanie; Biskup, Saskia

2018-06-01

Idiopathic toe walking (ITW) is a pathological gait pattern in which children walk on their tip toes with no orthopedic or neurological reason. Physiological characteristics of the gastrocnemius muscles, the Achilles tendon, and the foot of toe walkers differ from subjects with a plantigrade walking pattern. McArdle's disease is characterized by the inability to break down muscle glycogen. It is an autosomal-recessive condition, characterized by low exercise tolerance, muscular atrophy at the shoulder girdle, episodes of myoglobinuria after vigorous physical activities and the occurrence of the second wind phenomenon. The aim of this review is to present the case studies of two subjects who were originally diagnosed as idiopathic toe walkers, but were then found to have McArdle's disease. This review will describe some physical characteristics that distinguish McArdle´s disease from Idiopathic toe walkers.

Spotlight on rotigotine transdermal patch in Parkinson's disease.

PubMed

Sanford, Mark; Scott, Lesley J

2011-12-01

Rotigotine transdermal patch (Neupro(®)) [referred to here as rotigotine] is a non-ergolinic dopamine agonist that is available in the EU as monotherapy for the treatment of early Parkinson's disease and as combination therapy with levodopa throughout the course of the disease. Daily application of the rotigotine patch provided predictable release and absorption of rotigotine, with steady-state rotigotine concentrations reached within 1-2 days. In early Parkinson's disease, compared with placebo, rotigotine monotherapy produced significantly greater improvements in the Unified Parkinson's Disease Rating Scale summed motor and activities of daily living (ADL) scores (primary endpoint), as well as significantly higher response rates. In advanced Parkinson's disease, rotigotine in combination with levodopa reduced 'off' time (primary endpoint) and improved motor functioning and ADL significantly more than levodopa plus placebo. In patients with inadequate early morning motor control despite antiparkinsonian treatment, rotigotine improved morning motor functioning and reduced sleep disturbances, night-time motor symptoms, depressive symptoms, pain and functioning, and quality of life to a significantly greater extent than placebo. The efficacy of rotigotine relative to other treatments requires further evaluation, as there were inconsistent results in noninferiority analyses that compared rotigotine to other dopamine agonists. Rotigotine was generally well tolerated across the trials, with the most common treatment-emergent adverse events being application-site reactions, gastrointestinal disturbances, somnolence and headache. No unexpected adverse effects were observed in extension studies of up to 6 years. Thus, rotigotine offers a novel approach to the treatment of Parkinson's disease and, given its ease of administration, efficacy in reducing disabling motor and non-motor symptoms, and acceptable tolerability profile, it has the potential to be an attractive

Medication use in people with late stage Parkinson's disease and parkinsonism living at home and in institutional care in north-east England: A balance of symptoms and side-effects?

PubMed

Hand, Annette; Gray, William K; Oates, Lloyd L; Woolford, Megan; Todd, Anna; Bale, Elizabeth; Jones, Catherine; Wood, Brian H; Walker, Richard W

2016-11-01

People with Parkinson's disease (PD) and parkinsonism living in care homes (residential or nursing care) in the UK represent around 10-15% of all people with PD and 3-5% of all care home residents. There are few previous data on medication use in those living in care homes with PD. In this study we aimed to compare medication use in a representative cohort of people with PD living in care homes in north-east England with those living in their own homes. All people with late stage (Hoehn and Yahr III-V) idiopathic PD, PD dementia, or atypical parkinsonian syndromes under the care of the Northumbria Healthcare NHS Foundation Trust PD service on 1st January 2015 were identified. Demographic, disease characteristics and medication use data were collected from an audit of medical notes of all those identified. We identified 377 people who met the inclusion criteria, 91 (24.1%) of whom were living in a care home. Disease stage, age and age at disease onset were all significantly higher and levodopa equivalent dose significantly lower in those living in care homes, although disease duration and levodopa dose were not. Greater age, lower levodopa equivalent dose and higher disease stage were independently associated with being in a care home. Although people in care homes had more advanced disease, they were on a significantly lower levodopa equivalent dose. This is likely to be due to the requirement to balance symptom management with drug side-effects. Copyright © 2016 Elsevier Ltd. All rights reserved.

Astrocyte-specific DJ-1 overexpression protects against rotenone-induced neurotoxicity in a rat model of Parkinson's disease.

PubMed

De Miranda, Briana R; Rocha, Emily M; Bai, Qing; El Ayadi, Amina; Hinkle, David; Burton, Edward A; Timothy Greenamyre, J

2018-07-01

DJ-1 is a redox-sensitive protein with several putative functions important in mitochondrial physiology, protein transcription, proteasome regulation, and chaperone activity. High levels of DJ-1 immunoreactivity are reported in astrocytes surrounding pathology associated with idiopathic Parkinson's disease, possibly reflecting the glial response to oxidative damage. Previous studies showed that astrocytic over-expression of DJ-1 in vitro prevented oxidative stress and mitochondrial dysfunction in primary neurons. Based on these observations, we developed a pseudotyped lentiviral gene transfer vector with specific tropism for CNS astrocytes in vivo to overexpress human DJ-1 protein in astroglial cells. Following vector delivery to the substantia nigra and striatum of adult Lewis rats, the DJ-1 transgene was expressed robustly and specifically within astrocytes. There was no observable transgene expression in neurons or other glial cell types. Three weeks after vector infusion, animals were exposed to rotenone to induce Parkinson's disease-like pathology, including loss of dopaminergic neurons, accumulation of endogenous α-synuclein, and neuroinflammation. Animals over-expressing hDJ-1 in astrocytes were protected from rotenone-induced neurodegeneration, and displayed a marked reduction in neuronal oxidative stress and microglial activation. In addition, α-synuclein accumulation and phosphorylation were decreased within substantia nigra dopaminergic neurons in DJ-1-transduced animals, and expression of LAMP-2A, a marker of chaperone mediated autophagy, was increased. Together, these data indicate that astrocyte-specific overexpression of hDJ-1 protects neighboring neurons against multiple pathologic features of Parkinson's disease and provides the first direct evidence in vivo of a cell non-autonomous neuroprotective function of astroglial DJ-1. Copyright © 2018 Elsevier Inc. All rights reserved.

Laterality of repetitive finger movement performance and clinical features of Parkinson's disease.

PubMed

Stegemöller, Elizabeth; Zaman, Andrew; MacKinnon, Colum D; Tillman, Mark D; Hass, Chris J; Okun, Michael S

2016-10-01

Impairments in acoustically cued repetitive finger movement often emerge at rates near to and above 2Hz in persons with Parkinson's Disease (PD) in which some patients move faster (hastening) and others move slower (bradykinetic). The clinical features impacting this differential performance of repetitive finger movement remain unknown. The purpose of this study was to compare repetitive finger movement performance between the more and less affected side, and the difference in clinical ratings among performance groups. Forty-one participants diagnosed with idiopathic PD completed an acoustically cued repetitive finger movement task while "on" medication. Eighteen participants moved faster, 10 moved slower, and 13 were able to maintain the appropriate rate at rates above 2Hz. Clinical measures of laterality, disease severity, and the UPDRS were obtained. There were no significant differences between the more and less affected sides regardless of performance group. Comparison of disease severity, tremor, and rigidity among performance groups revealed no significant differences. Comparison of posture and postural instability scores revealed that the participants that demonstrated hastening had worse posture and postural instability scores. Consideration of movement rate during the clinical evaluation of repetitive finger movement may provide additional insight into varying disease features in persons with PD. Copyright © 2016 Elsevier B.V. All rights reserved.

Management of dysphagia in Parkinson's disease and amyotrophic lateral sclerosis.

PubMed

Luchesi, Karen Fontes; Kitamura, Satoshi; Mourão, Lucia Figueiredo

2013-01-01

To describe swallowing management in patients with amyotrophic lateral sclerosis (ALS) and Parkinson' disease (PD), to investigate whether physiopathology determines the choice of therapeutic approaches, and to investigate whether the disease duration modifies the therapeutic approaches. This is a long-term study comprising 24 patients with idiopathic PD and 27 patients with ALS. The patients were followed-up in a dysphagia outpatient clinic between 2006 and 2011. The patients underwent clinic evaluation and Fiberoptic Endoscopic Evaluation of Swallowing, Functional Oral Intake Scale, and therapeutic intervention every 3 months. The swallowing management was based on orientation about the adequate food consistency and volume, besides the necessary maneuvers or exercises to improve swallowing functionality. An exploratory analysis of data was used to investigate associations between the groups of disease (PD or ALS) and clinic aspects and to know about the association between the groups of diseases and the application of maneuver or exercises over the follow-up. The most frequent recommended maneuvers in PD were bolus effect (83.3%), bolus consistency (79.2%), and swallowing frequency (79%). To patients with ALS, the bolus consistency (92%) and the bolus effect (74.1%) were more recommended. Strengthening-tongue (p=0.01), tongue control (p=0.05), and vocal exercises (p<0.001) were significantly more recommended in PD than in ALS. Compensatory and sensorial maneuvers are more recommended to rehabilitee program in both diseases. The physiopathology of the diseases determined the choice of therapeutic approaches. The disease duration of the patients did not interfere directly in the therapeutic approaches.

Parkinson's disease: the spectrum of disabilities.

PubMed Central

Pentland, B; Barnes, M P; Findley, L J; Oxtoby, M; Pearce, V R; Quinn, N P; Scott, S

1992-01-01

The needs of people with Parkinson's disease (PD) go beyond the purely medical domain and often require collaborative management. A Panel Discussion at the "Hither neurology" Symposium included neurologists, a speech therapist, a geriatrician and a sociologist. Their discussion highlighted certain aspects of the disability and disadvantage associated with PD. The starting point was a video recording, "Parkinson's Disease: the personal view", in which the contributors were patients and carers. Topics covered included counselling at the time of diagnosis; subsequent access to clinics and to neurological advice; access to therapy; support in the community; fluctuating disability associated with "on-off" phenomena; driving; and sexual problems. PMID:1564503

[Nature of speech disorders in Parkinson disease].

PubMed

Pawlukowska, W; Honczarenko, K; Gołąb-Janowska, M

2013-01-01

The aim of the study was to discuss physiology and pathology of speech and review of the literature on speech disorders in Parkinson disease. Additionally, the most effective methods to diagnose the speech disorders in Parkinson disease were also stressed. Afterward, articulatory, respiratory, acoustic and pragmatic factors contributing to the exacerbation of the speech disorders were discussed. Furthermore, the study dealt with the most important types of speech treatment techniques available (pharmacological and behavioral) and a significance of Lee Silverman Voice Treatment was highlighted.

Restless legs syndrome: an early clinical feature of Parkinson disease in men.

PubMed

Wong, Janice C; Li, Yanping; Schwarzschild, Michael A; Ascherio, Alberto; Gao, Xiang

2014-02-01

The association between restless legs syndrome (RLS) and Parkinson disease has been extensively studied, but the temporal relationship between the two remains unclear. We thus conduct the first prospective study to examine the risk of developing Parkinson disease in RLS. Prospective study from 2002-2010. United States. There were 22,999 US male health professionals age 40-75 y enrolled in the Health Professionals Follow-up Study without Parkinson disease, arthritis, or diabetes mellitus at baseline. RLS was assessed in 2002 using a set of standardized questions recommended by the International RLS Study Group. Incident Parkinson disease was identified by biennial questionnaires and then confirmed by review of participants' medical records by a movement disorder specialist. We documented 200 incident Parkinson disease cases during 8 y of follow-up. Compared to men without RLS, men with RLS symptoms who had symptoms greater than 15 times/mo had higher risk of Parkinson disease development (adjusted relative risk = 1.47; 95% confidence interval: 0.59, 3.65; P = 0.41). This was statistically significant only for cases diagnosed within 4 y of follow-up (adjusted relative risk = 2.77; 95% confidence interval: 1.08, 7.11; P = 0.03). Severe restless legs syndrome may be an early feature of Parkinson disease.

Predicting early cognitive decline in newly-diagnosed Parkinson's patients: A practical model.

PubMed

Hogue, Olivia; Fernandez, Hubert H; Floden, Darlene P

2018-06-19

To create a multivariable model to predict early cognitive decline among de novo patients with Parkinson's disease, using brief, inexpensive assessments that are easily incorporated into clinical flow. Data for 351 drug-naïve patients diagnosed with idiopathic Parkinson's disease were obtained from the Parkinson's Progression Markers Initiative. Baseline demographic, disease history, motor, and non-motor features were considered as candidate predictors. Best subsets selection was used to determine the multivariable baseline symptom profile that most accurately predicted individual cognitive decline within three years. Eleven per cent of the sample experienced cognitive decline. The final logistic regression model predicting decline included five baseline variables: verbal memory retention, right-sided bradykinesia, years of education, subjective report of cognitive impairment, and REM behavior disorder. Model discrimination was good (optimism-adjusted concordance index = .749). The associated nomogram provides a tool to determine individual patient risk of meaningful cognitive change in the early stages of the disease. Through the consideration of easily-implemented or routinely-gathered assessments, we have identified a multidimensional baseline profile and created a convenient, inexpensive tool to predict cognitive decline in the earliest stages of Parkinson's disease. The use of this tool would generate prediction at the individual level, allowing clinicians to tailor medical management for each patient and identify at-risk patients for clinical trials aimed at disease modifying therapies. Copyright © 2018. Published by Elsevier Ltd.

Progression marker of Parkinson's disease: a 4-year multi-site imaging study.

PubMed

Burciu, Roxana G; Ofori, Edward; Archer, Derek B; Wu, Samuel S; Pasternak, Ofer; McFarland, Nikolaus R; Okun, Michael S; Vaillancourt, David E

2017-08-01

Progression markers of Parkinson's disease are crucial for successful therapeutic development. Recently, a diffusion magnetic resonance imaging analysis technique using a bitensor model was introduced allowing the estimation of the fractional volume of free water within a voxel, which is expected to increase in neurodegenerative disorders such as Parkinson's disease. Prior work demonstrated that free water in the posterior substantia nigra was elevated in Parkinson's disease compared to controls across single- and multi-site cohorts, and increased over 1 year in Parkinson's disease but not in controls at a single site. Here, the goal was to validate free water in the posterior substantia nigra as a progression marker in Parkinson's disease, and describe the pattern of progression of free water in patients with a 4-year follow-up tested in a multicentre international longitudinal study of de novo Parkinson's disease (http://www.ppmi-info.org/). The analyses examined: (i) 1-year changes in free water in 103 de novo patients with Parkinson's disease and 49 controls; (ii) 2- and 4-year changes in free water in a subset of 46 patients with Parkinson's disease imaged at baseline, 12, 24, and 48 months; (iii) whether 1- and 2-year changes in free water predict 4-year changes in the Hoehn and Yahr scale; and (iv) the relationship between 4-year changes in free water and striatal binding ratio in a subgroup of Parkinson's disease who had undergone both diffusion and dopamine transporter imaging. Results demonstrated that: (i) free water level in the posterior substantia nigra increased over 1 year in de novo Parkinson's disease but not in controls; (ii) free water kept increasing over 4 years in Parkinson's disease; (iii) sex and baseline free water predicted 4-year changes in free water; (iv) free water increases over 1 and 2 years were related to worsening on the Hoehn and Yahr scale over 4 years; and (v) the 4-year increase in free water was associated with the 4-year

Parkinson's disease: current and future challenges.

PubMed

Langston, J William

2002-10-01

In 15 years, we will mark the 200th anniversary of the James Parkinson's original description of the disease that now bears his name (An Essay on the Shaking Palsy, Sherwood, Neely and Jones London, 1817). Perhaps, one of the most exciting but daunting questions we face at this moment is whether or not we can unravel the etiology of the disease by that time. If we are to accomplish such an ambitious goal, we must determine the resources that will be required to make it happen, and identify the areas of scientific focus that should receive the greatest attention. One issue that will have great bearing on the allocation of research resources relates to the relative roles of genes versus environment in disease causation. For reasons that will become clear in this article, this has a remained surprisingly controversial area. Ironically, this controversy has even spilled over to the very definition of Parkinson's disease, and even whether or not it should be considered a disease entity. In this article, the enduring "genes versus environment" debate is reviewed, with a goal of putting it into a broader perspective. Issues surrounding disease definition and terminology are also addressed in detail, because of the need to have clarity of thought and vision if research on the cause is to proceed in an orderly (and hopefully expeditious) manner. Finally, issues relating future research directions are summarized, with the goal of identifying the pieces of the Parkinson's puzzle that are going to have to be put together if we are to solve this mysterious disease.

Effects of exercise on mobility in people with Parkinson's disease.

PubMed

van der Kolk, Nicolien M; King, Laurie A

2013-09-15

Parkinson's disease is a prevalent neurodegenerative disorder for which only symptomatic treatment exists. Gait and balance disturbance is common in Parkinson's disease and is a major contributor to increased disability and decreased health-related quality of life and survival. Balance and gait deficits in Parkinson's disease are notoriously difficult to treat and are not significantly helped by pharmacological or surgical treatment. The last two decades have seen a dramatic increase in the research and clinical interest in using exercise as a treatment for mobility problems in people with Parkinson's disease. With exciting advances in basic science research suggesting neurochemical and neuroplastic changes after exercise, an increasing number of high-quality studies are documenting particular aspects of mobility improving after exercise. Exercise has the potential to help both motor (gait, balance, strength) and nonmotor (depression, apathy, fatigue, constipation) aspects of Parkinson's disease as well as secondary complications of immobility (cardiovascular, osteoporosis). This perspective article focuses primarily on recent evidence on the effects of exercise in improving mobility while highlighting the importance of targeted exercise intervention for maximizing the benefits of exercise. Suggestions for exercise guidelines, adherence issues, and directions for future research are provided. © 2013 Movement Disorder Society.

Toxoplasma gondii exposure and Parkinson's disease: a case-control study.

PubMed

Alvarado-Esquivel, Cosme; Méndez-Hernández, Edna Madai; Salas-Pacheco, José Manuel; Ruano-Calderón, Luis Ángel; Hernández-Tinoco, Jesús; Arias-Carrión, Oscar; Sánchez-Anguiano, Luis Francisco; Castellanos-Juárez, Francisco Xavier; Sandoval-Carrillo, Ada Agustina; Liesenfeld, Oliver; Ramos-Nevárez, Agar

2017-02-13

To determine the association between Toxoplasma gondii infection and Parkinson's disease and to investigate whether T. gondii seropositivity is associated with the general characteristics of patients with Parkinson's disease. Case-control study. Cases and controls were enrolled in Durango City, Mexico. 65 patients with Parkinson's disease and 195 age- and gender-matched control subjects without Parkinson's disease. Serum samples of participants were analysed for anti- T. gondii IgG and IgM antibodies by commercially available enzyme-linked immunoassays. Prevalence of T. gondii DNA was determined in seropositive subjects using PCR. The association between clinical data and infection was examined by bivariate analysis. Anti- T. gondii IgG antibodies were found in 6/65 cases (9.2%) and in 21/195 controls (10.8%) (OR 0.84; 95% CI 0.32 to 2.18; p=0.81). The frequency of high (>150 IU/mL) antibody levels was similar among cases and controls (p=0.34). None of the anti- T. gondii IgG positive cases and four of the anti- T. gondii IgG positive controls had anti- T. gondii IgM antibodies (p=0.54). The prevalence of T. gondii DNA was comparable in seropositive cases and controls (16.7% and 25%, respectively; p=1.0). Seroprevalence of T. gondii infection was associated with a young age onset of disease (p=0.03), high Unified Parkinson Disease Rating Scale scores (p=0.04) and depression (p=0.02). Seropositivity to T. gondii infection was lower in patients treated with pramipexole than in patients without this treatment (p=0.01). However, none of the associations remained significant after Bonferroni correction. The results do not support an association between T. gondii infection and Parkinson's disease. However, T. gondii infection might have an influence on certain symptoms of Parkinson's disease. Further research to elucidate the role of T. gondii exposure on Parkinson's disease is warranted. Published by the BMJ Publishing Group Limited. For permission to use (where not

Primary Health Care Providers' Knowledge Gaps on Parkinson's Disease

ERIC Educational Resources Information Center

Thompson, Megan R.; Stone, Ramona F.; Ochs, V. Dan; Litvan, Irene

2013-01-01

In order to determine primary health care providers' (PCPs) knowledge gaps on Parkinson's disease, data were collected before and after a one-hour continuing medical education (CME) lecture on early Parkinson's disease recognition and treatment from a sample of 104 PCPs participating at an annual meeting. The main outcome measure was the…

Role of Neurotrophic Factors in Parkinson's Disease.

PubMed

Tome, Diogo; Fonseca, Carla Pais; Campos, Filipa Lopes; Baltazar, Graca

2017-01-01

Parkinson's disease is an age-associated progressive neurodegenerative disorder that has gained crescent social and economic impact due to the aging of the western society. All current therapies are symptomatic and fail to reverse or halt the progression of dopaminergic neurons loss. The discovery of the capability of neurotrophic factors to protect these neurons lead numerous research groups to focus their efforts in developing therapies aiming at promoting the control of Parkinson´s disease through the delivery of neurotrophic factors to the brain or by boosting their endogenous levels. Both strategies were successful in inducing protection of dopaminergic neurons and motor recovery in preclinical models of the disease. Contrariwise, very limited success was obtained in clinical studies, where glial cell line-derived neurotrophic factor and neurturin were the neurotrophic factors of choice for Parkinson's disease therapy. These drawbacks motivate the development of novel forms of delivery or the modification of the injected molecules aiming at providing a more stable and effective administration with improved diffusion in the target tissue, and without the immune responses observed in the earliest clinical studies. Although promising results were obtained with some of these new approaches performed in experimental models of the disease, they were not yet tested in human studies. In this review, we present the current knowledge on neurotrophic factors and their role in Parkinson's disease, focusing on the strategies that have been developed to increase their levels in target areas of the brain to achieve protection of dopaminergic neurons and motor behaviour recovery. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Mitochondrial Dysfunction in Parkinson's Disease.

PubMed

Moon, Hyo Eun; Paek, Sun Ha

2015-06-01

Parkinson's disease (PD) is characterized by the selective loss of dopaminergic neurons of the substantia nigra pars compacta (SNc) with motor and nonmotor symptoms. Defective mitochondrial function and increased oxidative stress (OS) have been demonstrated as having an important role in PD pathogenesis, although the underlying mechanism is not clear. The etiopathogenesis of sporadic PD is complex with variable contributions of environmental factors and genetic susceptibility. Both these factors influence various mitochondrial aspects, including their life cycle, bioenergetic capacity, quality control, dynamic changes of morphology and connectivity (fusion, fission), subcellular distribution (transport), and the regulation of cell death pathways. Mitochondrial dysfunction has mainly been reported in various non-dopaminergic cells and tissue samples from human patients as well as transgenic mouse and fruit fly models of PD. Thus, the mitochondria represent a highly promising target for the development of PD biomarkers. However, the limited amount of dopaminergic neurons prevented investigation of their detailed study. For the first time, we established human telomerase reverse transcriptase (hTERT)-immortalized wild type, idiopathic and Parkin deficient mesenchymal stromal cells (MSCs) isolated from the adipose tissues of PD patients, which could be used as a good cellular model to evaluate mitochondrial dysfunction for the better understanding of PD pathology and for the development of early diagnostic markers and effective therapy targets of PD. In this review, we examine evidence for the roles of mitochondrial dysfunction and increased OS in the neuronal loss that leads to PD and discuss how this knowledge further improve the treatment for patients with PD.

Herpes zoster correlates with increased risk of Parkinson's disease in older people

PubMed Central

Lai, Shih-Wei; Lin, Chih-Hsueh; Lin, Hsien-Feng; Lin, Cheng-Li; Lin, Cheng-Chieh; Liao, Kuan-Fu

2017-01-01

Abstract Little is known on the relationship between herpes zoster and Parkinson's disease in older people. This study aimed to explore whether herpes zoster could be associated with Parkinson's disease in older people in Taiwan. We conducted a retrospective cohort study using the claim data of the Taiwan National Health Insurance Program. There were 10,296 subjects aged 65 years and older with newly diagnosed herpes zoster as the herpes zoster group and 39,405 randomly selected subjects aged 65 years and older without a diagnosis of herpes zoster as the nonherpes zoster group from 1998 to 2010. Both groups were followed up until subjects received a diagnosis of Parkinson's disease. This follow-up design would explore whether subjects with herpes zoster were at an increased risk of Parkinson's disease. Relative risks were estimated by adjusted hazard ratio (HR) and 95% confidence interval (CI) using the multivariable Cox proportional hazards regression model. The incidence of Parkinson's disease was higher in the herpes zoster group than that in the nonherpes zoster group (4.86 vs 4.00 per 1000 person-years, 95% CI 1.14, 1.29). After adjustment for confounding factors, the multivariable Cox proportional hazards regression model revealed that the adjusted HR of Parkinson's disease was 1.17 for the herpes zoster group (95% CI 1.10, 1.25), compared with the nonherpes zoster group. Older people with herpes zoster confer a slightly increased hazard of developing Parkinson's disease when compared to those without herpes zoster. We think that herpes zoster correlates with increased risk of Parkinson's disease in older people. When older people with herpes zoster seek help, clinicians should pay more attention to the development of the cardinal symptoms of Parkinson's disease. PMID:28207515

Management of neurodegenerative disorders: Parkinson's disease and Alzheimer's disease.

PubMed

Pal, P K; Netravathi, M

2005-03-01

Neurodegenerative disorders result from premature progressive degeneration of specific neurons, and manifest as diseases or syndromes with varied combinations of cognitive, motor, sensory and autonomic dysfunctions. The management involves pharmacotherapy as well as non-pharmacological measures and also to lessen the burden of the care-givers. The medications available for medical treatment are: Levodopa, dopamine agonists, amantadine, anticholinergics, enzyme inhibitors, etc. Advanced Parkinson's disease is concerned with management of motor complications and non-motor complications. Recently surgical treatment is a great option for managing motor complication. Orthostatic hypotension, gait distiurbances, emotional and psychiatric problems, sleep disturbances can be managed and had been discussed in brief. Currently there is no medication available for the cure of Alzheimer's disease. The specific medications claimed to improve patient's well being and cognition include cholinesterase inhibitors, N-methyl-D-aspartate receptor antagonist, anti-oxidants, and anti-amyloid therapy. While medical and surgical treatments for Parkinson's disease have revolutionised the management, still drug therapy for Alzheimer's disease is dismal.

[Dopamine agonists--clinical applications beyond Parkinson's disease].

PubMed

Kuran, Włodzimierz

2007-01-01

Contemporary experience and results of clinical trials concerning dopamine agonist application in the treatment of many different diseases (apart from Parkinson's disease) are presented in the paper. A basic clinical recommendation for agonists is restless legs syndrome. In this syndrome almost all agonists give a considerable subjective and objective improvement. Treatment of atypical parkinsonism (MSA, PSP, CBD) in the majority of patients is ineffective. The author also presents promising results of treatment with agonists in such diverse diseases as hyperkinetic syndromes, cocaine dependence, drug-resistant depression and erectile dysfunction (apomorphine). Dopamine partial agonists (e.g. aripiprazol) are recommended in the modern treatment of schizophrenia.

Initial treatment of Parkinson's disease.

PubMed

Tarsy, Daniel

2006-05-01

Initial treatment of early idiopathic Parkinson's disease (PD) begins with diagnosis based on clinical evaluation supplemented by laboratory studies and brain imaging to exclude causes of secondary parkinsonism. In most cases, testing is normal and the diagnosis of PD rests on clinical criteria. In patients with mild symptoms and signs, the diagnosis of PD may not initially be apparent, and follow-up evaluation is needed to arrive at a diagnosis. Once the diagnosis is made, pharmacologic treatment may not be the first step. First, patient education is essential, especially because PD is a high-profile disease for which information and misinformation are readily available to patients and families. Counseling concerning prognosis, future symptoms, future disability, and treatment must be provided. Questions from patients concerning diet, lifestyle, and exercise are especially common at this point. The decision of when to initiate treatment is the next major consideration. Much controversy but relatively little light has been brought to bear on this issue. L-dopa was the first major antiparkinson medication to be introduced and remains the "gold standard" of treatment. Next in efficacy are the dopamine agonists (DAs). A debate has raged concerning whether initial dopaminergic treatment should be with L-dopa or DAs. Physicians have been concerned about forestalling the appearance of dyskinesias and motor fluctuations, whereas patients have incorrectly understood that L-dopa and possibly other antiparkinson drugs have a finite duration of usefulness, making it important to defer treatment for as long as possible. This has created "L-dopa phobia," which may stand in the way of useful treatment. In spite of this controversy, there is uniform agreement that the appropriate time to treat is when the patient is beginning to be disabled. This varies from patient to patient and depends on age, employment status, nature of job, level of physical activity, concern about

Living with advanced Parkinson's disease: a constant struggle with unpredictability.

PubMed

Haahr, Anita; Kirkevold, Marit; Hall, Elisabeth O C; Ostergaard, Karen

2011-02-01

This paper is a report of an exploration of patients' lifeworld and way of managing life with advanced Parkinson's disease prior to Deep Brain Stimulation and what they expect from life following this treatment. Parkinson's disease is a progressive neurodegenerative disease, which is initially well-treated with L-dopa. Living with Parkinson's disease means living with the experience of continuous loss of independence and self-esteem and unpredictable ON/OFF phenomena. Thus, in the advanced stage of the disease, treatment with Deep Brain Stimulation may become relevant. Eleven patients eligible for Deep Brain Stimulation were interviewed prior to treatment. Data were collected in 2007 and analysed according to the hermeneutic phenomenological methodology of van Manen, using the four existentials as analytic tools. Living with advanced Parkinson's disease can be described as the experience of living with and managing unpredictability. The disease gradually took over, and participants had to struggle with unpredictability on a daily basis. Themes in relation to this were: The body - setting the agenda, Always a struggle to be on time, Living in dependence and compromise - being a burden, and Living with restrained space and changes in social life. Parkinson's disease leads to profound bodily restrictions. Living with an unpredictable body affects all aspects of life, and nurses need to be aware of the impact the disease has on the entire lifeworld, and how this may affect the way treatment is perceived. © 2010 Blackwell Publishing Ltd.

Ambulatory ECG and analysis of heart rate variability in Parkinson's disease.

PubMed

Haapaniemi, T H; Pursiainen, V; Korpelainen, J T; Huikuri, H V; Sotaniemi, K A; Myllylä, V V

2001-03-01

Cardiovascular reflex tests have shown both sympathetic and parasympathetic failure in Parkinson's disease. These tests, however, describe the autonomic responses during a restricted time period and have great individual variability, providing a limited view of the autonomic cardiac control mechanisms. Thus, they do not reflect tonic autonomic regulation. The aim was to examine tonic autonomic cardiovascular regulation in untreated patients with Parkinson's disease. 24 Hour ambulatory ECG was recorded in 54 untreated patients with Parkinson's disease and 47 age matched healthy subjects. In addition to the traditional spectral (very low frequency, VLF; low frequency, LF; high frequency, HF) and non-spectral components of heart rate variability, instantaneous beat to beat variability (SD1) and long term continuous variability (SD2) derived from Poincaré plots, and the slope of the power law relation were analysed. All spectral components (p<0.01) and the slope of the power-law relation (p<0.01) were lower in the patients with Parkinson's disease than in the control subjects. The Unified Parkinson's disease rating scale total and motor scores had a negative correlation with VLF and LF power spectrum values and the power law relation slopes. Patients with mild hypokinesia had higher HF values than patients with more severe hypokinesia. Tremor and rigidity were not associated with the HR variability parameters. Parkinson's disease causes dysfunction of the diurnal autonomic cardiovascular regulation as demonstrated by the spectral measures of heart rate variability and the slope of the power law relation. This dysfunction seems to be more profound in patients with more severe Parkinson's disease.

[Emotional facial expression recognition impairment in Parkinson disease].

PubMed

Lachenal-Chevallet, Karine; Bediou, Benoit; Bouvard, Martine; Thobois, Stéphane; Broussolle, Emmanuel; Vighetto, Alain; Krolak-Salmon, Pierre

2006-03-01

some behavioral disturbances observed in Parkinson's disease (PD) could be related to impaired recognition of various social messages particularly emotional facial expressions. facial expression recognition was assessed using morphed faces (five emotions: happiness, fear, anger, disgust, neutral), and compared to gender recognition and general cognitive assessment in 12 patients with Parkinson's disease and 14 controls subjects. facial expression recognition was impaired among patients, whereas gender recognitions, visuo-perceptive capacities and total efficiency were preserved. Post hoc analyses disclosed a deficit for fear and disgust recognition compared to control subjects. the impairment of emotional facial expression recognition in PD appears independent of other cognitive deficits. This impairment may be related to the dopaminergic depletion in basal ganglia and limbic brain regions. They could take a part in psycho-behavioral disorders and particularly in communication disorders observed in Parkinson's disease patients.

Recent advances in Parkinson's disease therapy: use of monoamine oxidase inhibitors.

PubMed

Henchcliffe, Claire; Schumacher, H Christian; Burgut, F Tuna

2005-11-01

Monoamine oxidase inhibitors inhibit dopamine metabolism and are therefore effective in treating Parkinson's disease, a condition associated with progressive striatal dopamine deficiency secondary to degeneration of dopaminergic neurons in the substantia nigra. Selegiline is currently the most widely used monoamine oxidase-B inhibitor for Parkinson's disease, but has a low and variable bioavailability, and is metabolized to L-methamphetamine and L-amphetamine that carry a risk for potential neurotoxicity. There are two new approaches that circumvent these potential disadvantages. First, selegiline orally disintegrating tablets provide a novel delivery form of selegiline, avoiding first pass metabolism by rapid absorption through the oral mucosa, thus leading to significantly lower plasma concentrations of L-metamphetamine and L-amphetamine. Selegiline orally disintegrating tablets prove to be clinically effective and safe in patients with moderately advanced Parkinson's disease. Second, rasagiline is a new monoamine oxidase inhibitor, without known neurotoxic metabolites. In large clinical trials, rasagiline proves effective as monotherapy in early Parkinson's disease, as well as adjunctive therapy to levodopa in advanced disease. Clinical data suggest, in addition, a disease-modifying effect of rasagiline that may correlate with neuroprotective activity of monoamine oxidase-B inhibitors in animal models of Parkinson's disease.

Role of rasagiline in treating Parkinson's disease: Effect on disease progression.

PubMed

Malaty, Irene A; Fernandez, Hubert H

2009-08-01

Rasagiline is a second generation, selective, irreversible monoamine oxidase type B (MAO-B) inhibitor. It has demonstrated efficacy in monotherapy for early Parkinson's disease (PD) patients in one large randomized, placebo-controlled trial (TVP-1012 in Early Monotherapy for Parkinson's Disease Outpatients), and has shown ability to reduce off time in more advanced PD patients with motor fluctuations in two large placebo-controlled trials (Parkinson's Rasagiline: Efficacy and Safety in the Treatment of "Off", and Lasting Effect in Adjunct Therapy With Rasagiline Given Once Daily). Preclinical data abound to suggest potential for neuroprotection by this compound against a variety of neurotoxic insults in cell cultures and in animals. The lack of amphetamine metabolites provides an advantage over the first generation MAO-B inhibitor selegiline. One large trial has investigated the potential for disease modification in PD patients (Attenuation of Disease progression with Azilect Given Once-daily) and preliminary results maintain some possible advantage to earlier initiation of the 1 mg/day dose. The clinical significance of the difference detected remains a consideration.

Database for Parkinson Disease Mutations and Rare Variants

DTIC Science & Technology

2016-09-01

AWARD NUMBER: W81XWH-14-1-0097 TITLE: “ Database for Parkinson Disease Mutations and Rare Variants” PRINCIPAL INVESTIGATOR: JEFFERY M. VANCE...TO THE ABOVE ADDRESS. 1. REPORT DATE September 2016 2. REPORT TYPE FINAL 3. DATES COVERED 1 Jul 2014 – 30 Jun 2016 4. TITLE AND SUBTITLE Database ...For Parkinson Disease (PD) specifically, the variant databases currently available are incomplete, don’t assess impact and/or are not equipped to

Cardiac autonomic denervation in Parkinson's disease is linked to REM sleep behavior disorder.

PubMed

Postuma, Ronald B; Montplaisir, Jacques; Lanfranchi, Paola; Blais, Hélène; Rompré, Sylvie; Colombo, Roberto; Gagnon, Jean-François

2011-07-01

Recent studies have suggested a close connection between autonomic dysfunction and rapid eye movement sleep behavior disorder, which differs in nature from other early-stage markers of Parkinson's disease. In this study we examined the relationship between rapid eye movement sleep behavior disorder and autonomic dysfunction in Parkinson's disease as measured by cardiac beat-to-beat variability. In 53 patients with Parkinson's disease and 36 controls, electrocardiographic trace from a polysomnogram was assessed for measures of beat-to-beat RR variability including RR-standard deviation and frequency domains (low- and high-frequency components). Results were compared between patients with Parkinson's disease and controls, and between patients with Parkinson's disease with and without rapid eye movement sleep behavior disorder. On numerous cardiac autonomic measures, patients with Parkinson's disease showed clear abnormalities compared with controls. However, these abnormalities were confined only to those patients with associated rapid eye movement sleep behavior; those without were not different than controls. As with other clinical autonomic variables, cardiac autonomic denervation is predominantly associated not with Parkinson's disease itself, but with the presence of rapid eye movement sleep behavior disorder. Copyright © 2011 Movement Disorder Society.

Effect of High-Intensity Treadmill Exercise on Motor Symptoms in Patients With De Novo Parkinson Disease: A Phase 2 Randomized Clinical Trial.

PubMed

Schenkman, Margaret; Moore, Charity G; Kohrt, Wendy M; Hall, Deborah A; Delitto, Anthony; Comella, Cynthia L; Josbeno, Deborah A; Christiansen, Cory L; Berman, Brian D; Kluger, Benzi M; Melanson, Edward L; Jain, Samay; Robichaud, Julie A; Poon, Cynthia; Corcos, Daniel M

2018-02-01

Parkinson disease is a progressive neurologic disorder. Limited evidence suggests endurance exercise modifies disease severity, particularly high-intensity exercise. To examine the feasibility and safety of high-intensity treadmill exercise in patients with de novo Parkinson disease who are not taking medication and whether the effect on motor symptoms warrants a phase 3 trial. The Study in Parkinson Disease of Exercise (SPARX) was a phase 2, multicenter randomized clinical trial with 3 groups and masked assessors. Individuals from outpatient and community-based clinics were enrolled from May 1, 2012, through November 30, 2015, with the primary end point at 6 months. Individuals with idiopathic Parkinson disease (Hoehn and Yahr stages 1 or 2) aged 40 to 80 years within 5 years of diagnosis who were not exercising at moderate intensity greater than 3 times per week and not expected to need dopaminergic medication within 6 months participated in this study. A total of 384 volunteers were screened by telephone; 128 were randomly assigned to 1 of 3 groups (high-intensity exercise, moderate-intensity exercise, or control). High-intensity treadmill exercise (4 days per week, 80%-85% maximum heart rate [n = 43]), moderate-intensity treadmill exercise (4 days per week, 60%-65% maximum heart rate [n = 45]), or wait-list control (n = 40) for 6 months. Feasibility measures were adherence to prescribed heart rate and exercise frequency of 3 days per week and safety. The clinical outcome was 6-month change in Unified Parkinson's Disease Rating Scale motor score. A total of 128 patients were included in the study (mean [SD] age, 64 [9] years; age range, 40-80 years; 73 [57.0%] male; and 108 [84.4%] non-Hispanic white). Exercise rates were 2.8 (95% CI, 2.4-3.2) days per week at 80.2% (95% CI, 78.8%-81.7%) maximum heart rate in the high-intensity group and 3.2 (95% CI, 2.8-3.6; P = .13) days per week at 65.9% (95% CI, 64.2%-67.7%) maximum heart rate in the

Welding occupations and mortality from Parkinson's disease and other neurodegenerative diseases among United States men, 1985-1999.

PubMed

Stampfer, Meir J

2009-05-01

Metal welding produces gaseous fumes that contain manganese, resulting in potential occupational exposure to welders. It has been hypothesized that occupational exposure among welders could increase risk of Parkinson's disease and other neurodegenerative diseases. The present study examines welding occupation and mortality from neurodegenerative diseases among men in the United States using the National Cause of Death databases 1985 to 1999. Information was abstracted from death certificates for states that collected data on occupation. Of 4,252,490 men who died during the study period, 107,773 had welding-related occupations. Multivariable logistic regression models were used to calculate mortality odds ratios (MOR) and 95% confidence intervals (CI) for odds of dying from Parkinson's disease or other neurodegenerative diseases among men who were welders as compared with men of other occupations, adjusting for attained age, race, region of residence, and year of death. During the study period, 49,174 deaths were attributed to Parkinson's disease, 54,892 to Alzheimer's disease, and 19,018 to presenile dementia. There was no evidence of an increased odds of Parkinson's disease mortality among welders as compared with men with other occupations (MOR = 0.83, 95% CI 0.78-0.88). Furthermore, welding occupation was unrelated to the odds of mortality from Alzheimer's disease (MOR = 0.94, 95% CI 0.89-1.00) or presenile dementia (MOR = 0.96, 95% CI 0.87-1.06). Earlier research suggested that welding exposures could predispose individuals to earlier onset Parkinson's disease. However, there was no evidence in this data of an increased mortality odds ratio associated with welding occupations among men younger than 65 (MOR = 1.03, 95% CI 0.74-1.44); while there was a suggestion of a lower odds Parkinson's disease death among men age 65 years and older (MOR = 0.82, 95% CI 0.77-0.88). Data from this large study do not support an association between welding occupations and death