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Sample records for early parkinson disease

  1. Parkinson disease

    Science.gov (United States)

    ... control movement. Surgery to destroy brain tissue that causes Parkinson symptoms. Stem cell transplant and other procedures are ... in brain function and early death. Possible Complications Parkinson disease may cause problems such as: Difficulty performing daily activities Difficulty ...

  2. Parkinson's Disease Videos

    Medline Plus

    Full Text Available ... Team Hope TM for Parkinson's Understanding Parkinson's What Is Parkinson's? Early Warning Signs Motor Symptoms Non-Motor ... Newly Diagnosed Living Well Caregiving Understanding Parkinson's There is a lot to know about Parkinson's disease. Learn ...

  3. Morbidity in early Parkinson's disease and prior to diagnosis

    DEFF Research Database (Denmark)

    Frandsen, Rune; Kjellberg, Jakob; Ibsen, Rikke;

    2014-01-01

    BACKGROUND: Nonmotor symptoms are probably present prior to, early on, and following, a diagnosis of Parkinson's disease. Nonmotor symptoms may hold important information about the progression of Parkinson's disease. OBJECTIVE: To evaluated the total early and prediagnostic morbidities in the 3...... years before a hospital contact leading to a diagnosis of Parkinson's disease. METHODS: Retrospective morbidity data from Danish National Patient Registry records (1997-2007) of 10,490 adult patients with a secondary care diagnosis of Parkinson's disease were compared with 42,505 control cases. RESULTS......: Parkinson's disease was associated with significantly higher morbidity rates associated with conditions in the following categories: mental and psychiatric, nervous system, gastrointestinal, musculoskeletal system and connective tissue, genitourinary, abnormal clinical and laboratory findings, injury...

  4. Improving Symptom Control in Early Parkinson's Disease

    OpenAIRE

    Isaacson, Stuart H; Hauser, Robert A.

    2009-01-01

    Motor symptoms in Parkinson's disease (PD) are caused by a severe loss of pigmented dopamine-producing nigro-striatal neurons. Symptomatic therapies provide benefit for motor features by restoring dopamine receptor stimulation. Studies have demonstrated that delaying the introduction of dopaminergic medical therapy is associated with a rapid decline in quality of life. Nonmotor s...

  5. [Cerebrospinal fluid biomarkers for the early diagnosis of Parkinson's disease].

    Science.gov (United States)

    da Costa, Andreia Gomes; Gago, Miguel Fernandes; Garrett, Carolina

    2011-12-01

    In current medical practice, the diagnosis of Parkinson's disease remains essentially clinical. This practice determines that the diagnosis of Parkinson's disease is done in an already advanced neuropathological stage of the disease. The aim of this study is to review the validity of cerebrospinal fluid protein biological markers in the early diagnosis of Parkinson's disease. The a-synuclein and DJ-1 proteins, due to their role in the hereditary Parkinson's disease, have been the most widely studied cerebrospinal biomarkers. Nevertheless, they have had divergent results mostly owing to different processing, identification and control of laboratory techniques. The new proteomic techniques, directed to the detection of multiple undifferentiated proteins in cerebrospinal fluid (eg. ceruloplasmin, chromogranin B, apoH), are promising. The early diagnosis of Parkinson's disease is imperious as it is a progressive neurodegenerative disorder that causes extensive morbidity. Most of current scientific research in Parkinson's disease is focused on the discovery of neuroprotective drugs. Thus, the definition of biomarkers for the early diagnosis of Parkinson's disease is highly relevant.

  6. Clinical correlates of raphe serotonergic dysfunction in early Parkinson's disease.

    Science.gov (United States)

    Qamhawi, Zahi; Towey, David; Shah, Bina; Pagano, Gennaro; Seibyl, John; Marek, Kenneth; Borghammer, Per; Brooks, David James; Pavese, Nicola

    2015-10-01

    Post-mortem and neuroimaging studies suggest that the serotonergic system, which originates from the brainstem raphe nuclei, is disrupted in Parkinson's disease. This could contribute to the occurrence of non-motor symptoms and tremor, which are only partially explained by dopamine loss. However, the level of involvement of the serotonergic raphe nuclei in early Parkinson's disease is still debated. (123)I-FP-CIT single photon emission computed tomography is a marker of dopamine and serotonin transporter availability. While (123)I-FP-CIT binds primarily to dopamine transporters in the striatum, its binding in the brainstem raphe nuclei reflects serotonin transporter availability. We interrogated baseline single photon emission computed tomography scans of subjects recruited by the Parkinson's Progression Markers Initiative to determine: (i) the integrity of the brainstem raphe nuclei in early Parkinson's disease; and (ii) whether raphe serotonin transporter levels correlate with severity of tremor and symptoms of fatigue, depression, and sleep disturbance. Three hundred and forty-five patients with early drug-naïve Parkinson's disease, 185 healthy controls, and 56 subjects with possible Parkinson's disease without evidence of dopaminergic deficit were included. In the Parkinson's disease cohort, 37 patients had a tremulous, 106 patients had a pure akinetic-rigid, and 202 had a mixed phenotype. Patients with Parkinson's disease had significantly lower serotonin transporter availability in the brainstem raphe nuclei compared to controls (P disease individually had reduced signals. Raphe serotonin transporter availability over the entire Parkinson's disease cohort were associated with rest tremor amplitude (β = -0.106, P disease subgroup had significantly lower raphe serotonin transporter availability but less severe striatal dopaminergic deficits compared to akinetic-rigid patients with no resting tremor (P disease. We conclude that the raphe nuclei are affected in

  7. Understanding Parkinson's disease: detection and early disease management.

    Science.gov (United States)

    Mackin, L A

    2000-01-01

    Parkinson's disease (PD) is a common, debilitating, neurodegenerative disorder characterized by neuronal loss within the basal ganglia and insufficient levels of the neurotransmitter dopamine. Symptoms include resting tremor, rigidity, bradykinesia (slowness of voluntary movement), and postural disturbances. Exact cause is unknown, but theories surrounding environmental or endogenous toxicities have been suggested. Differential diagnoses include genetic and other neurologic disorders that may share symptoms similar to those seen in PD. Clinical progression has been categorized into three phases of the disease: early, nonfluctuating, and fluctuating. Medications generally offer good symptom relief during the early and nonfluctuating phases of the disease. Classifications of anti-PD medications include anticholinergics, dopamine agonists, amantadine, MAO-B inhibitors, levodopa-carbidopa, and Catechol-o-methyl transferase inhibitors. Surgical intervention may be an option for select patients whose conditions are not well controlled though medical management strategies. Primary care providers often can manage patients in the early stage of PD, but later stages require expert neurologic management. Patient/family education and anticipatory guidance is imperative.

  8. Neurostimulation for Parkinson's disease with early motor complications

    NARCIS (Netherlands)

    Schuepbach, W.M.; Rau, J.; Knudsen, K.; Volkmann, J.; Krack, P.; Timmermann, L.; Halbig, T.D.; Hesekamp, H.; Navarro, S.M.; Meier, N.; Falk, D.; Mehdorn, M.; Paschen, S.; Maarouf, M.; Barbe, M.T.; Fink, G.R.; Kupsch, A.; Gruber, D.; Schneider, G.H.; Seigneuret, E.; Kistner, A.; Chaynes, P.; Ory-Magne, F.; Brefel Courbon, C.; Vesper, J.; Schnitzler, A.; Wojtecki, L.; Houeto, J.L.; Bataille, B.; Maltete, D.; Damier, P.; Raoul, S.; Sixel-Doering, F.; Hellwig, D.; Gharabaghi, A.; Kruger, R.; Pinsker, M.O.; Amtage, F.; Regis, J.M.; Witjas, T.; Thobois, S.; Mertens, P.; Kloss, M.; Hartmann, A.; Oertel, W.H.; Post, B.; Speelman, H.; Agid, Y.; Schade-Brittinger, C.; Deuschl, G.

    2013-01-01

    BACKGROUND: Subthalamic stimulation reduces motor disability and improves quality of life in patients with advanced Parkinson's disease who have severe levodopa-induced motor complications. We hypothesized that neurostimulation would be beneficial at an earlier stage of Parkinson's disease. METHODS:

  9. Biomarkers in the early diagnosis of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    CHEN Sheng-di

    2013-08-01

    Full Text Available Parkinson's disease (PD is a chronic and progressive neurodegenerative disorder. It has become clear that PD can have a preclinical phase, a period during which neurodegeneration has already begun years before the onset of typical motor symptoms. Consequently, if the early neurodegeneration in PD can be timely diagnosed, it will significantly slow down the progression of the disease and improve the quality of life. To date, there is no fully reliable and validated biomarker for the early diagnosis of PD, but some promising biomarker candidates exist.

  10. Parkinson's disease therapy: treatment of early and late disease

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Purpose To summarize the current strategies for the treatment of early and late Parkinson's disease (PD). Data sources The presented guidelines are based on the review of the literature as well as the author's extensive experience with the treatment of 7000 patients with PD over the past 25 years. Results An analysis of reported data as well as personal experience suggest that while young patients seem to have a slower progression of the disease, they are at a higher risk for developing levodopa induced complications, such as motor fluctuations and dyskinesias. It is, therefore, prudent practice to delay levodopa therapy, particularly in younger patients, until the PD symptoms become troublesome and interfere with social or occupational functioning. Other strategies, such as the use of deprenyl, amantadine, trihexyphenidyl and dopamine agonists, should be employed before instituting levodopa therapy. Entacopone and dopamine agonists are useful in smoothing out levodopa related motor fluctuations. Surgical interventions, such as pallidotomy and pallidal or subthalamic deep brain stimulation, are effective therapeutic strategies, but should be reserved only for patients in whom optimal medical therapy fails to provide satisfactory control of symptoms. Conclusion The medical and surgical treatment of patients with PD must be individualized and tailored to the needs of the individual patient.

  11. Cognitive impairment in early-stage non-demented Parkinson's disease patients

    DEFF Research Database (Denmark)

    Pfeiffer, Helle Cecilie Viekilde; Løkkegaard, A; Zoetmulder, Marielle

    2013-01-01

    In Parkinson's disease (PD), Parkinson's disease dementia (PDD) and Parkinson's disease-mild cognitive impairment (PD-MCI) are common. PD-MCI is a risk factor for developing PDD. Knowledge of cognition in early-stages PD is essential in understanding and predicting the dementia process....

  12. Body mass index is reduced early in Parkinson's disease.

    Science.gov (United States)

    Cheshire, William P; Wszolek, Zbigniew K

    2005-01-01

    Mean body mass index (BMI) in 100 cases of idiopathic Parkinson's disease (PD) was found to be 9% reduced in comparison to that in patients with either essential tremor or no neurologic disease. A similar reduction in BMI was also discovered among the 24 cases of PD in whom retrospective BMI data were available from their presymptomatic years. These results suggest that alterations in nutrient intake or metabolism could reflect early changes in the central autonomic network preceding the emergence of classical extrapyramidal manifestations of PD.

  13. Treatment strategies in early and advanced Parkinson disease.

    Science.gov (United States)

    Ossig, Christiana; Reichmann, Heinz

    2015-02-01

    The initiation of therapy in Parkinson disease (PD), altering the medication, adding new substances, and switching to alternative therapies throughout the disease is always a matter of debate. In the past, experts in PD have propagated different medication strategies. Even though there is no new medical treatment on the horizon, much has changed in consideration of the known treatments in the early and advanced therapy for PD. Therapeutic regimens have to be adapted and adjusted on a regular basis to accomplish the best medical care for the predominant symptom of the individual patient with PD. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Parkinson's Disease

    Science.gov (United States)

    ... messages it needs to move normally. continue What Causes Parkinson's Disease? Experts agree that low dopamine levels in ... or other chemicals. No one knows the exact cause of Parkinson's disease, but we do know that it has ...

  15. Sex Differences in Clinical Features of Early, Treated Parkinson's Disease.

    Directory of Open Access Journals (Sweden)

    Erika F Augustine

    Full Text Available To improve our understanding of sex differences in the clinical characteristics of Parkinson's Disease, we sought to examine differences in the clinical features and disease severity of men and women with early treated Parkinson's Disease (PD enrolled in a large-scale clinical trial.Analysis was performed of baseline data from the National Institutes of Health Exploratory Trials in Parkinson's Disease (NET-PD Long-term Study-1, a randomized, multi-center, double-blind, placebo-controlled study of 10 grams of oral creatine/day in individuals with early, treated PD. We compared mean age at symptom onset, age at PD diagnosis, and age at randomization between men and women using t-test statistics. Sex differences in clinical features were evaluated, including: symptoms at diagnosis (motor and symptoms at randomization (motor, non-motor, and daily functioning.1,741 participants were enrolled (62.5% male. No differences were detected in mean age at PD onset, age at PD diagnosis, age at randomization, motor symptoms, or daily functioning between men and women. Differences in non-motor symptoms were observed, with women demonstrating better performance compared to men on SCOPA-COG (Z = 5.064, p<0.0001 and Symbol Digit Modality measures (Z = 5.221, p<0.0001.Overall, men and women did not demonstrate differences in clinical motor features early in the course of PD. However, the differences observed in non-motor cognitive symptoms suggests further assessment of the influence of sex on non-motor symptoms in later stages of PD is warranted.

  16. Early postural changes in individuals with idiopathic Parkinson's disease.

    Science.gov (United States)

    Khallaf, Mohamed Elsayed; Fayed, Eman Elsayed

    2015-01-01

    Background and Objectives. Postural changes are frequent and disabling complications of Parkinson's disease (PD). Many contributing factors have been evident either related to disease pathology or to adaptive changes. This study aimed at studying the postural changes in subjects with Parkinson's disease and its relation to duration of illness and disease severity. Methods. Eighteen patients with PD and 18 healthy matched volunteers represented the sample of the study. The patients were at stage 1 or 1.5 according to the Modified Hoehn and Yahr Staging with duration of illness between 18 and 36 months. Three-dimensional analysis of the back surface was conducted to explore the postural changes in the sagittal and frontal planes in both the patients and the healthy subjects. Results. Kyphotic angle, lordotic angle, fleche cervicale, fleche lombaire, scoliotic angle, and associated vertebral rotation and pelvic obliquity were significantly increased in patients with PD compared to the healthy subjects (P ≤ 0.05). There was no association between the measured postural changes and duration of illness as well as the severity of the IPD (P ≤ 0.05). Conclusion. Postural changes start in the early stages of idiopathic PD and they have no relationship to the duration of illness and disease severity.

  17. CSF biomarkers associated with disease heterogeneity in early Parkinson's disease: the Parkinson's Progression Markers Initiative study.

    Science.gov (United States)

    Kang, Ju-Hee; Mollenhauer, Brit; Coffey, Christopher S; Toledo, Jon B; Weintraub, Daniel; Galasko, Douglas R; Irwin, David J; Van Deerlin, Vivianna; Chen-Plotkin, Alice S; Caspell-Garcia, Chelsea; Waligórska, Teresa; Taylor, Peggy; Shah, Nirali; Pan, Sarah; Zero, Pawel; Frasier, Mark; Marek, Kenneth; Kieburtz, Karl; Jennings, Danna; Tanner, Caroline M; Simuni, Tanya; Singleton, Andrew; Toga, Arthur W; Chowdhury, Sohini; Trojanowski, John Q; Shaw, Leslie M

    2016-06-01

    The development of biomarkers to predict the progression of Parkinson's disease (PD) from its earliest stage through its heterogeneous course is critical for research and therapeutic development. The Parkinson's Progression Markers Initiative (PPMI) study is an ongoing international multicenter, prospective study to validate biomarkers in drug-naïve PD patients and matched healthy controls (HC). We quantified cerebrospinal fluid (CSF) alpha-synuclein (α-syn), amyloid-beta1-42 (Aβ1-42), total tau (t-tau), and tau phosphorylated at Thr181 (p-tau) in 660 PPMI subjects at baseline, and correlated these data with measures of the clinical features of these subjects. We found that CSF α-syn, t-tau and p-tau levels, but not Aβ1-42, were significantly lower in PD compared with HC, while the diagnostic value of the individual CSF biomarkers for PD diagnosis was limited due to large overlap. The level of α-syn, but not other biomarkers, was significantly lower in PD patients with non-tremor-dominant phenotype compared with tremor-dominant phenotype. In addition, in PD patients the lowest Aβ1-42, or highest t-tau/Aβ1-42 and t-tau/α-syn quintile in PD patients were associated with more severe non-motor dysfunction compared with the highest or lowest quintiles, respectively. In a multivariate regression model, lower α-syn was significantly associated with worse cognitive test performance. APOE ε4 genotype was associated with lower levels of Aβ1-42, but neither with PD diagnosis nor cognition. Our data suggest that the measurement of CSF biomarkers in early-stage PD patients may relate to disease heterogeneity seen in PD. Longitudinal observations in PPMI subjects are needed to define their prognostic performance.

  18. DNAJC6 Mutations Associated With Early-Onset Parkinson's Disease.

    Science.gov (United States)

    Olgiati, Simone; Quadri, Marialuisa; Fang, Mingyan; Rood, Janneke P M A; Saute, Jonas A; Chien, Hsin Fen; Bouwkamp, Christian G; Graafland, Josja; Minneboo, Michelle; Breedveld, Guido J; Zhang, Jianguo; Verheijen, Frans W; Boon, Agnita J W; Kievit, Anneke J A; Jardim, Laura Bannach; Mandemakers, Wim; Barbosa, Egberto Reis; Rieder, Carlos R M; Leenders, Klaus L; Wang, Jun; Bonifati, Vincenzo

    2016-02-01

    DNAJC6 mutations were recently described in two families with autosomal recessive juvenile parkinsonism (onset age < 11), prominent atypical signs, poor or absent response to levodopa, and rapid progression (wheelchair-bound within ∼10 years from onset). Here, for the first time, we report DNAJC6 mutations in early-onset Parkinson's disease (PD). The DNAJC6 open reading frame was analyzed in 274 patients with early-onset sporadic or familial PD. Selected variants were followed up by cosegregation, homozygosity mapping, linkage analysis, whole-exome sequencing, and protein studies. We identified two families with different novel homozygous DNAJC6 mutations segregating with PD. In each family, the DNAJC6 mutation was flanked by long runs of homozygosity within highest linkage peaks. Exome sequencing did not detect additional pathogenic variants within the linkage regions. In both families, patients showed severely decreased steady-state levels of the auxilin protein in fibroblasts. We also identified a sporadic patient carrying two rare noncoding DNAJC6 variants possibly effecting RNA splicing. All these cases fulfilled the criteria for a clinical diagnosis of early-onset PD, had symptoms onset in the third-to-fifth decade, and slow disease progression. Response to dopaminergic therapies was prominent, but, in some patients, limited by psychiatric side effects. The phenotype overlaps that of other monogenic forms of early-onset PD. Our findings delineate a novel form of hereditary early-onset PD. Screening of DNAJC6 is warranted in all patients with early-onset PD compatible with autosomal recessive inheritance. Our data provide further evidence for the involvement of synaptic vesicles endocytosis and trafficking in PD pathogenesis. © 2016 American Neurological Association.

  19. James Parkinson: Parkinson's disease.

    Science.gov (United States)

    Ellis, Harold

    2013-11-01

    Parkinson's disease is a condition that anyone with a modicum of medical knowledge can recognise in the street--as indeed how it was studied by James Parkinson himself. Its three characteristic features are: 1. Increase in the tone of the voluntary muscles (rigidity). 2. Slowness of movement (bradykinesis). 3. Tremor (the characteristic 'pill rolling' movements of the fingers).

  20. Magnetic resonance imaging markers for early diagnosis of Parkinson's disease

    Institute of Scientific and Technical Information of China (English)

    Silvia Marino; Rosella Ciurleo; Giuseppe Di Lorenzo; Marina Barresi; Simona De Salvo; Sabrina Giacoppo; Alessia Bramanti; Pietro Lanzafame; Placido Bramanti

    2012-01-01

    Parkinson's disease (PD) is a neurodegenerative disorder characterized by selective and progressive degeneration, as well as loss of dopaminergic neurons in the substantia nigra. In PD, approximately 60-70% of nigrostriatal neurons are degenerated and 80% of content of the striatal dopamine is reduced before the diagnosis can be established according to widely accepted clinical diagnostic criteria. This condition describes a stage of disease called "prodromal", where non-motor symptoms, such as olfactory dysfunction, constipation, rapid eye movement behaviour disorder, depression, precede motor sign of PD. Detection of prodromal phase of PD is becoming an important goal for determining the prognosis and choosing a suitable treatment strategy. In this review, we present some non-invasive instrumental approaches that could be useful to identify patients in the prodromal phase of PD or in an early clinical phase, when the first motor symptoms begin to be apparent. Conventional magnetic resonance imaging (MRI) and advanced MRI techniques, such as magnetic resonance spectroscopy imaging, diffusion-weighted and diffusion tensor imaging and functional MRI, are useful to differentiate early PD with initial motor symptoms from atypical parkinsonian disorders, thus, making easier early diagnosis. Functional MRI and diffusion tensor imaging techniques can show abnormalities in the olfactory system in prodromal PD.

  1. Anatomical correlates of cognitive functions in early Parkinson's disease patients.

    Directory of Open Access Journals (Sweden)

    Roberta Biundo

    Full Text Available BACKGROUND: Cognitive deficits may occur early in Parkinson's disease (PD but the extent of cortical involvement associated with cognitive dysfunction needs additional investigations. The aim of our study is to identify the anatomical pattern of cortical thickness alterations in patients with early stage PD and its relationship with cognitive disability. METHODS: We recruited 29 PD patients and 21 healthy controls. All PD patients performed an extensive neuropsychological examination and 14 were diagnosed with mild cognitive impairment (PD-MCI. Surface-based cortical thickness analysis was applied to investigate the topographical distribution of cortical and subcortical alterations in early PD compared with controls and to assess the relationship between cognition and regional cortical changes in PD-MCI. RESULTS: Overall PD patients showed focal cortical (occipital-parietal areas, orbito-frontal and olfactory areas and subcortical thinning when compared with controls. PD-MCI showed a wide spectrum of cognitive deficits and related significant regional thickening in the right parietal-frontal as well as in the left temporal-occipital areas. CONCLUSION: Our results confirm the presence of changes in grey matter thickness at relatively early PD stage and support previous studies showing thinning and atrophy in the neocortex and subcortical regions. Relative cortical thickening in PD-MCI may instead express compensatory neuroplasticity. Brain reserve mechanisms might first modulate cognitive decline during the initial stages of PD.

  2. Longitudinal assessment of excessive daytime sleepiness in early Parkinson's disease.

    Science.gov (United States)

    Amara, Amy W; Chahine, Lama M; Caspell-Garcia, Chelsea; Long, Jeffrey D; Coffey, Christopher; Högl, Birgit; Videnovic, Aleksandar; Iranzo, Alex; Mayer, Geert; Foldvary-Schaefer, Nancy; Postuma, Ron; Oertel, Wolfgang; Lasch, Shirley; Marek, Ken; Simuni, Tanya

    2017-08-01

    Excessive daytime sleepiness (EDS) is common and disabling in Parkinson's disease (PD). Predictors of EDS are unclear, and data on biological correlates of EDS in PD are limited. We investigated clinical, imaging and biological variables associated with longitudinal changes in sleepiness in early PD. The Parkinson's Progression Markers Initiative is a prospective cohort study evaluating progression markers in participants with PD who are unmedicated at baseline (n=423) and healthy controls (HC; n=196). EDS was measured with the Epworth Sleepiness Scale (ESS). Clinical, biological and imaging variables were assessed for associations with EDS for up to 3 years. A machine learning approach (random survival forests) was used to investigate baseline predictors of incident EDS. ESS increased in PD from baseline to year 3 (mean±SD 5.8±3.5 to 7.55±4.6, p<0.0001), with no change in HC. Longitudinally, EDS in PD was associated with non-tremor dominant phenotype, autonomic dysfunction, depression, anxiety and probable behaviour disorder, but not cognitive dysfunction or motor severity. Dopaminergic therapy was associated with EDS at years 2 and 3, as dose increased. EDS was also associated with presynaptic dopaminergic dysfunction, whereas biofluid markers at year 1 showed no significant associations with EDS. A predictive index for EDS was generated, which included seven baseline characteristics, including non-motor symptoms and cerebrospinal fluid phosphorylated-tau/total-tau ratio. In early PD, EDS increases significantly over time and is associated with several clinical variables. The influence of dopaminergic therapy on EDS is dose dependent. Further longitudinal analyses will better characterise associations with imaging and biomarkers. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  3. Pramipexole for the treatment of early Parkinson's disease.

    Science.gov (United States)

    Perez-Lloret, Santiago; Perez Lloret, Santiago; Rey, María Verónica; Ratti, Luca; Rascol, Olivier

    2011-07-01

    Pramipexole is a nonergolinic dopamine agonist, with high affinity for the D2 subfamily of dopamine receptors. Pramipexole is efficacious for the symptomatic treatment of early Parkinson's Disease (PD) and its early use, before that of levodopa can delay the emergence of levodopa-related motor complication. Dosage should be increased gradually from a starting dose of 0.375 mg/day up to a maximum of 4.5 mg/day in equally divided doses taken three times per day with pramipexole immediate-release or equivalent daily dosages once-daily with pramipexole extended-release. Pramipexole can also improve depressive symptoms and possibly health-related quality of life in PD. Nonetheless, its use is not devoid of tolerability problems. While peripheral adverse drug reactions, such as nausea, vomiting or orthostatic hypotension, can be effectively treated and usually pose few problems to most patients, neuropsychiatric events can seriously limit the use of pramipexole in some cases. Indeed, excessive daytime somnolence, impulse-control disorders, hallucinations or delusions can severely affect patients, causing important personal or social handicap. Patients should be informed about the risk of such neuropsychiatric complications and their presence should be actively detected at each consultation. More effort will have to be put into further studying the risk-benefit ratio of pramipexole and other dopamine agonists in the treatment of early PD.

  4. DNAJC6 Mutations Associated With Early-Onset Parkinson's Disease

    NARCIS (Netherlands)

    Olgiati, Simone; Quadri, Marialuisa; Fang, Mingyan; Rood, Janneke P. M. A.; Saute, Jonas A.; Chien, Hsin Fen; Bouwkamp, Christian G.; Graafland, Josja; Minneboo, Michelle; Breedveld, Guido J.; Zhang, Jianguo; Verheijen, Frans W.; Boon, Agnita J. W.; Kievit, Anneke J. A.; Jardim, Laura Bannach; Mandemakers, Wim; Barbosa, Egberto Reis; Rieder, Carlos R. M.; Leenders, Klaus L.; Wang, Jun; Bonifati, Vincenzo

    ObjectiveDNAJC6 mutations were recently described in two families with autosomal recessive juvenile parkinsonism (onset age MethodsThe DNAJC6 open reading frame was analyzed in 274 patients with early-onset sporadic or familial PD. Selected variants were followed up by cosegregation, homozygosity

  5. Subthalamic nucleus deep brain stimulation in early stage Parkinson's disease.

    Science.gov (United States)

    Charles, David; Konrad, Peter E; Neimat, Joseph S; Molinari, Anna L; Tramontana, Michael G; Finder, Stuart G; Gill, Chandler E; Bliton, Mark J; Kao, Chris; Phibbs, Fenna T; Hedera, Peter; Salomon, Ronald M; Cannard, Kevin R; Wang, Lily; Song, Yanna; Davis, Thomas L

    2014-07-01

    Deep brain stimulation (DBS) is an effective and approved therapy for advanced Parkinson's disease (PD), and a recent study suggests efficacy in mid-stage disease. This manuscript reports the results of a pilot trial investigating preliminary safety and tolerability of DBS in early PD. Thirty subjects with idiopathic PD (Hoehn & Yahr Stage II off medication), age 50-75, on medication ≥6 months but ≤4 years, and without motor fluctuations or dyskinesias were randomized to optimal drug therapy (ODT) (n = 15) or DBS + ODT (n = 15). Co-primary endpoints were the time to reach a 4-point worsening from baseline in the UPDRS-III off therapy and the change in levodopa equivalent daily dose from baseline to 24 months. As hypothesized, the mean UPDRS total and part III scores were not significantly different on or off therapy at 24 months. Medication requirements in the DBS + ODT group were lower at all time points with a maximal difference at 18 months. With a few exceptions, differences in neuropsychological functioning were not significant. Two subjects in the DBS + ODT group suffered serious adverse events; remaining adverse events were mild or transient. This study demonstrates that subjects with early stage PD will enroll in and complete trials testing invasive therapies and provides preliminary evidence that DBS is well tolerated in early PD. The results of this trial provide the data necessary to design a large, phase III, double-blind, multicenter trial investigating the safety and efficacy of DBS in early PD. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Associations between Early Markers of Parkinson's Disease and Sarcopenia

    Science.gov (United States)

    Drey, Michael; Hasmann, Sandra E.; Krenovsky, Jan-Peter; Hobert, Markus A.; Straub, Stefanie; Elshehabi, Morad; von Thaler, Anna-Katharina; Fallgatter, Andreas J.; Eschweiler, Gerhard W.; Suenkel, Ulrike; Berg, Daniela; Maetzler, Walter

    2017-01-01

    Introduction: Sarcopenia and Parkinson's disease (PD) are both common age-related syndromes, and there is preliminary evidence that the probability of the co-occurrence of these syndromes within one individual is higher than expected. However, it is unclear to date whether one of the syndromes induces the other, or whether there may be common underlying causes. This pilot study thus aimed at investigating the association of the features of increased risk for PD with early stage sarcopenia (ESS). Method: Two hundred and fifty-five community-dwelling individuals were recruited from the Tübinger evaluation of Risk factors for Early detection of NeuroDegeneration (TREND) study. The following features that are associated with an increased risk for future PD were evaluated: the motor part of the Unified PD Rating Scale (UPDRS-III), hyperechogenicity of the substantia nigra, prevalence of lifetime depression, hyposmia, REM sleep behavior disorder and the recently introduced probability score for prodromal PD. Sarcopenia was defined according to the European Working Group on Sarcopenia in Older People, which was adapted to this cohort of healthy adults. Multiple linear regression analysis was used to identify associations of PD-related features with ESS. Results: The UPDRS-III score was significantly associated with ESS. The result remained significant after the adjustment for age, gender and physical activity. No association was found between the other PD-related features and ESS. Conclusion: The significant association of the UPDRS-III score with ESS in this cohort might indicate a common and early pathway in both diseases and supports the existence of an “extended neurodegenerative overlap syndrome.” Moreover, the potential of EES to serve as a prodromal marker of PD should be evaluated in future studies. PMID:28326036

  7. Primary vision and facial emotion recognition in early Parkinson's disease.

    Science.gov (United States)

    Hipp, Géraldine; Diederich, Nico J; Pieria, Vannina; Vaillant, Michel

    2014-03-15

    In early stages of idiopathic Parkinson's disease (IPD), lower order vision (LOV) deficits including reduced colour and contrast discrimination have been consistently reported. Data are less conclusive concerning higher order vision (HOV) deficits, especially for facial emotion recognition (FER). However, a link between both visual levels has been hypothesized. To screen for both levels of visual impairment in early IPD. We prospectively recruited 28 IPD patients with disease duration of 1.4+/-0.8 years and 25 healthy controls. LOV was evaluated by Farnsworth-Munsell 100 Hue Test, Vis-Tech and Pelli-Robson test. HOV was examined by the Ekman 60 Faces Test and part A of the Visual Object and Space recognition test. IPD patients performed worse than controls on almost all LOV tests. The most prominent difference was seen for contrast perception at the lowest spatial frequency (p=0.0002). Concerning FER IPD patients showed reduced recognition of "sadness" (p=0.01). "Fear" perception was correlated with perception of low contrast sensitivity in IPD patients within the lowest performance quartile. Controls showed a much stronger link between "fear" perception" and low contrast detection. At the early IPD stage there are marked deficits of LOV performances, while HOV performances are still intact, with the exception of reduced recognition of "sadness". At this stage, IPD patients seem still to compensate the deficient input of low contrast sensitivity, known to be pivotal for appreciation of negative facial emotions and confirmed as such for healthy controls in this study. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  8. Cerebral oxygen metabolism in patients with early Parkinson's disease

    DEFF Research Database (Denmark)

    Borghammer, Per; Cumming, Paul; Østergaard, Karen;

    2012-01-01

    AIM: Decreased activity of the mitochondrial electron transport chain (ETC) has been implicated in the pathogenesis of Parkinson's disease (PD). This model would most likely predict a decrease in the rate of cerebral oxygen consumption (CMRO(2)). To test this hypothesis, we compared CMRO(2...

  9. Parkinson's Disease Videos

    Medline Plus

    Full Text Available ... of Parkinson's Disease OHSU - Parkinson's Disease: Managing Depression, Anxiety & Psychosis OHSU - Parkinson's Disease: Pharmacological Management of Depression, Anxiety & Psychosis OHSU - Therapeutic ...

  10. Parkinson's Disease

    Science.gov (United States)

    ... sleep behavior disorder, which involves acting out your dreams. Medications may help your sleep problems. Bladder problems. ... will diagnose Parkinson's disease based on your medical history, a review of your signs and symptoms, and ...

  11. Parkinson's Disease Dementia

    Science.gov (United States)

    ... Find your local chapter Join our online community Parkinson's Disease Dementia Parkinson's disease dementia is an impairment in ... disease. About Symptoms Diagnosis Causes & risks Treatments About Parkinson's disease dementia The brain changes caused by Parkinson's disease ...

  12. Unilateral Subthalamic Nucleus Stimulation in the Treatment of Asymmetric Parkinson"s Disease with Early Motor Complications.

    Science.gov (United States)

    Sobstyl, Michal; Zabek, Miroslaw; Zaczynski, Artur; Gorecki, Wojciech; Mossakowski, Zbigniew; Brzuszkiewicz-Kuzmicka, Grazyna

    2017-01-01

    The aim of this study was to assess the results of unilateral subthalamic nucleus (STN) stimulation for the treatment of Parkinson"s disease (PD) with marked asymmetry of parkinsonian motor symptoms and early motor complications. The clinical series consisted of 32 consecutive PD patients, in whom unilateral STN stimulation was performed. All patients were assessed according to the Unified Parkinson"s Disease Rating Scale (UPDRS), and Hoehn and Yahr staging. The patients were assessed preoperatively, and at 12, and 24 months after unilateral STN stimulation. 22 patients were followed for 2 years. Medication off/stimulation on total UPDRS motor scores were improved by 29% when compared to the baseline medication off motor scores. The contralateral motor scores improved by 49%, whereas the axial motor scores by 18% in medication off/stimulation on condition. The duration and severity of levodopa induced dyskinesia were reduced respectively by 73% and by 77%. The daily levodopa dose was decreased by only 10%. Unilateral STN stimulation is a safe and effective procedure for selected patients with marked asymmetry Parkinson"s disease motor symptoms and early motor complications.

  13. Locomotor function in the early stage of Parkinson's disease.

    Science.gov (United States)

    Carpinella, Ilaria; Crenna, Paolo; Calabrese, Elena; Rabuffetti, Marco; Mazzoleni, Paolo; Nemni, Raffaello; Ferrarin, Maurizio

    2007-12-01

    The cardinal motor symptoms of Parkinson's disease (PD) have been widely investigated with particular reference to abnormalities of steady-state walking. The great majority of studies, however are related to severe forms of PD patients (phases > = 3 of Hoehn and Yahr scale), where locomotor abnormalities are clearly manifested. Goal of the present study was to quantitatively describe locomotor symptoms in subjects with mild PD. Accordingly, a multitask protocol involving instrumental analysis of steady-state linear walking, initiation of gait, and turning while walking was applied to a group of patients with idiopathic PD in their early clinical stage (phases 1 and 2 of Hoehn and Yahr scale), as well as in age-matched elderly controls. Kinematic, kinetic, and myoelectric measures were obtained by optoelectronic motion analysis, force platform, and telemetric electromyography. Results in PD patients showed a tendency to bradykinetic gait, with reduction of walking speed and cadence. Impairments of gait initiation consisted in reduction of the backward shift of the center of pressure (CoP) and prolongation of the stepping phase. Alterations of the turning task were more consistent and included delayed reorientation of the head toward the new direction, altered head-upper trunk rotational strategy, and adoption of a greater number of steps to complete the turning. It is concluded that patients in the early stage of PD reveal mild alterations of steady-state linear walking and more significant anomalies in the transitional conditions, especially during changes in the travel direction. Quantitative analysis of nonstationary locomotor tasks might be a potentially useful starting point for further studies on the pathophysiology of PD.

  14. Spatial disorientation as an early symptom of Parkinson's disease.

    Science.gov (United States)

    Hovestadt, A; de Jong, G J; Meerwaldt, J D

    1987-03-01

    In 44 consecutive outpatients with idiopathic Parkinson's disease (PD) without levodopa substitution therapy, we tested spatial orientation. Spatial orientation was impaired on the rod orientation test in 43 patients, on the line orientation test in 7 patients, and on the facial recognition test in 17 patients. There was no correlation between severity of spatial disorientation and age, length of illness, verbal WAIS score, or severity of PD. Impairment of spatial orientation is part of PD even in mild cases.

  15. Olfactory Loss in Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Antje Haehner

    2011-01-01

    Full Text Available Impairment of olfaction is a characteristic and early feature of Parkinson's disease. Recent data indicate that >95% of patients with Parkinson's disease present with significant olfactory loss. Deficits in the sense of smell may precede clinical motor symptoms by years and can be used to assess the risk for developing Parkinson's disease in otherwise asymptomatic individuals. This paper summarizes the available information about olfactory function in Parkinson's disease, indicating the advantageous use of olfactory probes in early and differential diagnosis.

  16. Dream features in the early stages of Parkinson's disease.

    Science.gov (United States)

    Bugalho, Paulo; Paiva, Teresa

    2011-11-01

    Few studies have investigated the relation between dream features and cognition in Parkinson's disease (PD), although vivid dreams, hallucinations and cognitive decline have been proposed as successive steps of a pathological continuum. Our objectives were therefore to characterize the dreams of early stage PD and to study the relation between dream characteristics, cognitive function, motor status, depression, dopaminergic treatment, and the presence of REM sleep behaviour disorder (RBD) and hallucinations. Dreams of 19 male PD patients and 21 matched control subjects were classified according to Hall and van de Castle system. h statistics was used to compare the dream content between patients and controls. We tested the relation between patients' dreams characteristics and cognitive function (Frontal assessment battery (FAB) and Mini-Mental State Examination tests) depression (Beck depression inventory), motor function (UPDRS), dopaminergic treatment, the presence of RBD (according to clinical criteria) and hallucinations, using general linear model statistics. Patients and controls differed only on FAB scores. Relevant differences in the Hall and van de Castle scale were found between patient's dreams and those of the control group, regarding animals, aggression/friendliness, physical aggression, befriender (higher in the patient group) and aggressor and bodily misfortunes (lower in the patient group) features. Cognitive and particularly frontal dysfunction had a significant influence on the frequency of physical aggression and animal related features, while dopaminergic doses, depressive symptoms, hallucinations and RBD did not. We found a pattern of dream alteration characterized by heightened aggressiveness and the presence of animals. These were related to more severe frontal dysfunction, which could be the origin of such changes.

  17. Parkinson's disease

    DEFF Research Database (Denmark)

    Astradsson, Arnar; Aziz, Tipu Z

    2015-01-01

    -derived therapy in people with Parkinson's disease? We searched: Medline, Embase, The Cochrane Library and other important databases up to September 2014 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from...

  18. Parkinson disease

    Science.gov (United States)

    In Parkinson disease, dopamine production becomes irregular and inadequate and nerve cells cannot properly transmit messages. This results in the loss of muscle function. By providing an even, adequate supply of medication that the body converts into dopamine, neurons are able to transmit ...

  19. Basal ganglia dysfunction in idiopathic REM sleep behaviour disorder parallels that in early Parkinson's disease.

    Science.gov (United States)

    Rolinski, Michal; Griffanti, Ludovica; Piccini, Paola; Roussakis, Andreas A; Szewczyk-Krolikowski, Konrad; Menke, Ricarda A; Quinnell, Timothy; Zaiwalla, Zenobia; Klein, Johannes C; Mackay, Clare E; Hu, Michele T M

    2016-08-01

    SEE POSTUMA DOI101093/AWW131 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Resting state functional magnetic resonance imaging dysfunction within the basal ganglia network is a feature of early Parkinson's disease and may be a diagnostic biomarker of basal ganglia dysfunction. Currently, it is unclear whether these changes are present in so-called idiopathic rapid eye movement sleep behaviour disorder, a condition associated with a high rate of future conversion to Parkinson's disease. In this study, we explore the utility of resting state functional magnetic resonance imaging to detect basal ganglia network dysfunction in rapid eye movement sleep behaviour disorder. We compare these data to a set of healthy control subjects, and to a set of patients with established early Parkinson's disease. Furthermore, we explore the relationship between resting state functional magnetic resonance imaging basal ganglia network dysfunction and loss of dopaminergic neurons assessed with dopamine transporter single photon emission computerized tomography, and perform morphometric analyses to assess grey matter loss. Twenty-six patients with polysomnographically-established rapid eye movement sleep behaviour disorder, 48 patients with Parkinson's disease and 23 healthy control subjects were included in this study. Resting state networks were isolated from task-free functional magnetic resonance imaging data using dual regression with a template derived from a separate cohort of 80 elderly healthy control participants. Resting state functional magnetic resonance imaging parameter estimates were extracted from the study subjects in the basal ganglia network. In addition, eight patients with rapid eye movement sleep behaviour disorder, 10 with Parkinson's disease and 10 control subjects received (123)I-ioflupane single photon emission computerized tomography. We tested for reduction of basal ganglia network connectivity, and for loss of tracer uptake in rapid eye movement sleep

  20. Early automatic detection of Parkinson's disease based on sleep recordings

    DEFF Research Database (Denmark)

    Kempfner, Jacob; Sorensen, Helge B D; Nikolic, Miki;

    2014-01-01

    SUMMARY: Idiopathic rapid-eye-movement (REM) sleep behavior disorder (iRBD) is most likely the earliest sign of Parkinson's Disease (PD) and is characterized by REM sleep without atonia (RSWA) and consequently increased muscle activity. However, some muscle twitching in normal subjects occurs...... the number of outliers during REM sleep was used as a quantitative measure of muscle activity. RESULTS: The proposed method was able to automatically separate all iRBD test subjects from healthy elderly controls and subjects with periodic limb movement disorder. CONCLUSION: The proposed work is considered...... during REM sleep. PURPOSE: There are no generally accepted methods for evaluation of this activity and a normal range has not been established. Consequently, there is a need for objective criteria. METHOD: In this study we propose a full-automatic method for detection of RSWA. REM sleep identification...

  1. Patient Perspectives on Deep Brain Stimulation Clinical Research in Early Stage Parkinson's Disease.

    Science.gov (United States)

    Heusinkveld, Lauren; Hacker, Mallory; Turchan, Maxim; Bollig, Madelyn; Tamargo, Christina; Fisher, William; McLaughlin, Lauren; Martig, Adria; Charles, David

    2017-01-01

    The FDA has approved a multicenter, double-blind, Phase III, pivotal trial testing deep brain stimulation (DBS) in 280 people with very early stage Parkinson's disease (PD; IDE#G050016). In partnership with The Michael J. Fox Foundation for Parkinson's Research, we conducted a survey to investigate motivating factors, barriers, and gender differences among potentially eligible patients for participation in a trial testing DBS in early PD compared to standard medical treatment. The majority of survey respondents (72%) indicated they would consider learning more about participating. Early PD patients are therefore likely to consider enrolling in trials of invasive therapies that may slow symptom progression and help future patients.

  2. Parkinson's disease

    DEFF Research Database (Denmark)

    Astradsson, Arnar; Aziz, Tipu Z

    2015-01-01

    INTRODUCTION: The mean age of onset of Parkinson's disease is about 65 years, with a median time of 9 years between diagnosis and death. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical question: What are the effects of fetal cell or stem cell......-derived therapy in people with Parkinson's disease? We searched: Medline, Embase, The Cochrane Library and other important databases up to September 2014 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from...... relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found two studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS...

  3. Update on Parkinson disease.

    Science.gov (United States)

    Siderowf, Andrew; Stern, Matthew

    2003-04-15

    This Update reviews developments in the pathophysiology and treatment of Parkinson disease during the past several years. In the area of pathophysiology, studies have addressed the contribution of environmental factors such as caffeine and pesticides. Large-scale epidemiologic studies have also expanded the role genetic factors are thought to play. Detailed studies of kindreds with familial Parkinson disease due to alpha-synuclein and parkin have catalyzed basic science investigations into the pathologic mechanisms of the disease. These studies have led to the development of a pathophysiologic model of Parkinson disease that emphasizes abnormal protein aggregation. Studies of treatment have clarified the relative roles of l-dopa and dopamine agonists in early Parkinson disease and shown the potential for surgical interventions, particularly deep-brain stimulation, to relieve the symptoms of advanced, medically refractory disease.

  4. Early Parkinson's May Prompt Vision Problems

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_167131.html Early Parkinson's May Prompt Vision Problems Changes in sight could ... in vision may be an early sign of Parkinson's disease, researchers report. The neurodegenerative condition is caused ...

  5. Parkinson's Disease Videos

    Medline Plus

    Full Text Available ... and Social Network? How Does Parkinson's Disease Affect Memory? How Does Parkinson's Disease Affect the Urinary System? ... Parkinson's Disease Patients with a Depression Diagnosis? What Type of Exercise or Exercise Programs Are Recommended? What ...

  6. Learning about Parkinson's Disease

    Science.gov (United States)

    ... About Parkinson's Disease Specific Genetic Disorders Specific Genetic Disorders Learning About Prostate Cancer See Also: Talking Glossary of ... diseases Journal of Biological Chemistry , June 9, 2011 Learning About Parkinson's Disease What do we know about heredity and Parkinson's ...

  7. Association between α-synuclein blood transcripts and early, neuroimaging-supported Parkinson's disease.

    Science.gov (United States)

    Locascio, Joseph J; Eberly, Shirley; Liao, Zhixiang; Liu, Ganqiang; Hoesing, Ashley N; Duong, Karen; Trisini-Lipsanopoulos, Ana; Dhima, Kaltra; Hung, Albert Y; Flaherty, Alice W; Schwarzschild, Michael A; Hayes, Michael T; Wills, Anne-Marie; Shivraj Sohur, U; Mejia, Nicte I; Selkoe, Dennis J; Oakes, David; Shoulson, Ira; Dong, Xianjun; Marek, Ken; Zheng, Bin; Ivinson, Adrian; Hyman, Bradley T; Growdon, John H; Sudarsky, Lewis R; Schlossmacher, Michael G; Ravina, Bernard; Scherzer, Clemens R

    2015-09-01

    There are no cures for neurodegenerative diseases and this is partially due to the difficulty of monitoring pathogenic molecules in patients during life. The Parkinson's disease gene α-synuclein (SNCA) is selectively expressed in blood cells and neurons. Here we show that SNCA transcripts in circulating blood cells are paradoxically reduced in early stage, untreated and dopamine transporter neuroimaging-supported Parkinson's disease in three independent regional, national, and international populations representing 500 cases and 363 controls and on three analogue and digital platforms with P disease of 2.45 compared to individuals in the highest quartile. Disease-relevant transcript isoforms were low even near disease onset. Importantly, low SNCA transcript abundance predicted cognitive decline in patients with Parkinson's disease during up to 5 years of longitudinal follow-up. This study reveals a consistent association of reduced SNCA transcripts in accessible peripheral blood and early-stage Parkinson's disease in 863 participants and suggests a clinical role as potential predictor of cognitive decline. Moreover, the three independent biobank cohorts provide a generally useful platform for rapidly validating any biological marker of this common disease. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  8. Early phenotypic differences between Parkinson's disease patients with and without freezing of gait

    NARCIS (Netherlands)

    Hall, J. M.; Shine, J. M.; Walton, C. C.; Gilat, M.; Kamsma, Y. P. T.; Naismith, S. L.; Lewis, S. J. G.

    2014-01-01

    Background: Previous studies have associated freezing of gait in Parkinson's disease with the presence of specific phenotypic features such as mood disturbances, REM sleep behavior disorder and selective cognitive impairments. However, it is not clear whether these features are present in the earlie

  9. The role of neuroimaging in the early diagnosis and evaluation of Parkinson's disease.

    Science.gov (United States)

    Seibyl, J; Jennings, D; Tabamo, R; Marek, K

    2005-10-01

    The development of imaging biomarkers which target specific sites in the brain represents a significant advance in neurodegenerative diseases and Parkinson's disease with the promise of new and improved approaches for the early and accurate diagnosis of disease as well as novel ways to monitor patients and assess treatment. The 3 major applications of imaging may play a role in Parkinson's disease include: 1) the use of neuroimaging as a biomarker of disease in order to improve the accuracy, timeliness, and reliability of diagnosis; 2) objective monitoring of the progression of disease to provide a molecular phenotype of Parkinson's disease which may illuminate some of the sources of clinical variability; 3) the evaluation of so-called ''disease-modifying'' treatments designed to retard the progression of disease by interfering with pathways thought implicated in the ongoing neuronal loss or replace dopamine-producing cells. Each of these areas has shown a numbers of critical clinical investigations which have better defined the utility of the imaging tools to these tasks. Nonetheless, current unresolved issues around the clinical role of neuroimaging in monitoring patients over time and validation of quantitative imaging measures of dopaminergic function are immediate issues for the field and the subject of current research efforts and the extension of the lessons learned in Parkinson's to other neurodegenerative diseases including Alzheimer's dementia.

  10. Parkinson's Disease Videos

    Medline Plus

    Full Text Available ... Sexual Functioning? How Does Depression Affect the Patient's Family and Social Network? How Does Parkinson's Disease Affect Memory? How Does Parkinson's Disease Affect the Urinary System? How Does Speech Therapy Help Parkinson's Patients? How ...

  11. What Is Parkinson's Disease?

    Science.gov (United States)

    ... million people in the US are living with Parkinson's disease. The cause is unknown, and although there is presently no ... a Diagnosis What is Parkinson’s Disease? ... Trials Statistics on Parkinson's What's New In Parkinson's Research? What's in the ...

  12. Managing Your Parkinson's Disease

    Science.gov (United States)

    ... Patient Advocates Sign Up for Funding News npj Parkinson's Disease Scientific Advisory Board Understanding Parkinson's Coping with a Diagnosis What is Parkinson’s Disease? National HelpLine Educational Publications Online Seminars Parkinson's News ...

  13. Pain in Parkinson's Disease

    Science.gov (United States)

    ... Patient Advocates Sign Up for Funding News npj Parkinson's Disease Scientific Advisory Board Understanding Parkinson's Coping with a Diagnosis What is Parkinson’s Disease? National HelpLine Educational Publications Online Seminars Parkinson's News ...

  14. Parkinson's Disease Foundation Newsletter

    Science.gov (United States)

    ... Patient Advocates Sign Up for Funding News npj Parkinson's Disease Scientific Advisory Board Understanding Parkinson's Coping with a Diagnosis What is Parkinson’s Disease? National HelpLine Educational Publications Online Seminars Parkinson's News ...

  15. Parkinson's Disease Foundation

    Science.gov (United States)

    ... Patient Advocates Sign Up for Funding News npj Parkinson's Disease Scientific Advisory Board Understanding Parkinson's Coping with a Diagnosis What is Parkinson’s Disease? National HelpLine Educational Publications Online Seminars Parkinson's News ...

  16. Parkinson's Disease Videos

    Medline Plus

    Full Text Available ... Parkinson's Disease Affect the Urinary System? How Does Speech Therapy Help Parkinson's Patients? How Does the DBS ... A Mind Guide to Parkinson’s Disease Nutrition Matters Speech and Swallowing Psychosis: A Mind Guide to Parkinson's ...

  17. THE РERSONALITY PROFILE OF PATIENTS WITH EARLY MANIFESTATIONS OF PARKINSON'S DISEASE

    Directory of Open Access Journals (Sweden)

    R. R. Bogdanov

    2016-01-01

    Full Text Available Background: Mental disorders that sometimes may precede motor dysfunction have an important value in Parkinson's disease, especially at its earlier stages. Personality characteristics of patients with Parkinson's disease have not been studied enough and require a  detailed assessment, because it is a  major factor contributing to treatment efficacy. Aim: To assess personality profiles of patients with early stages of Parkinson's disease and an impact of a dopamine receptor agonist on the personality profile. Materials and methods: We assessed 33 treatment-naïve patients with early symptoms of Parkinson's disease (Hoehn-Yahr stage I and II. The following scales were used before treatment and at 1, 3 and 6 months of treatment with pramipexol: for motor disorders (UPDRS, Unified Parkinson's Disease Rating Scale, depressive disorders (MADRS, Montgomery Asberg Depression Rating Scale and anxiety disorders (HARS, Hamilton Anxiety Rating Scale, as well as personality profile (MMPI, Minnesota Multiphasic Personality Inventory. Results: The personality profile assessed by MMPI in patients with early stage Parkinson's disease was characterized by highest T scores on scales 2 (pessimism (74 [64; 86], 1 (neurotic excess control (67 [63; 74], 3  (emotional instability (64 [56; 70], 7 (anxiousness (63 [52; 70], 8 (autism (64 [58; 74], 0  (introversion (63 [59; 66]. This indicates basic pathopsychological characteristics of patients with early stages of the disease. In particular, their emotional sphere demonstrated anxiety- and depression-related affective disorders. Their personality structure was characterized by dysthymic, anxious, rigid and explosive traits, and susceptibility to hypochondriasis. With a background of a dramatic motivational conflict, frustration of high-level need in self-actualization and recognition due to a chronic disease with motor dysfunction triggered a depressive response type. Pharmacological treatment with

  18. "DASH" symptoms in patients with Parkinson's disease: red flags for early cognitive decline.

    Science.gov (United States)

    Naismith, Sharon L; Lewis, Simon J G

    2011-03-01

    Neuropsychiatric features in Parkinson's Disease (PD) are associated with developing dementia longitudinally. Therefore, identifying appropriate screening methods for such features, and their association with early cognitive dysfunction, may help to inform early intervention approaches. In this study, 53 PD patients without dementia underwent detailed neurological and neuropsychological assessment. The sum scores of the four items detailing Depression, Anxiety, Sleep disturbance and Hallucinosis (DASH) were calculated from the Parkinson's Disease Questionnaire (PDQ-39) and examined in relation to cognitive tasks. Results demonstrated that higher DASH scores were significantly correlated with poorer working memory and set-shifting performance, even after controlling for age, predicted intellect, depression, disease stage and duration. These data indicate that DASH symptoms are related to executive dysfunction even in non-demented patients with PD. The DASH score may represent a simple screening method for highlighting early cognitive decline, which in turn is associated with the development of dementia in PD.

  19. DNAJC6 Mutations Associated with Early-Onset Parkinson's Disease

    NARCIS (Netherlands)

    S. Olgiati (Simone); M. Quadri (Marialuisa); M. Fang (Mingyan); J.P.M.A. Rood (Janneke P.M.A.); J.A. Saute (Jonas A.); H.F. Chien (Hsin Fen); C.G. Bouwkamp (Christian); J. Graafland (Josja); M. Minneboo (Michelle); G.J. Breedveld (Guido J.); J. Zhang (Jianguo); F.W. Verheijen (Frans W.); A.J.W. Boon (Agnita J.W.); A.J.A. Kievit (Anneke J.A.); L.B. Jardim (L.); W.J. Mandemakers (Wim); E.R. Barbosa (Egberto Reis); C.R.M. Rieder (Carlos); K.L. Leenders (Klaus L.); J. Wang (Jinxia); V. Bonifati (Vincenzo)

    2016-01-01

    markdownabstract_Objective_ DNAJC6 mutations were recently described in two families with autosomal recessive juvenile parkinsonism (onset age < 11), prominent atypical signs, poor or absent response to levodopa, and rapid progression (wheelchair-bound within ∼10 years from onset). Here, for the

  20. Perspective: Identification of genetic variants associated with dopaminergic compensatory mechanisms in early Parkinson's disease

    OpenAIRE

    2013-01-01

    Parkinson's disease (PD) is slowly progressive, and heterogeneity of its severity among individuals may be due to endogenous mechanisms that counterbalance the striatal dopamine loss. In this perspective paper, we introduce a neuroimaging-genetic approach to identify genetic variants, which may contribute to this compensation. First, we briefly review current known potential compensatory mechanisms for premotor and early disease PD, located in the striatum and other brain regions. Then, we c...

  1. PGC-1{alpha}, A Potential Therapeutic Target for Early Intervention in Parkinson's Disease

    DEFF Research Database (Denmark)

    Zheng, B.; Liao, Z.; Locascio, J.J.;

    2010-01-01

    Parkinson's disease affects 5 million people worldwide, but the molecular mechanisms underlying its pathogenesis are still unclear. Here, we report a genome-wide meta-analysis of gene sets (groups of genes that encode the same biological pathway or process) in 410 samples from patients with sympt......Parkinson's disease affects 5 million people worldwide, but the molecular mechanisms underlying its pathogenesis are still unclear. Here, we report a genome-wide meta-analysis of gene sets (groups of genes that encode the same biological pathway or process) in 410 samples from patients...... with symptomatic Parkinson's and subclinical disease and healthy controls. We analyzed 6.8 million raw data points from nine genome-wide expression studies, and 185 laser-captured human dopaminergic neuron and substantia nigra transcriptomes, followed by two-stage replication on three platforms. We found 10 gene...... by mutant α-synuclein or the pesticide rotenone in cellular disease models. Our systems biology analysis of Parkinson's disease identifies PGC-1α as a potential therapeutic target for early intervention....

  2. Frequency of LRRK2 mutations in early- and late-onset Parkinson disease.

    Science.gov (United States)

    Clark, L N; Wang, Y; Karlins, E; Saito, L; Mejia-Santana, H; Harris, J; Louis, E D; Cote, L J; Andrews, H; Fahn, S; Waters, C; Ford, B; Frucht, S; Ottman, R; Marder, K

    2006-11-28

    To evaluate the frequency of leucine-rich repeat kinase gene (LRRK2) mutations and single nucleotide polymorphisms (SNPs) in early-onset Parkinson disease (EOPD) and late-onset Parkinson disease (LOPD). We genotyped five previously reported LRRK2 mutations (G2019S, L1114L, I1122V, R1441C, and Y1699C) and 17 coding SNPs for haplotype analysis in 504 cases with PD and 314 controls enrolled in the Genetic Epidemiology of PD Study. Cases and controls were recruited without knowledge of family history of PD and cases were oversampled in the 50 (p = 0.56). All cases with PD with the G2019S mutation shared the same disease-associated haplotype. The frequency of the LRRK2 G2019S mutation was higher in the subset of 181 cases reporting four Jewish grandparents (9.9%) than in other cases (3.1%) (p Parkinson disease and confirms the previous report of a greater frequency of the G2019S mutation in Jewish than in non-Jewish cases with Parkinson disease.

  3. Biomarkers for Parkinson's disease.

    Science.gov (United States)

    Sherer, Todd B

    2011-04-20

    Biomarkers for detecting the early stages of Parkinson's disease (PD) could accelerate development of new treatments. Such biomarkers could be used to identify individuals at risk for developing PD, to improve early diagnosis, to track disease progression with precision, and to test the efficacy of new treatments. Although some progress has been made, there are many challenges associated with developing biomarkers for detecting PD in its earliest stages.

  4. The impact of rotigotine on cardiovascular autonomic function in early Parkinson's disease.

    Science.gov (United States)

    Rocchi, Camilla; Pierantozzi, Mariangela; Pisani, Valerio; Marfia, Girolama Alessandra; Di Giorgio, Alessandra; Stanzione, Paolo; Bernardi, Giorgio; Stefani, Alessandro

    2012-01-01

    Dysautonomia can occur in early stages of Parkinson's disease (PD) influencing tolerance to dopaminergic therapies. Rotigotine, a non-ergot dopamine agonist, has recently been developed as an effective alternative antiparkinsonian drug, but its influence on the autonomic nervous system was not investigated. Twenty subjects out of 34 consecutive de novo PD patients were submitted to full assessment of cardiovascular autonomic function before and after reaching a stable rotigotine regimen [6 mg/24 h (n = 3) or 8 mg/24 h (n = 17)]. Patients reached significant clinical improvement (-27% on the Unified Parkinson's Disease Rating Scale part III) and did not show significant differences in cardiovascular tests compared to baseline data. However, an unexpected trend towards increasing systolic blood pressure after head-up tilt test was detected. Our study demonstrates that rotigotine does not influence cardiovascular autonomic responses in early de novo PD patients. Consequently, it may represent a well-tolerated and efficacious therapeutic option in newly diagnosed PD subjects.

  5. Parkinson Disease and Dementia.

    Science.gov (United States)

    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.

  6. Dopamine Transporter Neuroimaging as an Enrichment Biomarker in Early Parkinson's Disease Clinical Trials: A Disease Progression Modeling Analysis.

    Science.gov (United States)

    Conrado, Daniela J; Nicholas, Timothy; Tsai, Kuenhi; Macha, Sreeraj; Sinha, Vikram; Stone, Julie; Corrigan, Brian; Bani, Massimo; Muglia, Pierandrea; Watson, Ian A; Kern, Volker D; Sheveleva, Elena; Marek, Kenneth; Stephenson, Diane T; Romero, Klaus

    2017-07-27

    Given the recognition that disease-modifying therapies should focus on earlier Parkinson's disease stages, trial enrollment based purely on clinical criteria poses significant challenges. The goal herein was to determine the utility of dopamine transporter neuroimaging as an enrichment biomarker in early motor Parkinson's disease clinical trials. Patient-level longitudinal data of 672 subjects with early-stage Parkinson's disease in the Parkinson's Progression Markers Initiative (PPMI) observational study and the Parkinson Research Examination of CEP-1347 Trial (PRECEPT) clinical trial were utilized in a linear mixed-effects model analysis. The rate of worsening in the motor scores between subjects with or without a scan without evidence of dopamine transporter deficit was different both statistically and clinically. The average difference in the change from baseline of motor scores at 24 months between biomarker statuses was -3.16 (90% confidence interval [CI] = -0.96 to -5.42) points. Dopamine transporter imaging could identify subjects with a steeper worsening of the motor scores, allowing trial enrichment and 24% reduction of sample size. Published 2017. This article is a U.S. Government work and is in the public domain in the USA. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  7. Parkinson's Disease Videos

    Medline Plus

    Full Text Available ... Parkinson's Disease Cognition: A Mind Guide to Parkinson’s Disease Nutrition Matters Speech and Swallowing Psychosis: A Mind Guide to Parkinson's Disease Guide to Deep Brain Stimulation You Can Make ...

  8. Parkinson disease - discharge

    Science.gov (United States)

    Your doctor has told you that you have Parkinson disease . This disease affects the brain and leads to ... have you take different medicines to treat your Parkinson disease and many of the problems that may come ...

  9. What Is Parkinson's Disease?

    Science.gov (United States)

    ... resources & more. Order Free Materials Today What is Parkinson’s Disease? Parkinson's disease (PD) is a chronic and progressive movement disorder, ... million people in the US are living with Parkinson's disease. The cause is unknown, and although there is ...

  10. Parkinson's disease.

    Science.gov (United States)

    Benninger, David H

    2013-01-01

    In advanced Parkinson's disease (PD), the emergence of symptoms refractory to conventional therapy poses therapeutic challenges. The success of deep brain stimulation (DBS) and advances in the understanding of the pathophysiology of PD have raised interest in noninvasive brain stimulation as an alternative therapeutic tool. The rationale for its use draws from the concept that reversing abnormalities in brain activity and physiology thought to cause the clinical deficits may restore normal functioning. Currently the best evidence in support of this concept comes from DBS, which improves motor deficits, and modulates brain activity and motor cortex physiology, although whether a causal interaction exists remains largely undetermined. Most trials of noninvasive brain stimulation in PD have applied repetitive transcranial magnetic stimulation (rTMS), targeting the motor cortex. Current studies suggest a possible therapeutic potential for rTMS and transcranial direct current stimulation (tDCS), but clinical effects so far have been small and negligible with regard to functional independence and quality of life. Approaches to potentiate the efficacy of rTMS include increasing stimulation intensity and novel stimulation parameters that derive their rationale from studies on brain physiology. These novel parameters are intended to simulate normal firing patterns or to act on the hypothesized role of oscillatory activity in the motor cortex and basal ganglia with regard to motor control and its contribution to the pathogenesis of motor disorders. Noninvasive brain stimulation studies will enhance our understanding of PD pathophysiology and might provide further evidence for potential therapeutic applications.

  11. Characterisation of foot clearance during gait in people with early Parkinson׳s disease: Deficits associated with a dual task.

    Science.gov (United States)

    Alcock, Lisa; Galna, Brook; Lord, Sue; Rochester, Lynn

    2016-09-06

    Tripping is a common cause of falls in older adults and people with Parkinson׳s disease (PD). Foot clearance during gait may be impaired when distracted by a dual task and thus inform trip risk. This study aimed to evaluate whether foot clearance is impaired in PD and is adversely affected by a dual task. 81 older adults and 76 PD walked at a comfortable pace for two minutes under single and dual task conditions (digit recall). Temporal spatial gait was measured using an instrumented walkway. Heel and toe trajectories were obtained bilaterally using 3-dimensional motion capture. Foot clearance was reduced in PD (pclearance in late swing) and gait velocity (landing gradient). Distinct differences in foot clearance were observed even in the early clinical stages of PD. Dual tasking may increase trip risk due to insufficient toe clearance (early swing) for both older adults and PD. Inadequate heel clearance (late swing) may increase falls risk in PD. Clearance deficits in PD are partially related to a reduced gait velocity and step length which may be targeted in tailored therapies. Further work is necessary to understand the mechanisms underlying this pathology-associated deficit.

  12. Genetics of Parkinson's disease.

    Science.gov (United States)

    Gasser, Thomas

    2005-08-01

    Parkinson's disease is the second most common neurodegenerative disorder and affects 2% of the population over the age of 60 years. Due to the increasing proportion of elderly individuals in developed countries, Parkinson's disease and related neurodegenerative disorders represent a growing burden on the health care system. In the majority of cases, the cause of the disease is still unknown, and its elucidation remains one of the major challenges of the neurosciences. Recent findings in rare genetic forms of Parkinson's disease have allowed the development of novel animal models, providing a basis for a better understanding of the molecular pathogenesis of the disease, setting the stage for the development of novel treatment strategies. Several novel genes for monogenic forms of Parkinson's disease, such as PINK-1 for an autosomal-recessive early-onset variant, and LRRK2 for a relatively common late-onset autosomal-dominant form have recently been discovered, and several novel animal models have been generated on the basis of genes that had been found earlier. The combination of genetic, pathologic and molecular findings provide increasing evidence that the pathways identified through the cloning of different disease genes are interacting on different levels and share several major pathogenic mechanisms.

  13. Predictors of Mild Cognitive Impairment in Early-Stage Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Brenda Hanna-Pladdy

    2013-05-01

    Full Text Available Aim: The aim of this study was to identify mild cognitive deficits in Parkinson's disease (PD prior to extensive neurodegeneration and to evaluate the extent to which dopamine depletion and other disease-related predictors can explain cognitive profiles. Methods: Neuropsychological performances of 40 nondemented early-stage PD patients and 42 healthy controls were compared across on or off dopaminergic medications. Stepwise regression evaluated cognitive predictors of early-stage PD and disease-related predictors of PD cognition (levodopa dose, disease duration, Unified Parkinson's Disease Rating Scale score, sleep, quality of life, and mood across on and off states. Results: Neuropsychological performance was lower in PD patients across cognitive domains with significant memory, naming, visuomotor, and complex attention/executive deficits, but with intact visuospatial, simple attention, and phonemic fluency functions. However, medication effects were absent except for simple attention. Regression analyses revealed age, working memory, and memory recall to be the best cognitive predictors of PD, while age, quality of life, disease duration, and anxiety predicted PD cognition in the off state. Conclusion: Nondemented early-stage PD patients presented with extensive mild cognitive deficits including prominent memory impairment. The profile was inconsistent with expected isolated frontostriatal dysfunction previously attributed to dopamine depletion and this highlights the need to further characterize extranigral sources of mild cognitive impairment in PD.

  14. Parkinson's Disease Videos

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    Full Text Available ... Care: Real Stories Betsaida Cruz, PT, Long Beach Memorial Medicinal: “Terapia fisica para el Parkinson” Building a ... and Social Network? How Does Parkinson's Disease Affect Memory? How Does Parkinson's Disease Affect the Urinary System? ...

  15. Parkinson's Disease Videos

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    Full Text Available ... Use for Freezing? Are There Any Ways to Control the Rate of Progression of the Disease? Ask ... Memory? How Does Parkinson's Disease Affect the Urinary System? How Does Speech Therapy Help Parkinson's Patients? How ...

  16. Parkinson's Disease Videos

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    Full Text Available ... Disease Nutrition Matters Speech and Swallowing Psychosis: A Mind Guide to Parkinson's Disease Guide to Deep Brain Stimulation You Can Make A Difference Your donation to the National Parkinson Foundation goes ...

  17. Parkinson disease: an update.

    Science.gov (United States)

    Gazewood, John D; Richards, D Roxanne; Clebak, Karl

    2013-02-15

    Parkinson disease is a progressive neurologic disorder afflicting approximately 1 percent of Americans older than 60 years. The cardinal features of Parkinson disease are bradykinesia, rigidity, tremor, and postural instability. There are a number of neurologic conditions that mimic the disease, making it difficult to diagnose in its early stages. Physicians who rarely diagnose Parkinson disease should refer patients suspected of having it to physicians with more experience in making the diagnosis, and should periodically reevaluate the accuracy of the diagnosis. Treatment is effective in reducing motor impairment and disability, and should be started when a patient begins to experience functional impairment. The combination of carbidopa and levodopa is the most effective treatment, but dopamine agonists and monoamine oxidase-B inhibitors are also effective, and are less likely to cause dyskinesias. For patients taking carbidopa/levodopa who have motor complications, adjunctive therapy with a dopamine agonist, a monoamine oxidase-B inhibitor, or a catechol O-methyltransferase inhibitor will improve motor symptoms and functional status, but with an increase in dyskinesias. Deep brain stimulation is effective in patients who have poorly controlled symptoms despite optimal medical therapy. Occupational, physical, and speech therapy improve patient function. Fatigue, sleep disturbances, dementia, and depression are common in patients with Parkinson disease. Although these conditions are associated with significantly lower quality of life, they may improve with treatment.

  18. Sensory Dysfunction in Early Parkinson’s Disease

    Science.gov (United States)

    2011-07-01

    Disease Rating Scale ( UPDRS ), Hoehn and Yahr Scale (H&Y) and Schwab and England ADL Scale (S&E). All contrl subjects were entirely free of motor...symptoms ( UPDRS score < 2, H&Y = 0, S&E = 100%). A careful family history was taken to insure that that no first-degree relatives had PD or any other...neurodegenerative disease. All PD patients were rated with mild PD motor characteristics ( UPDRS score < 25, H&Y ≤ 2, S&E ≥ 90%) and were newly

  19. Assessment of voice and speech symptoms in early Parkinson's disease by the Robertson dysarthria profile.

    Science.gov (United States)

    Defazio, Giovanni; Guerrieri, Marta; Liuzzi, Daniele; Gigante, Angelo Fabio; di Nicola, Vincenzo

    2016-03-01

    Changes in voice and speech are thought to involve 75-90% of people with PD, but the impact of PD progression on voice/speech parameters is not well defined. In this study, we assessed voice/speech symptoms in 48 parkinsonian patients staging dysarthria profile (a clinical-perceptual method exploring all components potentially involved in speech difficulties), the Voice handicap index (a validated measure of the impact of voice symptoms on quality of life) and the speech evaluation parameter contained in the Unified Parkinson's Disease Rating Scale part III (UPDRS-III). Accuracy and metric properties of the Robertson dysarthria profile were also measured. On Robertson dysarthria profile, all parkinsonian patients yielded lower scores than healthy control subjects. Differently, the Voice Handicap Index and the speech evaluation parameter contained in the UPDRS-III could detect speech/voice disturbances in 10 and 75% of PD patients, respectively. Validation procedure in Parkinson's disease patients showed that the Robertson dysarthria profile has acceptable reliability, satisfactory internal consistency and scaling assumptions, lack of floor and ceiling effects, and partial correlations with UPDRS-III and Voice Handicap Index. We concluded that speech/voice disturbances are widely identified by the Robertson dysarthria profile in early parkinsonian patients, even when the disturbances do not carry a significant level of disability. Robertson dysarthria profile may be a valuable tool to detect speech/voice disturbances in Parkinson's disease.

  20. DYT1 mutations in early onset primary torsion dystonia and Parkinson disease patients in Chinese populations.

    Science.gov (United States)

    Yang, Jing-Fang; Wu, Tao; Li, Jian-Yu; Li, Yong-Jie; Zhang, Yan-Li; Chan, Piu

    2009-01-30

    Torsion dystonia is an autosomal dominant movement disorder characterized by involuntary, repetitive muscle contractions and twisted postures. The most severe early onset form of dystonia has been linked to mutations in the human DYT1 (TOR1A) gene encoding a protein termed torsinA. Moreover, dystonia and Parkinson disease share the common feature of reduced dopamine neurotransmission in the striatum, so we assumed that mutations in the DYT1 gene might have the same role in cases of early onset primary torsion dystonia (EOPTD) and early onset Parkinson disease (EOPD) that present dystonia. In this present study, 17 patients with EOPTD, 221 patients with EOPD and 164 control subjects were screened for mutations of the DYT1 gene by denaturing high performance liquid chromatography (DHPLC), polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis and DNA sequencing. Our results showed that the GAG deletion was identified in 7 EOPTD patients, which results in Glu302del of DYT1 gene. No mutations were found in EOPD patients and control subjects. By carefully reviewing the available literature on studies of sporadic, non-Ashkenazi Jewish populations, the results showed that the prevalence rate of DYT1 mutation was not significantly different (p=0.267) between European (27.3%) and Asian (22.2%) patients with early onset primary torsion dystonia.

  1. Parkinson's Disease Glossary

    Science.gov (United States)

    ... rarer) forms of Parkinson's disease. See also: familial Parkinson's disease Stem cells Very immature cells with potential to differentiate into ... mutations in UCH-L1 may increase risk of Parkinson's onset. See also: protein handling , ... stem cells Undifferentiated cells taken from umbilical cord blood. These ...

  2. Parkinson's Disease Videos

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    Full Text Available ... How Does Depression Affect the Patient's Family and Social Network? How Does Parkinson's Disease Affect Memory? How Does Parkinson's Disease Affect the Urinary System? How Does Speech Therapy Help Parkinson's ... our Helpline: 1-800-4PD-INFO (473-4636) Staffed by nurses, social workers and therapists, our Helpline is here to ...

  3. Parkinson's Disease Videos

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    Full Text Available ... How Does Depression Affect the Patient's Family and Social Network? How Does Parkinson's Disease Affect Memory? How Does Parkinson's Disease Affect the Urinary System? How Does Speech Therapy Help Parkinson's ... our Helpline: 1-800-4PD-INFO (473-4636) Staffed by nurses, social workers and therapists, our Helpline is here to ...

  4. Parkinson's Disease Videos

    Science.gov (United States)

    ... Dra. Claudia Martinez, MAPC - Parkinson- Pasion, Positivismo y Participacion” Hallucinations and Delusions How Can Caregivers Help with ... How Does Depression Affect the Patient's Family and Social Network? How Does Parkinson's Disease Affect Memory? How ...

  5. Parkinson's Disease Videos

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    Full Text Available ... Dra. Claudia Martinez, MAPC - Parkinson- Pasion, Positivismo y Participacion” Hallucinations and Delusions How Can Caregivers Help with ... How Does Depression Affect the Patient's Family and Social Network? How Does Parkinson's Disease Affect Memory? How ...

  6. Parkinson's Disease Videos

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    Full Text Available ... We fight for people with Parkinson's and their families every day. We are in this together. Learn ... Sexual Functioning? How Does Depression Affect the Patient's Family and Social Network? How Does Parkinson's Disease Affect ...

  7. Parkinson's Disease Videos

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    Full Text Available ... Research Research Funding Centers of Excellence Parkinson's Outcomes Project Grants Telemedicine & Virtual Care Professional Training Expert Care & ... Managing Depression, Anxiety & Psychosis OHSU - Parkinson's Disease: ... of Depression, Anxiety & Psychosis OHSU - Therapeutic Approaches for ...

  8. Parkinson's Disease Videos

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    Full Text Available ... We fight for people with Parkinson's and their families every day. We are in this together. Learn ... Sexual Functioning? How Does Depression Affect the Patient's Family and Social Network? How Does Parkinson's Disease Affect ...

  9. Blood Biomarkers Associated with Cognitive Decline in Early Stage and Drug-Naive Parkinson's Disease Patients.

    Directory of Open Access Journals (Sweden)

    Jose A Santiago

    Full Text Available Early diagnosis of Parkinson's disease (PD continues to be a major challenge in the field. The lack of a robust biomarker to detect early stage PD patients has considerably slowed the progress toward the development of potential therapeutic agents. We have previously evaluated several RNA biomarkers in whole blood from participants enrolled in two independent clinical studies. In these studies, PD patients were medicated, thus, expression of these biomarkers in de novo patients remains unknown. To this end, we tested ten RNA biomarkers in blood samples from 99 untreated PD patients and 101 HC nested in the cross-sectional Parkinson's Progression Markers Initiative by quantitative real-time PCR. One biomarker out of ten, COPZ1 trended toward significance (nominal p = 0.009 when adjusting for age, sex, and educational level. Further, COPZ1, EFTUD2 and PTBP1 mRNAs correlated with clinical features in PD patients including the Hoehn and Yahr scale, Movement Disorder Society revision of Unified Parkinson's Disease Rating Scale (MDS-UPDRS and Montreal Cognitive Assessment (MoCA score. Levels of EFTUD2 and PTBP1 were significantly higher in cognitively normal PD patients (PD-CN compared to cognitively impaired PD patients (PD-MCI. Interestingly, blood glucose levels were significantly higher in PD and PD-MCI patients (≥ 100 mg/dL, pre-diabetes compared to HC. Collectively, we report the association of three RNA biomarkers, COPZ1, EFTUD2 and PTBP1 with clinical features including cognitive decline in early drug-naïve PD patients. Further, our results show that drug-naïve PD and PD-MCI patients have glucose levels characteristic of pre-diabetes patients, suggesting that impaired glucose metabolism is an early event in PD. Evaluation of these potential biomarkers in a larger longitudinal study is warranted.

  10. Blood Biomarkers Associated with Cognitive Decline in Early Stage and Drug-Naive Parkinson's Disease Patients.

    Science.gov (United States)

    Santiago, Jose A; Potashkin, Judith A

    2015-01-01

    Early diagnosis of Parkinson's disease (PD) continues to be a major challenge in the field. The lack of a robust biomarker to detect early stage PD patients has considerably slowed the progress toward the development of potential therapeutic agents. We have previously evaluated several RNA biomarkers in whole blood from participants enrolled in two independent clinical studies. In these studies, PD patients were medicated, thus, expression of these biomarkers in de novo patients remains unknown. To this end, we tested ten RNA biomarkers in blood samples from 99 untreated PD patients and 101 HC nested in the cross-sectional Parkinson's Progression Markers Initiative by quantitative real-time PCR. One biomarker out of ten, COPZ1 trended toward significance (nominal p = 0.009) when adjusting for age, sex, and educational level. Further, COPZ1, EFTUD2 and PTBP1 mRNAs correlated with clinical features in PD patients including the Hoehn and Yahr scale, Movement Disorder Society revision of Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and Montreal Cognitive Assessment (MoCA) score. Levels of EFTUD2 and PTBP1 were significantly higher in cognitively normal PD patients (PD-CN) compared to cognitively impaired PD patients (PD-MCI). Interestingly, blood glucose levels were significantly higher in PD and PD-MCI patients (≥ 100 mg/dL, pre-diabetes) compared to HC. Collectively, we report the association of three RNA biomarkers, COPZ1, EFTUD2 and PTBP1 with clinical features including cognitive decline in early drug-naïve PD patients. Further, our results show that drug-naïve PD and PD-MCI patients have glucose levels characteristic of pre-diabetes patients, suggesting that impaired glucose metabolism is an early event in PD. Evaluation of these potential biomarkers in a larger longitudinal study is warranted.

  11. A prospective study of freezing of gait with early Parkinson disease in Chinese patients.

    Science.gov (United States)

    Zhang, Hongbo; Yin, Xifan; Ouyang, Zhiyuan; Chen, Jing; Zhou, Shenghua; Zhang, Changguo; Pan, Xin; Wang, Shiliang; Yang, Junxiang; Feng, Yaoyao; Yu, Ping; Zhang, Qiangchun

    2016-06-01

    This study investigated the risk factors for freezing of gait (FOG) in the early stage of Parkinson disease in China, using a sample of 248 patients who were followed for 3 years. Part III of the Unified Parkinson Disease Rating Scale and the modified Hoehn-Yahr grading scale were used to evaluate the severity of motor symptoms. Nonmotor symptoms were assessed using the Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale (HAMD), and Non-Motor Symptoms Scale (NMSS). The end-point was the presence of FOG at the end of follow-up; patients with FOG were classified as freezers. The risk factors for FOG were analyzed at the end of the first, second, and third years after baseline. There were 40 freezers (16.13%) 1 year later, 98 (39.52%) 2 years later, and 128 (51.61%) 3 years later. FOG 3 years later was associated with the following variables: depression (P = 0.003), older age, living in the countryside, lower education, akinetic-rigid style, lower limbs as site of onset, early use of levodopa, higher daily dose of levodopa, and not using amantadine or selegiline and dopamine receptor agonists (P Parkinson disease were more likely to experience FOG if: they were older, or from the countryside; had an akinetic-rigid style, anxiety, or higher NMSS scores; they used levodopa early or did not use amantadine or selegiline; their lower limbs were the site of onset; or they had more severe motor disability or higher HAMD scores at baseline.

  12. Six psychotropics for pre-symptomatic & early Alzheimer's (MCI, Parkinson's, and Huntington's disease modification

    Directory of Open Access Journals (Sweden)

    Edward C Lauterbach

    2016-01-01

    Full Text Available The quest for neuroprotective drugs to slow the progression of neurodegenerative diseases (NDDs, including Alzheimer's disease (AD, Parkinson's disease (PD, and Huntington's disease (HD, has been largely unrewarding. Preclinical evidence suggests that repurposing quetiapine, lithium, valproate, fluoxetine, donepezil, and memantine for early and pre-symptomatic disease-modification in NDDs may be promising and can spare regulatory barriers. The literature of these psychotropics in early stage and pre-symptomatic AD, PD, and HD is reviewed and propitious findings follow. Mild cognitive impairment (MCI phase of AD: salutary human randomized controlled trial findings for low-dose lithium and, in selected patients, donepezil await replication. Pre-symptomatic AD: human epidemiological data indicate that lithium reduces AD risk. Animal model studies (AMS reveal encouraging results for quetiapine, lithium, donepezil, and memantine. Early PD: valproate AMS findings show promise. Pre-symptomatic PD: lithium and valproate AMS findings are encouraging. Early HD: uncontrolled clinical data indicate non-progression with lithium, fluoxetine, donepezil, and memantine. Pre-symptomatic HD: lithium and valproate are auspicious in AMS. Many other promising findings awaiting replication (valproate in MCI; lithium, valproate, fluoxetine in pre-symptomatic AD; lithium in early PD; lithium, valproate, fluoxetine in pre-symptomatic PD; donepezil in early HD; lithium, fluoxetine, memantine in pre-symptomatic HD are reviewed. Dose- and stage-dependent effects are considered. Suggestions for signal-enhancement in human trials are provided for each NDD stage.

  13. ATP13A2 variants in early-onset Parkinson's disease patients and controls

    DEFF Research Database (Denmark)

    Djarmati, Ana; Hagenah, Johann; Reetz, Kathrin

    2009-01-01

    Four genes responsible for recessively inherited forms of Parkinson's disease (PD) have been identified, including the recently discovered ATP13A2 (PARK9) gene. Our objective was to investigate the role of this gene in a large cohort of PD patients and controls. We extensively screened all 29 exons...... of the ATP13A2 coding region in 112 patients with early-onset PD (EOPD; origin and of 55 controls. We identified four carriers (3.6%) of novel single heterozygous ATP13A2 missense changes that were absent in controls. Interestingly, the carrier of one of these variants...

  14. Meta-Analysis of Early Nonmotor Features and Risk Factors for Parkinson Disease

    OpenAIRE

    Noyce, Alastair J.; Jonathan P Bestwick; Silveira-Moriyama, Laura; Hawkes, Christopher H; Giovannoni, Gavin; Andrew J. Lees; Schrag, Anette

    2012-01-01

    Objective To evaluate the association between diagnosis of Parkinson disease (PD) and risk factors or early symptoms amenable to population-based screening. Methods A systematic review and meta-analysis of risk factors for PD. Results The strongest associations with later diagnosis of PD were found for having a first-degree or any relative with PD (odds ratio [OR], 3.23; 95% confidence interval [CI], 2.65–3.93 and OR, 4.45; 95% CI, 3.39–5.83) or any relative with tremor (OR, 2.74; 95% CI, 2.1...

  15. Genetic mutations in early-onset Parkinson's disease Mexican patients: molecular testing implications.

    Science.gov (United States)

    Monroy-Jaramillo, Nancy; Guerrero-Camacho, Jorge Luis; Rodríguez-Violante, Mayela; Boll-Woehrlen, Marie-Catherine; Yescas-Gómez, Petra; Alonso-Vilatela, María Elisa; López-López, Marisol

    2014-04-01

    Mutations in PARK2, PINK1, and DJ-1 have been associated with autosomal recessive early-onset Parkinson's disease. Here, we report the prevalence of sequence and structural mutations in these three main recessive genes in Mexican Mestizo patients. The complete sequences of these three genes were analyzed by homo/heteroduplex DNA formation and direct sequencing; exon dosage was determined by multiplex ligation-dependent probe amplification and real-time PCR in 127 patients belonging to 122 families and 120 healthy Mexican Mestizo controls. All individuals had been previously screened for the three most common LRRK2 mutations. The presence of two mutations in compound heterozygous or homozygous genotypes was found in 16 unrelated patients, 10 had mutations in PARK2, six in PINK1, and none in DJ-1. Two PARK2-PINK1 and one PARK2-LRRK2 digenic cases were observed. Novel mutations were identified in PARK2 and PINK1 genes, including PINK1 duplication for the first time. Exon dosage deletions were the most frequent mutations in PARK2 (mainly in exons 9 and 12), followed by those in PINK1. The high prevalence of heterozygous mutations in PARK2 (12.3%) and the novel heterozygous and homozygous point mutations in PINK1 observed in familial and sporadic cases from various states of Mexico support the concept that single heterozygous mutations in recessive Parkinson's disease genes play a pathogenic role. These data have important implications for genetic counseling of Mexican Mestizo patients with early-onset Parkinson's disease. The presence of digenic inheritance underscores the importance of studying several genes in this disease. A step-ordered strategy for molecular diagnosis is proposed.

  16. Predictive motor timing performance dissociates between early diseases of the cerebellum and Parkinson's disease.

    Science.gov (United States)

    Bares, Martin; Lungu, Ovidiu V; Husárová, Ivica; Gescheidt, Tomás

    2010-03-01

    There is evidence that both the basal ganglia and the cerebellum play a role in the neural representation of time in a variety of behaviours, but whether one of them is more important is not yet clear. To address this question in the context of predictive motor timing, we tested patients with various movement disorders implicating these two structures in a motor-timing task. Specifically, we investigated four different groups: (1) patients with early Parkinson's disease (PD); (2) patients with sporadic spinocerebellar ataxia (SCA); (3) patients with familial essential tremor (ET); and (4) matched healthy controls. We used a predictive motor-timing task that involved mediated interception of a moving target, and we assessed the effect of movement type (acceleration, deceleration and constant), speed (slow, medium and fast) and angle (0 degrees , 15 degrees and 30 degrees) on performance (hit, early error and late error). The main results showed that PD group and arm ET subgroup did not significantly differ from the control group. SCA and head ET subjects (severe and mild cerebellar damage, respectively) were significantly worse at interception than the other two groups. Our findings support the idea that the basal ganglia play a less significant role in predictive motor timing than the cerebellum. The fact that SCA and ET subjects seemed to have a fundamental problem with predictive motor timing suggests that the cerebellum plays an essential role in integrating incoming visual information with the motor output in a timely manner, and that ET is a heterogeneous entity that deserves increased attention from clinicians.

  17. Parkinson's Disease Videos

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    Full Text Available ... CareMAP: Managing Advanced Parkinson's Website CareMAP: Managing Caregiver Stress CareMAP: Mealtime and Swallowing: Part 1 CareMAP: Mealtime ... Help Parkinson's Patients? How Does the DBS Device Work? How Is Parkinson's Disease Diagnosed? Interview with Nathan ...

  18. Parkinson's Disease Videos

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    Full Text Available ... CareMAP: Managing Advanced Parkinson's Website CareMAP: Managing Caregiver Stress CareMAP: Mealtime and Swallowing: Part 1 CareMAP: Mealtime ... Help Parkinson's Patients? How Does the DBS Device Work? How Is Parkinson's Disease Diagnosed? Interview with Nathan ...

  19. Prodromal symptoms and early detection of Parkinson's disease in general practice: a nested case-control study

    NARCIS (Netherlands)

    Plouvier, A.O.A.; Hameleers, R.J.M.G.; Heuvel, E.A. van den; Bor, H.H.; Olde Hartman, T.C.; Bloem, B.R.; Weel, C. van; Lagro-Janssen, A.

    2014-01-01

    BACKGROUND: Timely diagnosis of Parkinson's disease (PD), facilitating early intervention, depends largely on the GP's awareness of early symptomatology. For general practice, it is unknown which prodromal symptoms (symptoms preceding the typical motor symptoms of PD) demand the GP's alertness. OBJE

  20. Parkinson's disease and osteoporosis.

    Science.gov (United States)

    Vaserman, Nathalie

    2005-12-01

    Parkinson's disease is associated with an increased risk of falls. The risk is greatest in patients with advanced disease. Because Parkinson's disease usually occurs late in life, the risk factors related to the neurological impairments add to those associated with aging. The incidence of fractures is high in patients with Parkinson's disease, with femoral neck fractures in older women being particularly common. Risk factors for fractures include a low body mass index, limited exposure to sunlight, an inadequate vitamin D intake with low 25-OH vitamin D levels, and bone loss. Several studies found decreased bone mineral density values at the femoral neck and lumbar spine in patients with Parkinson's disease. Although this decrease is ascribable in part to factors unrelated with Parkinson's disease, such as older age and female gender, Parkinson's disease itself also plays a role, most notably in patients with severe neurological impairments (Hoehn and Yahr stages III and IV).

  1. Therapeutic singing as an early intervention for swallowing in persons with Parkinson's disease.

    Science.gov (United States)

    Stegemöller, E L; Hibbing, P; Radig, H; Wingate, J

    2017-04-01

    For persons with Parkinson's disease (PD), secondary motor symptoms such as swallow impairment impact the quality of life and are major contributors to mortality. There is a present need for therapeutic interventions aimed at improving swallow function during the early stages of PD. The purpose of this pilot study was to examine the effects of a group therapeutic singing intervention on swallowing in persons with PD with no significant dysphagia symptoms. Cohort study. University in the United States. Twenty-four participants with PD. Eight weeks of group therapeutic singing. Electromyography (EMG) was used to assess muscle activity associated with swallow pre and post the group singing intervention. Swallow quality of life (SWAL-QOL) and the Unified Parkinson's Disease Rating Scale (UPDRS) were also obtained pre- and post-intervention. Participants reported minimal difficulty with swallowing, yet results revealed a significant increase in EMG outcome measures, as well as significant improvement in UPDRS total and UPDRS motor scores. No significant differences were revealed for SWAL-QOL. Increases in EMG timing measures may suggest that group singing results in the prolongation of laryngeal elevation, protecting the airway from foreign material for longer periods of time during swallow. Combined with the improvement in UPDRS clinical measures, therapeutic singing may be an engaging early intervention strategy to address oropharyngeal dysphagia while also benefiting additional clinical symptoms of PD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Genetic Analysis of PARK2 and PINK1 Genes in Brazilian Patients with Early-Onset Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Karla Cristina Vasconcelos Moura

    2013-01-01

    Full Text Available Parkinson's disease is the second most frequent neurodegenerative disorder in the world, affecting 1-2% of individuals over the age of 65. The etiology of Parkinson's disease is complex, with the involvement of gene-environment interactions. Although it is considered a disease of late manifestation, early-onset forms of parkinsonism contribute to 5–10% of all cases. In the present study, we screened mutations in coding regions of PARK2 and PINK1 genes in 136 unrelated Brazilian patients with early-onset Parkinson's disease through automatic sequencing. We identified six missense variants in PARK2 gene: one known pathogenic mutation, two variants of uncertain role, and three nonpathogenic changes. No pathogenic mutation was identified in PINK1 gene, only benign polymorphisms. All putative pathogenic variants found in this study were in heterozygous state. Our data show that PARK2 point mutations are more common in Brazilian early-onset Parkinson's disease patients (2.9% than PINK1 missense variants (0%, corroborating other studies worldwide.

  3. Parkinson's disease and genetics.

    Science.gov (United States)

    Lester, Jacobo; Otero-Siliceo, Enrique

    2006-09-01

    Idiopathic Parkinson disease (IPD) is a condition of unknown cause. Several factors are believed to contribute to its onset, and many studies have been conducted in search of the possible etiology of Parkinson disease. Genetic factors have become relevant when trying to explain the onset of Parkinson disease. The studies are divided into 2 categories: epidemiological and studies that analyze twins from families with members suffering from Parkinson disease, thus looking for the responsible genetic mutations. In this article we address this controversial topic, reviewing some of the most significant studies trying to provide evidence which relates genetics to Parkinson disease. We present current epidemiological studies and the most important genetic factors related to Parkinson disease, including the latest information currently available on each issue.

  4. Differential sialylation of serpin A1 in the early diagnosis of Parkinson's disease dementia.

    Directory of Open Access Journals (Sweden)

    Sarah Jesse

    Full Text Available The prevalence of Parkinson's disease (PD increases with age. Up to 50% of PD show cognitive decline in terms of a mild cognitive impairment already in early stages that predict the development of dementia, which can occur in up to 80% of PD patients over the long term, called Parkinson's disease dementia (PDD. So far, diagnosis of PD/PDD is made according to clinical and neuropsychological examinations while laboratory data is only used for exclusion of other diseases. The aim of this study was the identification of possible biomarkers in cerebrospinal fluid (CSF of PD, PDD and controls (CON which predict the development of dementia in PD. For this, a proteomic approach optimized for CSF was performed using 18 clinically well characterized patients in a first step with subsequent validation using 84 patients. Here, we detected differentially sialylated isoforms of Serpin A1 as marker for differentiation of PD versus PDD in CSF. Performing 2D-immunoblots, all PDD patients could be identified correctly (sensitivity 100%. Ten out of 24 PD patients showed Serpin A1 isoforms in a similar pattern like PDD, indicating a specificity of 58% for the test-procedure. In control samples, no additional isoform was detected. On the basis of these results, we conclude that differentially sialylated products of Serpin A1 are an interesting biomarker to indicate the development of a dementia during the course of PD.

  5. Parkinson's Disease Videos

    Medline Plus

    Full Text Available ... Anxiety & Psychosis OHSU - Therapeutic Approaches for PD: Depression, Anxiety & ... Parkinson's Disease? Are There Disorders That Have Similar Symptoms? What Are the Common ...

  6. Parkinson's Disease Videos

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    Full Text Available ... Disease: Pharmacological Management of Depression, Anxiety & Psychosis OHSU - Therapeutic Approaches for PD: Depression, Anxiety & Psychosis Out of the Park for Parkinson's: ...

  7. Parkinson's Disease Videos

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    Full Text Available ... Managing Depression, Anxiety & Psychosis OHSU - Parkinson's Disease: Pharmacological Management of Depression, Anxiety & Psychosis OHSU - Therapeutic Approaches for PD: Depression, Anxiety & Psychosis Out of the ...

  8. Parkinson's Disease Videos

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    Full Text Available ... Anxiety & Psychosis OHSU - Parkinson's Disease: Pharmacological Management of Depression, Anxiety & Psychosis OHSU - Therapeutic Approaches for PD: Depression, Anxiety & Psychosis Out of ...

  9. Cognitive impairment in Parkinson's disease.

    Science.gov (United States)

    Ransmayr, Gerhard

    2015-12-01

    Parkinson's disease is the second most frequent neurodegenerative disorder. There is significantly elevated risk of cognitive decline and associated neuropsychiatric symptoms. Dementia may develop insidiously several years after manifestation of Parkinson motor symptoms (dementia associated with Parkinson's disease; Parkinson's disease dementia) or in close temporal relationship (within one year) after onset of motor symptoms (Dementia with Lewy bodies). There are clinical, pathophysiological and therapeutic similarities between these two conditions. Men are more frequently affected than women. Risk factor or indicators are advanced age at disease onset, disease duration, rigidity, akinesia and posture and gait impairment and falls as opposed to tremor dominance, and associated neuropsychiatric symptoms (depression, apathy, hallucinosis, delirium). Dementia is treatable with cholinesterase inhibitors (rivastigmine, donepezil), memantine, and adjustment of the pharmacological regimen of parkinsonian motor symptoms. Concomitant autonomic nervous system symptoms and neuropsychiatric complications warrant early clinical awareness and are accessible to pharmacological therapy.

  10. Parkinson's Disease: Diagnosis and Treatment

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Parkinson's Disease Parkinson's Disease: Diagnosis and Treatment Past Issues / Winter 2014 Table of Contents Medications for Parkinson's disease can help many patients live productive lives and ...

  11. Aberrant cerebral network topology and mild cognitive impairment in early Parkinson's disease.

    Science.gov (United States)

    Pereira, Joana B; Aarsland, Dag; Ginestet, Cedric E; Lebedev, Alexander V; Wahlund, Lars-Olof; Simmons, Andrew; Volpe, Giovanni; Westman, Eric

    2015-08-01

    The aim of this study was to assess whether mild cognitive impairment (MCI) is associated with disruption in large-scale structural networks in newly diagnosed, drug-naïve patients with Parkinson's disease (PD). Graph theoretical analyses were applied to 3T MRI data from 123 PD patients and 56 controls from the Parkinson's progression markers initiative (PPMI). Thirty-three patients were classified as having Parkinson's disease with mild cognitive impairment (PD-MCI) using the Movement Disorders Society Task Force criteria, while the remaining 90 PD patients were classified as cognitively normal (PD-CN). Global measures (clustering coefficient, characteristic path length, global efficiency, small-worldness) and regional measures (regional clustering coefficient, regional efficiency, hubs) were assessed in the structural networks that were constructed based on cortical thickness and subcortical volume data. PD-MCI patients showed a marked reduction in the average correlation strength between cortical and subcortical regions compared with controls. These patients had a larger characteristic path length and reduced global efficiency in addition to a lower regional efficiency in frontal and parietal regions compared with PD-CN patients and controls. A reorganization of the highly connected regions in the network was observed in both groups of patients. This study shows that the earliest stages of cognitive decline in PD are associated with a disruption in the large-scale coordination of the brain network and with a decrease of the efficiency of parallel information processing. These changes are likely to signal further cognitive decline and provide support to the role of aberrant network topology in cognitive impairment in patients with early PD.

  12. Pramipexole in patients with early Parkinson's disease (PROUD): a randomised delayed-start trial.

    Science.gov (United States)

    Schapira, Anthony H V; McDermott, Michael P; Barone, Paolo; Comella, Cynthia L; Albrecht, Stefan; Hsu, Helen H; Massey, Daniel H; Mizuno, Yoshikuni; Poewe, Werner; Rascol, Olivier; Marek, Kenneth

    2013-08-01

    In models of dopaminergic neuronal loss, the dopamine agonist pramipexole has exhibited neuroprotective properties. The Pramipexole On Underlying Disease (PROUD) study was designed to identify whether early versus delayed pramipexole initiation has clinical and neuroimaging benefits in patients with Parkinson's disease (PD). Between May 24, 2006, and April 22, 2009, at 98 centres, we recruited patients with PD diagnosed within 2 years and aged 30-79 years. We randomly assigned eligible patients (ratio 1:1), by a centralised, computerised randomisation schedule, to receive double-blind either placebo or pramipexole (1·5 mg a day) and followed them up for 15 months. At 9 months, or as early as 6 months if considered necessary, placebo recipients were assigned to pramipexole. In a neuroimaging substudy, striatal dopamine-transporter binding was assessed by SPECT. All patients, investigators, and independent raters were masked to study treatment. The primary endpoint was the 15-month change from baseline in total score on the unified Parkinson's disease rating scale (UPDRS). This trial is registered with ClinicalTrials.gov, number NCT00321854. Of 535 patients, 261 were randomly assigned to receive pramipexole and 274 to receive placebo. At 15 months (n=411), adjusted mean change in UPDRS total score showed no significant difference between early and delayed pramipexole (-0·4 points, 95% CI -2·2 to 1·4, p=0·65). 62 patients in the early pramipexole group and 61 patients in the delayed pramipexole group were included in the neuroimaging substudy, for which the adjusted mean 15-month change in striatal (123)I-FP-CIT binding was -15·1% (SE 2·1) for early and -14·6% (2·0) for delayed pramipexole (difference -0·5 percentage points, 95% CI -5·4 to 4·4, p=0·84). Overall, 180 (81%) of patients given early pramipexole and 179 (84%) patients given delayed pramipexole reported adverse events (most frequently nausea), and 22 (10%) patients in the early pramipexole

  13. The relationship between clinical phenotype and early staged bilateral deep brain stimulation in Parkinson disease.

    Science.gov (United States)

    Sung, Victor W; Watts, Ray L; Schrandt, Christian J; Guthrie, Stephanie; Wang, Deli; Amara, Amy W; Guthrie, Barton L; Walker, Harrison C

    2013-12-01

    While many centers place bilateral deep brain stimulation (DBS) systems simultaneously, unilateral subthalamic nucleus (STN) DBS followed by a staged contralateral procedure has emerged as a treatment option for many patients. However, little is known about whether the preoperative phenotype predicts when staged placement of a DBS electrode in the opposite STN will be required. The authors aimed to determine whether preoperative clinical phenotype predicts early staged placement of a second STN DBS electrode in patients who undergo unilateral STN DBS for Parkinson disease (PD). Eighty-two consecutive patients with advanced PD underwent unilateral STN DBS contralateral to the most affected hemibody and had at least 2 years of follow-up. Multivariate logistic regression analysis determined preoperative characteristics that predicted staged placement of a second electrode in the opposite STN. Preoperative measurements included aspects of the Unified Parkinson's Disease Rating Scale (UPDRS), motor asymmetry index, and body weight. At 2-year follow-up, 28 (34%) of the 82 patients had undergone staged placement of a contralateral electrode while the remainder chose to continue with unilateral stimulation. Statistically significant improvements in UPDRS total and Part 3 scores were retained at the end of the 2-year follow-up period in both subsets of patients. Multivariate logistic regression analysis showed that the most important predictors for early staged placement of a second subthalamic stimulator were low asymmetry index (OR 13.4, 95% CI 2.8-64.9), high tremor subscore (OR 7.2, CI 1.5-35.0), and low body weight (OR 5.5, 95% CI 1.4-22.3). This single-center study provides evidence that elements of the preoperative PD phenotype predict whether patients will require early staged bilateral STN DBS. These data may aid in the management of patients with advanced PD who undergo STN DBS.

  14. Deep brain stimulation in early stage Parkinson's disease: operative experience from a prospective randomised clinical trial.

    Science.gov (United States)

    Kahn, Elyne; D'Haese, Pierre-Francois; Dawant, Benoit; Allen, Laura; Kao, Chris; Charles, P David; Konrad, Peter

    2012-02-01

    Recent evidence suggests that deep brain stimulation of the subthalamic nucleus (STN-DBS) may have a disease modifying effect in early Parkinson's disease (PD). A randomised, prospective study is underway to determine whether STN-DBS in early PD is safe and tolerable. 15 of 30 early PD patients were randomised to receive STN-DBS implants in an institutional review board approved protocol. Operative technique, location of DBS leads and perioperative adverse events are reported. Active contact used for stimulation in these patients was compared with 47 advanced PD patients undergoing an identical procedure by the same surgeon. 14 of the 15 patients did not sustain any long term (>3 months) complications from the surgery. One subject suffered a stroke resulting in mild cognitive changes and slight right arm and face weakness. The average optimal contact used in symptomatic treatment of early PD patients was: anterior -1.1±1.7 mm, lateral 10.7±1.7 mm and superior -3.3±2.5 mm (anterior and posterior commissure coordinates). This location is statistically no different (0.77 mm, p>0.05) than the optimal contact used in the treatment of 47 advanced PD patients. The perioperative adverse events in this trial of subjects with early stage PD are comparable with those reported for STN-DBS in advanced PD. The active contact position used in early PD is not significantly different from that used in late stage disease. This is the first report of the operative experience from a randomised, surgical versus best medical therapy trial for the early treatment of PD.

  15. Discriminative power of different nonmotor signs in early Parkinson's disease. A case-control study.

    Science.gov (United States)

    Diederich, Nico J; Pieri, Vannina; Hipp, Géraldine; Rufra, Olivier; Blyth, Sara; Vaillant, Michel

    2010-05-15

    The objective of this study was to evaluate the discriminative power of different nonmotor signs for early diagnosis of Parkinson's disease (PD). Thirty patients with PD with controls. Six deficit domains (DD) were defined: hyposmia, sleep abnormalities, dysautonomia, visual deficits, executive dysfunction, and depression. Plotting of Receiver operating characteristic (ROC) curves and exact conditional logistic modeling, followed by manual stepwise descending procedure were used to identify a model for nonmotor signs that detects early PD. Patients with PD and controls did not differ in terms of age, gender, and educational level. Several DD discriminated patients with PD from healthy controls. Visual deficits showed the largest area under the ROC curve (0.83), followed by hyposmia (0.81) and dysautonomia (0.80). When combining the DD visual deficits and dysautonomia, the best residual model was obtained; it maximized both sensitivity and specificity for PD at a level of 0.77. At an early disease stage, several nonmotor domains were already able to discriminate patients with PD from healthy controls. Visual deficits had the best discriminatory power. Being brief and inexpensive, visual tests should be further investigated in larger cohorts as potential screening tool for early PD.

  16. Role and clinical utility of pramipexole extended release in the treatment of early Parkinson's disease.

    Science.gov (United States)

    Hametner, Eva-Maria; Seppi, Klaus; Poewe, Werner

    2012-01-01

    The aim of this article is to provide a short review of the most relevant pharmacological and clinical data on pramipexole extended release (ER) as well as to address the clinical utility and potential advantages of a once-daily formulation especially in the treatment of early Parkinson's disease (PD). Pramipexole is widely established as a symptomatic treatment in early as well as advanced PD. The development of an ER formulation, with stable pramipexole plasma concentration over 24 hours, now offers a bioequivalent once-daily alternative. Double-blind randomized controlled trials in early and advanced PD, have established noninferiority of pramipexole ER compared with immediate release as well as superiority of both formulations over placebo. The overnight switch from the standard to the once-daily formulation was shown to be successful in >80% of patients without requiring any dose adjustments. Potential benefits of the prolonged-release design, which have not yet been formally demonstrated in the pivotal trial program, include improved compliance and a potential for better symptomatic control, particularly in patients with early disease that can be managed with monotherapy.

  17. Falls in Parkinson's disease.

    NARCIS (Netherlands)

    Grimbergen, Y.A.M.; Munneke, M.; Bloem, B.R.

    2004-01-01

    PURPOSE OF REVIEW: To summarize the latest insights into the clinical significance, assessment, pathophysiology and treatment of falls in Parkinson's disease. RECENT FINDINGS: Recent studies have shown that falls are common in Parkinson's disease, even when compared with other fall-prone populations

  18. Neuroprotective effects of riluzole in early phase Parkinson's disease on clinically relevant parameters in the marmoset MPTP model

    NARCIS (Netherlands)

    Verhave, P.S.; Jongsma, M.J.; Berg, R.M. van den; Vanwersch, R.A.P.; Smit, A.B.; Philippens, I.H.C.H.M.

    2012-01-01

    The present study evaluates neuroprotection in a marmoset MPTP (1-methyl-1,2,3,6-tetrahydropyridine) model representing early Parkinson's disease (PD). The anti-glutamatergic compound riluzole is used as a model compound for neuroprotection. The compound is one of the few protective compounds used i

  19. Randomized, double-blind, multicenter evaluation of pramipexole extended release once daily in early Parkinson's disease.

    Science.gov (United States)

    Hauser, Robert A; Schapira, Anthony H V; Rascol, Olivier; Barone, Paolo; Mizuno, Yoshikuni; Salin, Laurence; Haaksma, Monika; Juhel, Nolwenn; Poewe, Werner

    2010-11-15

    The objective of this study was to evaluate the efficacy and safety of pramipexole extended release (ER) administered once daily in early Parkinson's disease (PD). Pramipexole immediate release (IR) administered three times daily (TID) is an efficacious and generally well-tolerated treatment for PD. A pramipexole ER formulation is now available. We performed a randomized, double-blind, placebo and active comparator-controlled trial in subjects with early PD. The primary efficacy and safety evaluation of pramipexole ER compared with placebo took place at week 18. Two hundred fifty-nine subjects were randomized 2:2:1 to treatment with pramipexole ER once daily, pramipexole IR TID, or placebo. Levodopa rescue was required by 7 subjects in the placebo group (14%), 3 subjects in the pramipexole ER group (2.9%, P = 0.0160), and 1 subject in the pramipexole IR group (1.0%, P = 0.0017). Adjusted mean [standard error (SE)] change in Unified Parkinson Disease Rating Scale (UPDRS) II [activities of daily living (ADL)] + III (motor) scores from baseline to week 18, including post-levodopa rescue evaluations, was -5.1 (1.3) in the placebo group, -8.1 (1.1) in the pramipexole ER group (P = 0.0282), and -8.4 (1.1) in the pramipexole IR group (P = 0.0153). Adjusted mean (SE) change in UPDRS ADL + motor scores, censoring post-levodopa rescue data, was -2.7 (1.3) in the placebo group, -7.4 (1.1) in the pramipexole ER group (P = 0.0010), and -7.5 (1.1) in the pramipexole IR group (P = 0.0006). Adverse events more common with pramipexole ER than placebo included somnolence, nausea, constipation, and fatigue. Pramipexole ER administered once daily was demonstrated to be efficacious compared with placebo and provided similar efficacy and tolerability as pramipexole IR administered TID.

  20. Early impairment of cognitive functions in Parkinson's disease Comprometimento precoce das funções cognitivas na doença de Parkinson

    Directory of Open Access Journals (Sweden)

    Florindo Stella

    2007-06-01

    Full Text Available BACKGROUND: Impairment in non-motor functions such as disturbances of some executive functions are also common events in Parkinson's disease patients. OBJECTIVE: To verify the performance of Parkinson's disease patients in activities requiring visuoconstructive and visuospatial skills. METHOD: Thirty elderly patients with mild or moderate stages of Parkinson's disease were studied. The assessment of the clinical condition was based on the unified Parkinson's disease rating scale (56.28; SD=33.48, Hoehn and Yahr (2.2; SD=0.83, Schwab and England (78.93%, clock drawing test (7.36; SD=2.51, and mini-mental state examination (26.48; SD=10.11. Pearson's correlation and stepwise multiple regression were used for statistical analyses. RESULTS: The patients presented deterioration in visuospatial and visuoconstructive skills. CONCLUSION: The clock drawing test proved to be a useful predictive tool for identifying early cognitive impairment in thesbe individuals.CONTEXTO: Comprometimento em funções não-motoras como perturbações em algumas funções executivas são também eventos comuns em pacientes com doença de Parkinson. OBJETIVO: Verificar as performances de pacientes com doença de Parkinson em atividades que requerem habilidades visuo-construtivas e visuo-espaciais. MÉTODO: Pacientes idosos (n=30 nos estágios leve ou moderado da doença de Parkinson foram estudados. O diagnóstico da condição clínica foi realizado por meio de: unified Parkinson's disease rating scale (56,28; SD=33,48, Hoehn e Yahr (2,2; SD=0,83, Schwab e England (78,93%, teste do desenho do relógio (7,36; SD=2,51, e mini-exame do estado mental (26,48; SD=10,11. A correlação de Pearson e a análise de regressão múltipla foram empregadas na análise estatística. RESULTADOS: Os pacientes apresentaram deterioração nas habilidades vísuo-espaciais e visuoconstrutivas. CONCLUSÃO: O teste do desenho do relógio provou ser uma ferramenta útil e preditiva para

  1. Clinical features and gene analysis in Korean patients with early-onset Parkinson disease.

    Science.gov (United States)

    Chung, Eun Joo; Ki, Chang-Seok; Lee, Won Yong; Kim, In-Suk; Kim, Ji-Youn

    2006-08-01

    Systematic analysis of clinical features and gene mutations has not been performed in Korean patients with early-onset Parkinson disease (PD). To investigate the clinical characteristics and genetic background of Korean patients with early-onset PD. Clinical and genetic study. University hospital. Ninety-four patients with early-onset PD (mean +/- SD age at onset, 39.8 +/- 7.3 years) of 1100 patients with PD. Analysis of clinical characteristics and mutation analysis of the parkin and PTEN-induced kinase (PINK1) genes by direct sequencing and gene-dosage analysis using the multiplex ligation-dependent probe amplification technique. The correlation between age at onset and clinical characteristics and the clinical features of patients with onset before age 30 years vs patients with onset after age 30 years. Because age at onset was younger, levodopa-induced dyskinesia and off-dystonia were more frequently observed (P=.008). Patients affected before age 30 years showed more frequent levodopa-induced dyskinesia and off-dystonia (P=.002). We identified 3 patients (5%) with parkin gene mutations but none with the PINK1 mutation. Earlier onset of levodopa-induced dyskinesia and off-dystonia were characteristic features of early-onset PD, especially before an onset age of 30 years. However, parkin gene mutations were less frequent in these patients than in Japanese groups reported elsewhere.

  2. Impaired Early Attentional Processes in Parkinson's Disease: A High-Resolution Event-Related Potentials Study.

    Directory of Open Access Journals (Sweden)

    Perrine Bocquillon

    Full Text Available The selection of task-relevant information requires both the focalization of attention on the task and resistance to interference from irrelevant stimuli. A previous study using the P3 component of the event-related potentials suggested that a reduced ability to resist interference could be responsible for attention disorders at early stages of Parkinson's disease (PD, with a possible role of the dorsolateral prefrontal cortex (DLPFC.Our objective was to better determine the origin of this impairment, by studying an earlier ERP component, the N2, and its subcomponents, as they reflect early inhibition processes and as they are known to have sources in the anterior cingulate cortex (ACC, which is involved together with the DLPFC in inhibition processes. Fifteen early-stage PD patients and 15 healthy controls (HCs performed a three-stimulus visual oddball paradigm, consisting in detecting target inputs amongst standard stimuli, while resisting interference from distracter ones. A 128-channel electroencephalogram was recorded during this task and the generators of the N2 subcomponents were identified using standardized weighted low-resolution electromagnetic tomography (swLORETA.PD patients displayed fewer N2 generators than HCs in both the DLPFC and the ACC, for all types of stimuli. In contrast to controls, PD patients did not show any differences between their generators for different N2 subcomponents.Our data suggest that impaired inhibition in PD results from dysfunction of the DLPFC and the ACC during the early stages of attentional processes.

  3. Transcranial magnetic stimulation follow-up study in early Parkinson's disease: A decline in compensation with disease progression?

    Science.gov (United States)

    Kojovic, Maja; Kassavetis, Panagiotis; Bologna, Matteo; Pareés, Isabel; Rubio-Agusti, Ignacio; Berardelli, Alfredo; Beraredelli, Alfredo; Edwards, Mark J; Rothwell, John C; Bhatia, Kailash P

    2015-07-01

    A number of neurophysiological abnormalities have been described in patients with Parkinson's disease, but very few longitudinal studies of how these change with disease progression have been reported. We describe measures of motor cortex inhibition and plasticity at 6 and 12 mo in 12 patients that we previously reported at initial diagnosis. Given the well-known interindividual variation in these measures, we were particularly concerned with the within-subject changes over time. Patients were assessed clinically, and transcranial magnetic stimulation (TMS) was used to measure motor cortical excitability, inhibition (short interval intracortical inhibition, cortical silent period), and plasticity (response to excitatory paired associative stimulation protocol) in both hemispheres. All measurements were performed 6 mo and 12 mo after the baseline experiments. Asymmetry in clinical motor symptoms was reflected in asymmetry of plasticity and inhibition. In the group as a whole, little change was seen in any of the parameters over 12 mo. However, analysis of within-individual data showed clear correlations between changes in clinical asymmetry and asymmetry of response to paired associative stimulation protocol and cortical silent period. Longitudinal changes in cortical silent period and response to paired associative stimulation protocol in Parkinson's disease reflect dynamic effects on motor cortex that are related to progression of motor signs. They are useful objective markers of early disease progression that could be used to detect effects of disease-modifying therapies. The decline in heightened plasticity that was present at disease onset may reflect failure of compensatory mechanisms that maintained function in the preclinical state. © 2015 International Parkinson and Movement Disorder Society.

  4. Deep Brain Stimulation for Parkinson's Disease with Early Motor Complications: A UK Cost-Effectiveness Analysis.

    Science.gov (United States)

    Fundament, Tomasz; Eldridge, Paul R; Green, Alexander L; Whone, Alan L; Taylor, Rod S; Williams, Adrian C; Schuepbach, W M Michael

    2016-01-01

    Parkinson's disease (PD) is a debilitating illness associated with considerable impairment of quality of life and substantial costs to health care systems. Deep brain stimulation (DBS) is an established surgical treatment option for some patients with advanced PD. The EARLYSTIM trial has recently demonstrated its clinical benefit also in patients with early motor complications. We sought to evaluate the cost-effectiveness of DBS, compared to best medical therapy (BMT), among PD patients with early onset of motor complications, from a United Kingdom (UK) payer perspective. We developed a Markov model to represent the progression of PD as rated using the Unified Parkinson's Disease Rating Scale (UPDRS) over time in patients with early PD. Evidence sources were a systematic review of clinical evidence; data from the EARLYSTIM study; and a UK Clinical Practice Research Datalink (CPRD) dataset including DBS patients. A mapping algorithm was developed to generate utility values based on UPDRS data for each intervention. The cost-effectiveness was expressed as the incremental cost per quality-adjusted life-year (QALY). One-way and probabilistic sensitivity analyses were undertaken to explore the effect of parameter uncertainty. Over a 15-year time horizon, DBS was predicted to lead to additional mean cost per patient of £26,799 compared with BMT (£73,077/patient versus £46,278/patient) and an additional mean 1.35 QALYs (6.69 QALYs versus 5.35 QALYs), resulting in an incremental cost-effectiveness ratio of £19,887 per QALY gained with a 99% probability of DBS being cost-effective at a threshold of £30,000/QALY. One-way sensitivity analyses suggested that the results were not significantly impacted by plausible changes in the input parameter values. These results indicate that DBS is a cost-effective intervention in PD patients with early motor complications when compared with existing interventions, offering additional health benefits at acceptable incremental cost

  5. Deep Brain Stimulation for Parkinson's Disease with Early Motor Complications: A UK Cost-Effectiveness Analysis.

    Directory of Open Access Journals (Sweden)

    Tomasz Fundament

    Full Text Available Parkinson's disease (PD is a debilitating illness associated with considerable impairment of quality of life and substantial costs to health care systems. Deep brain stimulation (DBS is an established surgical treatment option for some patients with advanced PD. The EARLYSTIM trial has recently demonstrated its clinical benefit also in patients with early motor complications. We sought to evaluate the cost-effectiveness of DBS, compared to best medical therapy (BMT, among PD patients with early onset of motor complications, from a United Kingdom (UK payer perspective.We developed a Markov model to represent the progression of PD as rated using the Unified Parkinson's Disease Rating Scale (UPDRS over time in patients with early PD. Evidence sources were a systematic review of clinical evidence; data from the EARLYSTIM study; and a UK Clinical Practice Research Datalink (CPRD dataset including DBS patients. A mapping algorithm was developed to generate utility values based on UPDRS data for each intervention. The cost-effectiveness was expressed as the incremental cost per quality-adjusted life-year (QALY. One-way and probabilistic sensitivity analyses were undertaken to explore the effect of parameter uncertainty.Over a 15-year time horizon, DBS was predicted to lead to additional mean cost per patient of £26,799 compared with BMT (£73,077/patient versus £46,278/patient and an additional mean 1.35 QALYs (6.69 QALYs versus 5.35 QALYs, resulting in an incremental cost-effectiveness ratio of £19,887 per QALY gained with a 99% probability of DBS being cost-effective at a threshold of £30,000/QALY. One-way sensitivity analyses suggested that the results were not significantly impacted by plausible changes in the input parameter values.These results indicate that DBS is a cost-effective intervention in PD patients with early motor complications when compared with existing interventions, offering additional health benefits at acceptable incremental

  6. Xenotransplantation in Parkinson's disease

    NARCIS (Netherlands)

    Koopmans, Jan

    2006-01-01

    Parkinson's disease is a neurodegenerative disorder characterised by loss of dopaminergic neurones in the substantia nigra pars compacta and subsequent shortage of dopamine in the striatum of the these patients causing the well known symptoms first described by James Parkinson in 1817. In this

  7. Xenotransplantation in Parkinson's disease

    NARCIS (Netherlands)

    Koopmans, Jan

    2006-01-01

    Parkinson's disease is a neurodegenerative disorder characterised by loss of dopaminergic neurones in the substantia nigra pars compacta and subsequent shortage of dopamine in the striatum of the these patients causing the well known symptoms first described by James Parkinson in 1817. In this thesi

  8. Vitamin D deficiency and its relationship with endothelial dysfunction in patients with early Parkinson's disease.

    Science.gov (United States)

    Yoon, Jung Han; Park, Dong Kyu; Yong, Seok Woo; Hong, Ji Man

    2015-12-01

    Increasing evidence has shown that individuals with Parkinson's disease (PD) have lower levels of 25-hydroxyvitamin D (25[OH]D) than healthy controls. Low vitamin D has been associated with endothelial dysfunction which may play a role in the pathogenesis and progression of PD. Flow-mediated dilation (FMD) is widely used as a clinical marker of overall endothelial function. We evaluated the relationship between serum 25(OH)D levels and FMD in PD. We enrolled 81 patients with early PD and 52 healthy controls, and we evaluate endothelial function based on vitamin D status and identify the association between FMD and vitamin D status in patients with early PD. The mean serum 25(OH)D levels were significantly lower in the PD patients than in the controls (21.8 ± 9.5 vs. 25.2 ± 9.3 ng/mL, p body mass index, motor Unified PD Rating Scale status and homocysteine levels (adjusted R (2) = 0.331, β = 0.494, p < 0.001). These findings provide evidence of a possible association between endothelial dysfunction as assessed by FMD and low vitamin D status in patients with early PD.

  9. Neuropsychological correlates of theory of mind in patients with early Parkinson's disease.

    Science.gov (United States)

    Santangelo, Gabriella; Vitale, Carmine; Trojano, Luigi; Errico, Domenico; Amboni, Marianna; Barbarulo, Anna Maria; Grossi, Dario; Barone, Paolo

    2012-01-01

    The theory of mind is the ability to attribute mental states to oneself and others and to understand that others have beliefs, desires and intentions different from one's own. The aim of the study was to explore the neuropsychological correlates of theory of mind in patients affected by early Parkinson's disease (PD). Thirty-three PD patients and 33 age-, sex-, and education-matched control subjects underwent the Frontal Assessment Battery, as well as tasks assessing "cognitive" and "affective" theory of mind, and memory abilities; questionnaires evaluating behavioral disorders and quality of life were also administrated. Although the 2 groups did not differ on neuropsychological tasks, PD patients' performance on tasks assessing cognitive and affective theory of mind was significantly worse than controls. Moreover, PD patients had more behavioral disorders and worse quality of life than controls. After covarying for behavioral and quality of life scores, the differences between patients and controls on theory of mind tasks remained significant. "Cognitive" theory of mind was associated with Frontal Assessment Battery score and 2 domains of quality of life scale, whereas "affective" theory of mind scores correlated only with behavioral scales such as the Frontal Behavioral Inventory and Apathy Evaluation Scale. The results demonstrate that both affective and cognitive aspects of theory of mind are simultaneously impaired in early PD and suggest that deficits in the 2 subcomponents of theory of mind may be linked to dysfunction of different frontosubcortical circuitries in early PD. Copyright © 2011 Movement Disorder Society.

  10. Imprecise vowel articulation as a potential early marker of Parkinson's disease: effect of speaking task.

    Science.gov (United States)

    Rusz, Jan; Cmejla, Roman; Tykalova, Tereza; Ruzickova, Hana; Klempir, Jiri; Majerova, Veronika; Picmausova, Jana; Roth, Jan; Ruzicka, Evzen

    2013-09-01

    The purpose of this study was to analyze vowel articulation across various speaking tasks in a group of 20 early Parkinson's disease (PD) individuals prior to pharmacotherapy. Vowels were extracted from sustained phonation, sentence repetition, reading passage, and monologue. Acoustic analysis was based upon measures of the first (F1) and second (F2) formant of the vowels /a/, /i/, and /u/, vowel space area (VSA), F2i/F2u and vowel articulation index (VAI). Parkinsonian speakers manifested abnormalities in vowel articulation across F2u, VSA, F2i/F2u, and VAI in all speaking tasks except sustained phonation, compared to 15 age-matched healthy control participants. Findings suggest that sustained phonation is an inappropriate task to investigate vowel articulation in early PD. In contrast, monologue was the most sensitive in differentiating between controls and PD patients, with classification accuracy up to 80%. Measurements of vowel articulation were able to capture even minor abnormalities in speech of PD patients with no perceptible dysarthria. In conclusion, impaired vowel articulation may be considered as a possible early marker of PD. A certain type of speaking task can exert significant influence on vowel articulation. Specifically, complex tasks such as monologue are more likely to elicit articulatory deficits in parkinsonian speech, compared to other speaking tasks.

  11. Neuroanatomical correlates of impaired decision-making and facial emotion recognition in early Parkinson's disease.

    Science.gov (United States)

    Ibarretxe-Bilbao, Naroa; Junque, Carme; Tolosa, Eduardo; Marti, Maria-Jose; Valldeoriola, Francesc; Bargallo, Nuria; Zarei, Mojtaba

    2009-09-01

    Decision-making and recognition of emotions are often impaired in patients with Parkinson's disease (PD). The orbitofrontal cortex (OFC) and the amygdala are critical structures subserving these functions. This study was designed to test whether there are any structural changes in these areas that might explain the impairment of decision-making and recognition of facial emotions in early PD. We used the Iowa Gambling Task (IGT) and the Ekman 60 faces test which are sensitive to the integrity of OFC and amygdala dysfunctions in 24 early PD patients and 24 controls. High-resolution structural magnetic resonance images (MRI) were also obtained. Group analysis using voxel-based morphometry (VBM) showed significant and corrected (P Ekman test performance in PD patients. We conclude that: (i) impairment in decision-making and recognition of facial emotions occurs at the early stages of PD, (ii) these neuropsychological deficits are accompanied by degeneration of OFC and amygdala, and (iii) bilateral OFC reductions are associated with impaired recognition of emotions, and GM volume loss in left lateral OFC is related to decision-making impairment in PD.

  12. REM sleep behavior disorder in the marmoset MPTP model of early Parkinson disease

    NARCIS (Netherlands)

    Verhave, P.S.; Jongsma, M.J.; Berg, R.M. van den; Vis, J.C.; Vanwersch, R.A.P.; Smit, A.B.; Someren, E.J.W. van; Philippens, I.H.C.H.M.

    2011-01-01

    Study Objectives: Sleep problems are a common phenomenon in most neurological and psychiatric diseases. In Parkinson disease (PD), for instance, sleep problems may be the most common and burdensome non-motor symptoms in addition to the well-described classical motor symptoms. Since sleep disturbance

  13. A deformation-based morphometry study of patients with early-stage Parkinson's disease

    DEFF Research Database (Denmark)

    Borghammer, P; Østergaard, Karen; Cumming, P;

    2010-01-01

    BACKGROUND AND PURPOSE: Previous volumetric magnetic resonance imaging (MRI) studies of Parkinson's disease (PD) utilized primarily voxel-based morphometry (VBM), and investigated mostly patients with moderate- to late-stage disease. We now use deformation-based morphometry (DBM), a method...

  14. REM sleep behavior disorder in the marmoset MPTP model of early Parkinson disease

    NARCIS (Netherlands)

    Verhave, P.S.; Jongsma, M.J.; Berg, R.M. van den; Vis, J.C.; Vanwersch, R.A.P.; Smit, A.B.; Someren, E.J.W. van; Philippens, I.H.C.H.M.

    2011-01-01

    Study Objectives: Sleep problems are a common phenomenon in most neurological and psychiatric diseases. In Parkinson disease (PD), for instance, sleep problems may be the most common and burdensome non-motor symptoms in addition to the well-described classical motor symptoms. Since sleep

  15. Quality of life and mild cognitive impairment in early Parkinson's disease: does subtype matter?

    Science.gov (United States)

    Lawson, Rachael A; Yarnall, Alison J; Duncan, Gordon W; Khoo, Tien K; Breen, David P; Barker, Roger A; Collerton, Daniel; Taylor, John-Paul; Burn, David J

    2014-01-01

    We evaluated the association between mild cognitive impairment (MCI) subtypes and quality of life (QoL) in 219 newly diagnosed Parkinson's disease (PD) patients without dementia. Participants completed neuropsychological tests of attention, executive function, visuospatial function, memory, and language, and reported QoL using the Parkinson's Disease Questionnaire. Impairments were most common in executive function, memory and attention. MCI subtypes were classified according to Movement Disorder Society Task Force criteria. More severe cognitive impairment was associated with poorer quality of life (p = 0.01), but subtype of impairment was not (p > 0.10), suggesting that the nature of cognitive impairment is less significant than its severity.

  16. Perspective: Identification of genetic variants associated with dopaminergic compensatory mechanisms in early Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Lior eGreenbaum

    2013-04-01

    Full Text Available Parkinson's disease (PD is slowly progressive, and heterogeneity of its severity among individuals may be due to endogenous mechanisms that counterbalance the striatal dopamine loss. In this perspective paper, we introduce a neuroimaging-genetic approach to identify genetic variants, which may contribute to this compensation. First, we briefly review current known potential compensatory mechanisms for premotor and early disease PD, located in the striatum and other brain regions. Then, we claim that a mismatch between mild symptomatic disease, manifested by low motor score on the Unified PD Rating Scale (UPDRS and extensive Nigro-Striatal degeneration, manifested by reduced uptake of [123I]FP-CIT is indicative of compensatory processes. If genetic variants are associated with the severity of motor symptoms, while the level of striatal terminals degeneration measured by ligand uptake is taken into account and controlled in the analysis, then these variants may be involved in functional compensatory mechanisms for striatal dopamine deficit. To demonstrate feasibility of this approach, we performed a small "proof of concept" study (candidate gene design in a sample of 28 Jewish PD patients, and preliminary results are presented.

  17. Clinical heterogeneity in patients with early-stage Parkinson's disease: a cluster analysis

    Institute of Scientific and Technical Information of China (English)

    Ping LIU; Tao FENG; Yong-jun WANG; Xuan ZHANG; Biao CHEN

    2011-01-01

    The aim of this study was to investigate the clinical heterogeneity of Parkinson's disease (PD) among a cohort of Chinese patients in early stages.Clinical data on demographics,motor variables,motor phenotypes,disease progression,global cognitive function,depression,apathy,sleep quality,constipation,fatigue,and L-dopa complications were collected from 138 Chinese PD subjects in early stages (Hoehn and Yahr stages 1-3).The PD subject subtypes were classified using k-means cluster analysis according to the clinical data from five- to three-cluster consecutively.Kappa statistical analysis was performed to evaluate the consistency among different subtype solutions.The cluster analysis indicated four main subtypes:the non-tremor dominant subtype (NTD,n=28,20.3%),rapid disease progression subtype (RDP,n=7,5.1%),young-onset subtype (YO,n=50,36.2%),and tremor dominant subtype (TD,n=53,38.4%).Overall,78.3% (108/138) of subjects were always classified between the same three groups (52 always in TD,7 in RDP,and 49 in NTD),and 98.6% (136/138) between five- and four-cluster solutions.However,subjects classified as NTD in the four-cluster analysis were dispersed into different subtypes in the three-cluster analysis,with low concordance between four- and three-cluster solutions (kappa value=-0.139,P=0.001 ).This study defines clinical heterogeneity of PD patients in early stages using a data-driven approach.The subtypes generated by the four-cluster solution appear to exhibit ideal internal cohesion and external isolation.

  18. Parkinson's Disease Videos

    Medline Plus

    Full Text Available ... What Does a Caregiver Need to Know About Cognitive Impairment? What Is Patient-Centered Care? What Is ... Depression and Parkinson's Disease? What Medications Help with Cognitive Impairment? What to Expect Emotionally What Treatments Exist ...

  19. Genetics of Parkinson's disease

    National Research Council Canada - National Science Library

    Klein, Christine; Westenberger, Ana

    2012-01-01

    Fifteen years of genetic research in Parkinson's disease (PD) have led to the identification of several monogenic forms of the disorder and of numerous genetic risk factors increasing the risk to develop PD...

  20. Parkinson's Disease Videos

    Medline Plus

    Full Text Available ... and Its Treatment Affect Sexual Functioning? How Does Depression Affect the Patient's Family and Social Network? How ... Behavior a Side Effect of PD Medications? Is Depression Under-Diagnosed in Patients with Parkinson's Disease? Is ...

  1. Parkinson's Disease Videos

    Medline Plus

    Full Text Available ... Larger You are here Home Search library Topic Type 2013 PSA Featuring Katie Couric Adolfo Diaz, PTA, ... Parkinson's Disease Patients with a Depression Diagnosis? What Type of Exercise or Exercise Programs Are Recommended? What ...

  2. Parkinson's Disease Videos

    Medline Plus

    Full Text Available ... and Its Treatment Affect Sexual Functioning? How Does Depression Affect the Patient's Family and Social Network? How ... Behavior a Side Effect of PD Medications? Is Depression Under-Diagnosed in Patients with Parkinson's Disease? Is ...

  3. Progression of Parkinson's Disease

    Science.gov (United States)

    ... Parkinson's is the United Parkinson’s Disease Rating Scale (UPDRS). It is more comprehensive than the Hoehn and ... on movement symptoms. In addition to these, the UPDRS takes into account cognitive difficulties, ability to carry ...

  4. Parkinson's Disease Videos

    Medline Plus

    Full Text Available ... Brother: Donna’s Story What Are Some of the Common Misconceptions About Parkinson's Disease? What Are Some Practical ... Disorders That Have Similar Symptoms? What Are the Common Sleep Disorders Encountered in Patients with PD? What ...

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

    Science.gov (United States)

    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.

  6. [Early recognition of Parkinson's disease. Objectifiable non-motor symptoms and biomarkers].

    Science.gov (United States)

    Mollenhauer, B; Sixel-Döring, F; Storch, A; Schneider, C; Hilker, R; Kalbe, E

    2013-08-01

    The clinical diagnosis of Parkinson's disease (PD) according to the UK Brain Bank criteria is based on the presence of motor symptoms and the response to dopaminergic medication. According to these criteria the clinical diagnosis is delineated too late when more than 50 % of the dopaminergic neurons are already degenerated. In recent years interest has shifted increasingly more towards non-motor symptoms (NMS), such as rapid eye movement (REM) sleep behavior disorder (RBD), constipation, hyposmia and neuropsychiatric as well as cognitive symptoms. It was shown that NMS can precede the motor symptoms by some years and may thus possibly enable support of an earlier clinical diagnosis. Furthermore, cerebrospinal fluid or blood biomarkers as well as brain imaging techniques can objectively support an earlier diagnosis of PD. This article reviews important NMSs (e.g. RBD, hyposmia and neuropsychiatric/cognitive symptoms) as well as the current status on biomarkers and brain imaging in early (premotor) phases of PD and their relevance for the early diagnosis.

  7. Blood-brain barrier P-glycoprotein function is not impaired in early Parkinson's disease.

    Science.gov (United States)

    Bartels, A L; van Berckel, B N M; Lubberink, M; Luurtsema, G; Lammertsma, A A; Leenders, K L

    2008-08-01

    The cause of Parkinson's disease (PD) is unknown. Genetic susceptibility and exposure to environmental toxins contribute to specific neuronal loss in PD. Decreased blood-brain barrier (BBB) P-glycoprotein (P-gp) efflux function has been proposed as a possible causative link between toxin exposure and PD neurodegeneration. In the present study BBB P-gp function was investigated in vivo in 10 early stage PD patients and 8 healthy control subjects using (R)-[(11)C]-verapamil and PET. Cerebral volume of distribution (V(d)) of verapamil was used as measure of P-gp function. Both region of interest (ROI) analysis and voxel analysis using statistical parametric mapping (SPM) were performed to assess regional brain P-gp function. In addition, MDR1 genetic polymorphism was assessed. In the present study, a larger variation in V(d) of (R)-[(11)C]-verapamil was seen in the PD group as compared to the control group. However, decreased BBB P-gp function in early stage PD patients could not be confirmed.

  8. Parkinson disease and smoking revisited

    DEFF Research Database (Denmark)

    Ritz, Beate; Lee, Pei-Chen; Lassen, Christina F

    2014-01-01

    OBJECTIVE: To assess whether being able to quit smoking is an early marker of Parkinson disease (PD) onset rather than tobacco being "neuroprotective," we analyzed information about ease of quitting and nicotine substitute use. METHODS: For this case-control study, we identified 1,808 patients...

  9. Subthalamic Nucleus Deep Brain Stimulation May Reduce Medication Costs in Early Stage Parkinson's Disease.

    Science.gov (United States)

    Hacker, Mallory L; Currie, Amanda D; Molinari, Anna L; Turchan, Maxim; Millan, Sarah M; Heusinkveld, Lauren E; Roach, Jonathon; Konrad, Peter E; Davis, Thomas L; Neimat, Joseph S; Phibbs, Fenna T; Hedera, Peter; Byrne, Daniel W; Charles, David

    2016-01-01

    Subthalamic nucleus deep brain stimulation (STN-DBS) is well-known to reduce medication burden in advanced stage Parkinson's disease (PD). Preliminary data from a prospective, single blind, controlled pilot trial demonstrated that early stage PD subjects treated with STN-DBS also required less medication than those treated with optimal drug therapy (ODT). The purpose of this study was to analyze medication cost and utilization from the pilot trial of DBS in early stage PD and to project 10 year medication costs. Medication data collected at each visit were used to calculate medication costs. Medications were converted to levodopa equivalent daily dose, categorized by medication class, and compared. Medication costs were projected to advanced stage PD, the time when a typical patient may be offered DBS. Medication costs increased 72% in the ODT group and decreased 16% in the DBS+ODT group from baseline to 24 months. This cost difference translates into a cumulative savings for the DBS+ODT group of $7,150 over the study period. Projected medication cost savings over 10 years reach $64,590. Additionally, DBS+ODT subjects were 80% less likely to require polypharmacy compared with ODT subjects at 24 months (p early PD reduced medication cost over the two-year study period. DBS may offer substantial long-term reduction in medication cost by maintaining a simplified, low dose medication regimen. Further study is needed to confirm these findings, and the FDA has approved a pivotal, multicenter clinical trial evaluating STN-DBS in early PD.

  10. Blood-brain barrier P-glycoprotein function is not impaired in early Parkinson's disease

    NARCIS (Netherlands)

    Bartels, A. L.; van Berckel, B. N. M.; Lubberink, M.; Luurtsema, G.; Lammertsma, A. A.; Leenders, K. L.

    2008-01-01

    The cause of Parkinson's disease (PD) is unknown. Genetic susceptibility and exposure to environmental toxins contribute to specific neuronal loss in PD. Decreased blood-brain barrier (BBB) P-glycoprotein (P-gp) efflux function has been proposed as a possible causative link between toxin exposure an

  11. Pergolide versus levodopa monotherapy in early Parkinson's disease patients : The PELMOPET study

    NARCIS (Netherlands)

    Oertel, WH; Wolters, E; Sampaio, C; Gimenez-Roldan, S; Bergamasco, B; Dujardin, M; Grosset, DG; Arnold, G; Leenders, KL; Hundemer, HP; Lledo, A; Wood, A; Frewer, P; Schwarz, J

    2006-01-01

    Dopamine agonists are used as initial treatment in patients with Parkinson's disease (PD) to reduce incidence and severity of motor complcations. This paradigm is based on longterm studies, allowing "rescue" therapy with levodopa. The present strict monotherapy study (PELMOPET, the acronym for the p

  12. Dopamine D2 receptor gene variants and response to rasagiline in early Parkinson's disease: a pharmacogenetic study.

    Science.gov (United States)

    Masellis, Mario; Collinson, Shannon; Freeman, Natalie; Tampakeras, Maria; Levy, Joseph; Tchelet, Amir; Eyal, Eli; Berkovich, Elijahu; Eliaz, Rom E; Abler, Victor; Grossman, Iris; Fitzer-Attas, Cheryl; Tiwari, Arun; Hayden, Michael R; Kennedy, James L; Lang, Anthony E; Knight, Jo

    2016-07-01

    The treatment of early Parkinson's disease with dopaminergic agents remains the mainstay of symptomatic therapy for this incurable neurodegenerative disorder. However, clinical responses to dopaminergic drugs vary substantially from person to person due to individual-, drug- and disease-related factors that may in part be genetically determined. Using clinical data and DNA samples ascertained through the largest placebo-controlled clinical trial of the monoamine oxidase B inhibitor, rasagiline (ClinicalTrials.gov number, NCT00256204), we examined how polymorphisms in candidate genes associate with the clinical response to rasagiline in early Parkinson's disease. Variants in genes that express proteins involved in the pharmacokinetics and pharmacodynamics of rasagiline, and genes previously associated with the risk to develop Parkinson's disease were genotyped. The LifeTechnologies OpenArray NT genotyping platform and polymerase chain reaction-based methods were used to analyse 204 single nucleotide polymorphisms and five variable number tandem repeats from 30 candidate genes in 692 available DNA samples from this clinical trial. The peak symptomatic response to rasagiline, the rate of symptom progression, and their relation to genetic variation were examined controlling for placebo effects using general linear and mixed effects models, respectively. Single nucleotide polymorphisms, rs2283265 and rs1076560, in the dopamine D2 receptor gene (DRD2) were found to be significantly associated with a favourable peak response to rasagiline at 12 weeks in early Parkinson's disease after controlling for multiple testing. From a linear regression, the betas were 2.5 and 2.38, respectively, with false discovery rate-corrected P-values of 0.032. These polymorphisms were in high linkage disequilibrium with each other (r(2) = 0.96) meaning that the same clinical response signal was identified by each of them. No polymorphisms were associated with slowing the rate of worsening in

  13. Polymorphism analysis of PARK2 gene mutations in Han Chinese patients with early-onset Parkinson's disease

    Institute of Scientific and Technical Information of China (English)

    Yuancheng Bao; Ting Guan; Yuanxun Yu; Huaizhou Jiang; Changshui Fang; Lijuan Chen

    2010-01-01

    The PARK2 gene is a common disease gene in Han Chinese patients with Parkinson's disease.The detection of mutations in the PARK2 gene remains low.To investigate the role PARK2 gene mutations play in the pathogenesis of Parkinson's disease,30 Han Chinese patients with early-onset Parkinson's disease and 38 normal controls were studied to determine the sequence changes of 1,4,6 and 7 exon sections.In the 30 patients with Parkinson's disease,a heterozygous intron mutation(nt 119,G→G/A)in exon 1 was detected in one case;a homozygous intron mutation(nt 526500,T→C)between intron 3 and exon 4 in fourteen cases was found;a heterozygous intron mutation(nt 526607,G→G/A)between intron 3 and exon 4 was observed in eight cases;an exon 6missense mutation(nt 754317,C→C/T;codon 193,CGG→CGG/TGG;aa 193,Arg→Arg/Trp)in three cases was seen;and an exon 7 missense mutation(nt 941943,C→A/C;codon 272,CTC→CTC/ATC;aa 272,Leu→Leu/lle)was found in one case.These changes were not found in the normal population.The results indicated that the PARK2 exons 6 and 7 mutations are possibly pathogenic mutations,along with the intron 3-exert 4 and exon 1 mutations.PARK2 gene mutations are possible factors leading to the onset of Parkinson's disease.

  14. Genetics Home Reference: Parkinson disease

    Science.gov (United States)

    ... on Aging National Institutes of Neurological Disorders and Stroke: Parkinson's Disease Research Web Educational Resources (9 links) Centre for Genetics Education (Australia) Disease InfoSearch: Parkinson Disease MalaCards: lrrk2- ...

  15. Analysis of possibilities of early diagnostics criteria for Parkinson's disease based on analysis of the input-output curve

    Directory of Open Access Journals (Sweden)

    Janković Marko

    2013-01-01

    Full Text Available In this paper, we analyze the possibilities of the diagnosis of Parkinson's disease at an early stage, based on characteristics of the input-output curve. The input-output (IO curve was analyzed in two ways: we analyzed the gain of the curve for low-level transcranial stimulation and we analyzed the overall 'quality' of the IO curve. The 'quality' of the curve calculation is based on basic concepts from quantum mechanics and calculation of Tsallis entropy.

  16. Genetics of Parkinson disease.

    Science.gov (United States)

    Pankratz, Nathan; Foroud, Tatiana

    2007-12-01

    During the past decade five genes have been identified that are important in autosomal dominant and autosomal recessive forms of Parkinson disease. The identification of these genes has increased our understanding of the likely pathogenic mechanisms resulting in disease. However, mutations in these genes likely contribute to disease in fewer than 5% of all cases of Parkinson disease. Thus, researchers have continued to search for genes that may influence disease susceptibility. Molecular diagnostic testing is currently available for four of the genes mutated in Parkinson disease. Evidence for reduced penetrance, possible effects of haploinsufficiency, and the identification of nondisease causing polymorphisms within several of these genes has made genetic counseling challenging. Current recommendations are to limit molecular testing only to those individuals who are symptomatic. Furthermore, because treatment is unaltered by the presence or absence of mutations in these genes, restraint is recommended when considering the value of screening for mutations in a clinical setting.

  17. Interest of active posturography to detect age-related and early Parkinson's disease-related impairments in mediolateral postural control.

    Science.gov (United States)

    Bonnet, Cédrick T; Delval, Arnaud; Defebvre, Luc

    2014-11-15

    Patients with Parkinson's disease display impairments of postural control most particularly in active, challenging conditions. The objective of the present study was to analyze early signs of disease-related and also age-related impairments in mediolateral body extension and postural control. Fifty-five participants (18 Hoehn and Yahr stage 2 patients in the off-drug condition, 18 healthy elderly control subjects, and 19 young adults) were included in the study. The participants performed a quiet stance task and two active tasks that analyzed the performance in mediolateral body motion: a limit of stability and a rhythmic weight shift task. As expected, the patients displayed significantly lower and slower body displacement (head, neck, lower back, center of pressure) than elderly control subjects when performing the two body excursion tasks. However, the behavioral variability in both tasks was similar between the groups. Under these active conditions, the patients showed significantly lower contribution of the hip postural control mechanisms compared with the elderly control subjects. Overall, the patients seemed to lower their performance in order to prevent a mediolateral postural instability. However, these patients, at an early stage of their disease, were not unstable in quiet stance. Complementarily, elderly control subjects displayed slower body performance than young adults, which therefore showed an additional age-related impairment in mediolateral postural control. Overall, the study illustrated markers of age-related and Parkinson's disease impairments in mediolateral postural control that may constrain everyday activities in elderly adults and even more in patients with Parkinson's disease.

  18. Axonal damage and loss of connectivity in nigrostriatal and mesolimbic dopamine pathways in early Parkinson's disease.

    Science.gov (United States)

    Caminiti, Silvia Paola; Presotto, Luca; Baroncini, Damiano; Garibotto, Valentina; Moresco, Rosa Maria; Gianolli, Luigi; Volonté, Maria Antonietta; Antonini, Angelo; Perani, Daniela

    2017-01-01

    A progressive loss of dopamine neurons in the substantia nigra (SN) is considered the main feature of idiopathic Parkinson's disease (PD). Recent neuropathological evidence however suggests that the axons of the nigrostriatal dopaminergic system are the earliest target of α-synuclein accumulation in PD, thus the principal site for vulnerability. Whether this applies to in vivo PD, and also to the mesolimbic system has not been investigated yet. We used [(11)C]FeCIT PET to measure presynaptic dopamine transporter (DAT) activity in both nigrostriatal and mesolimbic systems, in 36 early PD patients (mean disease duration in months ± SD 21.8 ± 10.7) and 14 healthy controls similar for age. We also performed anatomically-driven partial correlation analysis to evaluate possible changes in the connectivity within both the dopamine networks at an early clinical phase. In the nigrostriatal system, we found a severe DAT reduction in the afferents to the dorsal putamen (DPU) (η(2) = 0.84), whereas the SN was the less affected region (η(2) = 0.31). DAT activity in the ventral tegmental area (VTA) and the ventral striatum (VST) were also reduced in the patient group, but to a lesser degree (VST η(2) = 0.71 and VTA η(2) = 0.31). In the PD patients compared to the controls, there was a marked decrease in dopamine network connectivity between SN and DPU nodes, supporting the significant derangement in the nigrostriatal pathway. These results suggest that neurodegeneration in the dopamine pathways is initially more prominent in the afferent axons and more severe in the nigrostriatal system. Considering PD as a disconnection syndrome starting from the axons, it would justify neuroprotective interventions even if patients have already manifested clinical symptoms.

  19. Non-motor symptoms in treated and untreated Chinese patients with early Parkinson's disease.

    Science.gov (United States)

    Zhang, Hui; Gu, Zhuqin; An, Jing; Wang, Chaodong; Chan, Piu

    2014-01-01

    Non-motor symptoms (NMS) are important preclinical features of Parkinson's disease (PD) and have become the leading cause of poor quality of life with disease progression. There are little data on how antiparkinsonian medications influence the NMS in PD at early stage. In this study, we explored the distribution of NMS in treated and untreated PD and investigated the association between NMS and antiparkinsonian medications in Chinese patients with early PD. Subjects were enrolled from a Chinese PD patient cohort based on 2 clinical trials. Face-to-face interviews and evaluations were performed for clinical information. NMS were compared in patients with or without antiparkinsonian treatment, and between subgroups of dopaminergic medications. Eight hundred and sixteen PD patients were enrolled in this study, of whom 428 were newly diagnosed PD. Only 5 in 646 patients who completed all these NMS measurements (0.6%) were free of NMS. PD patients with antiparkinsonian medications had a significantly higher frequency of poor sleep (p = 0.001), depression (p = 0.0001) and constipation (p = 0.0001) after adjusted gender, onset age, duration, and Hoehn & Yahr stage. Moreover, patients treated by levodopa plus dopamine agonist had a higher percentage of bad sleepers (adjusted p = 0.040), and correlation analysis revealed that Levodopa Equivalent Dose (LED) was associated with constipation (coefficient 0.146, p = 0.005). These findings suggest that although NMS exist in the prodromal stage of PD, antiparkinsonian treatment is associated with increased frequency of some NMS, which may challenge the management for PD.

  20. Behavioral phenotyping of Parkin-deficient mice: looking for early preclinical features of Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Daniel Rial

    Full Text Available There is considerable evidence showing that the neurodegenerative processes that lead to sporadic Parkinson's disease (PD begin many years before the appearance of the characteristic motor symptoms. Neuropsychiatric, sensorial and cognitive deficits are recognized as early non-motor manifestations of PD, and are not attenuated by the current anti-parkinsonian therapy. Although loss-of-function mutations in the parkin gene cause early-onset familial PD, Parkin-deficient mice do not display spontaneous degeneration of the nigrostriatal pathway or enhanced vulnerability to dopaminergic neurotoxins such as 6-OHDA and MPTP. Here, we employed adult homozygous C57BL/6 mice with parkin gene deletion on exon 3 (parkin-/- to further investigate the relevance of Parkin in the regulation of non-motor features, namely olfactory, emotional, cognitive and hippocampal synaptic plasticity. Parkin-/- mice displayed normal performance on behavioral tests evaluating olfaction (olfactory discrimination, anxiety (elevated plus-maze, depressive-like behavior (forced swimming and tail suspension and motor function (rotarod, grasping strength and pole. However, parkin-/- mice displayed a poor performance in the open field habituation, object location and modified Y-maze tasks suggestive of procedural and short-term spatial memory deficits. These behavioral impairments were accompanied by impaired hippocampal long-term potentiation (LTP. These findings indicate that the genetic deletion of parkin causes deficiencies in hippocampal synaptic plasticity, resulting in memory deficits with no major olfactory, emotional or motor impairments. Therefore, parkin-/- mice may represent a promising animal model to study the early stages of PD and for testing new therapeutic strategies to restore learning and memory and synaptic plasticity impairments in PD.

  1. Dream Robber: Living with Parkinson's Disease

    Science.gov (United States)

    Skip Navigation Bar Home Current Issue Past Issues Dream Robber: Living with Parkinson's disease Past Issues / Summer ... the disease itself. Read More "Parkinson's disease" Articles Dream Robber: Living with Parkinson's disease / Unraveling Parkinson's: Three ...

  2. Osteoporosis in Parkinson's disease.

    Science.gov (United States)

    Invernizzi, Marco; Carda, Stefano; Viscontini, Giovanni Sguazzini; Cisari, Carlo

    2009-06-01

    Patients affected by Parkinson's disease are at a high risk for fractures, mainly of the hip. These fractures are caused by falls due to postural imbalance, neurological impairment and reduced bone mass. The purpose of this study was (1) to investigate the correlations and the pathophysiological mechanisms underlying bone loss in Parkinson's disease and appraise bone loss or fracture risk reduction interventions; (2) to develop a research agenda that informs the design and development of risk reduction strategies. Osteoporosis and osteopenia are very common findings in patients with Parkinson's disease, affecting up to 91% of women and 61% of men. Reduced bone mass in Parkinsonian patients seems to be caused mainly by reduced mobility through a mechanism similar to that observed in other neurological diseases. Endocrine (such as vitamin D deficiency), nutritional and iatrogenic factors also play an important role in bone mass depletion. Female gender, disease duration and severity (Hoehn and Yahr stages III and IV), old age and low body mass index are related to more severe osteoporosis. Vitamin D supplementation and bisphosphonates seem to be effective in reducing the risk of nonvertebral fractures in patients affected by Parkinson's disease. Prevention and evaluation of osteoporosis through bone mass density assessment should be considered in all patients with Parkinson's disease.

  3. Pramipexole extended release: in Parkinson's disease.

    Science.gov (United States)

    Chwieduk, Claudine M; Curran, Monique P

    2010-04-01

    Pramipexole extended release (ER) is a non-ergolinic dopamine receptor agonist available for use as a once-daily oral treatment for the signs and symptoms of early and advanced idiopathic Parkinson's disease. Once-daily pramipexole ER and three times-daily pramipexole immediate release (IR) have similar exposure over 24 hours. The ER formulation is associated with fewer fluctuations in plasma pramipexole concentrations over this period. Pramipexole ER improved the symptoms of Parkinson's disease in three well designed trials in adults with early or advanced disease, as measured by changes from baseline in the sum of the Unified Parkinson's Disease Rating Scale (UPDRS) parts II and III subtotal scores. In a 9-week study, the majority of patients with early Parkinson's disease who were receiving stable pramipexole IR treatment were successfully switched to pramipexole ER. Relative to placebo at week 18, pramipexole ER 0.375-4.5 mg (of the salt) once daily significantly decreased the sum of the UPDRS parts II and III subtotal scores from baseline in two trials in patients with early or advanced Parkinson's disease, and also reduced the percentage of off-time during waking hours in patients with advanced disease. The efficacy of pramipexole ER was maintained after 33 weeks of treatment in the trials in patients with early or advanced Parkinson's disease. Pramipexole ER was generally well tolerated in patients with Parkinson's disease, with the rate of adverse events being generally similar to that with pramipexole IR.

  4. Cooperative genome-wide analysis shows increased homozygosity in early onset Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Javier Simón-Sánchez

    Full Text Available Parkinson's disease (PD occurs in both familial and sporadic forms, and both monogenic and complex genetic factors have been identified. Early onset PD (EOPD is particularly associated with autosomal recessive (AR mutations, and three genes, PARK2, PARK7 and PINK1, have been found to carry mutations leading to AR disease. Since mutations in these genes account for less than 10% of EOPD patients, we hypothesized that further recessive genetic factors are involved in this disorder, which may appear in extended runs of homozygosity.We carried out genome wide SNP genotyping to look for extended runs of homozygosity (ROHs in 1,445 EOPD cases and 6,987 controls. Logistic regression analyses showed an increased level of genomic homozygosity in EOPD cases compared to controls. These differences are larger for ROH of 9 Mb and above, where there is a more than three-fold increase in the proportion of cases carrying a ROH. These differences are not explained by occult recessive mutations at existing loci. Controlling for genome wide homozygosity in logistic regression analyses increased the differences between cases and controls, indicating that in EOPD cases ROHs do not simply relate to genome wide measures of inbreeding. Homozygosity at a locus on chromosome19p13.3 was identified as being more common in EOPD cases as compared to controls. Sequencing analysis of genes and predicted transcripts within this locus failed to identify a novel mutation causing EOPD in our cohort.There is an increased rate of genome wide homozygosity in EOPD, as measured by an increase in ROHs. These ROHs are a signature of inbreeding and do not necessarily harbour disease-causing genetic variants. Although there might be other regions of interest apart from chromosome 19p13.3, we lack the power to detect them with this analysis.

  5. Critical Dysphagia is Common in Parkinson Disease and Occurs Even in Early Stages: A Prospective Cohort Study.

    Science.gov (United States)

    Pflug, Christina; Bihler, Moritz; Emich, Katharina; Niessen, Almut; Nienstedt, Julie Cläre; Flügel, Till; Koseki, Jana-Christiane; Plaetke, Rosemarie; Hidding, Ute; Gerloff, Christian; Buhmann, Carsten

    2017-08-21

    To assess the prevalence of dysphagia and its typical findings in unselected "real-world" Parkinson patients using an objective gold-standard method. This was a prospective, controlled, cross-sectional study conducted in 119 consecutive Parkinson patients of all stages independent of subjective dysphagia. Patients and 32 controls were clinically and endoscopically examined by flexible endoscopic evaluation of swallowing (FEES) to evaluate the deglutition with regard to three consistencies (water, biscuit, and bread). Typical findings of dysphagia like penetration and aspiration, residues, and leakage were assessed. Dysphagia was common in Parkinson patients and occurred in all, even early, disease stages. Only 5% (6/119) of patients showed a completely unremarkable deglutition. Aspiration was seen in 25% (30/119) of patients and always related to water. Residues occurred in 93% (111/119), most commonly for bread. Leakage was much less frequent and was found in only 3-18%, depending on consistency. In a significant fraction of patients, objective dysphagia was not subjectively perceived. A total of 16% of asymptomatic patients suffered from critical aspiration. Significant swallowing deficiencies already occurred in early disease. Aspiration was found in 4 of 20 (20%) patients with disease duration of less than 2 years. Seven of 57 patients (12%) with Hoehn and Yahr stage 2 suffered from severe aspiration. Given the high frequency of critical aspiration in Parkinson disease, these patients should be evaluated early for dysphagia to avoid complications and recommend an adequate therapy. FEES is a simple, cost efficient, minimally invasive method that is ideally suited for this purpose.

  6. Protagonists with Parkinson's disease.

    Science.gov (United States)

    Haan, Joost

    2013-01-01

    Parkinson's disease is a complex disorder with many fascinating features. Its onset is creeping, the progression is slow but inevitable. There are motor symptoms, such as a tremor, rigidity, bradykinesia, mask-like facial expression, and postural abnormalities, but also hallucinations, cognitive deterioration, and depression. In many novels, fictive patients with Parkinson's disease play a role. It seems that authors have used many aspects of the disease to emphasize their messages. Their narratives include themes such as rigidity, petrifaction, confusion, dementia, and hallucinations. In this chapter, as examples, several protagonists with Parkinson's disease will be described from works of John Updike, Jonathan Franzen, Sue Miller, J.M. Coetzee, and John Harding, among others.

  7. Catechol-O-methyltransferase Val158Met polymorphism influences prefrontal executive function in early Parkinson's disease.

    Science.gov (United States)

    Zhang, Youwen; Feng, Shujun; Nie, Kun; Zhao, Xin; Gan, Rong; Wang, Limin; Zhao, Jiehao; Tang, Hongmei; Gao, Liang; Zhu, Ruiming; Wang, Lijuan; Zhang, Yuhu

    2016-10-15

    The catechol-O-methyltransferase (COMT) Val158Met polymorphism has been proposed to be associated with increased risk of Parkinson's disease (PD) and have a specific impact on dopamine-mediated prefrontal executive function in an inverted-U curve manner. We explored the influence of this genetic polymorphism on prefrontal executive function in a well-established Chinese cohort of early PD patients with no current or past history of motor fluctuations or dyskinesias. Cognitive functions were assessed in 250 patients with early PD using Wechsler Adult Intelligence Scale-Chinese Revision (WAIS-RC) and Wechsler Memory Scale-Chinese Revision (WMS-RC). These patients and 300 healthy controls were subsequently genotyped for the COMT gene Val158Met polymorphism. We employed analysis of covariance (ANCOVA) and a stratified analysis to determine the associations between the COMT Val158Met genotype and cognitive functions. The COMT Val158Met allele frequency and genotype distributions showed no statistically significant differences between PD patients and controls. However, patients with met/met genotype performed significantly worse on WAIS-RC similarities, a measure of executive function, compared to individuals with val/val genotype. Subsequent ANCOVA analysis revealed that COMT genotype interacted with sex and daily levodopa equivalent dose (LED) to influence executive function. Further stratified analysis showed that the lower-activity COMT met/met genotype has a detrimental effect on executive function among women. Our results demonstrate that COMT Val158Met polymorphism is probably not associated with increased risk of PD, but has an effect on prefrontal executive function interacting with gender and dopaminergic medication. Copyright © 2016. Published by Elsevier B.V.

  8. Parkinson's Disease Foundation News

    Science.gov (United States)

    ... You are here Home / Understanding Parkinson's / Parkinson's News Parkinson's News What's new in Parkinson's? What do the ... Science News Community News PDF in the News Parkinson's HelpLine Learn More Educational Materials Do you want ...

  9. Parkinson's Disease Videos

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    Full Text Available ... with Parkinson's General Gift Tribute Gift Moving Day ® Team Hope TM for Parkinson's DONATE Your gift can ... with Parkinson's General Gift Tribute Gift Moving Day ® Team Hope TM for Parkinson's Understanding Parkinson's What Is ...

  10. Health-related quality of life in early Parkinson's disease: the impact of nonmotor symptoms.

    Science.gov (United States)

    Duncan, Gordon W; Khoo, Tien K; Yarnall, Alison J; O'Brien, John T; Coleman, Shirley Y; Brooks, David J; Barker, Roger A; Burn, David J

    2014-02-01

    Nonmotor symptoms (NMS) are common in patients with established Parkinson's disease (PD) and have a major impact upon quality of life. We investigated the significance of NMS in relation to health-related quality of life (HRQoL) in patients with newly diagnosed PD. Patients and healthy controls were recruited as part of the Incidence of Cognitive Impairment in Cohorts with Longitudinal Evaluation in Parkinson's Disease Study. Prevalence of NMS was determined with the Non-Motor Symptom Questionnaire. HRQoL was recorded with the 39-item Parkinson's Disease Quality of Life Questionnaire (PDQ-39). Further assessments included measures of motor disability, depression, sleep, and cognition. One hundred and fifty-eight patients with newly diagnosed PD and 99 controls participated in this cross-sectional study. Patients reported greater numbers of NMS than controls (mean 8.3 ± 4.3 versus 2.8 ± 2.5 symptoms; P disease. Depression (P quality of life. Cognitive, neuropsychiatric, and sleep disturbances are particularly associated with reduced well-being. Screening and management of these symptoms should be prioritized at the time of diagnosis.

  11. Speech disorders in Parkinson's disease: early diagnostics and effects of medication and brain stimulation.

    Science.gov (United States)

    Brabenec, L; Mekyska, J; Galaz, Z; Rektorova, Irena

    2017-03-01

    Hypokinetic dysarthria (HD) occurs in 90% of Parkinson's disease (PD) patients. It manifests specifically in the areas of articulation, phonation, prosody, speech fluency, and faciokinesis. We aimed to systematically review papers on HD in PD with a special focus on (1) early PD diagnosis and monitoring of the disease progression using acoustic voice and speech analysis, and (2) functional imaging studies exploring neural correlates of HD in PD, and (3) clinical studies using acoustic analysis to evaluate effects of dopaminergic medication and brain stimulation. A systematic literature search of articles written in English before March 2016 was conducted in the Web of Science, PubMed, SpringerLink, and IEEE Xplore databases using and combining specific relevant keywords. Articles were categorized into three groups: (1) articles focused on neural correlates of HD in PD using functional imaging (n = 13); (2) articles dealing with the acoustic analysis of HD in PD (n = 52); and (3) articles concerning specifically dopaminergic and brain stimulation-related effects as assessed by acoustic analysis (n = 31); the groups were then reviewed. We identified 14 combinations of speech tasks and acoustic features that can be recommended for use in describing the main features of HD in PD. While only a few acoustic parameters correlate with limb motor symptoms and can be partially relieved by dopaminergic medication, HD in PD seems to be mainly related to non-dopaminergic deficits and associated particularly with non-motor symptoms. Future studies should combine non-invasive brain stimulation with voice behavior approaches to achieve the best treatment effects by enhancing auditory-motor integration.

  12. How Is Parkinson's Disease Treated?

    Science.gov (United States)

    ... Parkinson's There is a lot to know about Parkinson's disease. Learn about symptoms, how it is diagnosed and ... awareness for the 1 million Americans living with Parkinson’s disease. Learn More > Our Impact Our Mission Our Team ...

  13. Parkinson's Disease: The Newest Advances

    Science.gov (United States)

    Skip Navigation Bar Home Current Issue Past Issues Parkinson's Disease: The Newest Advances Past Issues / Summer 2006 Table ... number of genes that cause or contribute to Parkinson's disease (PD), as well as potential environmental risk factors. ...

  14. Predictors of time to initiation of symptomatic therapy in early Parkinson's disease.

    Science.gov (United States)

    Simuni, Tanya; Long, Jeffrey D; Caspell-Garcia, Chelsea; Coffey, Christopher S; Lasch, Shirley; Tanner, Caroline M; Jennings, Danna; Kieburtz, Karl D; Marek, Kenneth

    2016-07-01

    To determine clinical and biological variables that predict time to initiation of symptomatic therapy in de novo Parkinson's disease patients. Parkinson's Progression Markers Initiative is a longitudinal case-control study of de novo, untreated Parkinson's disease participants at enrolment. Participants contribute a wide range of motor and non-motor measures, including biofluids and imaging biomarkers. The machine learning method of random survival forests was used to examine the ability of baseline variables to predict time to initiation of symptomatic therapy since study enrollment (baseline). There were 423 PD participants enrolled in PPMI and 33 initial baseline variables. Cross-validation results showed that the three-predictor subset of disease duration (time from diagnosis to enrollment), the modified Schwab and England activities of daily living scale, and the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) total score modestly predicted time to initiation of symptomatic therapy (C = 0.70, pseudo-R (2) = 0.13). Prediction using the three variables was similar to using the entire set of 33. None of the biological variables increased accuracy of the prediction. A prognostic index for time to initiation of symptomatic therapy was created using the linear and nonlinear effects of the three top variables based on a post hoc Cox model. Our findings using a novel machine learning method support previously reported clinical variables that predict time to initiation of symptomatic therapy. However, the inclusion of biological variables did not increase prediction accuracy. Our prognostic index constructed, based on the group-level survival curve can provide an indication of the risk of initiation of ST for PD patients based on functions of the three top predictors.

  15. Recent developments in biomarkers in Parkinson disease

    OpenAIRE

    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....

  16. Oxysterols and Parkinson's disease

    DEFF Research Database (Denmark)

    Björkhem, Ingemar; Lövgren-Sandblom, Anita; Leoni, Valerio

    2013-01-01

    Oxysterols are important for cholesterol homeostasis in the brain and may be affected in neurodegenerative diseases. The levels of the brain-derived oxysterol 24S-hydroxycholesterol (24S-OH) have been reported to be markedly reduced in the circulation of patients with Parkinson's disease (PD) (Lee...

  17. Parkinson's Disease: Research

    Science.gov (United States)

    ... toxins, that may trigger the disorder, and study genetic factors to determine how defective genes play a role. Other scientists are working to develop new protective drugs that can delay, prevent, or reverse the disease. Parkinson's Disease Research No breakthroughs, but steady progress The ...

  18. Mutations in the glucocerebrosidase gene are associated with early-onset Parkinson disease.

    Science.gov (United States)

    Clark, L N; Ross, B M; Wang, Y; Mejia-Santana, H; Harris, J; Louis, E D; Cote, L J; Andrews, H; Fahn, S; Waters, C; Ford, B; Frucht, S; Ottman, R; Marder, K

    2007-09-18

    To evaluate the frequency of glucocerebrosidase (GBA) mutations in cases and controls enrolled in the Genetic Epidemiology of Parkinson's Disease (GEPD) study. We sequenced all exons of the GBA gene in 278 Parkinson disease (PD) cases and 179 controls enrolled in GEPD, with a wide range of age at onset (AAO), and that included a subset of 178 Jewish cases and 85 Jewish controls. Cases and controls were recruited without knowledge of family history of PD, and cases were oversampled in the AAO 50 years (OR 2.7, 95% CI 1.3 to 5.3). Adjusting for age at the time of evaluation, sex, family history of PD, and Jewish ancestry, GBA carriers had a 1.7-year-earlier AAO of PD (95% CI 0.5 to 3.3, p 50 years group. The frequency of GBA mutations was higher in a subset of 178 cases that reported four Jewish grandparents (16.9%) than in cases who did not report Jewish ancestry (8.0%) (p Parkinson disease and that Glucocerebrosidase mutations may modify age at onset.

  19. Pancreatic Polypeptide in Parkinson's Disease

    DEFF Research Database (Denmark)

    Knudsen, Karoline; Hartmann, Bolette; Fedorova, Tatyana D

    2017-01-01

    BACKGROUND AND OBJECTIVES: Parkinson's disease (PD) patients experience several non-motor symptoms from the gastrointestinal tract that may partly be caused by parasympathetic deficiency. The pancreas is densely innervated by the vagus nerve, which mediates early meal-induced secretion of pancrea......BACKGROUND AND OBJECTIVES: Parkinson's disease (PD) patients experience several non-motor symptoms from the gastrointestinal tract that may partly be caused by parasympathetic deficiency. The pancreas is densely innervated by the vagus nerve, which mediates early meal-induced secretion...... and 17 controls were included. PP, insulin, and blood glucose levels were measured before, during, and after sham feeding with white bread and chocolate spread. GITT was measured using radiopaque markers. Furthermore, faeces samples were analyzed for pancreatic elastase enzyme as a marker of exocrine...

  20. Parkinson's Disease Videos

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    Full Text Available ... How Does Depression Affect the Patient's Family and Social Network? How Does Parkinson's Disease Affect Memory? How ... 800-4PD-INFO (473-4636) Staffed by nurses, social workers and therapists, our Helpline is here to ...

  1. Parkinson's Disease Videos

    Medline Plus

    Full Text Available ... know about Parkinson's disease. Learn about symptoms, how it is diagnosed and what treatment options are available. ... Travel and Transportation: Part 2 CareMAP: When Is It Time to Get Help? CareMAP: Where to Find ...

  2. Nondipping in Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Sita Sommer

    2011-01-01

    Full Text Available Objective. The aim of this study was to identify patients with Parkinson's disease who showed loss or decrease of nocturnal blood pressure fall (nondipper patients as a marker of autonomic dysfunction. Presence or absence of orthostatic hypotension was considered to investigate whether alterations in circadian blood pressure pattern are associated with posture-related dysregulation of blood pressure. Methods. 40 patients with Parkinson's disease underwent 24-hour blood pressure monitoring. 21 patients were diagnosed with arterial hypertension and received anti-hypertensive drugs. Nondipper patients were defined as having nocturnal decrease of mean systolic and diastolic blood pressure less than 10%. Presence or absence of orthostatic hypotension was determined by Schellong's test. Results. We identified 35 nondipper patients (88%. Nondipping was detected in 20 patients with orthostatic hypotension (95% and in 15 patients without orthostatic hypotension (79%. 18 patients with hypertensive and 22 patients with normal blood pressure values were detected. Conclusions. In conclusion 24-hour blood pressure monitoring showed a high prevalence of nondipping in 40 patients with Parkinson's disease with and without orthostatic hypotension independent of coexisting arterial hypertension and antihypertensive treatment. 24-hour blood pressure monitoring may be useful to identify non-dipping as a marker of autonomic dysfunction in patients with Parkinson's disease.

  3. Parkinson's Disease Videos

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    Full Text Available ... 1 CareMAP: Movement and Falls: Part 2 CareMAP: Movimientos y Caídas, Parte 1 CareMAP: Movimientos y Caídas, Parte 2 CareMAP: Peace in Caring ... How Does Depression Affect the Patient's Family and Social Network? How Does Parkinson's Disease Affect Memory? How ...

  4. Parkinson's Disease Videos

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    Full Text Available ... Are There Any Interactions With Non-Parkinson's Disease Medications? Are There Any Tips to Use for Freezing? ... y la Salud en General, Parte 2 CareMAP: Medications and General Health Part 1 CareMAP: Medications and ...

  5. Parkinson's Disease Videos

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    Full Text Available ... know about Parkinson's disease. Learn about symptoms, how it is diagnosed and what treatment options are available. ... Travel and Transportation: Part 2 CareMAP: When Is It Time to Get Help? CareMAP: Where to Find ...

  6. Postural deformities in Parkinson's disease

    NARCIS (Netherlands)

    Doherty, K.M.; Warrenburg, B.P.C. van de; Peralta, M.C.; Silveira-Moriyama, L.; Azulay, J.P.; Gershanik, O.S.; Bloem, B.R.

    2011-01-01

    Postural deformities are frequent and disabling complications of Parkinson's disease (PD) and atypical parkinsonism. These deformities include camptocormia, antecollis, Pisa syndrome, and scoliosis. Recognition of specific postural syndromes might have differential diagnostic value in patients prese

  7. Genetics of Parkinson's disease and parkinsonism.

    Science.gov (United States)

    Douglas, Michael R; Lewthwaite, Alistair J; Nicholl, David J

    2007-06-01

    The past 10 years has seen a shift in our etiological concepts of Parkinson's disease, moving from a nearly exclusively environmentally mediated disease towards a complex disorder with important genetic contributors. The identification of responsible mutations in certain genes, particularly alpha-synuclein, Parkin, PINK1, DJ-1 and LRRK2, has increased our understanding of the clinical and pathological changes underlying Parkinson's disease, with implications for patient diagnosis, management and future research. This review will outline the specific genetic advances, discuss their implications for clinical practice and hint at future directions for research into this common and disabling disease.

  8. Motor-language coupling: direct evidence from early Parkinson's disease and intracranial cortical recordings.

    Science.gov (United States)

    Ibáñez, Agustín; Cardona, Juan F; Dos Santos, Yamil Vidal; Blenkmann, Alejandro; Aravena, Pía; Roca, María; Hurtado, Esteban; Nerguizian, Mirna; Amoruso, Lucía; Gómez-Arévalo, Gonzalo; Chade, Anabel; Dubrovsky, Alberto; Gershanik, Oscar; Kochen, Silvia; Glenberg, Arthur; Manes, Facundo; Bekinschtein, Tristán

    2013-04-01

    Language and action systems are functionally coupled in the brain as demonstrated by converging evidence using Functional magnetic resonance imaging (fMRI), electroencephalography (EEG), transcranial magnetic stimulation (TMS), and lesion studies. In particular, this coupling has been demonstrated using the action-sentence compatibility effect (ACE) in which motor activity and language interact. The ACE task requires participants to listen to sentences that described actions typically performed with an open hand (e.g., clapping), a closed hand (e.g., hammering), or without any hand action (neutral); and to press a large button with either an open hand position or closed hand position immediately upon comprehending each sentence. The ACE is defined as a longer reaction time (RT) in the action-sentence incompatible conditions than in the compatible conditions. Here we investigated direct motor-language coupling in two novel and uniquely informative ways. First, we measured the behavioural ACE in patients with motor impairment (early Parkinson's disease - EPD), and second, in epileptic patients with direct electrocorticography (ECoG) recordings. In experiment 1, EPD participants with preserved general cognitive repertoire, showed a much diminished ACE relative to non-EPD volunteers. Moreover, a correlation between ACE performance and action-verb processing (kissing and dancing test - KDT) was observed. Direct cortical recordings (ECoG) in motor and language areas (experiment 2) demonstrated simultaneous bidirectional effects: motor preparation affected language processing (N400 at left inferior frontal gyrus and middle/superior temporal gyrus), and language processing affected activity in movement-related areas (motor potential at premotor and M1). Our findings show that the ACE paradigm requires ongoing integration of preserved motor and language coupling (abolished in EPD) and engages motor-temporal cortices in a bidirectional way. In addition, both experiments

  9. Diffusion imaging of nigral alterations in early Parkinson's disease with dopaminergic deficits.

    Science.gov (United States)

    Schuff, Norbert; Wu, I-Wei; Buckley, Shannon; Foster, Eric D; Coffey, Christopher S; Gitelman, Darren R; Mendick, Susan; Seibyl, John; Simuni, Tanya; Zhang, Yu; Jankovic, Joseph; Hunter, Christine; Tanner, Caroline M; Rees, Linda; Factor, Stewart; Berg, Daniela; Wurster, Isabel; Gauss, Katharina; Sprenger, Fabienne; Seppi, Klaus; Poewe, Werner; Mollenhauer, Brit; Knake, Susanne; Mari, Zoltan; McCoy, Arita; Ranola, Madelaine; Marek, Kenneth

    2015-12-01

    This study reports the baseline characteristics of diffusion tensor imaging data in Parkinson's disease (PD) patients and healthy control subjects from the Parkinson's Progression Markers Initiative. The main goals were to replicate previous findings of abnormal diffusion imaging values from the substantia nigra. in a large multicenter cohort and determine whether nigral diffusion alterations are associated with dopamine deficits. Two hundred twenty subjects (PD = 153; control = 67) from 10 imaging sites were included. All subjects had a full neurological exam, a ((123) I)ioflupane dopamine transporter (DAT) single-photon emission computer tomography scan, and diffusion tensor imaging. Fractional anisotropy as well as radial and axial diffusivity was computed within multiple regions across the substantia nigra. A repeated-measures analysis of variance found a marginally nonsignificant interaction between regional fractional anisotropy of the substantia nigra and disease status (P = 0.08), conflicting with an earlier study. However, a linear mixed model that included control regions in addition to the nigral regions revealed a significant interaction between regions and disease status (P = 0.002), implying a characteristic distribution of reduced fractional anisotropy across the substantia nigra in PD. Reduced fractional anisotropy in PD was also associated with diminished DAT binding ratios. Both axial and radial diffusivity were also abnormal in PD. Although routine nigral measurements of fractional anisotropy are clinically not helpful, the findings in this study suggest that more-sophisticated diffusion imaging protocols should be used when exploring the clinical utility of this imaging modality. © 2015 International Parkinson and Movement Disorder Society.

  10. Disturbed intracortical excitability in early Parkinson's disease is l-DOPA dose related: a prospective 12-month paired TMS study.

    Science.gov (United States)

    Bares, Martin; Kanovský, Petr; Rektor, Ivan

    2007-12-01

    We were interested to know if chronic l-DOPA treatment in Parkinson's disease (PD) patients could restore impairment of the intracortical excitability, when this difference could occur, and if it was related to the total daily dose of l-DOPA. Twelve patients with early PD were studied using paired transcranial magnetic stimulation before the administration of l-DOPA, and then after 3, 6, and 12 months of l-DOPA treatment. The level of disturbed intracortical excitability strongly correlated with the total daily dose of l-DOPA. The level of cortical excitability in PD patients seems to be indirectly related to the nigro-striatal functioning.

  11. Twice-daily, low-dose pramipexole in early Parkinson's disease: a randomized, placebo-controlled trial.

    Science.gov (United States)

    Kieburtz, Karl

    2011-01-01

    To compare the safety and efficacy of low dosages of pramipexole given twice daily (bid) in early Parkinson's disease (PD) with those of a standard 3 times daily (tid) regimen in a randomized, double-blind, placebo controlled trial involving 311 early PD patients not receiving dopaminergic treatment. Subjects were randomly assigned and followed on assigned treatment for 12 weeks with pramipexole at dosages of 0.5 mg bid, 0.75 mg bid, or 0.5 mg tid, or matching placebo. All subjects were dosed 3 times daily, with placebo if necessary, to maintain blinding. The primary outcome was the change from baseline to Week 12 in the Unified Parkinson Disease Rating Scale (UPDRS) total score (Parts I-III). All active dosages had similar antiparkinson efficacy showing reductions of 4-5 UPDRS points relative to placebo (p pramipexole administered twice daily at a total daily dosage of 1.0-1.5 mg daily was of comparable efficacy and tolerability to a dosage of 0.5 mg tid over a 12-week treatment period in early PD.

  12. Alteration in nicotine binding sites in Parkinson's disease, Lewy body dementia and Alzheimer's disease: possible index of early neuropathology.

    Science.gov (United States)

    Perry, E K; Morris, C M; Court, J A; Cheng, A; Fairbairn, A F; McKeith, I G; Irving, D; Brown, A; Perry, R H

    1995-01-01

    High-affinity nicotine binding, considered to primarily reflect the presence of CNS alpha 4 beta 2 nicotinic receptor subunits, was examined autoradiographically in brain regions most severely affected by Alzheimer and Parkinson types of pathology. In the midbrain, the high density of binding associated with the pars compacta of the substantia nigra was extensively reduced (65-75%, particularly in the lateral portion) in both Lewy body dementia and Parkinson's disease. Since loss of dopaminergic neurons in Lewy body dementia was only moderate (40%), loss or down-regulation of the nicotinic receptor may precede degeneration of dopaminergic neurons in this region. In the dorsolateral tegmentum, where diffuse cholinergic perikarya are located, nicotine binding was highly significantly decreased in both Lewy body dementia and Parkinson's disease with almost no overlap between the normal and disease groups, indicative of a major pathological involvement in or around the pedunculopontine cholinergic neurons. In the hippocampus, binding was decreased around the granular layer in Lewy body dementia and Alzheimer's disease, although unchanged in the stratum lacunosum moleculare, where binding was relatively higher. Dense bands of receptor binding in the presubiculum and parahippocampal gyrus--areas of highest binding in human cortex--were diminished in Alzheimer's disease but not Lewy body dementia. In temporal neocortex there were reductions in Alzheimer's disease throughout the cortical layers but in Lewy body dementia only in lower layers, in which Lewy bodies are concentrated. Abnormalities of the nicotinic receptor in the diseases examined appear to be closely associated with primary histopathological changes: dopaminergic cell loss in Parkinson's disease and Lewy body dementia, amyloid plaques and tangles in subicular and entorhinal areas in Alzheimer's disease. Loss or down-regulation of the receptor may precede neurodegeneration.

  13. Placebo-associated improvements in motor function: comparison of subjective and objective sections of the UPDRS in early Parkinson's disease.

    Science.gov (United States)

    Goetz, Christopher G; Leurgans, Sue; Raman, Rema

    2002-03-01

    The Unified Parkinson's Disease Rating Scale (UPDRS) is primarily composed of an investigator-derived objective rating of motor function and a patient-derived assessment of activities of daily living (ADL). Using a stringent definition of placebo effect, we examined the frequency, temporal development, and stability of improvements during placebo treatment over 6 months in a large placebo-controlled trial of deprenyl and tocopherol in early Parkinson's disease (DATATOP). One hundred ninety-nine subjects received placebo treatment in the randomized, multicenter, placebo-controlled DATATOP study. We compared the baseline UPDRS motor section scores with follow-up scores at 4, 13, and 26 weeks. Placebo-associated improvement was defined as an improvement over baseline score in motor UPDRS of at least 50% or a change in at least two motor items at any one visit by two or more points. Seventeen percent of the 185 subjects who qualified for analysis met the placebo response criteria. The group prevalence of response was steady (7% to 10%) at any one visit without a marked predominance of an early study effect. Older subjects with more motor impairment at baseline were most likely to show a placebo-associated improvement. ADL scores were low throughout the study, and ADL improvements did not identify the subjects with objectively defined placebo-associated improvement. Prominent improvements in investigator-derived objective measures of Parkinson's disease motor impairment occur during clinical trials, including one that was not aimed at showing improved short-term efficacy. Although the notion of placebo effect often implies patient-based perceptions, we found subjective changes to be infrequent in placebo-treated patients, suggesting that either: (1) the placebo effect was rater-driven; (2) the ADL questionnaire is insensitive to transient but objectively demonstrable motor changes; or (3) that the objective changes, albeit major, are within the realm of natural

  14. Postprandial ghrelin response is reduced in patients with Parkinson's disease and idiopathic REM sleep behaviour disorder: a peripheral biomarker for early Parkinson's disease?

    Science.gov (United States)

    Unger, Marcus M; Möller, Jens C; Mankel, Katharina; Eggert, Karla M; Bohne, Katharina; Bodden, Maren; Stiasny-Kolster, Karin; Kann, Peter H; Mayer, Geert; Tebbe, Johannes J; Oertel, Wolfgang H

    2011-06-01

    Ghrelin, an orexigenic peptide, has multiple functions, which include promoting gastrointestinal motility and influencing higher brain functions. Experimental data suggest that ghrelin has neuroprotective potential in the MPTP mouse model of Parkinson's disease (PD). PD patients show delayed gastric emptying and other symptoms that may relate to disturbed excretion of ghrelin. No data are available on postprandial ghrelin response in patients with PD and idiopathic REM sleep behaviour disorder (iRBD)--a condition considered a putative preclinical stage of PD. We measured fasting and postprandial ghrelin serum concentrations in 20 healthy controls, 39 (including 19 drug-naïve) PD patients and 11 iRBD patients using a commercial radioimmunoassay for total ghrelin. For statistical analysis we employed ANCOVA and post-hoc testing with Bonferroni's method. Controls showed a decrease of mean fasting ghrelin serum concentrations in the early postprandial phase, followed by a recuperation starting 60 min after the test meal and reaching a maximum at 300 min. This recuperation was less pronounced in PD and iRBD; the slope of relative postprandial ghrelin recovery was different between the investigated groups (p = 0.007). Post-hoc testing showed a difference between controls and PD patients (p = 0.002) and between controls and iRBD patients (p = 0.037). The dynamic regulation of ghrelin in response to food intake is partially impaired in subjects at putative preclinical (iRBD) and clinical stages of PD. Reduced ghrelin excretion might increase the vulnerability of nigrostriatal dopaminergic neurons as suggested by animal studies. The impaired ghrelin excretion might qualify as a peripheral biomarker and be of diagnostic or therapeutic value.

  15. Subthalamic Nucleus Deep Brain Stimulation in Early Stage Parkinson's Disease Is Not Associated with Increased Body Mass Index.

    Science.gov (United States)

    Millan, Sarah H; Hacker, Mallory L; Turchan, Maxim; Molinari, Anna L; Currie, Amanda D; Charles, David

    2017-01-01

    Previous studies suggest that deep brain stimulation of the subthalamic nucleus (STN-DBS) for Parkinson's disease (PD) leads to weight gain. This study analyzes changes in body mass index (BMI) in 29 subjects from a prospective, single-blind trial of DBS in early stage PD (age 50-75, Hoehn & Yahr stage II off medication, treated with antiparkinsonian medications for ≥6 months but 0.05). BMI change over two years was not different between the groups (p = 0.62, ODT = -0.89; DBS+ODT = -0.17). This study suggests that STN-DBS is not associated with weight gain in subjects with early stage PD. This finding will be tested in an upcoming FDA-approved phase III multicenter, randomized, double-blind, placebo-controlled, pivotal clinical trial evaluating DBS in early stage PD (ClinicalTrials.gov identifier NCT00282152).

  16. Psychosis in Parkinson's disease

    OpenAIRE

    Thanvi, B; Lo, T.; Harsh, D

    2005-01-01

    Psychosis is common in Parkinson's disease (PD), particularly in its later stages. The symptoms range from comparatively minor illusions, vivid dreams, and occasional, non-disturbing visual hallucinations to frank psychosis. The pathogenesis of psychosis in PD is not fully known. Management of psychosis in PD requires a multidisciplinary approach. Some of the newer atypical antipsychotics are effective against psychosis with no significant worsening of PD. Psychosis in PD is associated with p...

  17. Psychosis in Parkinson's disease.

    Science.gov (United States)

    Thanvi, B R; Lo, T C N; Harsh, D P

    2005-10-01

    Psychosis is common in Parkinson's disease (PD), particularly in its later stages. The symptoms range from comparatively minor illusions, vivid dreams, and occasional, non-disturbing visual hallucinations to frank psychosis. The pathogenesis of psychosis in PD is not fully known. Management of psychosis in PD requires a multidisciplinary approach. Some of the newer atypical antipsychotics are effective against psychosis with no significant worsening of PD. Psychosis in PD is associated with poor quality of life for patients and the carers.

  18. Neurodegenerative disorders: Parkinson's disease and Huntington's disease

    Science.gov (United States)

    Hague, S; Klaffke, S; Bandmann, O

    2005-01-01

    Parkinson's disease and Huntington's disease are both model diseases. Parkinson's disease is the most common of several akinetic-rigid syndromes and Huntington's disease is only one of an ever growing number of trinucleotide repeat disorders. Molecular genetic studies and subsequent molecular biological studies have provided fascinating new insights into the pathogenesis of both disorders and there is now real hope for disease modifying treatment in the not too distant future for patients with Parkinson's disease or Huntington's disease. PMID:16024878

  19. Neurodegenerative disorders: Parkinson's disease and Huntington's disease.

    Science.gov (United States)

    Hague, S M; Klaffke, S; Bandmann, O

    2005-08-01

    Parkinson's disease and Huntington's disease are both model diseases. Parkinson's disease is the most common of several akinetic-rigid syndromes and Huntington's disease is only one of an ever growing number of trinucleotide repeat disorders. Molecular genetic studies and subsequent molecular biological studies have provided fascinating new insights into the pathogenesis of both disorders and there is now real hope for disease modifying treatment in the not too distant future for patients with Parkinson's disease or Huntington's disease.

  20. Parkinson's Disease Videos

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    Full Text Available ... Wellness PD Library Aware in Care Kit Legal / Financial / Insurance Parkinson's Today Blog Find Help A Parkinson's ... Parkinson's Foundation Board Key Milestones Press Room Partnerships Financial Reports Contact Us Our Impact We fight for ...

  1. Progression of Parkinson's Disease

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    ... out daily activities, and treatment complications. Severity of Parkinson's Below are some descriptions of mild, moderate and ... National HelpLine Educational Publications Online Seminars Parkinson's News Parkinson's HelpLine Learn More Educational Materials Do you want ...

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  4. Protocol of a randomised delayed-start double-blind placebo-controlled multi-centre trial for Levodopa in EArly Parkinson's disease: the LEAP-study

    NARCIS (Netherlands)

    Verschuur, C.V.; Suwijn, S.R.; Post, B.; Dijkgraaf, M.; Bloem, B.R.; Hilten, J.J. van; Laar, T. van; Tissingh, G.; Deuschl, G.; Lang, A.E.; Haan, R.J. de; Bie, R.M. de

    2015-01-01

    BACKGROUND: The aim of this study is to investigate if early treatment with levodopa has a beneficial disease modifying effect on Parkinson's disease (PD) symptoms and functional health, improves the ability to (maintain) work, and reduces the use of (informal) care, caregiver burden, and costs. Add

  5. Integrated molecular landscape of Parkinson's disease

    NARCIS (Netherlands)

    Klemann, C.J.H.M.; Martens, G.J.; Sharma, M.; Martens, M.B.; Isacson, O.; Gasser, T.; Visser, J.E.; Poelmans, G.J.V.

    2017-01-01

    Parkinson's disease is caused by a complex interplay of genetic and environmental factors. Although a number of independent molecular pathways and processes have been associated with familial Parkinson's disease, a common mechanism underlying especially sporadic Parkinson's disease is still largely

  6. 帕金森病运动前期研究进展%Premotor Phase of Early Parkinson Disease (review)

    Institute of Scientific and Technical Information of China (English)

    焦淑军; 袁红

    2011-01-01

    Clinical, neuroimaging, and pathologic studies suggested that a variety of nonmotor symptoms, such as olfactory dysfunction, dysautonomia, and mood and sleep disorders, can precede the typic motor features of Parkinson disease (PD) by years and, perhaps, even decades.The period when these symptoms arise can be referred as the premotor phase of the disease.This paper reviewed the conception, clinical manifestation, pathology, diogose of the premotor phase of early Parkinson disease.%临床症状学及神经影像学、病理学的资料均提示各种帕金森病(PD)非运动症状(NMS),如嗅觉障碍、自主神经机能异常、情感障碍、睡眠紊乱等,先于运动症状出现数年至十数年,这段时期称为运动前期(premotor phase).本文对帕金森病运动前期概念、临床表现、病理基础、诊断的研究进展做一综述.

  7. Diagnostic Accuracy and Confidence in the Clinical Detection of Cognitive Impairment in Early-Stage Parkinson Disease.

    Science.gov (United States)

    Wyman-Chick, Kathryn A; Martin, Phillip K; Barrett, Matthew J; Manning, Carol A; Sperling, Scott A

    2017-05-01

    Mild cognitive impairment (MCI) is present in up to 34% of patients with early-stage Parkinson disease (PD); however, it is difficult to detect subtle impairment without objective cognitive testing. Data were obtained from the Parkinson Progression Marker Initiative. All 341 participants were administered the Montreal Cognitive Assessment (MoCA) and a brief neuropsychological battery. Participants were classified as PD-MCI if MoCA was <26 or if they scored ≥1 standard deviation below the normative mean in 2 or more domains, based upon established criteria. The sensitivity/specificity for the clinical detection of PD-MCI was determined. Overall accuracy for clinical detection of PD-MCI was 67.4%. Although clinical determination was highly specific (96.3%; 95% confidence interval [CI]: 0.92-0.98), sensitivity was poor (32.0%; 95% CI: 0.25-0.40). Identifying MCI in early-stage PD based on clinical interview alone appears to be insufficient. The inclusion of objective cognitive tests allowing for normative sample comparisons is needed to increase the detection of cognitive impairment in this population.

  8. Deep Brain Stimulation for Parkinson's Disease

    Science.gov (United States)

    ... You are here Home » Disorders » All Disorders Deep Brain Stimulation for Parkinson's Disease Information Page Deep Brain Stimulation for Parkinson's Disease Information Page Search Disorders ...

  9. Epigenetic approach to early-onset Parkinson's disease: low methylation status of SNCA and PARK2 promoter regions.

    Science.gov (United States)

    Eryilmaz, Isil Ezgi; Cecener, Gulsah; Erer, Sevda; Egeli, Unal; Tunca, Berrin; Zarifoglu, Mehmet; Elibol, Bulent; Bora Tokcaer, Ayse; Saka, Esen; Demirkiran, Meltem; Akbostanci, Cenk; Dogu, Okan; Colakoglu, Beril; Kenangil, Gulay; Kaleagasi, Hakan

    2017-08-22

    Background and aim The effect of epigenetic modifications in the genes related to Parkinson's disease (PD) is still unclear. In the present study, we investigated methylation status of SNCA and PARK2 genes in patients with early-onset Parkinson's disease (EOPD). Materials and methods The promoter region methylation status of SNCA and PARK2 genes was evaluated by methylation specific-PCR (MSP) in 91 patients with EOPD and 52 healthy individuals. Results The methylation of SNCA and PARK2 promoter regions were significantly lower in EOPD patients compared to the control group (P = 0.013 and P = 0.03, respectively). We also found that the methylation status of the SNCA might be associated with positive family history of PD (P = 0.042). Conclusion Although it should be supported by further analysis, based on the results of the present study, the methylation status of SNCA and PARK2 genes might contribute to EOPD pathogenesis.

  10. Subthalamic nucleus-deep brain stimulation for early motor complications in Parkinson's disease-the EARLYSTIM trial: early is not always better.

    Science.gov (United States)

    Mestre, Tiago A; Espay, Alberto J; Marras, Connie; Eckman, Mark H; Pollak, Pierre; Lang, Anthony E

    2014-12-01

    Subthalamic nucleus deep brain stimulation (STN-DBS) has revolutionized the management of disabling motor complications in Parkinson's disease. The EARLYSTIM trial applied this treatment to patients who had been experiencing motor complications for less than three years. STN-DBS significantly improved all primary and secondary outcome measures while best medical therapy failed to provide any improvement at the two-year follow-up time point. On face value these results strongly favor the application of STN-DBS far earlier than is currently applied, when patients are just beginning to experience problems with motor complications. Here we review the application of early DBS and the EARLYSTIM trial from the perspectives of clinical issues, health economics and study design and patient expectation of benefit. We conclude that the most relevant issue is not when to operate but on whom and that early is not always better. © 2014 International Parkinson and Movement Disorder Society. © 2014 International Parkinson and Movement Disorder Society.

  11. Gender differences in Parkinson's disease.

    NARCIS (Netherlands)

    Haaxma, C.A.; Bloem, B.R.; Borm, G.F.; Oyen, W.J.G.; Leenders, K.L.; Eshuis, S.; Booij, J.; Dluzen, D.E.; Horstink, M.W.I.M.

    2007-01-01

    OBJECTIVE: To investigate gender differences in basic disease characteristics, motor deterioration and nigrostriatal degeneration in Parkinson's disease (PD). METHODS: We studied 253 consecutive PD patients who were not receiving levodopa or dopamine agonists (disease duration < or = 10 years). W

  12. [Neurochemistry of Parkinson's disease and parkinsonism plus].

    Science.gov (United States)

    Pascual, J; Misiego, M

    1997-08-01

    The neurochemistry of Parkinson's disease and other degenerative parkinsonisms is reviewed, emphasizing the changes described in the dopaminergic system. Presynaptic dopaminergic markers are reduced over the striatum in all these degenerative parkinsonisms, dopamine receptor changes being more heterogeneous. While in Parkinson's disease D1 and D2 receptors remain preserved as compared to controls, in progressive supranuclear palsy there is a loss of nigral D1 receptors and of striatal D2 receptors. This finding has also been described in striatonigral degeneration. There are no clear data about the status of D3, D4 and D5 dopamine receptors in these conditions. The alterations in other neurotransmission systems, cholinegic, adrenergic, serotoninergic and peptidergic are, in general, less dramatic, although they have not been studied in detail. To conclude, further studies are necessary in these field, in these moment, however, the preservation of striatal D2 dopamine receptors is the neurochemical finding with the best correlation with the response to levodopa or other dopaminergic agonists.

  13. Constipation in parkinson's disease

    DEFF Research Database (Denmark)

    Knudsen, Karoline; Krogh, Klaus; Østergaard, Karen;

    2016-01-01

    , and the same is probably true for de novo PD patients. Thus, the prevalence of objective colonic dysfunction exceeds the prevalence of subjective constipation. Colonic transit time measures are simple, widely available, and hold promise as a useful biomarker in manifest PD. More research is needed to elucidate...... the role of gastrointestinal dysfunction in disease progression of PD. Moreover, colonic transit measures may have utility as a more accurate risk factor for predicting PD in the prodromal phase. © 2016 International Parkinson and Movement Disorder Society....

  14. [Proteomic biomarkers in Parkinson's disease].

    Science.gov (United States)

    Bandrés, Sara; Durán, Raquel; Barrero, Francisco; Ramírez, Manuel; Vives, Francisco

    2014-02-16

    Parkinson's disease (PD) is a neurodegenerative disorder that affects movement and is caused by the death of the dopaminergic neurons in the compact part of the substantia nigra. Its diagnosis is essentially clinical, but although the signs and symptoms of PD are well known, the rate of diagnostic error is relatively high. It is estimated that 10-30% of patients initially diagnosed with PD are later reclassified. This disease has a high prevalence beyond the age of 60, and one of its biggest problems is that it is diagnosed when the degenerative process is already at a very advanced stage. Therefore, it is necessary to look for other biomarkers that make it possible to carry out an early diagnosis of PD, follow up its development, distinguish it from other related pathologies (parkinsonisms) and help monitor the effect of novel therapies. The fact that there are mutations that lead to PD, as well as polygenetic combinations that can act as risk factors, suggests the possibility of measuring the proteins resulting from the expression of these genes in peripheral tissues. And once their sensitivity and specificity have been proved they could be used as biomarkers for PD, even in the early phases of the disease. The aim of this work is to focus on a detailed review of the main candidate proteomic biomarkers researched to date by discussing the most recent literature.

  15. Reproductive factors and Parkinson's disease risk in Danish women

    DEFF Research Database (Denmark)

    Greene, N; Lassen, C F; Rugbjerg, K

    2014-01-01

    BACKGROUND AND PURPOSE: Parkinson's disease is more common in men than women by a ratio of about 1.5:1 and yet there is no consensus to date as to whether female reproductive factors including hormone use affect Parkinson's disease risk. Our objective was to examine the relationship between...... and lifestyle factors. RESULTS: After adjusting for smoking, caffeine and alcohol use, education, age, and family Parkinson's disease history, inverse associations between Parkinson's disease and early menarche (first period at ≤11 years), oral contraceptives, high parity (≥4 children) and bilateral...... Parkinson's disease and female reproductive factors in the largest population-based Parkinson's disease case-control study to date. METHODS: Seven hundred and forty-three female Parkinson's disease cases diagnosed between 1996 and 2009 were selected from the Danish National Hospital Register, diagnoses...

  16. Biomarkers in Parkinson's disease.

    Science.gov (United States)

    Morgan, John C; Mehta, Shyamal H; Sethi, Kapil D

    2010-11-01

    Biomarkers are objectively measured characteristics that are indicators of normal biological processes, pathogenic processes, or responses to therapeutic interventions. To date, clinical assessment remains the gold standard in the diagnosis of Parkinson's disease (PD) and clinical rating scales are well established as the gold standard for tracking progression of PD. Researchers have identified numerous potential biomarkers that may aid in the differential diagnosis of PD and/or tracking disease progression. Clinical, genetic, blood and cerebrospinal fluid (proteomics, transcriptomics, metabolomics), and neuroimaging biomarkers may provide useful tools in the diagnosis of PD and in measuring disease progression and response to therapies. Some potential biomarkers are inexpensive and do not require much technical expertise, whereas others are expensive or require specialized equipment and technical skills. Many potential biomarkers in PD show great promise; however, they need to be assessed for their sensitivity and specificity over time in large and varied samples of patients with and without PD.

  17. Non-Linear EMG Parameters for Differential and Early Diagnostics of Parkinson's Disease.

    Science.gov (United States)

    Meigal, Alexander Y; Rissanen, Saara M; Tarvainen, Mika P; Airaksinen, Olavi; Kankaanpää, Markku; Karjalainen, Pasi A

    2013-01-01

    The pre-clinical diagnostics is essential for management of Parkinson's disease (PD). Although PD has been studied intensively in the last decades, the pre-clinical indicators of that motor disorder have yet to be established. Several approaches were proposed but the definitive method is still lacking. Here we report on the non-linear characteristics of surface electromyogram (sEMG) and tremor acceleration as a possible diagnostic tool, and, in prospective, as a predictor for PD. Following this approach we calculated such non-linear parameters of sEMG and accelerometer signal as correlation dimension, entropy, and determinism. We found that the non-linear parameters allowed discriminating some 85% of healthy controls from PD patients. Thus, this approach offers considerable potential for developing sEMG-based method for pre-clinical diagnostics of PD. However, non-linear parameters proved to be more reliable for the shaking form of PD, while diagnostics of the rigid form of PD using EMG remains an open question.

  18. Statistical parametric mapping with 18F-dopa PET shows bilaterally reduced striatal and nigral dopaminergic function in early Parkinson's disease

    OpenAIRE

    Ito, K.; Morrish, P; Rakshi, J; Uema, T; Ashburner, J.; Bailey, D.; Friston, K.; Brooks, D

    1999-01-01

    OBJECTIVE—To apply statistical parametric mapping to 18F-dopa PET data sets, to examine the regional distribution of changes in dopaminergic metabolism in early asymmetric Parkinson's disease.
METHODS—Thirteen normal volunteers (age 57.7 (SD 16.5) years; four women, nine men ) and six patients (age 50.3 (SD 13.5) years; three women, three men) with asymmetric (right sided) Parkinson's disease were studied. Images from each dynamic dopa PET dataset were aligned and parametric...

  19. Automated analysis of connected speech reveals early biomarkers of Parkinson's disease in patients with rapid eye movement sleep behaviour disorder.

    Science.gov (United States)

    Hlavnička, Jan; Čmejla, Roman; Tykalová, Tereza; Šonka, Karel; Růžička, Evžen; Rusz, Jan

    2017-02-02

    For generations, the evaluation of speech abnormalities in neurodegenerative disorders such as Parkinson's disease (PD) has been limited to perceptual tests or user-controlled laboratory analysis based upon rather small samples of human vocalizations. Our study introduces a fully automated method that yields significant features related to respiratory deficits, dysphonia, imprecise articulation and dysrhythmia from acoustic microphone data of natural connected speech for predicting early and distinctive patterns of neurodegeneration. We compared speech recordings of 50 subjects with rapid eye movement sleep behaviour disorder (RBD), 30 newly diagnosed, untreated PD patients and 50 healthy controls, and showed that subliminal parkinsonian speech deficits can be reliably captured even in RBD patients, which are at high risk of developing PD or other synucleinopathies. Thus, automated vocal analysis should soon be able to contribute to screening and diagnostic procedures for prodromal parkinsonian neurodegeneration in natural environments.

  20. Parkinson's Disease Videos

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    Full Text Available ... for PD: Depression, Anxiety & Psychosis Out of the Park for Parkinson's: Gordon Beckham Leads Stretches Overview of ... Can Make A Difference Your donation to the National Parkinson Foundation goes directly to support and develop ...

  1. Parkinson's Disease Videos

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  2. Emotion recognition in early Parkinson's disease patients undergoing deep brain stimulation or dopaminergic therapy: a comparison to healthy participants.

    Science.gov (United States)

    McIntosh, Lindsey G; Mannava, Sishir; Camalier, Corrie R; Folley, Bradley S; Albritton, Aaron; Konrad, Peter E; Charles, David; Park, Sohee; Neimat, Joseph S

    2014-01-01

    Parkinson's disease (PD) is traditionally regarded as a neurodegenerative movement disorder, however, nigrostriatal dopaminergic degeneration is also thought to disrupt non-motor loops connecting basal ganglia to areas in frontal cortex involved in cognition and emotion processing. PD patients are impaired on tests of emotion recognition, but it is difficult to disentangle this deficit from the more general cognitive dysfunction that frequently accompanies disease progression. Testing for emotion recognition deficits early in the disease course, prior to cognitive decline, better assesses the sensitivity of these non-motor corticobasal ganglia-thalamocortical loops involved in emotion processing to early degenerative change in basal ganglia circuits. In addition, contrasting this with a group of healthy aging individuals demonstrates changes in emotion processing specific to the degeneration of basal ganglia circuitry in PD. Early PD patients (EPD) were recruited from a randomized clinical trial testing the safety and tolerability of deep brain stimulation (DBS) of the subthalamic nucleus (STN-DBS) in early-staged PD. EPD patients were previously randomized to receive optimal drug therapy only (ODT), or drug therapy plus STN-DBS (ODT + DBS). Matched healthy elderly controls (HEC) and young controls (HYC) also participated in this study. Participants completed two control tasks and three emotion recognition tests that varied in stimulus domain. EPD patients were impaired on all emotion recognition tasks compared to HEC. Neither therapy type (ODT or ODT + DBS) nor therapy state (ON/OFF) altered emotion recognition performance in this study. Finally, HEC were impaired on vocal emotion recognition relative to HYC, suggesting a decline related to healthy aging. This study supports the existence of impaired emotion recognition early in the PD course, implicating an early disruption of fronto-striatal loops mediating emotional function.

  3. 2015 Update on Parkinson disease.

    Science.gov (United States)

    Fernandez, Hubert H

    2015-09-01

    Parkinson disease is still diagnosed by clinical signs, and its most effective treatment is still levodopa. However, an improved understanding of the disease is leading to new diagnostic tools and treatments.

  4. Bladder dysfunction in advanced Parkinson's disease

    DEFF Research Database (Denmark)

    Winge, Kristian; Nielsen, Kurt K

    2012-01-01

    Parkinson's disease (PD) patients often have lower urinary tract symptoms. Seventy-four percent of patients with early-to-moderate disease report more than one bladder disturbance symptom. Severe bladder symptoms are reported in 27-39% of PD patients. The aim of this study was to evaluate...

  5. Misperceptions and Parkinson's disease.

    Science.gov (United States)

    Friedman, Joseph H

    2017-03-15

    Most of the neurobehavioral aspects of Parkinson's disease have been well established and studied, but many are not well known, and hardly studied. This article focuses on several behavioral abnormalities that are common, and frequently cause difficulty for the patient and family due to lack of recognition as part of the disease. While it is well known that L-Dopa dyskinesias are frequently not recognized or under appreciated by patients, a similar lack of recognition may affect the patient's own speech volume, where their center of gravity is located, whether they are tilted to one side, and their under-recognition of others' emotional displays. In addition, PD patients are often misperceived by others incorrect impression of their emotional and cognitive state based purely on facial expression. These changes and others are briefly reviewed.

  6. Parkinson's Disease and Cognitive Impairment.

    Science.gov (United States)

    Yang, Yang; Tang, Bei-Sha; Guo, Ji-Feng

    2016-01-01

    Parkinson's disease (PD) is a progressive neurodegenerative disease primarily characterized by the hallmarks of motor symptoms, such as tremor, bradykinesia, rigidity, and postural instability. However, through clinical investigations in patients and experimental findings in animal models of Parkinson's disease for years, it is now well recognized that Parkinson's disease is more than just a motor-deficit disorder. The majority of Parkinson's disease patients suffer from nonmotor disabilities, for instance, cognitive impairment, autonomic dysfunction, sensory dysfunction, and sleep disorder. So far, anti-PD prescriptions and surgical treatments have been mainly focusing on motor dysfunctions, leaving cognitive impairment a marginal clinical field. Within the nonmotor symptoms, cognitive impairment is one of the most common and significant aspects of Parkinson's disease, and cognitive deficits such as dysexecutive syndrome and visuospatial disturbances could seriously affect the quality of life, reduce life expectancy, prolong the duration of hospitalization, and therefore increase burdens of caregiver and medical costs. In this review, we have done a retrospective study of the recent related researches on epidemiology, clinical manifestation and diagnosis, genetics, and potential treatment of cognitive deficits in Parkinson's disease, aiming to provide a summary of cognitive impairment in Parkinson's disease and make it easy for clinicians to tackle this challenging issue in their future practice.

  7. Parkinson's Disease and Cognitive Impairment

    Science.gov (United States)

    Tang, Bei-sha

    2016-01-01

    Parkinson's disease (PD) is a progressive neurodegenerative disease primarily characterized by the hallmarks of motor symptoms, such as tremor, bradykinesia, rigidity, and postural instability. However, through clinical investigations in patients and experimental findings in animal models of Parkinson's disease for years, it is now well recognized that Parkinson's disease is more than just a motor-deficit disorder. The majority of Parkinson's disease patients suffer from nonmotor disabilities, for instance, cognitive impairment, autonomic dysfunction, sensory dysfunction, and sleep disorder. So far, anti-PD prescriptions and surgical treatments have been mainly focusing on motor dysfunctions, leaving cognitive impairment a marginal clinical field. Within the nonmotor symptoms, cognitive impairment is one of the most common and significant aspects of Parkinson's disease, and cognitive deficits such as dysexecutive syndrome and visuospatial disturbances could seriously affect the quality of life, reduce life expectancy, prolong the duration of hospitalization, and therefore increase burdens of caregiver and medical costs. In this review, we have done a retrospective study of the recent related researches on epidemiology, clinical manifestation and diagnosis, genetics, and potential treatment of cognitive deficits in Parkinson's disease, aiming to provide a summary of cognitive impairment in Parkinson's disease and make it easy for clinicians to tackle this challenging issue in their future practice. PMID:28058128

  8. Central Pain Processing in Early-Stage Parkinson's Disease: A Laser Pain fMRI Study

    Science.gov (United States)

    Petschow, Christine; Scheef, Lukas; Paus, Sebastian; Zimmermann, Nadine; Schild, Hans H.; Klockgether, Thomas; Boecker, Henning

    2016-01-01

    Background & Objective Pain is a common non-motor symptom in Parkinson’s disease. As dopaminergic dysfunction is suggested to affect intrinsic nociceptive processing, this study was designed to characterize laser-induced pain processing in early-stage Parkinson’s disease patients in the dopaminergic OFF state, using a multimodal experimental approach at behavioral, autonomic, imaging levels. Methods 13 right-handed early-stage Parkinson’s disease patients without cognitive or sensory impairment were investigated OFF medication, along with 13 age-matched healthy control subjects. Measurements included warmth perception thresholds, heat pain thresholds, and central pain processing with event-related functional magnetic resonance imaging (erfMRI) during laser-induced pain stimulation at lower (E = 440 mJ) and higher (E = 640 mJ) target energies. Additionally, electrodermal activity was characterized during delivery of 60 randomized pain stimuli ranging from 440 mJ to 640 mJ, along with evaluation of subjective pain ratings on a visual analogue scale. Results No significant differences in warmth perception thresholds, heat pain thresholds, electrodermal activity and subjective pain ratings were found between Parkinson’s disease patients and controls, and erfMRI revealed a generally comparable activation pattern induced by laser-pain stimuli in brain areas belonging to the central pain matrix. However, relatively reduced deactivation was found in Parkinson’s disease patients in posterior regions of the default mode network, notably the precuneus and the posterior cingulate cortex. Conclusion Our data during pain processing extend previous findings suggesting default mode network dysfunction in Parkinson’s disease. On the other hand, they argue against a genuine pain-specific processing abnormality in early-stage Parkinson’s disease. Future studies are now required using similar multimodal experimental designs to examine pain processing in more advanced

  9. Early Use of 60 Hz Frequency Subthalamic Stimulation in Parkinson's Disease: A Case Series and Review.

    Science.gov (United States)

    Ramdhani, Ritesh A; Patel, Amar; Swope, David; Kopell, Brian H

    2015-12-01

    Deep brain stimulation (DBS) is effective in treating the segmental symptoms of Parkinson's disease (PD) as well as axial symptoms that are levodopa responsive. PD patients on chronic DBS who develop axial symptoms and gait disturbances several years later oftentimes are refractory to high frequency stimulation (HFS). Several studies report benefit produced by low frequency subthalamic nucleus (STN) stimulation in such patients, though the sustainability of the effects has been mixed. To report the clinical outcomes of a series of patients with Parkinson's disease and levodopa responsive axial and gait disturbances who were switched to 60 Hz stimulation within one year of their DBS surgery. A retrospective review of 5 patients, whose severe pre-DBS, levodopa responsive gait disorders worsened on HFS STN-DBS and were subsequently switched to 60 Hz stimulation within 1 year of their surgery. The median age of this cohort was 66 years with median disease duration of 14 years. Four of 5 patients' experienced acute worsening of their axial and gait UPDRS III scores on HFS. All patients' gait disorder improved with 60 Hz along with amelioration of their segmental symptoms and reduction of their levodopa induced dyskinesia. The median time on HFS prior to switching to 60 Hz was two months. Stimulation through the ventral contacts was utilized in all patients with relatively modest changes achieved in levodopa equivalent daily dose. This case series demonstrates the clinical efficacy of utilizing low frequency (60 Hz) STN stimulation early in the DBS programming course in more advanced PD patients with levodopa responsive gait disturbance and freezing of gait. Activation of a broader stimulation field likely contributed to both axial and segmental symptom improvement while possibly aiding in the reduction of dyskinesia. © 2015 International Neuromodulation Society.

  10. Early-onset Parkinson's disease due to PINK1 p.Q456X mutation - clinical and functional study

    Science.gov (United States)

    Siuda, Joanna; Jasinska-Myga, Barbara; Boczarska-Jedynak, Magdalena; Opala, Grzegorz; Fiesel, Fabienne C.; Moussaud-Lamodière, Elisabeth L.; Scarffe, Leslie A.; Dawson, Valina L.; Ross, Owen A.; Springer, Wolfdieter; Dawson, Ted M.; Wszolek, Zbigniew K.

    2014-01-01

    Background Recessive mutations in the PTEN-induced putative kinase 1 (PINK1) gene cause early-onset Parkinson's disease (EOPD). The clinical phenotype of families that have this PINK1-associated disease may present with different symptoms, including typical PD. The loss of the PINK1 protein may lead to mitochondrial dysfunction, which causes dopaminergic neuron death. Methods The clinical phenotypes of a large Polish family with EOPD and an identified PINK1 homozygous nonsense mutation were assessed. Ubiquitination and degradation of mitochondrial parkin substrates as well as mitochondrial bioenergetics were investigated as direct functional readouts for PINK1's kinase activity in biopsied dermal fibroblasts. Results A four-generation family was genealogically evaluated. Genetic screening identified two affected subjects who were both homozygous carriers of the pathogenic PINK1 p.Q456X substitution. Both patients presented with dystonia and gait disorders at symptom onset. Seven heterozygous mutation carriers remained unaffected. Functional studies revealed that the PINK1 p.Q456X protein is non-functional in activating the downstream ubiquitin ligase parkin and priming the ubiquitination of its substrates, and that the RNA levels of PINK1 were significantly reduced. Conclusions The PINK1 p.Q456X mutation leads to a decrease in mRNA and a loss of protein function. The foot dystonia and gait disorders seen at disease onset in affected members of our family, which were accompanied by parkinsonism had a similar clinical presentation to what has been described in previous reports of PINK1 mutation carriers. PMID:25226871

  11. Brain MRI in Parkinson's disease

    NARCIS (Netherlands)

    Meijer, F.J.A.; Goraj, B.M.

    2014-01-01

    In this review article, conventional brain MRI and advanced MRI techniques in Parkinson`s disease (PD) are discussed, with emphasis on clinical relevance. Conventional brain MRI sequences generally demonstrate limited abnormalities specific for PD and in clinical practice brain MRI is mainly used to

  12. Cellular models for Parkinson's disease.

    Science.gov (United States)

    Falkenburger, Björn H; Saridaki, Theodora; Dinter, Elisabeth

    2016-10-01

    Developing new therapeutic strategies for Parkinson's disease requires cellular models. Current models reproduce the two most salient changes found in the brains of patients with Parkinson's disease: The degeneration of dopaminergic neurons and the existence of protein aggregates consisting mainly of α-synuclein. Cultured cells offer many advantages over studying Parkinson's disease directly in patients or in animal models. At the same time, the choice of a specific cellular model entails the requirement to focus on one aspect of the disease while ignoring others. This article is intended for researchers planning to use cellular models for their studies. It describes for commonly used cell types the aspects of Parkinson's disease they model along with technical advantages and disadvantages. It might also be helpful for researchers from other fields consulting literature on cellular models of Parkinson's disease. Important models for the study of dopaminergic neuron degeneration include Lund human mesencephalic cells and primary neurons, and a case is made for the use of non-dopaminergic cells to model pathogenesis of non-motor symptoms of Parkinson's disease. With regard to α-synuclein aggregates, this article describes strategies to induce and measure aggregates with a focus on fluorescent techniques. Cellular models reproduce the two most salient changes of Parkinson's disease, the degeneration of dopaminergic neurons and the existence of α-synuclein aggregates. This article is intended for researchers planning to use cellular models for their studies. It describes for commonly used cell types and treatments the aspects of Parkinson's disease they model along with technical advantages and disadvantages. Furthermore, this article describes strategies to induce and measure aggregates with a focus on fluorescent techniques. This article is part of a special issue on Parkinson disease.

  13. SPECT Molecular Imaging in Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Ling Wang

    2012-01-01

    Full Text Available Parkinson's disease (PD is a common disorder, and the diagnosis of Parkinson's disease is clinical and relies on the presence of characteristic motor symptoms. The accuracy of the clinical diagnosis of PD is still limited. Functional neuroimaging using SPECT technique is helpful in patients with first signs of parkinsonism. The changes detected may reflect the disease process itself and/or compensatory responses to the disease, or they may arise in association with disease- and/or treatment-related complications. This paper addresses the value of SPECT in early differential diagnosis of PD and its potential as a sensitive tool to assess the pathophysiology and progression, as well as the therapeutic efficacy of PD.

  14. Genetics of Parkinson Disease

    Science.gov (United States)

    Pankratz, Nathan; Foroud, Tatiana

    2004-01-01

    Summary: Parkinson disease (PD) is the second most common neurodegenerative disorder. Recent studies have consistently demonstrated that in some families, disease is attributable to a mutation in a single gene. To date, genetic analyses have detected linkage to six chromosomal regions and have identified three causative genes: PARK1 (alpha-synuclein), PARK2 (parkin), and PARK7 (DJ-1). In addition, mutations in several other genes have been implicated in familial PD. Identification of the mutations in these genes has led to the recognition that the ubiquitin-proteasome system is an important pathway that may be disrupted in PD. Studies are ongoing to identify additional genes that may contribute to PD susceptibility, particularly in late-onset families without a clear pattern of disease inheritance. With the identification of mutations in particular genes and the likely role of additional genes that are important in PD risk-susceptibility, appropriate protocols must be developed so that accurate and informative genetic counseling can be offered to families in which one or more members has PD. Further diagnostic testing should be delayed until more is learned about the frequency, penetrance, and risk assessment of certain gene mutations. Important lessons can be learned from the implementation of counseling protocols for other neurodegenerative disorders, such as Huntington disease and Alzheimer disease. PMID:15717024

  15. Genetics of Parkinson disease.

    Science.gov (United States)

    Pankratz, Nathan; Foroud, Tatiana

    2004-04-01

    Parkinson disease (PD) is the second most common neurodegenerative disorder. Recent studies have consistently demonstrated that in some families, disease is attributable to a mutation in a single gene. To date, genetic analyses have detected linkage to six chromosomal regions and have identified three causative genes: PARK1 (alpha-synuclein), PARK2 (parkin), and PARK7 (DJ-1). In addition, mutations in several other genes have been implicated in familial PD. Identification of the mutations in these genes has led to the recognition that the ubiquitin-proteasome system is an important pathway that may be disrupted in PD. Studies are ongoing to identify additional genes that may contribute to PD susceptibility, particularly in late-onset families without a clear pattern of disease inheritance. With the identification of mutations in particular genes and the likely role of additional genes that are important in PD risk-susceptibility, appropriate protocols must be developed so that accurate and informative genetic counseling can be offered to families in which one or more members has PD. Further diagnostic testing should be delayed until more is learned about the frequency, penetrance, and risk assessment of certain gene mutations. Important lessons can be learned from the implementation of counseling protocols for other neurodegenerative disorders, such as Huntington disease and Alzheimer disease.

  16. [Biotherapies and Parkinson's disease].

    Science.gov (United States)

    Cesaro, P; Fenelon, G; Remy, P

    2009-11-01

    In the last years, several experimental biotherapies have been developed to treat Parkinson's disease. Initially, fetal dopaminergic transplants were proposed. Although a proof of concept and encouraging results have been provided, limitations of this treatment emerged over the years and the failure of controlled trials have conducted to a pause in the development of strategies based on fetal cells. Alternative approaches such as the use of retinal pigmented cells recently provided disappointing results in patients and much hope has now been reported on other sources of dopaminergic neurons such as those originating from stem cells. This strategy is however not yet ready for clinical trials in patients. Eventually, gene therapy is a new original experimental technique which has elicited several trials in the last few years some of them being promising.

  17. Neurorehabilitation in Parkinson disease.

    Science.gov (United States)

    Archibald, Neil; Miller, Nick; Rochester, Lynn

    2013-01-01

    Parkinson disease (PD) is the second commonest neurodegenerative disorder in the UK with an increasing prevalence in our aging population. The clinical features of PD are varied with a variety of "motor" and "nonmotor" symptoms and the condition is best thought of as a multisystem neurodegenerative disorder rather than as a "pure" movement disorder. Although the mainstay of treatment is pharmacological, nonpharmacological interventions are vital as part of a multidisciplinary approach to the disorder. Neurorehabilitative interventions have been used for some time in the treatment of PD but, until recently, there has been little evidence to support the clinical impression that physiotherapy, occupational therapy, and speech and language therapy have a positive impact on both motor and nonmotor symptoms. This chapter will review the current evidence base for neurorehabilitation in PD and discuss the challenges of service provision within healthcare systems. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Dementia in Parkinson's disease.

    Science.gov (United States)

    Kurtz, Avrom L; Kaufer, Daniel I

    2011-06-01

    Dementia in Parkinson's disease encompasses a spectrum relating to motor, psychiatric, and cognitive symptoms that are classified as either Dementia with Lewy Bodies (DLB) (initial cognitive symptoms) or Parkinson's Disease Dementia (PDD) (initial motor signs preceding cognitive symptoms by at least a year). Anticholinergic and antipsychotic drugs have a high risk of adverse cognitive and/or motor effects, so their use should be minimized or avoided. Neuroleptic sensitivity is a severe psychomotor adverse reaction that is particularly associated with potent dopamine-blocking agents such as haloperidol. It occurs in up to 50% of individuals with PDD or DLB. Mild psychotic symptoms should first be addressed by reducing anticholinergic and/or dopaminergic agents, if possible. Patients with psychotic symptoms that threaten the safety of the patient or caregiver may benefit from treatment with quetiapine or, in refractory cases, clozapine. Cholinesterase inhibitors as a drug class have been shown to have beneficial effects on cognition in DLB and PDD, and may help to alleviate some psychiatric symptoms, such as apathy, anxiety, hallucinations, and delusions. Memantine may help to moderate cognitive symptoms in DLB and PDD, although current data suggest a more variable response, particularly in PDD. Parkinsonian motor signs that are accompanied by clinically significant cognitive impairment should be treated with carbidopa/levodopa only, as dopamine agonists and other antiparkinsonian medications generally carry a higher risk of provoking or exacerbating psychotic symptoms. Excessive daytime sleepiness and REM sleep behavior disorder are common associated features of PDD and DLB. Minimizing sedating medications during the day and promoting nocturnal sleep may help the daytime sleepiness; melatonin, clonazepam, gabapentin, and possibly memantine may be useful in treating REM sleep behavior disorder. Orthostatic hypotension can be managed with various nonpharmacologic

  19. Analysis of balance function, falling risk and gait in the early and middle stages of patients with Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Wang-shu YUAN

    2017-07-01

    Full Text Available Objective To analyze the balance function, falling risk and gait in the early and middle stages of patients with Parkinson's disease (PD for provide clinical basis for patients' rehabilitation treatment.  Methods There were 30 PD patients in the early and middle stages and 15 healthy subjects matched in gender, age and degree of education. Berg Balance Scale (BBS was used to evaluate balance function. Timed Up and Go Test (TUGT, Chair Rising Test (CRT and Tandem Gait Test (TGT were used to evaluate falling risk. The gait analysis system was used to evaluate gait.  Results Compared with healthy subjects, PD patients obtained lower scores on BBS (P = 0.001. In the falling risk, PD patients spent more seconds in performing TUGT (P = 0.003 and CRT (P = 0.002 and finished fewer numbers of steps on TGT (P = 0.041. In 10 - Meter Walk Test (10MWT, PD patients had shorter step length (P =0.020, decreased step speed (P = 0.038, increased ratio of toe touches (P = 0.000 and decreased left and right ankle dorsiflexion in swing phase (P = 0.005, 0.006.  Conclusions In the early and middle stages, PD patients have decreased balance function, increased falling risk and unusual gait. The rehabilitation treatment should be given as soon as possible. DOI: 10.3969/j.issn.1672-6731.2017.05.007

  20. RNA metabolism in the pathogenesis of Parkinson׳s disease.

    Science.gov (United States)

    Lu, Bingwei; Gehrke, Stephan; Wu, Zhihao

    2014-10-10

    Neurodegenerative diseases such as Parkinson׳s disease are progressive disorders of the nervous system that affect the function and maintenance of specific neuronal populations. While most disease cases are sporadic with no known cause, a small percentage of disease cases are caused by inherited genetic mutations. The identification of genes associated with the familial forms of the diseases and subsequent studies of proteins encoded by the disease genes in cellular or animal models have offered much-needed insights into the molecular and cellular mechanisms underlying disease pathogenesis. Recent studies of the familial Parkinson׳s disease genes have emphasized the importance of RNA metabolism, particularly mRNA translation, in the disease process. It is anticipated that continued studies on the role of RNA metabolism in Parkinson׳s disease will offer unifying mechanisms for understanding the cause of neuronal dysfunction and degeneration and facilitate the development of novel and rational strategies for treating this debilitating disease.

  1. Baseline prevalence and longitudinal evolution of non-motor symptoms in early Parkinson's disease: the PPMI cohort.

    Science.gov (United States)

    Simuni, Tanya; Caspell-Garcia, Chelsea; Coffey, Christopher S; Weintraub, Daniel; Mollenhauer, Brit; Lasch, Shirley; Tanner, Caroline M; Jennings, Danna; Kieburtz, Karl; Chahine, Lana M; Marek, Kenneth

    2017-10-06

    To examine the baseline prevalence and longitudinal evolution in non-motor symptoms (NMS) in a prospective cohort of, at baseline, patients with de novo Parkinson's disease (PD) compared with healthy controls (HC). Parkinson's Progression Markers Initiative (PPMI) is a longitudinal, ongoing, controlled study of de novo PD participants and HC. NMS were rated using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part I score and other validated NMS scales at baseline and after 2 years. Biological variables included cerebrospinal fluid (CSF) markers and dopamine transporter imaging. 423 PD subjects and 196 HC were enrolled and followed for 2 years. MDS-UPDRS Part I total mean (SD) scores increased from baseline 5.6 (4.1) to 7.7 (5.0) at year 2 in PD subjects (p<0.001) versus from 2.9 (3.0) to 3.2 (3.0) in HC (p=0.38), with a significant difference between the groups (p<0.001). In the multivariate analysis, higher baseline NMS score was associated with female sex (p=0.008), higher baseline MDS-UPDRS Part II scores (p<0.001) and more severe motor phenotype (p=0.007). Longitudinal increase in NMS severity was associated with the older age (0.008) and lower CSF Aβ1-42 (0.005) at baseline. There was no association with the dose or class of dopaminergic therapy. This study of NMS in early PD identified clinical and biological variables associated with both baseline burden and predictors of progression. The association of a greater longitudinal increase in NMS with lower baseline Aβ1-42 level is an important finding that will have to be replicated in other cohorts. ClinicalTrials.gov identifier: NCT01141023. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  2. Argentine tango in Parkinson disease.

    Science.gov (United States)

    2016-10-28

    This article reports on a meta-analysis of 13 studies of the effects of Argentine tango (AT) as a music-based movement therapy for people with Parkinson's disease (PD). Nine studies involved randomised controlled trials.

  3. Parkinson's disease guidelines for pharmacists

    National Research Council Canada - National Science Library

    Tejal Patel; Feng Chang

    2014-01-01

      Parkinsons disease (PD) is a chronic, progressive, neurodegenerative disorder, characterized by the loss of dopaminergic neurons from the substantia nigra that subsequently results in the loss of control of voluntary movement over time...

  4. Current management of Parkinson's disease

    African Journals Online (AJOL)

    Although Parkinson's disease (PD) is still incurable, a large number of different treatments have become ... (impaired balance); and pathologically by neuronal ..... neurons and at the same time, a reduction in the .... produce energy inside cells.

  5. Combined Diffusion Tensor Imaging and Arterial Spin Labeling as Markers of Early Parkinson's disease.

    Science.gov (United States)

    Wei, Xiaobo; Yan, Ronghua; Chen, Zhaoyu; Weng, Ruihui; Liu, Xu; Gao, Huimin; Xu, Xiaofeng; Kang, Zhuang; Liu, Zhexing; Guo, Yan; Liu, Zhenhua; Larsen, Jan Petter; Wang, Jin; Tang, Beisha; Hallett, Mark; Wang, Qing

    2016-09-20

    This study aimed to identify a PD-specific MRI pattern using combined diffusion tensor imaging (DTI) and arterial spin labeling (ASL) to discriminate patients with early PD from healthy subjects and evaluate disease status. Twenty-one early and 22 mid-late PD patients, and 22 healthy, age/gender-matched controls underwent 3-T MRI with apparent diffusion coefficient (ADC), fractional anisotropy (FA), fiber number (FN) and cerebral blood flow (CBF) measurements. We found that compared with healthy subjects, there was a profound reduction in FN passing through the SN in PD. FA in the SN and CBF in the caudate nucleus were inversely correlated with motor dysfunction. A negative correlation was observed between FA in the hippocampus (Hip) and the NMSS-Mood score, whereas CBF in the Hip and the prefrontal cortex(PFC) correlated with declined cognition. Stratified five-fold cross-validation identified FA in the SN(FA-SNAv), CBF in the PFC(CBF-PFCAv) and FA in the parietal white matter(FA-PWMAv), and the combination of these measurements offered relatively high accuracy (AUC 0.975, 90% sensitivity and 100% specificity) in distinguishing those with early PD from healthy subjects. We demonstrate that the decreased FNs through SN in combination with changes in FA-SNAv, CBF-PFCAv and FA-PWMAv values might serve as potential markers of early-stage PD.

  6. Testosterone level and the effect of levodopa and agonists in early Parkinson disease: results from the INSPECT cohort.

    Science.gov (United States)

    Okun, Michael S; Wu, Samuel S; Jennings, Dana; Marek, Kenneth; Rodriguez, Ramon L; Fernandez, Hubert H

    2014-01-01

    To determine if testosterone levels are influenced by dopaminergic therapy in Parkinson disease (PD) patients. Testosterone level has been reported to be low in patients with PD and other neurodegenerative diseases. In this study, we sought to determine whether dopaminergic therapy (i.e. levodopa and dopamine agonist) influenced testosterone levels. We used a cohort of consecutive male patients from the INSPECT trial--a multi-center, prospective, study that primarily investigated the effects of short-term treatment with pramipexole or levodopa on [(123)I] B-CIT SPECT imaging in early PD. Testosterone levels were drawn on consenting male subjects with early PD who enrolled in the INSPECT trial at three study visits (baseline, 12 weeks post-treatment, and 8-12 weeks post-washout). Subjects were randomized to: no treatment, pramipexole (up to 3 mg) or levodopa (up to 600 mg). Testosterone levels were obtained twice (prior to 10 AM) and averaged for each of three study visits. Thirty two male patients participated in this sub-study and there were no significant differences in disease characteristics in the 3 groups at baseline. Twenty-nine patients completed the follow-up visits and were suitable for analysis. There were statistically significant differences in the change in free testosterone level, increased in both the levodopa group and pramipexole group but decreased in the untreated group at 12-weeks post-treatment. There were no significant differences in the changes of UPDRS total or motor scores, although there was a strong trend toward improvement in motor scores. The testosterone level persisted in its increase only in the pramipexole group at the end of the washout period. These preliminary data support the premise that dopaminergic medications do not reduce testosterone levels in early PD patients.

  7. Parkinson's Disease Videos

    Medline Plus

    Full Text Available ... PD Library Aware in Care Kit Legal / Financial / Insurance Parkinson's Today Blog Find Help A Parkinson's diagnosis ... en General, Parte 2 CareMAP: Medications and General Health Part 1 CareMAP: Medications and General Health Part ...

  8. MDS research criteria for prodromal Parkinson's disease

    NARCIS (Netherlands)

    Berg, D; Postuma, R.B.; Adler, C.H.; Bloem, B.R.; Chan, P.; Dubois, B.; Gasser, T.; Goetz, C.G.; Halliday, G.; Joseph, L.; Lang, A.E.; Liepelt-Scarfone, I.; Litvan, I.; Marek, K.; Obeso, J.; Oertel, W.; Olanow, C.W.; Poewe, W.; Stern, M.; Deuschl, G.

    2015-01-01

    This article describes research criteria and probability methodology for the diagnosis of prodromal PD. Prodromal disease refers to the stage wherein early symptoms or signs of PD neurodegeneration are present, but classic clinical diagnosis based on fully evolved motor parkinsonism is not yet

  9. MDS research criteria for prodromal Parkinson's disease

    NARCIS (Netherlands)

    Berg, D; Postuma, R.B.; Adler, C.H.; Bloem, B.R.; Chan, P.; Dubois, B.; Gasser, T.; Goetz, C.G.; Halliday, G.; Joseph, L.; Lang, A.E.; Liepelt-Scarfone, I.; Litvan, I.; Marek, K.; Obeso, J.; Oertel, W.; Olanow, C.W.; Poewe, W.; Stern, M.; Deuschl, G.

    2015-01-01

    This article describes research criteria and probability methodology for the diagnosis of prodromal PD. Prodromal disease refers to the stage wherein early symptoms or signs of PD neurodegeneration are present, but classic clinical diagnosis based on fully evolved motor parkinsonism is not yet possi

  10. Nutraceuticals in Parkinson's Disease.

    Science.gov (United States)

    Hang, Liting; Basil, Adeline Henry; Lim, Kah-Leong

    2016-09-01

    Current pharmacological strategies for Parkinson's disease (PD), the most common neurological movement disorder worldwide, are predominantly symptom relieving and are often plagued with undesirable side effects after prolonged treatment. Despite this, they remain as the mainstay treatment for PD due to the lack of better alternatives. Nutraceuticals are compounds derived from natural food sources that have certain therapeutic value and the advent of which has opened doors to the use of alternative strategies to tackle neurodegenerative diseases such as PD. Notably, nutraceuticals are able to position themselves as a "safer" strategy due to the fact that they are naturally derived compounds, therefore possibly having less side effects. Significant efforts have been put into better comprehending the role of nutraceuticals in PD, and we will look at some of them in this review. Broadly speaking, these compounds execute their positive effects via modulating signalling pathways, inhibiting oxidative stress, inflammation and apoptosis, as well as regulating mitochondrial homoeostasis. Importantly, we will highlight how a component of green tea, epigallocatechin-3-gallate (EGCG), confers neuroprotection in PD via its ability to activate AMP kinase and articulate how its beneficial effects in PD are possibly due to enhancing mitochondrial quality control.

  11. Neuropsychological effects of deep brain stimulation in subjects with early stage Parkinson's disease in a randomized clinical trial.

    Science.gov (United States)

    Tramontana, Michael G; Molinari, Anna L; Konrad, Peter E; Davis, Thomas L; Wylie, Scott A; Neimat, Joseph S; May, Alexandra T; Phibbs, Fenna T; Hedera, Peter; Gill, Chandler E; Salomon, Ronald M; Wang, Lily; Song, Yanna; Charles, David

    2015-01-01

    Deep brain stimulation (DBS) is an effective treatment for patients with advanced Parkinson's disease (PD) and motor symptom complications. Recently, attention has been focused on whether offering DBS earlier in the course of PD is beneficial. The purpose of this study was to determine the effects of DBS on neuropsychological functioning in subjects with early stage PD. Thirty subjects with early PD (Hoehn & Yahr Stage II off medication) were randomized to optimal drug therapy (ODT) (n = 15) or bilateral subthalamic nucleus (STN) DBS+ODT (n = 15) after completing an expanded informed consent process specially designed for the study and administered by a medical ethicist and the study team. Comprehensive neuropsychological testing was completed in the treatment-withdrawn state at baseline and at 12 month and 24 month follow-ups. Two serious adverse events occurred in the DBS+ODT group. One subject experienced a stroke and another developed infected hardware that contributed to specific declines in cognitive functioning. However, compared to the ODT group, the remaining subjects in the DBS+ODT group exhibited modest reductions on a few measures of attention, executive function, and word fluency at 12 months. These differences were largely diminished at 24 months, especially when those with the adverse events were excluded. The results of this trial provide novel data regarding the effects of DBS on cognitive function in early PD. We believe that the findings and insights from this trial can help guide the safety analysis and risk-benefit evaluations in future discussions of DBS in early stage PD.

  12. Associations among Cognitive Functions, Plasma DNA, and White Matter Integrity in Patients with Early-Onset Parkinson's Disease

    Science.gov (United States)

    Chen, Yueh-Sheng; Chen, Meng-Hsiang; Lu, Cheng-Hsien; Chen, Pei-Chin; Chen, Hsiu-Ling; Yang, I-Hsiao; Tsai, Nai-Wen; Lin, Wei-Che

    2017-01-01

    Early-onset Parkinson's disease (EOPD) patients are symptomatic at a relatively young age, and the impacts of the disease on both the patients and their caregivers are dramatic. Few studies have reported on the cognitive impairments seen in EOPD, and the results of these studies have been diverse. Furthermore, it is still unclear what microstructural white matter (WM) changes are present in EOPD patients. As such, we conducted this study to investigate the microstructural WM changes experienced by EOPD patients and their association with cognitive function and plasma DNA levels. We enrolled 24 EOPD patients and 33 sex- and age-matched healthy volunteers who underwent complete neuro-psychological testing (NPT) to evaluate their cognitive function and diffusion tensor imaging (DTI) scanning to determine their fiber integrity. The plasma DNA measurements included measurements of nuclear and mitochondrial DNA levels. Fractional anisotropy (FA) maps were compared using voxel-based statistics to determine differences between the two groups. The differences in DTI indices and NPT scores were correlated after adjusting for age, sex, and education. Our results demonstrate that patients with EOPD have elevated nuclear DNA levels and wide spectrums of impairments in NPT, especially in the executive function and visuospatial function domains. Exploratory group-wise comparisons of the DTI indices revealed that the patients with EOPD exhibited lower DTI parameters in several brain locations. These poorer DTI parameters were associated with worse cognitive performances and elevated plasma nuclear DNA levels, especially in the anterior thalamic radiation region. Our findings suggest that the thalamus and its adjacent anterior thalamic radiation may be important in the pathogenesis of EOPD, as they appear to become involved in the disease process at an early stage. PMID:28174514

  13. Molecular pathogenesis of Parkinson disease.

    Science.gov (United States)

    Eriksen, Jason L; Wszolek, Zbigniew; Petrucelli, Leonard

    2005-03-01

    Parkinson disease (PD), the most common neurodegenerative movement disorder, is characterized by an extensive and progressive loss of dopaminergic neurons in the substantia nigra pars compacta. One of the pathological hallmarks of PD is the presence of Lewy bodies, intracellular inclusions of aggregated alpha-synuclein. Although the cause and pathogenesis of selective loss of dopamine neurons and the accumulation of alpha-synuclein in PD remain elusive, growing lines of evidence from environmental risk factors and early-onset genetics point to a convergence between energy metabolism and the disposal of damaged proteins in the development of PD. These findings suggest that impairments in mitochondrial and ubiquitin-proteasome system function can significantly contribute to the pathogenesis of PD. This review will summarize recent insights gained from genetic and environmental studies of PD that underscore this association.

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

    Science.gov (United States)

    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…

  15. Noradrenaline and Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Claire eDelaville

    2011-05-01

    Full Text Available Parkinson’s disease (PD is characterized by the degeneration of dopamine (DA neurons in the substantia nigra pars compacta, and motor symptoms including bradykinesia, rigidity and tremor at rest. These symptoms are manifest when around 70% of striatal DA is lost. In addition to motor deficits, PD is also characterized by the manifestation of non-motor symptoms. However, depletion of DA alone in animal models has failed to simultaneously elicit both the motor and non-motor deficits of PD because the disease is a multi-system disorder that features a profound loss of other neurotransmitter systems. There is growing evidence that additional loss of noradrenaline (NA neurons of the locus coeruleus, the principal source of NA in the brain, could be involved in the clinical expression of motor as well as in non-motor deficits. In the present review, we analyzed the latest data obtained from animal models of parkinsonism and from parkinsonian patients providing evidence for the implication of NA in the pathophysiology of PD. Recent studies have shown that NA depletion alone or combined with DA depletion resulted in motor as well as in non-motor dysfunctions. In addition, by using selective agonists and antagonists of alpha receptors we, and others, have shown that α2 receptors are implicated in the control of motor activity and that α2 receptor antagonists can improve PD motor symptoms as well as L-Dopa-induced dyskinesia. Here we provide arguments that the loss of NA neurons in PD has an impact on all PD symptoms and that the association of NAergic agents to dopaminergic medication can be beneficial in the treatment of the disease.

  16. Mutations in RAB39B cause X-linked intellectual disability and early-onset Parkinson disease with α-synuclein pathology.

    Science.gov (United States)

    Wilson, Gabrielle R; Sim, Joe C H; McLean, Catriona; Giannandrea, Maila; Galea, Charles A; Riseley, Jessica R; Stephenson, Sarah E M; Fitzpatrick, Elizabeth; Haas, Stefan A; Pope, Kate; Hogan, Kirk J; Gregg, Ronald G; Bromhead, Catherine J; Wargowski, David S; Lawrence, Christopher H; James, Paul A; Churchyard, Andrew; Gao, Yujing; Phelan, Dean G; Gillies, Greta; Salce, Nicholas; Stanford, Lynn; Marsh, Ashley P L; Mignogna, Maria L; Hayflick, Susan J; Leventer, Richard J; Delatycki, Martin B; Mellick, George D; Kalscheuer, Vera M; D'Adamo, Patrizia; Bahlo, Melanie; Amor, David J; Lockhart, Paul J

    2014-12-04

    Advances in understanding the etiology of Parkinson disease have been driven by the identification of causative mutations in families. Genetic analysis of an Australian family with three males displaying clinical features of early-onset parkinsonism and intellectual disability identified a ∼45 kb deletion resulting in the complete loss of RAB39B. We subsequently identified a missense mutation (c.503C>A [p.Thr168Lys]) in RAB39B in an unrelated Wisconsin kindred affected by a similar clinical phenotype. In silico and in vitro studies demonstrated that the mutation destabilized the protein, consistent with loss of function. In vitro small-hairpin-RNA-mediated knockdown of Rab39b resulted in a reduction in the density of α-synuclein immunoreactive puncta in dendritic processes of cultured neurons. In addition, in multiple cell models, we demonstrated that knockdown of Rab39b was associated with reduced steady-state levels of α-synuclein. Post mortem studies demonstrated that loss of RAB39B resulted in pathologically confirmed Parkinson disease. There was extensive dopaminergic neuron loss in the substantia nigra and widespread classic Lewy body pathology. Additional pathological features included cortical Lewy bodies, brain iron accumulation, tau immunoreactivity, and axonal spheroids. Overall, we have shown that loss-of-function mutations in RAB39B cause intellectual disability and pathologically confirmed early-onset Parkinson disease. The loss of RAB39B results in dysregulation of α-synuclein homeostasis and a spectrum of neuropathological features that implicate RAB39B in the pathogenesis of Parkinson disease and potentially other neurodegenerative disorders. Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  17. Parkinson's Disease Videos

    Medline Plus

    Full Text Available ... Day to Day? Ask the Helpline: Why Is Exercise Important for People with Parkinson's? Aware in Care: ... with PD? What Are the Neuroprotective Benefits of Exercise for PD Patients? What Are the Risks and ...

  18. Parkinson's Disease Videos

    Medline Plus

    Full Text Available ... Day to Day? Ask the Helpline: Why Is Exercise Important for People with Parkinson's? Aware in Care: ... with PD? What Are the Neuroprotective Benefits of Exercise for PD Patients? What Are the Risks and ...

  19. Parkinson's Disease Videos

    Medline Plus

    Full Text Available ... Day to Day? Ask the Helpline: Why Is Exercise Important for People with Parkinson's? Aware in Care: ... with Nathan Slewett Is Compulsive Behavior a Side Effect of PD Medications? Is Depression Under-Diagnosed in ...

  20. Parkinson's Disease Videos

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    Full Text Available ... Our Impact Our Mission Our Team Parkinson's Foundation Board Key Milestones Press Room Partnerships Financial Reports Contact ... consultation.jpg How Do PD and Its Treatment Affect Sexual Functioning? How Does Depression Affect the Patient's ...

  1. Parkinson's Disease Videos

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    Full Text Available ... Warning Signs Motor Symptoms Non-Motor Symptoms Diagnosis Treatment Newly Diagnosed Living Well Caregiving Understanding Parkinson's There ... about symptoms, how it is diagnosed and what treatment options are available. Learn More > Find Help NPF ...

  2. Parkinson's Disease Videos

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    Full Text Available ... the answers you need. Learn More > Expert Care & Research Research Funding Centers of Excellence Parkinson's Outcomes Project Grants Telemedicine & Virtual Care Professional Training Expert Care & Research Our research has led to breakthroughs in treatment ...

  3. Parkinson's Disease Videos

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    Full Text Available ... Beyond This Life CareMAP: Long-Distance Caregiving CareMAP: Managing Advanced Parkinson's Website CareMAP: Managing Caregiver Stress CareMAP: Mealtime and Swallowing: Part 1 ...

  4. Parkinson's Disease Videos

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    Full Text Available ... Warning Signs Motor Symptoms Non-Motor Symptoms Diagnosis Treatment Newly Diagnosed Living Well Caregiving Understanding Parkinson's There ... about symptoms, how it is diagnosed and what treatment options are available. Learn More > Find Help NPF ...

  5. Parkinson's Disease Videos

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    Full Text Available ... Research Research Funding Centers of Excellence Parkinson's Outcomes Project Grants Telemedicine & Virtual Care Professional Training Expert Care & Research Our research has led to breakthroughs in treatment ...

  6. Four Cases of Parkinson Disease Diagnosed During the Postpartum Period.

    Science.gov (United States)

    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.

  7. Treatment with a substance P receptor antagonist is neuroprotective in the intrastriatal 6-hydroxydopamine model of early Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Emma Thornton

    Full Text Available Neuroinflammation and blood brain barrier (BBB dysfunction have been implicated in the pathogenesis of Parkinson's disease (PD. The neuropeptide substance P (SP is an important mediator of both neuroinflammation and BBB dysfunction through its NK1 receptor in a process known as neurogenic inflammation. Increased SP content has previously been reported following 6-OHDA treatment in vitro, with the levels of SP correlating with cell death. The present study used an in vivo 6-OHDA lesion model to determine if dopaminergic degeneration was associated with increased SP in the substantia nigra and whether this degeneration could be prevented by using a SP, NK1 receptor antagonist. Unilateral, intrastriatal 6-OHDA lesions were induced and SP (10 µg/2 µL or the NK1 receptor antagonists, N-acetyl-L-tryptophan (2 µL at 50 nM or L-333,060 (2 µL at 100 nM, administered immediately after the neurotoxin. Nigral SP content was then determined using immunohistochemical and ELISA methods, neuroinflammation and barrier integrity was assessed using Iba-1, ED-1, GFAP and albumin immunohistochemistry, while dopaminergic cell loss was assessed with tyrosine hydroxylase immunohistochemistry. Motor function in all animals was assessed using the rotarod task. Intrastriatal 6-OHDA lesioning produced an early and sustained increase in ipsilateral nigral SP content, along with a breakdown of the BBB and activation of microglia and astrocytes. Further exacerbation of SP levels accelerated disease progression, whereas NK1 receptor antagonist treatment protected dopaminergic neurons, preserved barrier integrity, reduced neuroinflammation and significantly improved motor function. We propose that neurogenic inflammation contributes to dopaminergic degeneration in early experimental PD and demonstrate that an NK1 receptor antagonist may represent a novel neuroprotective therapy.

  8. Camptocormia in Parkinson's disease.

    Science.gov (United States)

    Melamed, Eldad; Djaldetti, Ruth

    2006-12-01

    Camptocormia is defined as an abnormal, severe and involuntary forward flexion of the thoracolumbar spine, which becomes manifest during standing and walking and subsides in the recumbent position. It was originally described as a psychogenic disorder, particularly in soldiers involved in long-term trench service during World War 1. It is becoming increasingly recognized as a prominent and disabling phenomenon during the course of Parkinson's disease (PD). In our experience, there is no clear correlation between camptocormia and levodopa treatment. In a few patients, the abnormal posture improved and in others it was unaltered or even became worse following levodopa administration. In a minority of fluctuating patients, there was a temporary deterioration during the "off" periods, but in most, the severity of camptocormia was unchanged during the "on" and "off" phases. In some patients it is associated with back pains, whereas in others it is painless. It occurs in sporadic PD as well as in postencephalitic and parkin-gene mutation PD and in other parkinsonian syndromes such as MSA. The pathogenesis of this striking clinical sign is unknown. It is definitely not due to a primary vertebral disease causing kyphosis such as ankylosing spondylitis, as the bent spine disappears when the patient lies on his back. The muscles involved may be the abdominal, paravertebral or both. It may by due to a peculiar dystonia or to an extreme form of rigidity. Local myopathic changes were suggested as a possible cause, but these may rather be a secondary phenomenon. Treatment is currently unsatisfactory in most cases. Occasional patients may benefit from intramuscular botulinum toxin injections or from deep brain stimulation.

  9. Camptocormia in Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Kazuo Abe

    2010-01-01

    Full Text Available Objectives. Abnormalities of posture represent one of the main features of Parkinson's disease (PD. Among them, camptocormia has been considered as rare in PD. We investigated frequency and clinical features of camptocormia in PD patients. Methods. 153 PD patients (mean 68.5±10.7 years old, duration 5.9±2.4 years outpatiently recruited. After neurologic examination, patients were rated on the Unified PD Rating Scale motor scale (UPDRS Part III, minimental state examination (MMSE. Also we evaluated patients with camptocormia by MRI. Of the 153 PD patients, 27 had camptocormia (mean age, 67.9±7.9 years old; disease duration, 6.1±3.9 years. For further evaluation, we recruited age- and sex-matched 27 PD patients without camptocormia (11 men and 16 women; mean age ±SD, 69.2±10.1 years, duration 6.0±2.7 years These selected 54 patients completed several self-assessments. Lumbar and thoracic paraspinal muscles were studied by EMG. Results. There were no significant differences in age, duration, severity, and drug dose between patients with and without camptocormia. Analysis of NMSS subitems indicated that PD patients tended to show lower scores for sleep/fatigue, attention/memory, and miscellaneous items. Conclusions. We found significant differences concerning nonmotor signs and symptoms evaluated by FAB, PDQ-8, FSQ, VAS-F, and NMSS between patients with and without camptocormia. Our findings indicate that camptocormia is a relatively common sign in PD and that patients with camptocormia scores on the PDQ-8 compared with PD patients without camptocormia. This suggests that improvements in camptocormia of PD patients may improve their QOL.

  10. Dysphagia in Parkinson's Disease.

    Science.gov (United States)

    Suttrup, Inga; Warnecke, Tobias

    2016-02-01

    More than 80 % of patients with Parkinson's disease (PD) develop dysphagia during the course of their disease. Swallowing impairment reduces quality of life, complicates medication intake and leads to malnutrition and aspiration pneumonia, which is a major cause of death in PD. Although the underlying pathophysiology is poorly understood, it has been shown that dopaminergic and non-dopaminergic mechanisms are involved in the development of dysphagia in PD. Clinical assessment of dysphagia in PD patients is challenging and often delivers unreliable results. A modified water test assessing maximum swallowing volume is recommended to uncover oropharyngeal dysphagia in PD. PD-specific questionnaires may also be useful to identify patients at risk for swallowing impairment. Fiberoptic endoscopic evaluation of swallowing and videofluoroscopic swallowing study are both considered to be the gold standard for evaluation of PD-related dysphagia. In addition, high-resolution manometry may be a helpful tool. These instrumental methods allow a reliable detection of aspiration events. Furthermore, typical patterns of impairment during the oral, pharyngeal and/or esophageal swallowing phase of PD patients can be identified. Therapy of dysphagia in PD consists of pharmacological interventions and swallowing treatment by speech and language therapists (SLTs). Fluctuating dysphagia with deterioration during the off-state should be treated by optimizing dopaminergic medication. The methods used during swallowing treatment by SLTs shall be selected according to the individual dysphagia pattern of each PD patient. A promising novel method is an intensive training of expiratory muscle strength. Deep brain stimulation does not seem to have a clinical relevant effect on swallowing function in PD. The goal of this review is giving an overview on current stages of epidemiology, pathophysiology, diagnosis, and treatment of PD-associated dysphagia, which might be helpful for neurologists

  11. Deep brain stimulation may reduce the relative risk of clinically important worsening in early stage Parkinson's disease.

    Science.gov (United States)

    Hacker, Mallory L; Tonascia, James; Turchan, Maxim; Currie, Amanda; Heusinkveld, Lauren; Konrad, Peter E; Davis, Thomas L; Neimat, Joseph S; Phibbs, Fenna T; Hedera, Peter; Wang, Lily; Shi, Yaping; Shade, David M; Sternberg, Alice L; Drye, Lea T; Charles, David

    2015-10-01

    The Vanderbilt pilot trial of deep brain stimulation (DBS) in early Parkinson's disease (PD) enrolled patients on medications six months to four years without motor fluctuations or dyskinesias. We conducted a patient-centered analysis based on clinically important worsening of motor symptoms and complications of medical therapy for all subjects and a subset of subjects with a more focused medication duration. Continuous outcomes were also analyzed for this focused cohort. A post hoc analysis was conducted on all subjects from the pilot and a subset of subjects taking PD medications 1-4 years at enrollment. Clinically important worsening is defined as both a ≥ 3 point increase in UPDRS Part III and a ≥ 1 point increase in Part IV. DBS plus optimal drug therapy (DBS + ODT) subjects experienced a 50-80% reduction in the relative risk of worsening after two years. The DBS + ODT group was improved compared to optimal drug therapy (ODT) at each time point on Total UPDRS and Part III (p = 0.04, p = 0.02, respectively, at 24 months). Total UPDRS, Part IV, and PDQ-39 scores significantly worsened in the ODT group after two years (p early PD may reduce the risk of clinically important worsening. These findings further confirm the need to determine if DBS + ODT is superior to medical therapy for managing symptoms, reducing the complications of medications, and improving quality of life. The FDA has approved the conduct of a large-scale, pivotal clinical trial of DBS in early stage PD. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Challenges in the reproducibility of clinical studies with resting state fMRI: An example in early Parkinson's disease.

    Science.gov (United States)

    Griffanti, Ludovica; Rolinski, Michal; Szewczyk-Krolikowski, Konrad; Menke, Ricarda A; Filippini, Nicola; Zamboni, Giovanna; Jenkinson, Mark; Hu, Michele T M; Mackay, Clare E

    2016-01-01

    Resting state fMRI (rfMRI) is gaining in popularity, being easy to acquire and with promising clinical applications. However, rfMRI studies, especially those involving clinical groups, still lack reproducibility, largely due to the different analysis settings. This is particularly important for the development of imaging biomarkers. The aim of this work was to evaluate the reproducibility of our recent study regarding the functional connectivity of the basal ganglia network in early Parkinson's disease (PD) (Szewczyk-Krolikowski et al., 2014). In particular, we systematically analysed the influence of two rfMRI analysis steps on the results: the individual cleaning (artefact removal) of fMRI data and the choice of the set of independent components (template) used for dual regression. Our experience suggests that the use of a cleaning approach based on single-subject independent component analysis, which removes non neural-related sources of inter-individual variability, can help to increase the reproducibility of clinical findings. A template generated using an independent set of healthy controls is recommended for studies where the aim is to detect differences from a "healthy" brain, rather than an "average" template, derived from an equal number of patients and controls. While, exploratory analyses (e.g. testing multiple resting state networks) should be used to formulate new hypotheses, careful validation is necessary before promising findings can be translated into useful biomarkers.

  13. Indirect comparisons of adverse events and dropout rates in early Parkinson's disease trials of pramipexole, ropinirole, and rasagiline.

    Science.gov (United States)

    Zagmutt, Francisco J; Tarrants, Marcy L

    2012-07-01

    The comparative safety profiles of monotherapeutic treatments for Parkinson's disease (PD) can provide valuable therapeutic information. The objective of this study was to perform an indirect comparison of Adverse Events (AEs) and Dropout Rates (DRs) among clinical trials of pramipexole, ropinirole, and rasagiline. Outcomes analyzed included DRs, total AEs, and AE categories: Cognitive (CG), Gastrointestinal (GI), and Sleep/Fatigue (SF). The odds-ratio (OR) and Credible Interval (CrI) of outcomes between products using placebo as common comparator was calculated using indirect meta-analytical methods. AEs incidences for subjects receiving rasagiline were not significantly different from placebo, whereas DRs were significantly lower than for placebo (OR = 0.55; 95% CrI = 0.34-0.88). Patients receiving pramipexole or ropinirole had higher incidence of all AEs and DRs than patients taking rasagiline, except for the nonsignificant incidence of CG for ropinirole vs. rasagiline (1.76; 0.69-4.70). The incidence of GI (2.11; 1.13-4.06) and SF (2.75; 1.42-5.47) was significantly higher for ropinirole than for pramipexole, whereas the incidence of CG was significantly lower for ropinirole than for pramipexole (0.22; 0.07-0.69). Findings suggest that subjects with early PD treated with rasagiline have fewer AEs and DRs than those treated with pramipexole or ropinirole. GI and SF AEs were highest for subjects treated with ropinirole, while individuals treated with pramipexole exhibited the highest incidence of cognitive AEs.

  14. [The genetics of Parkinson disease].

    Science.gov (United States)

    Toft, Mathias; Aasly, Jan

    2004-04-01

    Parkinson's disease, PD, is the second most common neurodegenerative disorder. A genetic component in Parkinson's disease was long thought to be unlikely, but recent genetic studies have identified several genes associated with the disease. A review of the literature and personal experiences from genetic studies in central Norway are presented. Nine loci on the human genome have been linked to Parkinson's disease. Mutations in the alfa-synuclein, parkin, DJ-1, and arguably UCH-L1 genes are identified for familial PD. Recently a locus on chromosome 1 was linked to common late-onset PD in the Icelandic population. Iceland's population is primarily of Norse descent. This locus may be of significant importance to Norwegian PD patients. The genes and loci identified have improved our understanding of the pathogenesis in PD significantly. This knowledge may help to create new treatment strategies for PD.

  15. Neuroendocrine abnormalities in Parkinson's disease.

    Science.gov (United States)

    De Pablo-Fernández, Eduardo; Breen, David P; Bouloux, Pierre M; Barker, Roger A; Foltynie, Thomas; Warner, Thomas T

    2017-02-01

    Neuroendocrine abnormalities are common in Parkinson's disease (PD) and include disruption of melatonin secretion, disturbances of glucose, insulin resistance and bone metabolism, and body weight changes. They have been associated with multiple non-motor symptoms in PD and have important clinical consequences, including therapeutics. Some of the underlying mechanisms have been implicated in the pathogenesis of PD and represent promising targets for the development of disease biomarkers and neuroprotective therapies. In this systems-based review, we describe clinically relevant neuroendocrine abnormalities in Parkinson's disease to highlight their role in overall phenotype. We discuss pathophysiological mechanisms, clinical implications, and pharmacological and non-pharmacological interventions based on the current evidence. We also review recent advances in the field, focusing on the potential targets for development of neuroprotective drugs in Parkinson's disease and suggest future areas for research.

  16. Levodopa and the progression of Parkinson's disease.

    Science.gov (United States)

    Fahn, Stanley; Oakes, David; Shoulson, Ira; Kieburtz, Karl; Rudolph, Alice; Lang, Anthony; Olanow, C Warren; Tanner, Caroline; Marek, Kenneth

    2004-12-09

    Despite the known benefit of levodopa in reducing the symptoms of Parkinson's disease, concern has been expressed that its use might hasten neurodegeneration. This study assessed the effect of levodopa on the rate of progression of Parkinson's disease. In this randomized, double-blind, placebo-controlled trial, we evaluated 361 patients with early Parkinson's disease who were assigned to receive carbidopa-levodopa at a daily dose of 37.5 and 150 mg, 75 and 300 mg, or 150 and 600 mg, respectively, or a matching placebo for a period of 40 weeks, and then to undergo withdrawal of treatment for 2 weeks. The primary outcome was a change in scores on the Unified Parkinson's Disease Rating Scale (UPDRS) between baseline and 42 weeks. Neuroimaging studies of 142 subjects were performed at baseline and at week 40 to assess striatal dopamine-transporter density with the use of iodine-123-labeled 2-beta-carboxymethoxy-3-beta-(4-iodophenyl)tropane ([123I]beta-CIT) uptake. The severity of parkinsonism increased more in the placebo group than in all the groups receiving levodopa: the mean difference between the total score on the UPDRS at baseline and at 42 weeks was 7.8 units in the placebo group, 1.9 units in the group receiving levodopa at a dose of 150 mg daily, 1.9 in those receiving 300 mg daily, and -1.4 in those receiving 600 mg daily (Pdisease or has a prolonged effect on the symptoms of the disease. In contrast, the neuroimaging data suggest either that levodopa accelerates the loss of nigrostriatal dopamine nerve terminals or that its pharmacologic effects modify the dopamine transporter. The potential long-term effects of levodopa on Parkinson's disease remain uncertain. Copyright 2004 Massachusetts Medical Society.

  17. Neuromuscular rate of force development deficit in Parkinson disease.

    Science.gov (United States)

    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.

  18. Imaging prodromal Parkinson disease

    Science.gov (United States)

    Siderowf, Andrew; Stern, Matthew; Seibyl, John; Eberly, Shirley; Oakes, David; Marek, Kenneth

    2014-01-01

    Objectives: The purpose of this study is to evaluate the relative risk of abnormal dopamine transporter (DAT) imaging for subjects with and without hyposmia and the feasibility of acquiring a large, community-based, 2-tiered biomarker assessment strategy to detect prodromal Parkinson disease (PD). Methods: In this observational study, individuals without a diagnosis of PD, recruited through 16 movement disorder clinics, underwent tier 1 assessments (olfactory testing, questionnaires). Tier 2 assessments (neurologic examination, DAT imaging, and other biomarker assessments) were completed by 303 subjects. The main outcome of the study is to compare age-expected [123I]β-CIT striatal binding ratio in hyposmic and normosmic subjects. Results: Tier 1 assessments were mailed to 9,398 eligible subjects and returned by 4,999; 669 were hyposmic. Three hundred three subjects (203 hyposmic, 100 normosmic) completed baseline evaluations. DAT deficit was present in 11% of hyposmic subjects compared with 1% of normosmic subjects. Multiple logistic regression demonstrates hyposmia (odds ratio [OR] 12.4; 95% confidence interval [CI] 1.6, 96.1), male sex (OR 5.5; 95% CI 1.7, 17.2), and constipation (OR 4.3; 95% CI 1.6, 11.6) as factors predictive of DAT deficit. Combining multiple factors (hyposmia, male sex, and constipation) increased the percentage of subjects with a DAT deficit to >40%. Conclusion: Subjects with DAT deficit who do not meet criteria for a diagnosis of PD can be identified by olfactory testing. Sequential biomarker assessment may identify those at risk of PD. Selecting hyposmic individuals enriches the population for DAT deficit, and combining hyposmia with other potential risk factors (male sex, constipation) increases the percentage of subjects with a DAT deficit compatible with prodromal PD. PMID:25298306

  19. The Role of Axonopathy in Parkinson's Disease

    OpenAIRE

    O'Malley, Karen L.

    2010-01-01

    New genetic and environmental studies of Parkinson's disease have revealed early problems in synaptic function and connectivity indicating that axonal impairment may be an important hallmark in this disorder. Since many studies suggest that axonal dysfunction precedes cell body loss, it is critical to target axons with treatments aimed at preserving "connectivity" as well as to develop and verify "biomarkers" with which to assess disease progression and drug efficacy.

  20. Could Parkinson's Disease Raise Stroke Risk?

    Science.gov (United States)

    ... news/fullstory_163751.html Could Parkinson's Disease Raise Stroke Risk? Or is the link the other way ... link between Parkinson's disease and the risk for stroke. However, the study can't prove that one ...

  1. Managing Parkinson's disease with continuous dopaminergic stimulation

    NARCIS (Netherlands)

    Wolters, Erik; Lees, Andrew J.; Volkmann, Jens; van Laar, Teus; Hovestadt, Ad

    The pathophysiology of Parkinson's disease is marked by the loss of dopaminergic neurons, which leads to striatal dopaminergic deficiency. This causes resting tremor, hypokinesia, rigidity, bradykinesia, and loss of postural reflexes. Most current treatments for Parkinson's disease aim to restore

  2. Testing objective measures of motor impairment in early Parkinson's disease: Feasibility study of an at-home testing device.

    Science.gov (United States)

    Goetz, Christopher G; Stebbins, Glenn T; Wolff, David; DeLeeuw, William; Bronte-Stewart, Helen; Elble, Rodger; Hallett, Mark; Nutt, John; Ramig, Lorraine; Sanger, Terence; Wu, Allan D; Kraus, Peter H; Blasucci, Lucia M; Shamim, Ejaz A; Sethi, Kapil D; Spielman, Jennifer; Kubota, Ken; Grove, Andrew S; Dishman, Eric; Taylor, C Barr

    2009-03-15

    We tested the feasibility of a computer based at-home testing device (AHTD) in early-stage, unmedicated Parkinson's disease (PD) patients over 6 months. We measured compliance, technical reliability, and patient satisfaction to weekly assessments of tremor, small and large muscle bradykinesia, speech, reaction/movement times, and complex motor control. relative to the UPDRS motor score. The AHTD is a 6.5'' x 10'' computerized assessment battery. Data are stored on a USB memory stick and sent by internet to a central data repository as encrypted data packets. Although not designed or powered to measure change, the study collected data to observe patterns relative to UPDRS motor scores. Fifty-two PD patients enrolled, and 50 completed the 6 month trial, 48 remaining without medication. Patients complied with 90.6% of weekly 30-minute assessments, and 98.5% of data packets were successfully transmitted and decrypted. On a 100-point scale, patient satisfaction with the program at study end was 87.2 (range: 80-100). UPDRS motor scores significantly worsened over 6 months, and trends for worsening over time occurred for alternating finger taps (P = 0.08), tremor (P = 0.06) and speech (P = 0.11). Change in tremor was a significant predictor of change in UPDRS (P = 0.047) and was detected in the first month of the study. This new computer-based technology offers a feasible format for assessing PD-related impairment from home. The high patient compliance and satisfaction suggest the feasibility of its incorporation into larger clinical trials, especially when travel is difficult and early changes or frequent data collection are considered important to document.

  3. Efficacy, safety, and tolerability of overnight switching from immediate- to once daily extended-release pramipexole in early Parkinson's disease.

    Science.gov (United States)

    Rascol, Olivier; Barone, Paolo; Hauser, Robert A; Mizuno, Yoshikuni; Poewe, Werner; Schapira, Anthony H V; Salin, Laurence; Sohr, Mandy; Debieuvre, Catherine

    2010-10-30

    The aim of this article is to test the feasibility, in early Parkinson's disease (PD), of an overnight switch from immediate-release (IR) pramipexole to a new once-daily extended-release (ER) formulation. Nonfluctuating patients on pramipexole IR three-times daily, alone or with levodopa, for early PD were randomly switched overnight to double-blind IR three-times daily (N = 52) or ER once-daily (N = 104) at initially unchanged daily dosage. Successful switching (defined as no worsening >15% of baseline UPDRS II+III score and no drug-related adverse event withdrawal) was assessed at 9 weeks, after optional dosage adjustments (primary endpoint), and at 4 weeks, before adjustment. Other secondary endpoints included adjusted mean changes from baseline in UPDRS scores and proportion of responders based on Clinical or Patient Global Impression (CGI/PGI). Absolute difference between percentage of successful switch to ER versus IR was tested for ER noninferiority, defined as a 95% confidence-interval lower bound not exceeding -15%. At 9 weeks, 84.5% of the ER group had been successfully switched, versus 94.2% for IR. Noninferiority was not demonstrated, with a difference of -9.76% (95% CI: [-18.81%, +1.66%]). At 4 weeks, 81.6% of the ER group had been successfully switched, versus 92.3% for IR, a difference of -10.75% (95% CI: [-20.51%, +1.48%]). UPDRS changes and CGI/PGI analyses showed no differences between the groups. Both formulations were safe and well tolerated. Pramipexole ER was not equivalent to IR, but the difference was marginal. The fact that >80% of the patients successfully switched overnight at unchanged dosage shows that this practice was feasible in most patients.

  4. Evaluation of Multiple System Atrophy and Early Parkinson's Disease Using {sup 123}I-FP-CIT SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Oh, So Won; Kim, Yu Kyeong; Lee, Byung Chul; Kim, Bom Sahn; Kim, Ji Sun; Kim, Jong Min; Kim, Sang Eun [Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam (Korea, Republic of)

    2009-02-15

    We investigated quantification of dopaminergic transporter (DAT) and serotonergic transporter (SERT) on {sup 123}I-FP-CIT SPECT for differentiating between multiple systemic atrophy (MSA) and idiopathic Parkinson's disease (IPD). N.fluoropropyl-2{beta}-carbomethoxy-3{beta}-4-[{sup 123}I]-iodophenylnortropane SPECT ({sup 123}I-FP-CIT SPECT) was performed in 8 patients with MSA (mean age: 64.0{+-}4.5yrs, m:f=6:2), 13 with early IPD (mean age: 65.5{+-}5.3yrs, m:f=9:4), and 12 healthy controls (mean age: 63.3{+-}5.7yrs, m:f=8:4). Standard regions of interests (ROIs) of striatum to evaluate DAT, and hypothalamus and midbrain for SERT were drawn on standard template images and applied to each image taken 4 hours after radiotracer injection. Striatal specific binding for DAT and hypothalamic and midbrain specific binding for SERT were calculated using region/reference ratio based on the transient equilibrium method. Group differences were tested using ANOVA with the postHoc analysis. DAT in the whole striatum and striatal subregions were significantly decreased in both patient groups with MSA and early IPD, compared with healthy control (p<0.05 in all). In early IPD, a significant increase in the uptake ratio in anterior and posterior putamen and a trend of increase in caudate to putamen ratio was observed. In MSA, the decrease of DAT was accompanied with no difference in the striatal uptake pattern compared with healthy controls. Regarding the brain regions where {sup 123}I-FP-CIT binding was predominant by SERT, MSA patients showed a decrease in the binding of {sup 123}I-FP-CIT in the pons compared with controls as well as early IPD patients (MSA: 0.22{+-}0.1 healthy controls: 0.33{+-}0.19, IPD: 0.29{+-}0.19), however, it did not reach the statistical significance. In this study, the differential patterns in the reduction of DAT in the striatum and the reduction of pontine {sup 123}I- FP-CIT binding predominant by SERT could be observed in MSA patients on {sup 123

  5. A community survey of Parkinson's disease.

    OpenAIRE

    1989-01-01

    In a rural community of 80,000 people 69 patients were identified as having a diagnosis of Parkinson's disease. After interview and examination we found that 55 met the generally accepted diagnostic criteria for Parkinson's disease, 4 had possible Parkinson's disease, 6 had essential tremor, 2 had dementia and 2 had other conditions. The patients with Parkinson's disease had clinical and epidemiologic characteristics similar to those of patients in previous, mainly hospital-based, studies. Th...

  6. The role of autophagy in Parkinson's disease

    Institute of Scientific and Technical Information of China (English)

    Lei Zhang; Yaru Dong; Xiaoheng Xu; Zhong Xu

    2012-01-01

    Although Parkinson's disease is the most common neurodegenerative movement disorder, the mechanisms of pathogenesis remain poorly understood. Recent findings have shown that deregulation of the autophagy-lysosome pathway is involved in the pathogenesis of Parkinson's disease. This review summarizes the most recent findings and discusses the unique role of the autophagy-lysosome pathway in Parkinson's disease to highlight the possibility of Parkinson's disease treatment strategies that incorporate autophagy-lysosome pathway modulation.

  7. Glycation in Parkinson's disease and Alzheimer's disease.

    Science.gov (United States)

    Vicente Miranda, Hugo; El-Agnaf, Omar M A; Outeiro, Tiago Fleming

    2016-06-01

    Glycation is a spontaneous age-dependent posttranslational modification that can impact the structure and function of several proteins. Interestingly, glycation can be detected at the periphery of Lewy bodies in the brain in Parkinson's disease. Moreover, α-synuclein can be glycated, at least under experimental conditions. In Alzheimer's disease, glycation of amyloid β peptide exacerbates its toxicity and contributes to neurodegeneration. Recent studies establish diabetes mellitus as a risk factor for several neurodegenerative disorders, including Parkinson's and Alzheimer's diseases. However, the mechanisms underlying this connection remain unclear. We hypothesize that hyperglycemia might play an important role in the development of these disorders, possibly by also inducing protein glycation and thereby dysfunction, aggregation, and deposition. Here, we explore protein glycation as a common player in Parkinson's and Alzheimer's diseases and propose it may constitute a novel target for the development of strategies for neuroprotective therapeutic interventions. © 2016 International Parkinson and Movement Disorder Society.

  8. Increased intestinal permeability correlates with sigmoid mucosa alpha-synuclein staining and endotoxin exposure markers in early Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Christopher B Forsyth

    Full Text Available UNLABELLED: Parkinson's disease (PD is the second most common neurodegenerative disorder of aging. The pathological hallmark of PD is neuronal inclusions termed Lewy bodies whose main component is alpha-synuclein protein. The finding of these Lewy bodies in the intestinal enteric nerves led to the hypothesis that the intestine might be an early site of PD disease in response to an environmental toxin or pathogen. One potential mechanism for environmental toxin(s and proinflammatory luminal products to gain access to mucosal neuronal tissue and promote oxidative stress is compromised intestinal barrier integrity. However, the role of intestinal permeability in PD has never been tested. We hypothesized that PD subjects might exhibit increased intestinal permeability to proinflammatory bacterial products in the intestine. To test our hypothesis we evaluated intestinal permeability in subjects newly diagnosed with PD and compared their values to healthy subjects. In addition, we obtained intestinal biopsies from both groups and used immunohistochemistry to assess bacterial translocation, nitrotyrosine (oxidative stress, and alpha-synuclein. We also evaluated serum markers of endotoxin exposure including LPS binding protein (LBP. Our data show that our PD subjects exhibit significantly greater intestinal permeability (gut leakiness than controls. In addition, this intestinal hyperpermeability significantly correlated with increased intestinal mucosa staining for E. coli bacteria, nitrotyrosine, and alpha-synuclein as well as serum LBP levels in PD subjects. These data represent not only the first demonstration of abnormal intestinal permeability in PD subjects but also the first correlation of increased intestinal permeability in PD with intestinal alpha-synuclein (the hallmark of PD, as well as staining for gram negative bacteria and tissue oxidative stress. Our study may thus shed new light on PD pathogenesis as well as provide a new method for

  9. Metallomic profiling and linkage map analysis of early Parkinson's disease: a new insight to aluminum marker for the possible diagnosis.

    Directory of Open Access Journals (Sweden)

    Shiek S S J Ahmed

    Full Text Available BACKGROUND: Parkinson's disease (PD is the most common neurodegenerative disorder. The diagnosis of PD is challenging and currently none of the biochemical tests have proven to help in diagnosis. Serum metallomic analysis may suggest the possibility of diagnosis of PD. METHODOLOGY/RESULTS: The metallomic analysis was targeted on 31 elements obtained from 42 healthy controls and 45 drug naive PD patients using ICP-AES and ICP-MS to determine the concentration variations of elements between PD and normal. The targeted metallomic analysis showed the significant variations in 19 elements of patients compared to healthy control (p<0.04. The partial least squares discriminant analysis (PLS-DA showed aluminium, copper, iron, manganese and zinc are the key elements, contributes the separation of PD patients from control samples. The correlation coefficient analysis and element-element ratio confirm the imbalance of inter-elements relationship in PD patients' serum. Furthermore, elements linkage map analysis showed aluminium is a key element involved in triggering of phosphorus, which subsequently lead to imbalance of homeostatic in PD serum. The execution of neural network using elements concentrations provides 95% accuracy in detection of disease. CONCLUSIONS/SIGNIFICANCE: These results suggest that there is a disturbance in the elements homeostasis and inter-elements relationship in PD patients' serum. The analysis of serum elements helps in linking the underlying cellular processes such as oxidative stress, neuronal dysfunction and apoptosis, which are the dominating factors in PD. Also, these results increase the prospect of detection of early PD from serum through neural network algorithm.

  10. Parkinson's Disease Videos

    Medline Plus

    Full Text Available ... Aware in Care: Real Stories Betsaida Cruz, PT, Long Beach Memorial Medicinal: “Terapia fisica para el Parkinson” ... en Casa CareMAP: Life Beyond This Life CareMAP: Long-Distance Caregiving CareMAP: Managing Advanced Parkinson's Website CareMAP: ...

  11. Parkinson's Disease Videos

    Medline Plus

    Full Text Available ... with Advanced Parkinson's CareMAP: Caring from Afar CareMAP: Challenges and Rewards of Caregiving CareMAP: Changes Around the ... Yoga & Stretching NPF Caregiver Summit 2016: Embracing The Challenge: A Panel Discussion NPF Caregiver Summit 2016: Maintaining ...

  12. Parkinson's Disease Videos

    Medline Plus

    Full Text Available ... for Caregivers, from Caregivers CareMAP: Ayudando a una Persona con la Enfermedad de Parkinson CareMAP: Balancing Life and Caregiving CareMAP: Bathroom: Part 1 CareMAP: Bathroom: Part 2 CareMAP: Cambios en el Pensamiento y el Comportamiento, Parte 1 CareMAP: Cambios en el Pensamiento y ...

  13. Parkinson's disease: Autoimmunity and neuroinflammation.

    Science.gov (United States)

    De Virgilio, Armando; Greco, Antonio; Fabbrini, Giovanni; Inghilleri, Maurizio; Rizzo, Maria Ida; Gallo, Andrea; Conte, Michela; Rosato, Chiara; Ciniglio Appiani, Mario; de Vincentiis, Marco

    2016-10-01

    Parkinson's disease is a neurodegenerative disease that causes the death of dopaminergic neurons in the substantia nigra. The resulting dopamine deficiency in the basal ganglia leads to a movement disorder that is characterized by classical parkinsonian motor symptoms. Parkinson's disease is recognized as the most common neurodegenerative disorder after Alzheimer's disease. PD ethiopathogenesis remains to be elucidated and has been connected to genetic, environmental and immunologic conditions. The past decade has provided evidence for a significant role of the immune system in PD pathogenesis, either through inflammation or an autoimmune response. Several autoantibodies directed at antigens associated with PD pathogenesis have been identified in PD patients. This immune activation may be the cause of, rather than a response to, the observed neuronal loss. Parkinsonian motor symptoms include bradykinesia, muscular rigidity and resting tremor. The non-motor features include olfactory dysfunction, cognitive impairment, psychiatric symptoms and autonomic dysfunction. Microscopically, the specific degeneration of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies, which are brain deposits containing a substantial amount of α-synuclein, have been recognized. The progression of Parkinson's disease is characterized by a worsening of motor features; however, as the disease progresses, there is an emergence of complications related to long-term symptomatic treatment. The available therapies for Parkinson's disease only treat the symptoms of the disease. A major goal of Parkinson's disease research is the development of disease-modifying drugs that slow or stop the neurodegenerative process. Drugs that enhance the intracerebral dopamine concentrations or stimulate dopamine receptors remain the mainstay treatment for motor symptoms. Immunomodulatory therapeutic strategies aiming to attenuate PD neurodegeneration have become an attractive option and

  14. Development of Parkinson's disease biomarkers.

    Science.gov (United States)

    Prakash, Kumar M; Tan, Eng-King

    2010-12-01

    Parkinson's disease (PD) is the most common neurodegenerative movement disorder, affecting over 6 million people worldwide. It is anticipated that the number of affected individuals may increase significantly in the most populous nations by 2030. During the past 20 years, much progress has been made in identifying and assessing various potential clinical, biochemical, imaging and genetic biomarkers for PD. Despite the wealth of information, development of a validated biomarker for PD is still ongoing. It is hoped that reliable and well-validated biomarkers will provide critical clues to assist in the diagnosis and management of Parkinson's disease patients in the near future.

  15. Sleep disorders in Parkinson's disease.

    Science.gov (United States)

    Schrempf, Wiebke; Brandt, Moritz D; Storch, Alexander; Reichmann, Heinz

    2014-01-01

    Sleep disorders in patients with Parkinson's disease (PD) are very common and have an immense negative impact on their quality of life. Insomnia, daytime sleepiness with sleep attacks, restless-legs syndrome (RLS) and REM-sleep behaviour disorder (RBD) are the most frequent sleep disorders in PD. Neurodegenerative processes within sleep regulatory brain circuitries, antiparkinsonian (e.g., levodopa and dopamine agonists) and concomitant medication (e.g., antidepressants) as well as comorbidities or other non-motor symptoms (such as depression) are discussed as causative factors. For the diagnosis of sleep disturbances we recommend regular screening using validated questionnaires such as the Pittsburgh Sleep Quality Index (PSQI) or the Medical Outcomes Study Sleep Scale (MOS), for evaluating daytime sleepiness we would suggest to use the Epworth Sleepiness Scale (ESS), the inappropriate sleep composite score (ISCS) or the Stanford sleepiness scale (SSS). All of these questionnaires should be used in combination with a detailed medical history focusing on common sleep disorders and medication. If necessary, patients should be referred to sleep specialists or sleep laboratories for further investigations. Management of sleep disorders in PD patients usually starts with optimization of (dopaminergic) antiparkinsonian therapy followed by specific treatment of the sleep disturbances. Aside from these clinical issues of sleep disorders in PD, the concept of REM-sleep behaviour disorder (RBD) as an early sign for emerging neurodegenerative diseases is of pivotal interest for future research on biomarkers and neuroprotective treatment strategies of neurodegenerative diseases, and particularly PD.

  16. Considerações a respeito da doença de Parkinson de início precoce revisão crítica da literatura A comprehensive critical review on early onset Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Luiz Augusto Franco de Andrade

    1996-12-01

    has arisen concerning the real pathology in these cases and, consequently, how should they be named. Early or young onset parkinsonism, early or young onset Parkinson's disease, juvenile parkinsonism, all these terms have been used indistinguishable. There have been few pathological descriptions in early onset parkinsonism. Some show striking differences from the cases of older patients but others are very similar to what has been considered classical Parkison's disease. Younger starting age usually corresponds to greater possibility of other family members being affected. Dyskinesias and fluctuations due to chronic levodopa treatment are an early and almost invariable complication in the course of young patients. Comments on several aspects based on an extensive literature review are presented.

  17. Diagnostic accuracy of [99mTc]TRODAT-1 SPECT imaging in early Parkinson's disease.

    Science.gov (United States)

    Chou, K L; Hurtig, H I; Stern, M B; Colcher, A; Ravina, B; Newberg, A; Mozley, P D; Siderowf, A

    2004-08-01

    We evaluated the diagnostic accuracy of SPECT imaging using [(99m)Tc]TRODAT-1 (TRODAT), a relatively inexpensive technetium-labeled dopamine transporter ligand, in distinguishing 29 patients with early PD from 38 healthy volunteers. Mean TRODAT uptake values were significantly decreased in the caudate (p=0.0097) and anterior and posterior putamen (p accuracy (sensitivity 0.79, specificity 0.92). These findings show that TRODAT imaging can accurately differentiate early PD patients from controls and has the potential to improve the diagnosis of patients with early signs of PD.

  18. Neuroimaging over the course of Parkinson's disease: from early detection of the at-risk patient to improving pharmacotherapy of later-stage disease.

    Science.gov (United States)

    Seibyl, John; Russell, David; Jennings, Danna; Marek, Kenneth

    2012-11-01

    Brain imaging of striatal dopamine terminal degeneration serves an important role in the clinical management of Parkinson's disease (PD). Imaging biomarkers for interrogating dopaminergic systems are used for clarifying diagnosis when only subtle motor symptoms are present. However, motor dysfunction is not the earliest symptom of PD. There is increasing interest in identifying premotor PD patients, particularly because potential disease-modifying therapies are developed and the clinical imperative becomes early and accurate diagnosis. On the other end of the spectrum of the disease course, during later stages of PD, significant clinical challenges like levo-dopa-induced dyskinesias and medication on-off phenomenon become more prevalent. In this instance, better understanding of altered PD motor pathways suggests the potential utility of novel treatments targeting neuronal systems that are impacted by degenerating dopamine neurons and chronic dopamine replacement treatment. Molecular neuroimaging serves unique roles in both very early PD and later-stage disease, in the former, potentially pushing back the time of diagnosis, and in the latter, elucidating pathology relevant to new drug development. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Behavioral characterization of A53T mice reveals early and late stage deficits related to Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Katrina L Paumier

    Full Text Available Parkinson's disease (PD pathology is characterized by the formation of intra-neuronal inclusions called Lewy bodies, which are comprised of alpha-synuclein (α-syn. Duplication, triplication or genetic mutations in α-syn (A53T, A30P and E46K are linked to autosomal dominant PD; thus implicating its role in the pathogenesis of PD. In both PD patients and mouse models, there is increasing evidence that neuronal dysfunction occurs before the accumulation of protein aggregates (i.e., α-syn and neurodegeneration. Characterization of the timing and nature of symptomatic dysfunction is important for understanding the impact of α-syn on disease progression. Furthermore, this knowledge is essential for identifying pathways and molecular targets for therapeutic intervention. To this end, we examined various functional and morphological endpoints in the transgenic mouse model expressing the human A53T α-syn variant directed by the mouse prion promoter at specific ages relating to disease progression (2, 6 and 12 months of age. Our findings indicate A53T mice develop fine, sensorimotor, and synaptic deficits before the onset of age-related gross motor and cognitive dysfunction. Results from open field and rotarod tests show A53T mice develop age-dependent changes in locomotor activity and reduced anxiety-like behavior. Additionally, digigait analysis shows these mice develop an abnormal gait by 12 months of age. A53T mice also exhibit spatial memory deficits at 6 and 12 months, as demonstrated by Y-maze performance. In contrast to gross motor and cognitive changes, A53T mice display significant impairments in fine- and sensorimotor tasks such as grooming, nest building and acoustic startle as early as 1-2 months of age. These mice also show significant abnormalities in basal synaptic transmission, paired-pulse facilitation and long-term depression (LTD. Combined, these data indicate the A53T model exhibits early- and late-onset behavioral and synaptic

  20. Neuroimaging in pre-motor Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Thomas R. Barber

    2017-01-01

    Full Text Available The process of neurodegeneration in Parkinson's disease begins long before the onset of clinical motor symptoms, resulting in substantial cell loss by the time a diagnosis can be made. The period between the onset of neurodegeneration and the development of motoric disease would be the ideal time to intervene with disease modifying therapies. This pre-motor phase can last many years, but the lack of a specific clinical phenotype means that objective biomarkers are needed to reliably detect prodromal disease. In recent years, recognition that patients with REM sleep behaviour disorder (RBD are at particularly high risk of future parkinsonism has enabled the development of large prodromal cohorts in which to investigate novel biomarkers, and neuroimaging has generated some of the most promising results to date. Here we review investigations undertaken in RBD and other pre-clinical cohorts, including modalities that are well established in clinical Parkinson's as well as novel imaging methods. Techniques such as high resolution MRI of the substantia nigra and functional imaging of Parkinsonian brain networks have great potential to facilitate early diagnosis. Further longitudinal studies will establish their true value in quantifying prodromal neurodegeneration and predicting future Parkinson's.

  1. Reading comprehension in Parkinson's disease.

    Science.gov (United States)

    Murray, Laura L; Rutledge, Stefanie

    2014-05-01

    Although individuals with Parkinson's disease (PD) self-report reading problems and experience difficulties in cognitive-linguistic functions that support discourse-level reading, prior research has primarily focused on sentence-level processing and auditory comprehension. Accordingly, the authors investigated the presence and nature of reading comprehension in PD, hypothesizing that (a) individuals with PD would display impaired accuracy and/or speed on reading comprehension tests and (b) reading performances would be correlated with cognitive test results. Eleven adults with PD and 9 age- and education-matched control participants completed tests that evaluated reading comprehension; general language and cognitive abilities; and aspects of attention, memory, and executive functioning. The PD group obtained significantly lower scores on several, but not all, reading comprehension, language, and cognitive measures. Memory, language, and disease severity were significantly correlated with reading comprehension for the PD group. Individuals in the early stages of PD without dementia or broad cognitive deficits can display reading comprehension difficulties, particularly for high- versus basic-level reading tasks. These reading difficulties are most closely related to memory, high-level language, and PD symptom severity status. The findings warrant additional research to delineate further the types and nature of reading comprehension impairments experienced by individuals with PD.

  2. Genetic predisposition to Parkinson's disease

    DEFF Research Database (Denmark)

    Halling, Jónrit; Petersen, Maria Skaalum; Grandjean, Philippe

    2008-01-01

    OBJECTIVE: To investigate whether the genetic variants of CYP2D6 and HFE are more frequent in Parkinson's disease (PD) patients compared with controls in a population where the prevalence of these variants and PD are increased. METHODS: Blood samples were collected from 79 PD patients and 154...

  3. Treatment of Advanced Parkinson's Disease

    OpenAIRE

    Sara Varanese; Zoe Birnbaum; Roger Rossi; Alessandro Di Rocco

    2010-01-01

    Patients at late stage Parkinson's disease (PD) develop several motor and nonmotor complications, which dramatically impair their quality of life. These complications include motor fluctuations, dyskinesia, unpredictable or absent response to medications, falls, dysautonomia, dementia, hallucinations, sleep disorders, depression, and psychosis. The therapeutic management should be driven by the attempt to create a balance between benefit and side effects of the pharmacological treatments avai...

  4. Sweating dysfunction in Parkinson's disease

    NARCIS (Netherlands)

    Swinn, L; Schrag, A; Viswanathan, R; Lees, A; Quinn, N; Bloem, Bastiaan R.

    2003-01-01

    We sought to determine the prevalence and nature of sweating disturbances in patients with Parkinson's disease (PD), and investigated their correlation with other clinical features and with Quality of Life (QoL) measures. A questionnaire on symptoms and consequences of sweating dysfunction was compl

  5. Physical inactivity in Parkinson's disease

    NARCIS (Netherlands)

    Nimwegen, M.L. van; Speelman, A.D.; Hofman-van Rossum, E.J.; Overeem, S.; Deeg, D.J.G.; Borm, G.F.; Horst, M.H. van der; Bloem, B.R.; Munneke, M.

    2011-01-01

    Patients with Parkinson's disease (PD) are likely to become physically inactive, because of their motor, mental, and emotional symptoms. However, specific studies on physical activity in PD are scarce, and results are conflicting. Here, we quantified daily physical activities in a large cohort of PD

  6. Genetic predisposition to Parkinson's disease

    DEFF Research Database (Denmark)

    Halling, Jónrit; Petersen, Maria Skaalum; Grandjean, Philippe

    2008-01-01

    OBJECTIVE: To investigate whether the genetic variants of CYP2D6 and HFE are more frequent in Parkinson's disease (PD) patients compared with controls in a population where the prevalence of these variants and PD are increased. METHODS: Blood samples were collected from 79 PD patients and 154...

  7. Parkinson's Disease: A Traffic Jam?

    Science.gov (United States)

    Clague, Michael J; Rochin, Leila

    2016-04-25

    Recent large-scale proteomic analyses of two protein kinases that are linked to Parkinson's disease have identified a remarkable convergence between their respective impacts on the phosphoproteome: activation of both LRRK2 and PINK1 leads to phosphorylation of several members of the Rab family of small GTPases, which regulate membrane trafficking.

  8. Oxidative stress in Parkinson's disease.

    Science.gov (United States)

    Nikam, Shashikant; Nikam, Padmaja; Ahaley, S K; Sontakke, Ajit V

    2009-01-01

    Oxidative stress contributes to the cascade, leading to dopamine cell degeneration in Parkinson's disease. However, oxidative stress is intimately linked to other components of the degenerative process, such as mitochondrial dysfunction, excitotoxicity, nitric oxide toxicity and inflammation. It is therefore difficult to determine whether oxidative stress leads to or is a consequence of, these events. Oxidative stress was assessed by estimating lipid peroxidation product in the form of thiobarbituric acid reactive substances, nitric oxide in the form of nitrite & nitrate. Enzymatic antioxidants in the form of superoxide dismutase, glutathione peroxidase, catalase, ceruloplasmin and non enzymatic antioxidant vitamins e.g. vitamin E and C in either serum or plasma or erythrocyte in 40 patients of Parkinson's disease in the age group 40-80 years. Trace elements e.g. copper, zinc and selenium were also estimated. Plasma thiobarbituric acid reactive substances and nitric oxide levels were Significantly high but superoxide dismutase, glutathione peroxidase, catalase, ceruloplasmin, vitamin-E, vitamin-C, copper, zinc and selenium levels were significantly low in Parkinson's disease when compared with control subjects. Present study showed that elevated oxidative stress may be playing a role in dopaminergic neuronal loss in substentia nigra pars compacta and involved in pathogenesis of the Parkinson's disease.

  9. Parkinson's disease: piecing together a genetic jigsaw.

    NARCIS (Netherlands)

    M.C.J. Dekker (Marieke); V. Bonifati (Vincenzo); C.M. van Duijn (Cock)

    2003-01-01

    textabstractThe role of genetics in the pathogenesis of Parkinson's disease has been subject to debate for decades. In recent years, the discovery of five genes and several more loci has provided important insight into its molecular aetiology. Some Parkinson's disease genes possibly cause Parkinson'

  10. Stimulus Timing by People with Parkinson's Disease

    Science.gov (United States)

    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…

  11. Predictors of onset of psychosis in patients with Parkinson's disease: Who gets it early?

    Science.gov (United States)

    Lenka, Abhishek; George, Lija; Arumugham, Shyam Sundar; Hegde, Shantala; Reddy, Venkateswara; Kamble, Nitish; Yadav, Ravi; Pal, Pramod Kumar

    2017-09-14

    Psychosis is one of the common non-motor symptoms of PD, which substantially worsens the quality of life. Hence, it is important to identify factors that are associated with early onset of psychosis in PD. In order to identify those factors, the current study aims to compare various demographic and clinical features of PD patients with early and late onset psychosis. In this prospective case-control study, 51 consecutive patients with PD having psychosis (PDP) were recruited. Median of the latency of onset of psychotic symptoms from the onset of motor symptoms was calculated (5.5 years) and after doing a median split, the cohort of PDP was divided into early onset PDP (EOP, n = 25) and late onset PDP (LOP, n = 26). Both the groups were compared for several demographic and clinical characteristics. Compared to those with LOP, patients with EOP had poor scores on frontal assessment battery (13.8 ± 2.0 vs 15.3 ± 1.8, p = 0.007), more frequently had Rapid Eye movement sleep Behavior Disorder (RBD) (80% vs 46.2%, p = 0.02), Postural Instability with Gait Difficulty (PIGD) phenotype (72% vs 26.9%, p = 0.002), and excessive daytime sleepiness (Epworth Sleepiness Scale: 8.04 ± 3.7 vs 3.9 ± 3.1). Patients with LOP were older (63.4 ± 7.0 years vs 56.5 ± 8.1 years, p = 0.002) and had higher Levodopa equivalent dose/day (LEDD: 819.1 ± 365.8 vs 608.5 ± 356.3, p = 0.04) compared to those with EOP. Presence of RBD, excessive daytime sleepiness, frontal lobe dysfunction, and PIGD phenotype of PD may be associated with early onset of psychosis in PD. Higher LEDD may not trigger early occurrence of psychosis in PD. Copyright © 2017. Published by Elsevier Ltd.

  12. Gambling, Sex, and…Parkinson's Disease?

    Science.gov (United States)

    ... spent, browse our financial information. Learn More Gambling, Sex, and…Parkinson's Disease? By Laura Marsh, M.D. ... and, in people with Parkinson's, most typically involve sex, gambling and abuse of anti-parkinsonian medications. Pathological ...

  13. Effect of memantine on CBF and CMRO2 in patients with early Parkinson's disease

    DEFF Research Database (Denmark)

    Borghammer, P; Vafaee, M; Ostergaard, K;

    2008-01-01

    Objectives –  Parkinson’s disease (PD) may be associated with increased energy metabolism in overactive regions of the basal ganglia. Therefore, we hypothesized that treatment with the N-methyl-d-aspartate receptor (NMDAR) antagonist memantine would decrease regional cerebral blood flow (r...

  14. Team management of Parkinson's disease.

    Science.gov (United States)

    Davis, J C

    1977-01-01

    This report describes a multidisciplinary approach to the treatment of Parkinson's disease. By using published sources, the disease process, clinical findings, and medical management of Parkinson's disease are reviewed. The continual change in the clinical picture as well as the therapeutic needs require that clinicians have a full understanding of the disease and drugs used. This is followed by a description of a group program, including the evaluation process, treatment goals, and individual and group activities employed. Rehabilitation services are needed as medical management alone is not sufficient to maintain patient's daily living skills. The occupational therapist is skilled in assessment and training of activities for daily living. As a result, occupational therapy can be an integral part of the treatment program.

  15. Parkinson's Disease and Cryptogenic Epilepsy.

    Science.gov (United States)

    Son, Andre Y; Biagioni, Milton C; Kaminski, Dorian; Gurevich, Alec; Stone, Britt; Di Rocco, Alessandro

    2016-01-01

    Epilepsy is an uncommon comorbidity of Parkinson's disease (PD) and has been considered not directly associated with PD. We present five patients (3 men and 2 women; ages 49-85) who had concomitant PD and cryptogenic epilepsy. Although rare, epilepsy can coexist with PD and their coexistence may influence the progression of PD. While this may be a chance association, an evolving understanding of the neurophysiological basis of either disease may suggest a mechanistic association.

  16. Parkinson's Disease and Cryptogenic Epilepsy

    Science.gov (United States)

    Kaminski, Dorian; Gurevich, Alec; Stone, Britt; Di Rocco, Alessandro

    2016-01-01

    Epilepsy is an uncommon comorbidity of Parkinson's disease (PD) and has been considered not directly associated with PD. We present five patients (3 men and 2 women; ages 49–85) who had concomitant PD and cryptogenic epilepsy. Although rare, epilepsy can coexist with PD and their coexistence may influence the progression of PD. While this may be a chance association, an evolving understanding of the neurophysiological basis of either disease may suggest a mechanistic association. PMID:27688919

  17. Proteomic analysis of the cerebrospinal fluid of Parkinson's disease patients

    Institute of Scientific and Technical Information of China (English)

    Jiguang Guo; Zhongwu Sun; Shifu Xiao; Dongping Liu; Guohua Jin; Ersong Wang; Jiangning Zhou; Jiawei Zhou

    2009-01-01

    @@ Dear Editor, Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease (AD). Although treatments for PD may be beneficial in the early stages of disease, accurate diagnosis during these stages remains a challenge. An ideal diagnosis for PD should be highly specific and sensitive, as well as be able to predict disease progression.

  18. Nonlinear EMG parameters for differential and early diagnostics of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Alexander eMeigal

    2013-09-01

    Full Text Available The pre-clinical diagnostics is essential for management of Parkinson’s disease (PD. . Although PD has been studied intensively in the last decades, the pre-clinical indicators of that motor disorder have yet to be established. Several approaches were proposed but the definitive method is still lacking. Here we report on the non-linear characteristics of surface electromyogram (sEMG and tremor acceleration as a possible diagnostic tool, and, in prospective, as a predictor for PD. Following this approach we calculated such nonlinear parameters of sEMG and accelerometer signal as correlation dimension, entropy and determinism. We found that the nonlinear parameters allowed discriminating some 85% of healthy controls from PD patients. Thus, this approach offers considerable potential for developing sEMG-based method for pre-clinical diagnostics of PD. However, non-linear parameters proved to be more reliable for the shaking form of PD, while diagnostics of the rigid form of PD using EMG remains an open question.

  19. [Physical therapy for parkinson's disease].

    Science.gov (United States)

    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.

  20. Diagnostic value of the impairment of olfaction in Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Swaantje Casjens

    Full Text Available 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

  1. Problems associated with fluid biomarkers for Parkinson's disease.

    Science.gov (United States)

    Nyhlén, Jakob; Constantinescu, Radu; Zetterberg, Henrik

    2010-10-01

    This article focuses on biochemical markers that may be used in the diagnostics of Parkinson's disease and associated disorders, and to identify early cases and stratify patients into subgroups. We present an updated account of some currently available candidate fluid biomarkers, and discuss their diagnostic performance and limitations. We also discuss some of the general problems with Parkinson's disease biomarkers and possible ways of moving forward. It may be concluded that a diagnostically useful fluid biomarker for Parkinson's disease is yet to be identified. However, some interesting candidates exist and may prove useful in the future, alone or when analyzed together in patterns.

  2. Swallowing disorders in Parkinson's disease.

    Science.gov (United States)

    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 SaO2 (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.

  3. Current therapy for Parkinson's disease

    Directory of Open Access Journals (Sweden)

    A. V. Obukhova

    2014-01-01

    Full Text Available The main goal of therapy for Parkinson's disease (PD is to correct dopamine deficiency in the nigrostriatal system. Levodopa preparations and dopamine receptor agonists (DRAs that are prescribed with regards to patient age and disease severity are mainly used now. Notwithstanding the fact that levodopa preparations are the gold standard of therapy, their long-term use gives rise to complications as motor fluctuations and drug-induced dyskinesias. The currently available DRAs are the drugs of choice for the therapy of early-stage PD as they are as effective as levodopa preparations. In extensive-stage PD, DRAs are used to enhance the therapy and correction of developed motor fluctuations and dyskinesias. Pramipexole is one of the most commonly used representatives of non-ergoline DRAs. The paper analyzes the efficacy of the medication used as both monotherapy and part of combined therapy, its effect on tremor and depression in PD. A novel extended-release formulation of pramipexole is considered separately. Both immediate- and extended-release pramipexole formulations contain the same active ingredient and have the same dopamine-receptor interaction profile, but differ in the tablet release rate of the active ingredient. The advantages of the novel formulation are its more steady-state plasma concentration and 24-hour action, which ensures continuous dopaminergic stimulation ofpostsynaptic receptors to prevent and treat already developed motor complications. The once-daily extended-release formulation of the drug makes its treatment regimen easier and patient compliance higher.

  4. Electroconvulsive therapy in Parkinson's disease.

    Science.gov (United States)

    Calderón-Fajardo, Humberto; Cervantes-Arriaga, Amin; Llorens-Arenas, Rodrigo; Ramírez-Bermudez, Jesús; Ruiz-Chow, Ángel; Rodríguez-Violante, Mayela

    2015-10-01

    Purpose To analyze the effectiveness of electroconvulsive therapy for the management of depression and/or psychosis refractory to drug therapy in patients with Parkinson disease.Methods A retrospective study was carried out including patients treated with electroconvulsive therapy during the period between 2002 and 2013. A review of the literature was performed.Results A total of 27 patients were included. In regards to the neuropsychiatric diagnosis, 14 patients had major depression, 12 patients had both psychosis and depression, and only one patient had isolated psychosis. The mean number of electroconvulsive therapy sessions was 12 ± 2.8. After electroconvulsive therapy, all patients showed a statistically significant improvement in the Brief Psychiatric Rating scale (reduction of 52% points) and Hamilton Depression Rating Scale (reduction of 50% points) independent of the presence of psychosis, depression or both.Conclusion Electroconvulsive therapy is effective for the treatment of refractory neuropsychiatric symptoms in Parkinson's disease.

  5. The effect of pramipexole therapy on balance disorder and fall risk in Parkinson's disease at early stage: clinical and posturographic assessment.

    Science.gov (United States)

    Güler, Sibel; Bir, Levent Sinan; Akdag, Beyza; Ardıc, Fusun

    2012-01-01

    The aim of this study was to determine balance problems and severity and ratio of postural instability of newly diagnosed, early stage Parkinson's patients who did not receive any antiparkinson treatment before, to evaluate fall risk clinically and posturographically and to examine the effects of pramipexole on these signs and symptoms. Detailed posturographic assessments which involved central vestibular, visual, peripheric vestibular somatosensory field tests were applied to both patient and control subjects and fall risk was determined. There was not statistically significant difference between patients and control subjects before and after drug therapy in the assesment of fall risk in posturography and there was not any improvement with drug usage in the patient group. However, in the analysis of subsystems separately, only the involvement in central vestibular field was more severe and could appear at all positions in Parkinson's patients comparing with the control group, and pramipexole was partially effective in improving this disorder. Central vestibular field is the subsystem that should be examined with first priority. Posturography is relatively reliable in defining fall risk and postural instability ratio in Parkinson's disease. But it should be considered that clinical assessment tools can be more sensitive in the evaluation of balance and postural disorders and in the follow-up of the response to drug therapy.

  6. Emotional impairment in Parkinson's disease

    Directory of Open Access Journals (Sweden)

    CHEN Hai-bo

    2013-08-01

    Full Text Available Emotional impairment is the common complication of Parkinson's disease (PD. Depression, anxiety and apathy affect the quality of life and the prognosis of PD patients. Neuropsychological and neuroimaging studies of emotional impairment in PD patients suggest abnormalities involving mesolimbic and mesocortical dopaminergic pathways, but the specific mechanism needs further study. In this review we discuss the clinical manifestation, possible pathological mechanism, diagnosis and treatment in PD patients.

  7. 帕金森病早期诊断之生物学标记物%Early Diagnosis Biomarkers of Parkinson's Disease

    Institute of Scientific and Technical Information of China (English)

    梁杨; 顾英; 孙亚南; 李晓红

    2014-01-01

    Parkinson's disease is a neurodegenerative disease in the elderly ,which is also the most common extrapyramidal disease in the elderly .The pathological features are nigra dopamine neurons degeneration and Lewy body forming .The main clinical symptoms include motor symptoms and nonmotor symptoms .At present ,Parkinson's disease is still lack of the most direct and effective diagnosis method ,so blood biochemicalmarkers ,cerebrospinal fluid biochemicalmarkers , functional neuro-imaging and genomics become new methods for early diagnosis of Parkinson's disease .%帕金森病是老年人神经系统变性疾病之一,也是老年人最常见的锥体外系疾病,以黑质多巴胺能神经元变性、缺失以及路易小体形成为其主要病理特征。其临床症状主要包括运动症状及非运动症状。目前对于帕金森病仍缺乏最直接有效的诊断方法,常导致帕金森病患者错过最佳的早期诊断时机,故近年来研究发现血液生物化学标记物、脑脊液生物化学标记物、功能神经影像学、基因学等有望成为帕金森病早期诊断的新方法,故本文将对此逐一进行介绍。

  8. Gender differences in Parkinson's disease.

    Science.gov (United States)

    Shulman, Lisa M

    2007-03-01

    Because estrogen has numerous effects on dopamine neurotransmission, many researchers are interested in its possible use to either slow the progression or reduce the risk of Parkinson's disease (PD). The incidence of PD is greater in men than in women. Gender differences in neurotoxicity have been observed, and basic research in experimental animals indicates that estrogen protects neurons from various forms of injury. However, the results of retrospective surveys of the neuroprotective effects of estrogen replacement in PD have been mixed, with some showing no effect on risk and others showing a reduction in risk. A mildly significant gender difference in disability and quality-of-life reporting has been noted, with women citing greater disability and reduced quality of life. Gender differences have been shown in response to treatment of PD, for example, in how levodopa is metabolized--women have greater levodopa bioavailability. In the Parkinson's Disease on Estrogen Therapy Replacement in the Menopause Years (POETRY) study, participants were found to have improved scores on the Unified Parkinson Disease Rating Scale. Based on the POETRY results, it is hypothesized that estrogen replacement therapy (ERT) may lead to improvement in PD symptoms and provide an opportunity to reduce the dosage of antiparkinsonian medication in women.

  9. Coping with Parkinson's disease in everyday life

    DEFF Research Database (Denmark)

    Haahr, Anita; Brincks, John; Sørensen, Dorthe

    2017-01-01

    REVIEW QUESTION/OBJECTIVE: The purpose of this systematic review is to synthesize the best available qualitative evidence on how individuals with Parkinson's disease cope with the disease in daily life.......REVIEW QUESTION/OBJECTIVE: The purpose of this systematic review is to synthesize the best available qualitative evidence on how individuals with Parkinson's disease cope with the disease in daily life....

  10. Diagnostic value of the impairment of olfaction in Parkinson's disease

    OpenAIRE

    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/PRINC...

  11. Dysgeusia in parkinson's disease: a systematic review

    OpenAIRE

    Gonçalves, Catarina Vieira Ferreira

    2016-01-01

    Trabalho de revisão do 6º ano médico com vista à atribuição do grau de mestre (área científica de otorrinolaringologia) no âmbito do ciclo de estudos de Mestrado Integrado em Medicina. Background: Taste has an extreme importance on individual nutrition, health and quality-of-life status. Parkinson's disease (PD), one of the most frequent neurodegenerative disorders, is becoming a systemic disease with an increasing awareness to the importance of non-motor symptoms for early PD diagnosis an...

  12. What contributes to depression in Parkinson's disease?

    OpenAIRE

    Schrag, A.; M. Jahanshahi; Quinn, N P

    2001-01-01

    Background: Depression is a common problem in patients with Parkinson's disease, but its mechanism is poorly understood. It is thought that neurochemical changes contribute to its occurrence, but it is unclear why some patients develop depression and others do not. Using a community-based sample of patients with Parkinson's disease, we investigated the contributions of impairment, disability and handicap to depression in Parkinson's disease. Methods: Ninety-seven patients seen in a popula...

  13. Stem cell transplantation for treating Parkinson's disease

    OpenAIRE

    Li, Runhui

    2012-01-01

    OBJECTIVE: To identify global research trends of stem cell transplantation for treating Parkinson's disease using a bibliometric analysis of the Web of Science. DATA RETRIEVAL: We performed a bibliometric analysis of data retrievals for stem cell transplantation for treating Parkinson's disease from 2002 to 2011 using the Web of Science. SELECTION CRITERIA: Inclusion criteria: (a) peer-reviewed articles on stem cell transplantation for treating Parkinson's disease which were published and ind...

  14. Nongenetic causes of Parkinson's disease.

    Science.gov (United States)

    Chade, A R; Kasten, M; Tanner, C M

    2006-01-01

    Study of the nongenetic causes of Parkinson's disease (PD) was encouraged by discovery of a cluster of parkinsonism produced by neurotoxic pyridine 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the 1980s. Since that time, epidemiologic investigations have suggested risk factors, though their results do not establish causality. Pesticide exposure has been associated with increased risk in many studies. Other proposed risks include rural residence and certain occupations. Cigarette smoking, use of coffee/caffeine, and non-steroidal antiinflammatory drugs (NSAIDs) all appear to lower risk of PD, while dietary lipid and milk consumption, high caloric intake, and head trauma may increase risk. The cause of PD is likely multifactorial. Underlying genetic susceptibility and combinations of risk and protective factors likely all contribute. The combined research effort by epidemiologists, geneticists, and basic scientists will be needed to clarify the cause(s) of PD.

  15. Parkinson's Disease Research Web - Information for Patients and Caregivers

    Science.gov (United States)

    ... Information Page Parkinson's Disease: Hope Through Research NINDS Deep Brain Stimulation for Parkinson's Disease Strategic Plans NINDS ... Syndrome Information Page Dandy-Walker Syndrome Information Page Deep Brain Stimulation for Parkinson's Disease Information Page Dementia ...

  16. Biomarker Research in Parkinson's Disease Using Metabolite Profiling

    DEFF Research Database (Denmark)

    Havelund, Jesper F; Heegaard, Niels H H; Færgeman, Nils J K

    2017-01-01

    Biomarker research in Parkinson's disease (PD) has long been dominated by measuring dopamine metabolites or alpha-synuclein in cerebrospinal fluid. However, these markers do not allow early detection, precise prognosis or monitoring of disease progression. Moreover, PD is now considered a multifa......Biomarker research in Parkinson's disease (PD) has long been dominated by measuring dopamine metabolites or alpha-synuclein in cerebrospinal fluid. However, these markers do not allow early detection, precise prognosis or monitoring of disease progression. Moreover, PD is now considered...

  17. Parkinson's Disease Videos

    Medline Plus

    Full Text Available ... Use for Freezing? Are There Any Ways to Control the Rate of Progression of the Disease? Ask ... What Are Some Practical Strategies for Improving the Quality of Sleep? What Are Some Strategies for Problems ...

  18. Parkinson's Disease Videos

    Medline Plus

    Full Text Available ... Disease Diagnosed? Interview with Nathan Slewett Is Compulsive Behavior a Side Effect of PD Medications? Is Depression ... What Do I Do if I Suspect Compulsive Behavior in a Loved One with PD? What Does ...

  19. A 200-year history of Parkinson's disease

    OpenAIRE

    Wang, Xiao-Dan; Ji, Yong

    2017-01-01

    In 1817, Dr. James Parkinson firstly described the concept, duration, and clinical characteristics of Parkinson's disease (PD). However, it was widely known until 1877 when it was named "Parkinson's disease" by Dr. Jean-Martin Charcot. In 1912, Frederic Henry Lewy, a neuropathologist, found a special abnormal protein in nerve cells of PD patients. Medical profession began to learn about the pathology of PD only when Konstantin Tretiakoff named the special abnormal protein "Lewy body (LB...

  20. Cell transplantation for Parkinson's disease

    Institute of Scientific and Technical Information of China (English)

    Jia Liu; Hongyun Huang

    2006-01-01

    OBJECTIVE: The motor symptoms of Parkinson's disease (PD) can be improved by cell transplantation,which has caught general attention from the field of the therapy for PD recently. In this paper, we summarize the cell-based therapy for PD.DATA SOURCES: A search for English literature related to the cellular transplantation of PD from January 1979to July 2006 was conducted in Medline with the key words of "Parkinson's disease, cell transplantation,embryonic stem cells, neural stem cells".STUDY SELECTTON: Data were checked in the first trial, and literatures about PD and cell transplantation were selected. Inclusive criteria: ① PD; ② Cell transplantation. Exclusive criteria: repetitive researches.DATA EXTRACTTON: A total of 100 papers related to cellular transplant and PD were collected and 41literatures were in accordance with the inclusive criteria.DATA SYNTHESIS: PD is a neural degeneration disease that threatens the health of the aged people, and most traditional therapeusis cannot delay its pathological proceeding. Cell transplantation is becoming popular as a new therapeutic tool, and the cells used to transplant mainly included dopamine-secreting cells, fetal ventral mesencephalic cells, embryonic stem cells and neural stem cells up to now. Animal experiment and clinical test demonstrate that cell transplantation can relieve the motor symptoms of Parkinson's disease obviously, but there are some problems need to be solved.CONCLUSTON: Cell transplantation has visible therapeutic efficacy on PD. Following the improvement of technique, and we have enough cause to credit that cell therapy may cure PD in the future.

  1. Quality of life in Parkinson's disease.

    Science.gov (United States)

    Opara, J A; Brola, W; Leonardi, M; Błaszczyk, B

    2012-12-15

    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.

  2. Parkinson's Disease Videos

    Medline Plus

    Full Text Available ... Use for Freezing? Are There Any Ways to Control the Rate of Progression of the Disease? Ask ... Hallucinations or Delusions? How Do I Manage Non-Motor Problems Such as ... Compulsive Behavior a Side Effect of PD Medications? Is Depression ...

  3. MDS research criteria for prodromal Parkinson's disease.

    Science.gov (United States)

    Berg, Daniela; Postuma, Ronald B; Adler, Charles H; Bloem, Bastiaan R; Chan, Piu; Dubois, Bruno; Gasser, Thomas; Goetz, Christopher G; Halliday, Glenda; Joseph, Lawrence; Lang, Anthony E; Liepelt-Scarfone, Inga; Litvan, Irene; Marek, Kenneth; Obeso, José; Oertel, Wolfgang; Olanow, C Warren; Poewe, Werner; Stern, Matthew; Deuschl, Günther

    2015-10-01

    This article describes research criteria and probability methodology for the diagnosis of prodromal PD. Prodromal disease refers to the stage wherein early symptoms or signs of PD neurodegeneration are present, but classic clinical diagnosis based on fully evolved motor parkinsonism is not yet possible. Given the lack of clear neuroprotective/disease-modifying therapy for prodromal PD, these criteria were developed for research purposes only. The criteria are based upon the likelihood of prodromal disease being present with probable prodromal PD defined as ≥80% certainty. Certainty estimates rely upon calculation of an individual's risk of having prodromal PD, using a Bayesian naïve classifier. In this methodology, a previous probability of prodromal disease is delineated based upon age. Then, the probability of prodromal PD is calculated by adding diagnostic information, expressed as likelihood ratios. This diagnostic information combines estimates of background risk (from environmental risk factors and genetic findings) and results of diagnostic marker testing. In order to be included, diagnostic markers had to have prospective evidence documenting ability to predict clinical PD. They include motor and nonmotor clinical symptoms, clinical signs, and ancillary diagnostic tests. These criteria represent a first step in the formal delineation of early stages of PD and will require constant updating as more information becomes available. © 2015 International Parkinson and Movement Disorder Society.

  4. Gait, posture and cognition in Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Alessandra Ferreira Barbosa

    Full Text Available ABSTRACT Gait disorders and postural instability are the leading causes of falls and disability in Parkinson's disease (PD. Cognition plays an important role in postural control and may interfere with gait and posture assessment and treatment. It is important to recognize gait, posture and balance dysfunctions by choosing proper assessment tools for PD. Patients at higher risk of falling must be referred for rehabilitation as early as possible, because antiparkinsonian drugs and surgery do not improve gait and posture in PD.

  5. [Perioperative management of Parkinson's disease].

    Science.gov (United States)

    Mariscal, A; Medrano, I Hernández; Cánovas, A Alonso; Lobo, E; Loinaz, C; Vela, L; Espiga, P García-Ruiz; Castrillo, J C Martínez

    2012-01-01

    One of the particular characteristics of Parkinson's disease (PD) is the wide clinical variation as regards the treatment that can be found in the same patient. This occurs with specific treatment for PD, as well as with other drug groups that can make motor function worse. For this reason, the perioperative management of PD requires experience and above all appropriate planning. In this article, the peculiarities of PD and its treatment are reviewed, and a strategy is set out for the perioperative management of these patients. Copyright © 2010 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  6. [The Idiopathic Parkinson's disease: A metabolic disease?].

    Science.gov (United States)

    Rieu, I; Boirie, Y; Morio, B; Derost, P; Ulla, M; Marques, A; Debilly, B; Bannier, S; Durif, F

    2010-10-01

    Parkinson's disease is a neurodegenerative disorder clinically characterized by motor impairments (tremor, bradykinesia, rigidity and postural instability) associated or not with non-motor complications (cognitive disorders, dysautonomia). Most of patients loose weight during evolution of their disease. Dysregulations of hypothalamus, which is considered as the regulatory center of satiety and energy metabolism, could play a major role in this phenomenon. Deep brain stimulation of the subthalamic nucleus (NST) is an effective method to treat patients with advanced Parkinson's disease providing marked improvement of motor impairments. This chirurgical procedure also induces a rapid and strong body weight gain and sometimes obesity. This post-operative weight gain, which exceeds largely weight lost recorded in non-operated patient, could be responsible of metabolic disorders (such as diabetes) and cardiovascular diseases. This review describes body weight variations generated by Parkinson' disease and deep brain stimulation of the NST, and focuses on metabolic disorders capable to explain them. Finally, this review emphasizes on the importance of an adequate nutritional follow up care for parkinsonian patient.

  7. Orthostatic Hypotension (Low Blood Pressure) and Parkinson's Disease

    Science.gov (United States)

    ... Patient Advocates Sign Up for Funding News npj Parkinson's Disease Scientific Advisory Board Understanding Parkinson's Coping with a Diagnosis What is Parkinson’s Disease? National HelpLine Educational Publications Online Seminars Parkinson's News ...

  8. Nonmotor symptoms in genetic Parkinson disease

    DEFF Research Database (Denmark)

    Kasten, Meike; Kertelge, Lena; Brüggemann, Norbert

    2010-01-01

    To review current knowledge on nonmotor symptoms (NMS), particularly psychiatric features, in genetic Parkinson disease (PD) and to provide original data for genetic and idiopathic PD.......To review current knowledge on nonmotor symptoms (NMS), particularly psychiatric features, in genetic Parkinson disease (PD) and to provide original data for genetic and idiopathic PD....

  9. Parkinson's disease: piecing together a genetic jigsaw.

    NARCIS (Netherlands)

    M.C.J. Dekker (Marieke); V. Bonifati (Vincenzo); C.M. van Duijn (Cock)

    2003-01-01

    textabstractThe role of genetics in the pathogenesis of Parkinson's disease has been subject to debate for decades. In recent years, the discovery of five genes and several more loci has provided important insight into its molecular aetiology. Some Parkinson's disease genes possibly cause

  10. Managing Parkinson's disease with continuous dopaminergic stimulation

    NARCIS (Netherlands)

    Wolters, Erik; Lees, Andrew J.; Volkmann, Jens; van Laar, Teus; Hovestadt, Ad

    2008-01-01

    The pathophysiology of Parkinson's disease is marked by the loss of dopaminergic neurons, which leads to striatal dopaminergic deficiency. This causes resting tremor, hypokinesia, rigidity, bradykinesia, and loss of postural reflexes. Most current treatments for Parkinson's disease aim to restore st

  11. Understanding Parkinson disease: an evolving case study.

    Science.gov (United States)

    Vernon, Gwyn M; Carty, Anne E S; Salemno, Christin M; Siskind, Michele M; Thomas, Cathi A

    2014-10-15

    Thirty years ago, Parkinson disease was described as a shortage of the neurotransmitter dopamine. Today, understanding of this disorder includes possible genetic influences, premorbid and nonmotor issues, and a variety of neurologic, cognitive, and psychiatric symptoms. Using a case study, this article presents the current science of Parkinson disease.

  12. Pathogenic mutations in Parkinson disease.

    Science.gov (United States)

    Tan, Eng-King; Skipper, Lisa M

    2007-07-01

    Parkinson disease (PD; Parkinson's) is the second most common neurodegenerative disease, characterized by the progressive loss of dopamine neurons and the accumulation of Lewy bodies. Increasing evidence suggests that deficits in mitochondrial function, oxidative and nitrosative stress, the accumulation of aberrant or misfolded proteins, and ubiquitin-proteasome system (UPS) dysfunction may represent the principal molecular pathways that commonly underlie the pathogenesis. The relative role of genetic and environmental factors has been the focus of research and debate. The recent discovery of a number of disease-causing genes (SNCA, Parkin/PARK2, UCHL1, PINK1, DJ1/PARK7, and LRRK2) in familial and sporadic forms of PD has provided considerable insights into the pathophysiology of this complex disorder. The frequency of these gene mutations may vary according to ethnicity and to the specific gene. A gene dosage effect is observed in some cases, and the phenotype of some of the mutation carriers closely resembles typical PD. Penetrance of some of the recurrent mutations is incomplete and may vary with age. Further research to unravel the etiopathology could identify biochemical or genetic markers for potential neuroprotective trials. (c) 2007 Wiley-Liss, Inc.

  13. Is "Parkinson's disease" one disease?

    OpenAIRE

    Calne, D B

    1989-01-01

    Consideration is given to how and why categories of ill health are divided into diseases. Aetiology is a fundamental criterion for the delineation of individual diseases. The same clinical and pathological picture may have many different causes; for example meningococcal meningitis and pneumococcal meningitis are distinct diseases that may display the same symptoms and signs. On the other hand, a single aetiology may lead to quite separate clinical and pathological phenomena; for example, neu...

  14. Parkinson's Disease and Systemic Inflammation

    Science.gov (United States)

    Ferrari, Carina C.; Tarelli, Rodolfo

    2011-01-01

    Peripheral inflammation triggers exacerbation in the central brain's ongoing damage in several neurodegenerative diseases. Systemic inflammatory stimulus induce a general response known as sickness behaviour, indicating that a peripheral stimulus can induce the synthesis of cytokines in the brain. In Parkinson's disease (PD), inflammation was mainly associated with microglia activation that can underlie the neurodegeneration of neurons in the substantia nigra (SN). Peripheral inflammation can transform the “primed” microglia into an “active” state, which can trigger stronger responses dealing with neurodegenerative processes. Numerous evidences show that systemic inflammatory processes exacerbate ongoing neurodegeneration in PD patient and animal models. Anti-inflammatory treatment in PD patients exerts a neuroprotective effect. In the present paper, we analyse the effect of peripheral infections in the etiology and progression in PD patients and animal models, suggesting that these peripheral immune challenges can exacerbate the symptoms in the disease. PMID:21403862

  15. Initiation of Parkinson's disease treatment.

    Science.gov (United States)

    Reichmann, Heinz

    2008-09-01

    Parkinson therapy should be commenced as soon as patients feel impaired by motor or other symptoms. Recently it has been stated, however, to start treatment immediately after the diagnosis of PD has been made, in order to offer some neuroprotection to active dopaminergic neurons and to prevent deleterious compensatory mechanisms in dopaminergic cells. The selection of the medication depends on the state of the disease, the clinical symptoms, concomitant diseases and age. In de novo patients, most guidelines, including those of the German Neurological Society, advocate to start with a dopamine agonist. In my opinion, initial treatment with a MAO-B-inhibitor and subsequent combination with a long-acting dopamine agonist may be even more promising with regard to neuroprotection, modification of the disease, avoidance of dyskinesia and good motor improvement.

  16. Excessive daytime sleepiness in patients with Parkinson's disease.

    Science.gov (United States)

    Knie, Bettina; Mitra, M Tanya; Logishetty, Kartik; Chaudhuri, K Ray

    2011-03-01

    Excessive daytime sleepiness (EDS) is described as inappropriate and undesirable sleepiness during waking hours and is a common non-motor symptom in Parkinson's disease, affecting up to 50% of patients. EDS has a large impact on the quality of life of Parkinson's disease patients as well as of their caregivers, in some cases even more than the motor symptoms of the disease. Drug-induced EDS is a particular problem as many dopamine agonists used for the treatment of Parkinson's disease have EDS as an adverse effect. Dopaminergic treatment may also render a subset of Parkinson's disease patients at risk for sudden-onset sleep attacks that occur without warning and can be particularly hazardous if the patient is driving. This demonstrates the need for early recognition and management not only to increase health-related quality of life but also to ensure patient safety. There are many assessment tools for EDS, including the Epworth Sleepiness Scale (ESS) and the Multiple Sleep Latency Test (MSLT), although only the Parkinson's Disease Sleep Scale (PDSS) and the SCales for Outcomes in PArkinson's Disease-Sleep (SCOPA-S) are specifically validated for Parkinson's disease. Polysomnography can be used when necessary. Management comprises non-pharmacological and pharmacological approaches. Non-pharmacological approaches can be the mainstay of treatment for mild to moderate EDS. Advice on good sleep hygiene is instrumental, as pharmacological approaches have yet to provide consistent and reliable results without significant adverse effects. The efficacy of pharmacological treatment of EDS in Parkinson's disease using wakefulness-promoting drugs such as modafinil remains controversial. Further areas of research are now also focusing on adenosine A(2A) receptor antagonists, sodium oxybate and caffeine to promote wakefulness. A definitive treatment for the highly prevalent drug-induced EDS has not yet been found.

  17. Advances in Biomarker Research in Parkinson's Disease.

    Science.gov (United States)

    Mehta, Shyamal H; Adler, Charles H

    2016-01-01

    Parkinson's disease (PD) is the second most common neurodegenerative disease, and the numbers are projected to double in the next two decades with the increase in the aging population. An important focus of current research is to develop interventions to slow the progression of the disease. However, prerequisites to it include the development of reliable biomarkers for early diagnosis which would identify at-risk groups and disease progression. In this review, we present updated evidence of already known clinical biomarkers (such as hyposmia and rapid eye movement (REM) sleep behavior disorder (RBD)) and neuroimaging biomarkers, as well as newer possible markers in the blood, CSF, and other tissues. While several promising candidates and methods to assess these biomarkers are on the horizon, it is becoming increasingly clear that no one candidate will clearly fulfill all the roles as a single biomarker. A multimodal and combinatorial approach to develop a battery of biomarkers will likely be necessary in the future.

  18. Free-water imaging in Parkinson's disease and atypical parkinsonism.

    Science.gov (United States)

    Planetta, Peggy J; Ofori, Edward; Pasternak, Ofer; Burciu, Roxana G; Shukla, Priyank; DeSimone, Jesse C; Okun, Michael S; McFarland, Nikolaus R; Vaillancourt, David E

    2016-02-01

    Conventional single tensor diffusion analysis models have provided mixed findings in the substantia nigra of Parkinson's disease, but recent work using a bi-tensor analysis model has shown more promising results. Using a bi-tensor model, free-water values were found to be increased in the posterior substantia nigra of Parkinson's disease compared with controls at a single site and in a multi-site cohort. Further, free-water increased longitudinally over 1 year in the posterior substantia nigra of Parkinson's disease. Here, we test the hypothesis that other parkinsonian disorders such as multiple system atrophy and progressive supranuclear palsy have elevated free-water in the substantia nigra. Equally important, however, is whether the bi-tensor diffusion model is able to detect alterations in other brain regions beyond the substantia nigra in Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy and to accurately distinguish between these diseases. Free-water and free-water-corrected fractional anisotropy maps were compared across 72 individuals in the basal ganglia, midbrain, thalamus, dentate nucleus, cerebellar peduncles, cerebellar vermis and lobules V and VI, and corpus callosum. Compared with controls, free-water was increased in the anterior and posterior substantia nigra of Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy. Despite no other changes in Parkinson's disease, we observed elevated free-water in all regions except the dentate nucleus, subthalamic nucleus, and corpus callosum of multiple system atrophy, and in all regions examined for progressive supranuclear palsy. Compared with controls, free-water-corrected fractional anisotropy values were increased for multiple system atrophy in the putamen and caudate, and increased for progressive supranuclear palsy in the putamen, caudate, thalamus, and vermis, and decreased in the superior cerebellar peduncle and corpus callosum. For all disease

  19. Pragmatic communication is impaired in Parkinson disease.

    Science.gov (United States)

    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 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.

  20. Blood biomarker for Parkinson disease: peptoids

    Science.gov (United States)

    Yazdani, Umar; Zaman, Sayed; Hynan, Linda S; Brown, L Steven; Dewey, Richard B; Karp, David; German, Dwight C

    2016-01-01

    Parkinson disease (PD) is the second most common neurodegenerative disease. Because dopaminergic neuronal loss begins years before motor symptoms appear, a biomarker for the early identification of the disease is critical for the study of putative neuroprotective therapies. Brain imaging of the nigrostriatal dopamine system has been used as a biomarker for early disease along with cerebrospinal fluid analysis of α-synuclein, but a less costly and relatively non-invasive biomarker would be optimal. We sought to identify an antibody biomarker in the blood of PD patients using a combinatorial peptoid library approach. We examined serum samples from 75 PD patients, 25 de novo PD patients, and 104 normal control subjects in the NINDS Parkinson’s Disease Biomarker Program. We identified a peptoid, PD2, which binds significantly higher levels of IgG3 antibody in PD versus control subjects (P<0.0001) and is 68% accurate in identifying PD. The PD2 peptoid is 84% accurate in identifying de novo PD. Also, IgG3 levels are significantly higher in PD versus control serum (P<0.001). Finally, PD2 levels are positively correlated with the United Parkinson’s Disease Rating Scale score (r = 0.457, P<0001), a marker of disease severity. The PD2 peptoid may be useful for the early-stage identification of PD, and serve as an indicator of disease severity. Additional studies are needed to validate this PD biomarker. PMID:27812535

  1. Biomarkers for dementia and mild cognitive impairment in Parkinson's disease.

    Science.gov (United States)

    Delgado-Alvarado, Manuel; Gago, Belén; Navalpotro-Gomez, Irene; Jiménez-Urbieta, Haritz; Rodriguez-Oroz, María C

    2016-06-01

    Cognitive decline is one of the most frequent and disabling nonmotor features of Parkinson's disease. Around 30% of patients with Parkinson's disease experience mild cognitive impairment, a well-established risk factor for the development of dementia. However, mild cognitive impairment in patients with Parkinson's disease is a heterogeneous entity that involves different types and extents of cognitive deficits. Because it is not currently known which type of mild cognitive impairment confers a higher risk of progression to dementia, it would be useful to define biomarkers that could identify these patients to better study disease progression and possible interventions. In this sense, the identification among patients with Parkinson's disease and mild cognitive impairment of biomarkers associated with dementia would allow the early detection of this process. This review summarizes studies from the past 25 years that have assessed the potential biomarkers of dementia and mild cognitive impairment in Parkinson's disease patients. Despite the potential importance, no biomarker has as yet been validated. However, features such as low levels of epidermal and insulin-like growth factors or uric acid in plasma/serum and of Aß in CSF, reduction of cerebral cholinergic innervation and metabolism measured by PET mainly in posterior areas, and hippocampal atrophy in MRI might be indicative of distinct deficits with a distinct risk of dementia in subgroups of patients. Longitudinal studies combining the existing techniques and new approaches are needed to identify patients at higher risk of dementia. © 2016 International Parkinson and Movement Disorder Society.

  2. Substantia nigra and Parkinson disease (image)

    Science.gov (United States)

    Parkinson disease is a slowly progressive disorder that affects movement, muscle control, and balance. Part of the disease process develops as cells are destroyed in certain parts of the brain stem, particularly the crescent-shaped cell ...

  3. Early Alzheimer's and Parkinson's Disease Pathology in Urban Children: Friend versus Foe Responses—It Is Time to Face the Evidence

    Science.gov (United States)

    Calderón-Garcidueñas, Lilian; Franco-Lira, Maricela; Mora-Tiscareño, Antonieta; Medina-Cortina, Humberto; Torres-Jardón, Ricardo; Kavanaugh, Michael

    2013-01-01

    Chronic exposure to particulate matter air pollution is known to cause inflammation leading to respiratory- and cardiovascular-related sickness and death. Mexico City Metropolitan Area children exhibit an early brain imbalance in genes involved in oxidative stress, inflammation, and innate and adaptive immune responses. Early dysregulated neuroinflammation, brain microvascular damage, production of potent vasoconstrictors, and perturbations in the integrity of the neurovascular unit likely contribute to progressive neurodegenerative processes. The accumulation of misfolded proteins coincides with the anatomical distribution observed in the early stages of both Alzheimer's and Parkinson's diseases. We contend misfolding of hyperphosphorylated tau (HPπ), alpha-synuclein, and beta-amyloid could represent a compensatory early protective response to the sustained systemic and brain inflammation. However, we favor the view that the chronic systemic and brain dysregulated inflammation and the diffuse vascular damage contribute to the establishment of neurodegenerative processes with childhood clinical manifestations. Friend turns Foe early; therefore, implementation of neuroprotective measures to ameliorate or stop the inflammatory and neurodegenerative processes is warranted in exposed children. Epidemiological, cognitive, structural, and functional neuroimaging and mechanistic studies into the association between air pollution exposures and the development of neuroinflammation and neurodegeneration in children are of pressing importance for public health. PMID:23509683

  4. [Nonpharmacological treatment procedures for Parkinson's disease].

    Science.gov (United States)

    Witt, K; Kalbe, E; Erasmi, R; Ebersbach, G

    2017-03-01

    Nonpharmacological treatment strategies in Parkinson' disease include heterogeneous treatment modalities, such as physiotherapy, occupational therapy, speech therapy, cognitive training and deep brain stimulation as well as noninvasive brain stimulation strategies. Even in the early stages of Parkinson's disease nonpharmacological interventions, such as active exercise therapy and speech therapy can be indicated taking the individual symptoms of a patient into account. Mild cognitive deficits are frequently detected in the course of the disease and progression of these disorders to dementia in the advanced stages of the disease is not uncommon. The starting point for a cognitive training, training strategy and training frequency is unknown and currently under investigation. Deep brain stimulation is an established treatment modality, which should be considered when motor fluctuations cannot be adequately controlled by pharmacological treatment. This therapeutic option depends on patient-specific needs and has to be managed by a multiprofessional team. Non-invasive neurostimulation techniques, such as transcranial magnetic stimulation and transcranial direct current stimulation are experimental tools and cannot currently be recommended for general use.

  5. Treatment of Advanced Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Sara Varanese

    2010-01-01

    Full Text Available Patients at late stage Parkinson's disease (PD develop several motor and nonmotor complications, which dramatically impair their quality of life. These complications include motor fluctuations, dyskinesia, unpredictable or absent response to medications, falls, dysautonomia, dementia, hallucinations, sleep disorders, depression, and psychosis. The therapeutic management should be driven by the attempt to create a balance between benefit and side effects of the pharmacological treatments available. Supportive care, including physical and rehabilitative interventions, speech therapy, occupational therapy, and nursing care, has a key role in the late stage of disease. In this review we discuss the several complications experienced by advance PD patients and their management. The importance of an integrative approach, including both pharmacological and supportive interventions, is emphasized.

  6. Dopamine Receptors and Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Shin Hisahara

    2011-01-01

    Full Text Available Parkinson's disease (PD is a progressive extrapyramidal motor disorder. Pathologically, this disease is characterized by the selective dopaminergic (DAergic neuronal degeneration in the substantia nigra. Correcting the DA deficiency in PD with levodopa (L-dopa significantly attenuates the motor symptoms; however, its effectiveness often declines, and L-dopa-related adverse effects emerge after long-term treatment. Nowadays, DA receptor agonists are useful medication even regarded as first choice to delay the starting of L-dopa therapy. In advanced stage of PD, they are also used as adjunct therapy together with L-dopa. DA receptor agonists act by stimulation of presynaptic and postsynaptic DA receptors. Despite the usefulness, they could be causative drugs for valvulopathy and nonmotor complication such as DA dysregulation syndrome (DDS. In this paper, physiological characteristics of DA receptor familyare discussed. We also discuss the validity, benefits, and specific adverse effects of pharmaceutical DA receptor agonist.

  7. Nuclear microscopy in Parkinson's disease

    Science.gov (United States)

    Watt, F.; Lee, T.; Thong, P. S. P.; Tang, S. M.

    1995-09-01

    Rats have been subjected to unilateral lesioning with the selective neurotoxin 6-OHDA in order to induce Parkinsonism. Analysis using the NUS Nuclear Microscope facility have shown that iron levels are raised by an average of 26% in the lesioned subtantia nigra region of the brain compared with the non-lesioned side. In addition the background tissue level of iron is also elevated by 31% in the lesioned side, indicating that there is a general increase in iron levels as a result of the lesioning. This result is consistent with the other observations that other diseases of the brain are frequently associated with altered iron levels (eg. progressive nuclear palsy, multiple system atrophy, Alzheimers disease, multiple sclerosis).

  8. Premotor Diagnosis of Parkinson's Disease.

    Science.gov (United States)

    Reichmann, Heinz

    2017-08-03

    Typical Parkinsonian symptoms consist of bradykinesia plus rigidity and/or resting tremor. Some time later postural instability occurs. Pre-motor symptoms such as hyposmia, constipation, REM sleep behavior disorder and depression may antecede these motor symptoms for years. It would be ideal, if we had a biomarker which would allow to predict who with one or two of these pre-motor symptoms will develop the movement disorder Parkinson's disease (PD). Thus, it is interesting to learn that biopsies of the submandibular gland or colon biopsies may be a means to predict PD, if there is a high amout of abnormally folded alpha-synuclein and phosphorylated alpha-synuclein. This would be of relevance if we would have available means to stop the propagation of abnormal alpha-synuclein which is otherwise one of the reasons of this spreading disease PD.

  9. Technology in Parkinson's disease: Challenges and opportunities.

    Science.gov (United States)

    Espay, Alberto J; Bonato, Paolo; Nahab, Fatta B; Maetzler, Walter; Dean, John M; Klucken, Jochen; Eskofier, Bjoern M; Merola, Aristide; Horak, Fay; Lang, Anthony E; Reilmann, Ralf; Giuffrida, Joe; Nieuwboer, Alice; Horne, Malcolm; Little, Max A; Litvan, Irene; Simuni, Tanya; Dorsey, E Ray; Burack, Michelle A; Kubota, Ken; Kamondi, Anita; Godinho, Catarina; Daneault, Jean-Francois; Mitsi, Georgia; Krinke, Lothar; Hausdorff, Jeffery M; Bloem, Bastiaan R; Papapetropoulos, Spyros

    2016-09-01

    The miniaturization, sophistication, proliferation, and accessibility of technologies are enabling the capture of more and previously inaccessible phenomena in Parkinson's disease (PD). However, more information has not translated into a greater understanding of disease complexity to satisfy diagnostic and therapeutic needs. Challenges include noncompatible technology platforms, the need for wide-scale and long-term deployment of sensor technology (among vulnerable elderly patients in particular), and the gap between the "big data" acquired with sensitive measurement technologies and their limited clinical application. Major opportunities could be realized if new technologies are developed as part of open-source and/or open-hardware platforms that enable multichannel data capture sensitive to the broad range of motor and nonmotor problems that characterize PD and are adaptable into self-adjusting, individualized treatment delivery systems. The International Parkinson and Movement Disorders Society Task Force on Technology is entrusted to convene engineers, clinicians, researchers, and patients to promote the development of integrated measurement and closed-loop therapeutic systems with high patient adherence that also serve to (1) encourage the adoption of clinico-pathophysiologic phenotyping and early detection of critical disease milestones, (2) enhance the tailoring of symptomatic therapy, (3) improve subgroup targeting of patients for future testing of disease-modifying treatments, and (4) identify objective biomarkers to improve the longitudinal tracking of impairments in clinical care and research. This article summarizes the work carried out by the task force toward identifying challenges and opportunities in the development of technologies with potential for improving the clinical management and the quality of life of individuals with PD. © 2016 International Parkinson and Movement Disorder Society.

  10. Non motor subtypes and Parkinson's disease.

    Science.gov (United States)

    Sauerbier, Anna; Jenner, Peter; Todorova, Antoniya; Chaudhuri, K Ray

    2016-01-01

    Non motor symptoms (NMS) represent a significant burden in Parkinson's disease (PD) with numerous studies highlighting the importance of NMS both in "pre-motor" phase of PD as well as throughout the course of disease. In part this has led the international Parkinson and Movement Disorder Society (IPMDS) task force to attempt a re-definition of PD incorporating NMS and not base the diagnosis solely on motor symptoms. While motor subtypes within PD have been recognized and researched, recent clinical and neurobiological research suggests the existence of discrete non motor subtypes in PD, particularly in untreated (drug naïve) and early PD patients. Several independent observers have reported specific "clusters of NMS dominant PD" using a data driven approach in early and untreated PD patients while others have reported on the burden of NMS in untreated PD and specific NMS dominant phenotypes in untreated or treated PD using observational case series based data. In this review we report on specific NMS dominant phenotypes of PD as described in the literature using clinical observational studies and address pathophysiological concepts. A proposal for several NMS subtypes are reported combining clinical reports with, where possible, evidence base supporting probable biomarkers.

  11. Vowel articulation in Parkinson's disease.

    Science.gov (United States)

    Skodda, Sabine; Visser, Wenke; Schlegel, Uwe

    2011-07-01

    The aim of the study was to analyze vowel articulation in Parkinson's disease (PD) speakers suffering from mild hypokinetic dysarthria as compared with healthy controls in correlation to net speech rate (NSR) and intonation variability (F(0)SD). Furthermore, we intended to reveal possible correlations among vowel articulation, global motor performance, and stage of disease. We examined 68 PD patients (34 male) with mild dysarthria (1 point according to the "speech" item 18 of the Unified Parkinson's Disease Rating Scale/UPDRS-III) and 32 age-matched control persons (16 male) using a reading task with subsequent acoustical analysis. F1 and F2 frequency values of the vowels /a/, /i/, and /u/ were extracted from defined words within the text. Description of vowel articulation was based on measures of triangular vowel space area (tVSA) and Vowel Articulation Index (VAI). PD patients were scored according to UPDRS-III and Hoehn and Yahr stages. VAI values were significantly reduced in male and female PD patients as compared with the accordant control group, whereas tVSA was only reduced in the male PD speakers. NSR was negatively correlated to tVSA and VAI only in female PD speakers. No correlations were seen between vowel articulation and UPDRS-III and stage of disease. VAI seem to be superior to tVSA in the description of impaired vowel articulation in PD. Reduced VAI could be detected in male and female parkinsonian speakers suffering only from mild dysarthria with preserved speech intelligibility and therefore might be applicable to identify subclinical changes of vowel articulation. Moreover, some aspects of altered speech performance in PD seem to feature some gender-specific patterns, which justify further investigation. Copyright © 2011 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

  12. Changes in neural circuitry associated with depression at pre-clinical, pre-motor and early motor phases of Parkinson's disease.

    Science.gov (United States)

    Borgonovo, Janina; Allende-Castro, Camilo; Laliena, Almudena; Guerrero, Néstor; Silva, Hernán; Concha, Miguel L

    2017-02-01

    Although Parkinson's Disease (PD) is mostly considered a motor disorder, it can present at early stages as a non-motor pathology. Among the non-motor clinical manifestations, depression shows a high prevalence and can be one of the first clinical signs to appear, even a decade before the onset of motor symptoms. Here, we review the evidence of early dysfunction in neural circuitry associated with depression in the context of PD, focusing on pre-clinical, pre-motor and early motor phases of the disease. In the pre-clinical phase, structural and functional changes in the substantia nigra, basal ganglia and limbic structures are already observed. Some of these changes are linked to motor compensation mechanisms while others correspond to pathological processes common to PD and depression and thus could underlie the appearance of depressive symptoms during the pre-motor phase. Studies of the early motor phase (less than five years post diagnosis) reveal an association between the extent of damage in different monoaminergic systems and the appearance of emotional disorders. We propose that the limbic loop of the basal ganglia and the lateral habenula play key roles in the early genesis of depression in PD. Alterations in the neural circuitry linked with emotional control might be sensitive markers of the ongoing neurodegenerative process and thus may serve to facilitate an early diagnosis of this disease. To take advantage of this, we need to improve the clinical criteria and develop biomarkers to identify depression, which could be used to determine individuals at risk to develop PD.

  13. Ophthalmologic Baseline Characteristics and 2-Year Ophthalmologic Safety Profile of Pramipexole IR Compared with Ropinirole IR in Patients with Early Parkinson's Disease

    Science.gov (United States)

    Jennings, Danna; Borchert, Leona; Canale, Lee; Fagan, Nora

    2016-01-01

    Background. Parkinson's disease (PD) progressively affects dopaminergic neurotransmission and may affect retinal dopaminergic functions and structures. Objective. This 2-year randomized, open-label, parallel-group, flexible-dose study, NCT00144300, evaluated ophthalmologic safety profiles of immediate-release (IR) pramipexole and ropinirole in patients with early idiopathic PD with ≤6 months' prior dopamine agonist exposure and without preexisting major eye disorders. Methods. Patients received labeled IR regimens of pramipexole (n = 121) or ropinirole (n = 125) for 2 years. Comprehensive ophthalmologic assessments (COA) included corrected acuity, Roth 28-color test, slit-lamp biomicroscopy, intraocular pressure, computerized visual field test, fundus photography, and electroretinography. Results. At baseline, we observed retinal pigmentary epithelium (RPE) hypopigmentation not previously reported in PD patients. The estimated relative risk of 2-year COA worsening with pramipexole versus ropinirole was 1.07 (95% CI: 0.71–1.60). Mean changes from baseline in Unified Parkinson's Disease Rating System parts II+III total scores (pramipexole: 1 year, −4.1 ± 8.9, and 2 years, −0.7 ± 10.1, and ropinirole: 1 year, −3.7 ± 8.2, and 2 years, −1.7 ± 10.5) and Hoehn–Yahr stage distribution showed therapeutic effects on PD symptoms. Safety profiles were consistent with labeling. Conclusions. The risk of retinal deterioration did not differ in early idiopathic PD patients receiving pramipexole versus ropinirole. RPE hypopigmentation at baseline was not previously reported in this population. This trial is registered with NCT00144300. PMID:28078162

  14. Mutational analysis of TARDBP in Parkinson's disease

    NARCIS (Netherlands)

    Blitterswijk, M. van; Es, M.A. van; Verbaan, D.; Hilten, J.J. van; Scheffer, H.; Warrenburg, B.P.C. van de; Veldink, J.H.; Berg, L.H. van den

    2013-01-01

    Mutations in TAR DNA-binding protein (TARDBP) are associated with heterogenic phenotypes, including amyotrophic lateral sclerosis, frontotemporal dementia, and Parkinson's disease. In this study, we investigated the presence of TARDBP mutations in a cohort of 429 Dutch patients with Parkinson's dise

  15. Corneal nerve microstructure in Parkinson's disease.

    Science.gov (United States)

    Misra, Stuti L; Kersten, Hannah M; Roxburgh, Richard H; Danesh-Meyer, Helen V; McGhee, Charles N J

    2017-03-03

    Ocular surface changes and blink abnormalities are well-established in Parkinson's disease. Blink rate may be influenced by corneal sub-basal nerve density, however, this relationship has not yet been investigated in Parkinson's disease. This case-control study examined the ocular surface in patients with moderately severe Parkinson's disease, including confocal microscopy of the cornea. Fifteen patients with moderately severe Parkinson's disease (modified Hoehn and Yahr grade 3 or 4) and fifteen control participants were recruited. Ophthalmic assessment included slit-lamp examination, blink rate assessment, central corneal aesthesiometry and in vivo corneal confocal microscopy. The effect of disease laterality was also investigated. Of the 15 patients with Parkinson's disease, ten were male and the mean age was 65.5±8.6years. The corneal sub-basal nerve plexus density was markedly reduced in patients with Parkinson's disease (7.56±2.4mm/mm(2)) compared with controls (15.91±2.6mm/mm(2)) (pParkinson's disease (0.79±1.2mBAR) and the control group (0.26±0.35mBAR), p=0.12. Sub-basal nerve density was not significantly different between the eye ipsilateral to the side of the body with most-severe motor symptoms, and the contralateral eye. There was a significant positive correlation between ACE-R scores and sub-basal corneal nerve density (R(2)=0.66, p=0.02). This is the first study to report a significant reduction in corneal sub-basal nerve density in Parkinson's disease and demonstrate an association with cognitive dysfunction. These results provide further evidence to support the involvement of the peripheral nervous system in Parkinson's disease, previously thought to be a central nervous system disorder.

  16. Increased intracranial volume in Parkinson's disease

    DEFF Research Database (Denmark)

    Krabbe, Katja; Karlsborg, Merete; Hansen, Andreas

    2005-01-01

    BACKGROUND: Parkinson's disease (PD) and multiple system atrophy (MSA) are neurodegenerative diseases that can be difficult to diagnose and distinguish from each other. STUDY AIMS AND METHODS: Patients with PD and MSA and controls were studied with magnetic resonance imaging (MRI) using tissue...... segmentation and outlining of regions in order to identify regional volume changes that might be useful in the diagnosis of the two diseases. RESULTS: Patients with PD had significantly larger intracranial volumes (ICVs) and significantly smaller putaminal and sustantia nigra volumes than controls. MSA...... or compensatory responses to early CNS damage. Atrophy of the amygdala in MSA patients has not been demonstrated with MR before. It might explain why these patients can have hyposmia. The putaminal atrophy found in the PD group may be a trait of the later stages of PD. Segmentation of the substantia nigra can...

  17. Perioperative management of patients with Parkinson's disease.

    Science.gov (United States)

    Katus, Linn; Shtilbans, Alexander

    2014-04-01

    Parkinson's disease is the second most common neurodegenerative disease worldwide, leading to a wide range of disability and medical complications. Managing patients with Parkinson's disease in the perioperative hospital setting can be particularly challenging. Suboptimal management can lead to medical complications, prolonged hospital stays, and delayed recovery. This review aims to address the most important issues related to caring for patients with Parkinson's disease perioperatively who are undergoing emergent or planned general surgery. It also intends to help hospitalists, internists, and other health care providers mitigate potential in-hospital morbidity and prevent prolonged recovery. Challenges in managing patients with Parkinson's disease in the perioperative hospital setting include disruption of medication schedules, "nothing by mouth" status, reduced mobility, and medication interactions and their side effects. Patients with Parkinson's disease are more prone to immobility and developing dysphagia, respiratory dysfunction, urinary retention, and psychiatric symptoms. These issues lead to higher rates of pneumonia, urinary tract infections, deconditioning, and falls compared with patients without Parkinson's disease, as well as prolonged hospital stays and a greater need for post-hospitalization rehabilitation. Steps can be taken to decrease these complications, including minimizing nothing by mouth status duration, using alternative routes of drugs administration when unable to give medications orally, avoiding drug interactions and medications that can worsen parkinsonism, assessing swallowing ability frequently, encouraging incentive spirometry, performing bladder scans, avoiding Foley catheters, and providing aggressive physical therapy. Knowing and anticipating these potential complications allow hospital physicians to mitigate nosocomial morbidity and shorten recovery times and hospital stays.

  18. Thiazolidinediones and Parkinson Disease: A Cohort Study.

    Science.gov (United States)

    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.

  19. Neuropsychiatric Manifestations of Parkinson`s Disease

    Directory of Open Access Journals (Sweden)

    Ana Peixinho

    2014-10-01

    Full Text Available Parkinson’s disease affects about 1% of the world population older than 65 years. It’s most frequently considered a movement disorder, but the neuropsychiatric manifestations associated with the disease and/or its treatment may be of equal or greater significance in some patients. We will discuss briefly the epidemiology, physiopathology and diagnosis of Parkinson’s disease, highlighting the neuropsychiatric manifestations: depression, anxiety, psychosis, dementia, sleep disorders, dopamine dysregulation syndrome.

  20. Neuropsychiatric Manifestations of Parkinson`s Disease

    OpenAIRE

    Peixinho, Ana; De Azevedo, Ana Luísa; Simões, Rita Moiron

    2006-01-01

    Parkinson’s disease affects about 1% of the world population older than 65 years. It’s most frequently considered a movement disorder, but the neuropsychiatric manifestations associated with the disease and/or its treatment may be of equal or greater significance in some patients. We will discuss briefly the epidemiology, physiopathology and diagnosis of Parkinson’s disease, highlighting the neuropsychiatric manifestations: depression, anxiety, psychosis, dementia, sleep disorders, dopamine d...

  1. Electroconvulsive Therapy Intervention for Parkinson's Disease.

    Science.gov (United States)

    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.

  2. Mitochondrial dysfunctions in Parkinson's disease.

    Science.gov (United States)

    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

  3. Reduced early visual emotion discrimination as an index of diminished emotion processing in Parkinson's disease? - Evidence from event-related brain potentials.

    Science.gov (United States)

    Wieser, Matthias J; Klupp, Elisabeth; Weyers, Peter; Pauli, Paul; Weise, David; Zeller, Daniel; Classen, Joseph; Mühlberger, Andreas

    2012-10-01

    Although Parkinson's disease (PD) is defined by its motor symptoms, it is now well recognized that cognitive and affective domains, such as recognition of emotion from facial expressions, may also be impaired. To examine brain mechanisms involved in processing of emotion recognition from facial expressions, we obtained affective ratings and visual event-related potentials (ERPs) in response to facial expressions from 18 PD patients under dopamine-replacement therapy, and 17 healthy age- and sex-matched controls. In control subjects, the early posterior negativity (EPN) of the ERP, which is thought to reflect early perceptual emotion discrimination, was larger in response to emotional compared to neutral facial expressions. In contrast, this emotional modulation of the EPN was absent in PD patients indicating impaired early emotion discrimination. Behaviorally, PD patients showed no impairments in emotion recognition as measured by affective ratings. These findings suggest that facial emotion processing may be disrupted at an early stage of visual neural processing in PD. Absence of behavioral impairment may point to compensatory strategies of emotion recognition in medicated PD patients. Further research should clarify these dissociations between behavioral and neurophysiological levels of emotion processing in PD. Copyright © 2011 Elsevier Srl. All rights reserved.

  4. Neurovestibular analysis and falls in Parkinson's disease and atypical parkinsonism

    NARCIS (Netherlands)

    Venhovens, J.; Meulstee, J.; Bloem, B.R.; Verhagen, W.I.

    2016-01-01

    The primary aim of our study was to determine the extent of vestibular dysfunction in patients with Parkinson's disease (PD). Our secondary aim was to determine if vestibular dysfunction in PD is a risk factor for falling. The tertiary aim was to determine both the extent of vestibular dysfunction a

  5. Biomarkers in Parkinson's disease: a funder's perspective.

    Science.gov (United States)

    Frasier, Mark; Chowdhury, Sohini; Eberling, Jamie; Sherer, Todd

    2010-10-01

    Therapeutic development in Parkinson's disease is hampered by the paucity of well-validated biomarkers that can assist with diagnosis and/or tracking the progression of the disease. Since its inception, the Michael J Fox Foundation for Parkinson's Research has invested heavily in biomarker research and continues to prioritize discovery and development efforts. This article summarizes the history and evolution of the Michael J Fox Foundation's role in supporting biomarker research and lays out the current challenges in successfully developing markers that can be used to test therapies, while also providing a vision of future funding efforts in Parkinson's disease biomarkers.

  6. Emotion recognition in early Parkinson's disease patients undergoing deep brain stimulation or dopaminergic therapy: a comparison to healthy participants

    Directory of Open Access Journals (Sweden)

    Lindsey G. McIntosh

    2015-01-01

    Full Text Available Parkinson’s disease (PD is traditionally regarded as a neurodegenerative movement disorder, however, nigrostriatal dopaminergic degeneration is also thought to disrupt non-motor loops connecting basal ganglia to areas in frontal cortex involved in cognition and emotion processing. PD patients are impaired on tests of emotion recognition, but it is difficult to disentangle this deficit from the more general cognitive dysfunction that frequently accompanies disease progression. Testing for emotion recognition deficits early in the disease course, prior to cognitive decline, better assesses the sensitivity of these non-motor corticobasal ganglia-thalamocortical loops involved in emotion processing to early degenerative change in basal ganglia circuits. In addition, contrasting this with a group of healthy aging individuals demonstrates changes in emotion processing specific to the degeneration of basal ganglia circuitry in PD. Early PD patients (EPD were recruited from a randomized clinical trial testing the safety and tolerability of deep brain stimulation of the subthalamic nucleus (STN-DBS in early-staged PD. EPD patients were previously randomized to receive optimal drug therapy only (ODT, or drug therapy plus STN-DBS (ODT+DBS. Matched healthy elderly controls (HEC and young controls (HYC also participated in this study. Participants completed two control tasks and three emotion recognition tests that varied in stimulus domain. EPD patients were impaired on all emotion recognition tasks compared to HEC. Neither therapy type (ODT or ODT+DBS nor therapy state (ON/OFF altered emotion recognition performance in this study. Finally, HEC were impaired on vocal emotion recognition relative to HYC, suggesting a decline related to healthy aging. This study supports the existence of impaired emotion recognition early in the PD course, implicating an early disruption of fronto-striatal loops mediating emotional function.

  7. Bipolar disorder, a precursor of Parkinson's disease?

    Directory of Open Access Journals (Sweden)

    Tânia M.S. Novaretti

    Full Text Available ABSTRACT Parkinson's disease is a neurodegenerative disorder predominantly resulting from dopamine depletion in the substantia nigra pars compacta. Some psychiatric disorders may have dopaminergic dysfunction as their substrate. We describe a well-documented case of Parkinson's disease associated with Bipolar Disorder. Although there is some knowledge about the association between these diseases, little is known about its pathophysiology and correlation. We believe that among various hypotheses, many neurotransmitters are linked to this pathophysiology.

  8. [Diet therapy in Parkinson disease].

    Science.gov (United States)

    Vilming, S T

    1995-04-20

    The significance of restrictions on protein for patients with Parkinson's disease is reviewed. Large neutral amino acids and levodopa share the same saturated carrier system through the blood-brain-barrier. Fluctuating patients are sensitive to a decreased supply of levodopa from the blood, and clinical studies show that an increased concentration of large neutral amino acids in the blood decreases mobility and reduces "on-time". A reduction of protein intake to 0.75-0.8 g/kg body weight/day has been recommended. A protein redistribution diet implying that less than 10% of the daily protein is taken in daytime and the rest in the evening, gives best results. However, in the elderly, protein restrictions may lead to a lasting negative nitrogen balance, and even in younger patients the supply of certain minerals and vitamins may become too low or marginally adequate. The diet must therefore be used with caution.

  9. Mitochondrial Dysfunction in Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    P. C. Keane

    2011-01-01

    Full Text Available Parkinson's disease (PD is a progressive, neurodegenerative condition that has increasingly been linked with mitochondrial dysfunction and inhibition of the electron transport chain. This inhibition leads to the generation of reactive oxygen species and depletion of cellular energy levels, which can consequently cause cellular damage and death mediated by oxidative stress and excitotoxicity. A number of genes that have been shown to have links with inherited forms of PD encode mitochondrial proteins or proteins implicated in mitochondrial dysfunction, supporting the central involvement of mitochondria in PD. This involvement is corroborated by reports that environmental toxins that inhibit the mitochondrial respiratory chain have been shown to be associated with PD. This paper aims to illustrate the considerable body of evidence linking mitochondrial dysfunction with neuronal cell death in the substantia nigra pars compacta (SNpc of PD patients and to highlight the important need for further research in this area.

  10. Biomarkers of cognitive decline in Parkinson's disease.

    Science.gov (United States)

    Lin, Chin-Hsien; Wu, Ruey-Meei

    2015-05-01

    Cognitive impairment is a frequent and devastating non-motor symptom of Parkinson's disease (PD). Impaired cognition has a major impact on either quality of life or mortality in patients with PD. Notably, the rate of cognitive decline and pattern of early cognitive deficits in PD are highly variable between individuals. Given that the underlying mechanisms of cognitive decline or dementia associated with PD remain unclear, there is currently no mechanism-based treatment available. Identification of biological markers, including neuroimaging, biofluids and common genetic variants, that account for the heterogeneity of PD related cognitive decline could provide important insights into the pathological processes that underlie cognitive impairment in PD. These combined biomarker approaches will enable early diagnosis and provide indicators of cognitive progression in PD patients. This review summarizes recent advances in the development of biomarkers for cognitive impairments in PD.

  11. Management of psychosis in Parkinson's disease.

    Science.gov (United States)

    Wolters, E C; Berendse, H W

    2001-08-01

    Psychosis is quite common in Parkinson's disease (approximately 25% of patients) and therefore constitutes a serious public health problem. All patients suffering from idiopathic Parkinson's disease, and especially elderly and demented patients, are at risk of developing delusions or hallucinations. The most prominent psychotogenic factors are dopaminomimetic agents, which may induce dopamine hypersensitivity in the frontal and limbic dopamine projection regions, and consequently, either directly or indirectly, elicit psychotic signs and symptoms. A Parkinson's disease-related cholinergic deficit in combination with an age-related further loss of cholinergic integrity also plays a prominent role. Psychosis in Parkinson's disease patients appears to be a more important contributor to caregiver distress than motor parkinsonism. Psychosis therefore probably represents the single greatest risk factor for nursing home placement. Typical antipsychotic drugs, because of their selective dopamine receptor antagonistic effects, can reduce psychotic signs but at the cost of an increase in parkinsonism. As a consequence of a non-selective antagonism at both serotonergic and dopaminergic receptors, atypical antipsychotic drugs are associated with fewer extrapyramidal side-effects. On the other hand, hypersensitivity to these agents may induce delirium or a malignant neuroleptic syndrome. Atypical antipsychotic agents such as clozapine, quetiapine and olanzapine should therefore be started at very low doses that are increased gradually. Cholinomimetic therapy may prove to be helpful in the prevention and treatment of psychotic manifestations in Parkinson's disease patients, given the effects observed in patients suffering from dementia with Lewy bodies.

  12. Is PIGD a legitimate motor subtype in Parkinson disease?

    Science.gov (United States)

    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.

  13. Mild cognitive impairment in Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Shu-hua LI

    2016-06-01

    Full Text Available Cognitive dysfunction is common non-motor symptom (NMS in Parkinson's disease (PD, which affects the patients' quality of life and increases the burden of caregivers. Cognitive dysfunction in PD can be mild cognitive impairment (MCI or dementia. MCI presents in the early stage of PD and the incidence rate is increasing with the disease progression. In some cases it can advance to dementia. The diagnosis of MCI in PD includes inclusion criteria, exclusion criteria and damage level evaluation. Non-pharmacological therapy, such as exercise and cognitive behavior therapy (CBT can improve the symptoms of MCI in PD, while the pharmacological treatment remains to be further studied. DOI: 10.3969/j.issn.1672-6731.2016.06.002

  14. Diagnosis of Parkinson's disease Using Tabu Search Algorithm

    Directory of Open Access Journals (Sweden)

    Amin Einipour

    2016-05-01

    Full Text Available Parkinson's disease is the second most common disease of the brain and nerves. The diseas is a progressive disease meaning that over time it becomes more difficult to treat. Although so far no definitive treatment for this disease but there are good drugs which if the condition is diagnosed early can help improve the lives of people affected. In recent years provided computer methods as medical decision support systems for fast and low-cost detection of the disease which uses speech disorders and accurate and fast analysis to be diagnosed Parkinson's disease early in the disease course. The purpose of this paper is development of a decision support system for the detection of Parkinson's disease. In the proposed system, relevant knowledge is the most important part of it. To obtain such knowledge, Tabu Search algorithm to be used. Tabu Search is able to search in a large space data of course, this search is also associated with a certain intelligence. Results on Parkinson's disease data set from UCI machine learning repository show that the proposed approach would be capable of diagnosis with high accuracy.

  15. Parkinson's disease between internal medicine and neurology.

    Science.gov (United States)

    Csoti, Ilona; Jost, Wolfgang H; Reichmann, Heinz

    2016-01-01

    General medical problems and complications have a major impact on the quality of life in all stages of Parkinson's disease. To introduce an effective treatment, a comprehensive analysis of the various clinical symptoms must be undertaken. One must distinguish between (1) diseases which arise independently of Parkinson's disease, and (2) diseases which are a direct or indirect consequence of Parkinson's disease. Medical comorbidity may induce additional limitations to physical strength and coping strategies, and may thus restrict the efficacy of the physical therapy which is essential for treating hypokinetic-rigid symptoms. In selecting the appropriate medication for the treatment of any additional medical symptoms, which may arise, its limitations, contraindications and interactions with dopaminergic substances have to be taken into consideration. General medical symptoms and organ manifestations may also arise as a direct consequence of the autonomic dysfunction associated with Parkinson's disease. As the disease progresses, additional non-parkinsonian symptoms can be of concern. Furthermore, the side effects of Parkinson medications may necessitate the involvement of other medical specialists. In this review, we will discuss the various general medical aspects of Parkinson's disease.

  16. Parkinson's Disease: The Mitochondria-Iron Link.

    Science.gov (United States)

    Muñoz, Yorka; Carrasco, Carlos M; Campos, Joaquín D; Aguirre, Pabla; Núñez, Marco T

    2016-01-01

    Mitochondrial dysfunction, iron accumulation, and oxidative damage are conditions often found in damaged brain areas of Parkinson's disease. We propose that a causal link exists between these three events. Mitochondrial dysfunction results not only in increased reactive oxygen species production but also in decreased iron-sulfur cluster synthesis and unorthodox activation of Iron Regulatory Protein 1 (IRP1), a key regulator of cell iron homeostasis. In turn, IRP1 activation results in iron accumulation and hydroxyl radical-mediated damage. These three occurrences-mitochondrial dysfunction, iron accumulation, and oxidative damage-generate a positive feedback loop of increased iron accumulation and oxidative stress. Here, we review the evidence that points to a link between mitochondrial dysfunction and iron accumulation as early events in the development of sporadic and genetic cases of Parkinson's disease. Finally, an attempt is done to contextualize the possible relationship between mitochondria dysfunction and iron dyshomeostasis. Based on published evidence, we propose that iron chelation-by decreasing iron-associated oxidative damage and by inducing cell survival and cell-rescue pathways-is a viable therapy for retarding this cycle.

  17. 帕金森病早期诊断的生物学标志物%Biomarkers in the early diagnosis of Parkinson's disease

    Institute of Scientific and Technical Information of China (English)

    孙倩; 陈伟; 陈生弟

    2013-01-01

    帕金森病是一种慢性进行性中枢神经系统退行性疾病.早在临床前期尚未出现典型临床症状时,帕金森病患者即已出现神经系统退行性病变.因此,如果能在退行性病变早期及时明确诊断并予以治疗,将会减缓疾病进程,提高患者生活质量.虽然目前尚未发现早期诊断帕金森病的理想标志物,但是已有许多生物学标志物具有研究和应用前景.%Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder.It has become clear that PD can have a preclinical phase,a period during which neurodegeneration has already begun years before the onset of typical motor symptoms.Consequently,if the early neurodegeneration in PD can be timely diagnosed,it will significantly slow down the progression of the disease and improve the quality of life.To date,there is no fully reliable and validated biomarker for the early diagnosis of PD,but some promising biomarker candidates exist.

  18. Predictors of future falls in Parkinson disease.

    Science.gov (United States)

    Kerr, G K; Worringham, C J; Cole, M H; Lacherez, P F; Wood, J M; Silburn, P A

    2010-07-13

    Falls are a major health and injury problem for people with Parkinson disease (PD). Despite the severe consequences of falls, a major unresolved issue is the identification of factors that predict the risk of falls in individual patients with PD. The primary aim of this study was to prospectively determine an optimal combination of functional and disease-specific tests to predict falls in individuals with PD. A total of 101 people with early-stage PD undertook a battery of neurologic and functional tests in their optimally medicated state. The tests included Tinetti, Berg, Timed Up and Go, Functional Reach, and the Physiological Profile Assessment of Falls Risk; the latter assessment includes physiologic tests of visual function, proprioception, strength, cutaneous sensitivity, reaction time, and postural sway. Falls were recorded prospectively over 6 months. Forty-eight percent of participants reported a fall and 24% more than 1 fall. In the multivariate model, a combination of the Unified Parkinson's Disease Rating Scale (UPDRS) total score, total freezing of gait score, occurrence of symptomatic postural orthostasis, Tinetti total score, and extent of postural sway in the anterior-posterior direction produced the best sensitivity (78%) and specificity (84%) for predicting falls. From the UPDRS items, only the rapid alternating task category was an independent predictor of falls. Reduced peripheral sensation and knee extension strength in fallers contributed to increased postural instability. Falls are a significant problem in optimally medicated early-stage PD. A combination of both disease-specific and balance- and mobility-related measures can accurately predict falls in individuals with PD.

  19. Mitochondrial DNA analysis in Parkinson's disease.

    Science.gov (United States)

    Schapira, A H; Holt, I J; Sweeney, M; Harding, A E; Jenner, P; Marsden, C D

    1990-01-01

    The reduced form of nicotinamide adenine dinucleotide coenzyme Q reductase (complex I) activity has recently been shown to be deficient in the substantia nigra of patients dying with Parkinson's disease. This biochemical defect is identical to that produced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which also produces parkinsonism in humans. Complex I comprises 25 polypeptides, seven of which are encoded by mitochondrial DNA. Restriction fragment analysis of substantia nigra DNA from six patients with Parkinson's disease did not show any major deletion. In two cases, there were different novel polymorphisms that were not observed in control brain (n = 6) or blood (n = 34) samples.

  20. Community walking in people with Parkinson's disease.

    Science.gov (United States)

    Lamont, Robyn M; Morris, Meg E; Woollacott, Marjorie H; Brauer, Sandra G

    2012-01-01

    People with Parkinson's disease often have walking difficulty, and this is likely to be exacerbated while walking in places in the community, where people are likely to face greater and more varied challenges. This study aims to understand the facilitators and the barriers to walking in the community perceived by people with Parkinson's disease. This qualitative study involved 5 focus groups (n = 34) of people with Parkinson's disease and their partners residing in metropolitan and rural regions in Queensland, Australia. Results found that people with PD reported to use internal personal strategies as facilitators to community walking, but identified primarily external factors, particularly the environmental factors as barriers. The adoption of strategies or the use of facilitators allows people with Parkinson's disease to cope so that participants often did not report disability.

  1. Incidence, Risk and Prognosis of Parkinson Disease

    NARCIS (Netherlands)

    L.M.L. de Lau (Lonneke)

    2006-01-01

    textabstractParkinson disease (PD) is the second most common neurodegenerative disorder, and is clinically characterized by resting tremor, rigidity, bradykinesia and postural imbalance. These typical motor symptoms result from a selective degeneration of dopamine-producing neurons in the

  2. Epigenetic regulation in Parkinson's disease.

    Science.gov (United States)

    Labbé, Catherine; Lorenzo-Betancor, Oswaldo; Ross, Owen A

    2016-10-01

    Recent efforts have shed new light on the epigenetic mechanisms driving gene expression alterations associated with Parkinson's disease (PD) pathogenesis. Changes in gene expression are a well-established cause of PD, and epigenetic mechanisms likely play a pivotal role in regulation. Studies in families with PD harboring duplications and triplications of the SNCA gene have demonstrated that gene dosage is associated with increased expression of both SNCA mRNA and protein, and correlates with a fulminant disease course. Furthermore, it is postulated that even subtle changes in SNCA expression caused by common variation is associated with disease risk. Of note, genome-wide association studies have identified over 30 loci associated with PD with most signals located in non-coding regions of the genome, thus likely influencing transcript expression levels. In health, epigenetic mechanisms tightly regulate gene expression, turning genes on and off to balance homeostasis and this, in part, explains why two cells with the same DNA sequence will have different RNA expression profiles. Understanding this phenomenon will be crucial to our interpretation of the selective vulnerability observed in neurodegeneration and specifically dopaminergic neurons in the PD brain. In this review, we discuss epigenetic mechanisms, such as DNA methylation and histone modifications, involved in regulating the expression of genes relevant to PD, RNA-based mechanisms, as well as the effect of toxins and potential epigenetic-based treatments for PD.

  3. Chromosome 5 and Parkinson disease.

    Science.gov (United States)

    Foroud, Tatiana; Pankratz, Nathan; Martinez, Maria

    2006-10-01

    Parkinson disease (PD) is the second most common neurodegenerative disorder. Despite the identification of five causative genes, the majority of PD etiology is still unknown. A region on chromosome 5q is one of the few regions of the genome found linked in multiple studies of familial PD. Analyses were performed using genotypic data from two independent research studies to evaluate rigorously the evidence of linkage on chromosome 5. The combined sample consisting of 1238 affected individuals from 569 multiplex PD families were genotyped for a common set of 20 microsatellite markers spanning an 80 cM region on chromosome 5q. Two disease models were employed and model-free linkage analyses were performed to detect linkage to a PD susceptibility gene and also to detect linkage to a quantitative phenotype, age of onset of PD. There was little evidence of linkage using either a narrower or broader disease definition (lod <0.5). Analyses employing age of onset of PD as the phenotype produced a lod score of 1.8. These results in a very large sample of familial PD suggest that it is unlikely that a PD susceptibility gene is located on chromosome 5q. Evidence for a locus contributing to the age of onset of PD is modest at best (empirical P-value=0.07).

  4. Parkinson's disease: the spectrum of disabilities.

    OpenAIRE

    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....

  5. Genetic Identification Is Critical for the Diagnosis of Parkinsonism: A Chinese Pedigree with Early Onset of Parkinsonism.

    Directory of Open Access Journals (Sweden)

    Yang Yang

    Full Text Available A number of hereditary neurological diseases display indistinguishable features at the early disease stage. Parkinsonian symptoms can be found in numerous diseases, making it difficult to get a definitive early diagnosis of primary causes for patients with onset of parkinsonism. The accurate and early diagnosis of the causes of parkinsonian patients is important for effective treatments of these patients.We have identified a Chinese family (82 family members over four generations with 21 affected individuals that manifested the characterized symptoms of parkinsonism and was initially diagnosed as Parkinson's disease. We followed up with the family for two years, during which we carried out clinical observations, Positron Emission Tomography-Computed Tomography neuroimaging analysis, and exome sequencing to correctly diagnose the case.During the two-year follow-up period, we performed comprehensive medical history collection, physical examination, and structural and functional neuroimaging studies of this Chinese family. We found that the patient exhibited progressive deteriorated parkinsonism with Parkinson disease-like neuropathology and also had a good response to the initial levodopa treatment. However, exome sequencing identified a missense mutation, N279K, in exon 10 of MAPT gene, verifying that the early parkinsonian symptoms in this family are caused by the genetic mutation for hereditary frontotemporal lobar dementia.For the inherited parkinsonian patients who even show the neuropathology similar to that in Parkinson's disease and have initial response to levodopa treatment, genetic identification of the molecular basis for the disease is still required for defining the early diagnosis and correct treatment.

  6. Early Postnatal but Not Late Adult Neurogenesis Is Impaired in the Pitx3-Mutant Animal Model of Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Moritz D. Brandt

    2017-08-01

    Full Text Available The generation of new neurons in the adult dentate gyrus has functional implications for hippocampal formation. Reduced hippocampal neurogenesis has been described in various animal models of hippocampal dysfunction such as dementia and depression, which are both common non-motor-symptoms of Parkinson's disease (PD. As dopamine plays an important role in regulating precursor cell proliferation, the loss of dopaminergic neurons in the substantia nigra (SN in PD may be related to the reduced neurogenesis observed in the neurogenic regions of the adult brain: subventricular zone (SVZ and dentate gyrus (DG. Here we examined adult hippocampal neurogenesis in the Pitx3-mutant mouse model of PD (aphakia mice, which phenotypically shows a selective embryonic degeneration of dopamine neurons within the SN and to a smaller extent in the ventral tegmental area (VTA. Proliferating cells were labeled with BrdU in aphakia mice and healthy controls from 3 to 42 weeks of age. Three weeks old mutant mice showed an 18% reduction of proliferating cells in the DG and of 26% in the SVZ. Not only proliferation but also the number of new neurons was impaired in young aphakia mice resulting in 33% less newborn cells 4 weeks after BrdU-labeling. Remarkably, however, the decline in the number of proliferating cells in the neurogenic regions vanished in older animals (8–42 weeks indicating that aging masks the effect of dopamine depletion on adult neurogenesis. Region specific reduction in precursor cells proliferation correlated with the extent of dopaminergic degeneration in mesencephalic subregions (VTA and SN, which supports the theory of age- and region-dependent regulatory effects of dopaminergic projections. Physiological stimulation of adult neurogenesis by physical activity (wheel running almost doubled the number of proliferating cells in the dentate gyrus of 8 weeks old aphakia mice to a number comparable to that of wild-type mice, abolishing the slight

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

    Energy Technology Data Exchange (ETDEWEB)

    Rubinsztein, D.C.; Leggo, J.; Barton, D.E. [Cambridge Univ. (United Kingdom)] [and others

    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. 12 refs., 2 figs.

  8. Heterogenous mechanisms of mild cognitive impairment in Parkinson's disease.

    Science.gov (United States)

    Jellinger, Kurt

    2012-03-01

    Mild cognitive impairment in Parkinson disease (PD-MCI) shows heterogeneity in the clinical presentation, neuropsychology, neuroimaging, and neuropathology, suggesting abnormal metabolic network activities involving several cortical and subcortical systems. Prospective studies using specific biomarkers, including amyloid imaging and CSF biomarkers are important for the diagnosis and prognostic assessment of early cognitive deficits in PD patients.

  9. Obesity, diabetes, and risk of Parkinson's disease.

    Science.gov (United States)

    Palacios, Natalia; Gao, Xiang; McCullough, Marjorie L; Jacobs, Eric J; Patel, Alpa V; Mayo, Tinisha; Schwarzschild, Michael A; Ascherio, Alberto

    2011-10-01

    The aim of this work was to investigate whether obesity and diabetes are related to risk of Parkinson's disease. We prospectively followed 147,096 participants in the Cancer Prevention Study II Nutrition Cohort from 1992 to 2005. Participants provided information on anthropometric variables and medical history at baseline and on waist circumference in 1997. Incident cases of Parkinson's disease (n = 656) were confirmed by treating neurologists and medical record review. Relative risks were estimated using proportional hazards models, adjusting for age, gender, smoking, and other risk factors. Neither body mass index nor waist circumference significantly predicted Parkinson's disease risk. Relative risk comparing individuals with a baseline body mass index of ≥ 30 to those with a body mass index Parkinson's disease risk (combined relative risks = 0.88; 95% confidence interval: 0.62, 1.25; P heterogeneity = 0.96). In addition, neither body mass index at age 18 nor changes in weight between age 18 and baseline were significantly associated with Parkinson's disease risk. The results did not differ significantly by gender. Our results do not provide evidence for a relationship between body mass index, weight change, waist circumference, or baseline diabetes and risk of Parkinson's disease.

  10. Motivational modes and learning in Parkinson's disease.

    Science.gov (United States)

    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.

  11. Genetics of Parkinson disease and essential tremor.

    Science.gov (United States)

    Wider, Christian; Ross, Owen A; Wszolek, Zbigniew K

    2010-08-01

    Elucidating the genetic background of Parkinson disease and essential tremor is crucial to understand the pathogenesis and improve diagnostic and therapeutic strategies. A number of approaches have been applied including familial and association studies, and studies of gene expression profiles to identify genes involved in susceptibility to Parkinson disease. These studies have nominated a number of candidate Parkinson disease genes and novel loci including Omi/HtrA2, GIGYF2, FGF20, PDXK, EIF4G1 and PARK16. A recent notable finding has been the confirmation for the role of heterozygous mutations in glucocerebrosidase (GBA) as risk factors for Parkinson disease. Finally, association studies have nominated genetic variation in the leucine-rich repeat and Ig containing 1 gene (LINGO1) as a risk for both Parkinson disease and essential tremor, providing the first genetic evidence of a link between the two conditions. Although undoubtedly genes remain to be identified, considerable progress has been achieved in the understanding of the genetic basis of Parkinson disease. This same effort is now required for essential tremor. The use of next-generation high-throughput sequencing and genotyping technologies will help pave the way for future insight leading to advances in diagnosis, prevention and cure.

  12. Ventricular dilatation and brain atrophy in patients with Parkinson's disease with incipient dementia.

    Science.gov (United States)

    Camicioli, Richard; Sabino, Jennifer; Gee, Myrlene; Bouchard, Thomas; Fisher, Nancy; Hanstock, Chris; Emery, Derek; Martin, W R Wayne

    2011-07-01

    Age-related ventricular enlargement is accelerated in Alzheimer's disease, but its relationship to cognitive decline in Parkinson's disease is less clear, even though dementia is common in Parkinson's disease. Our goals were to determine if greater enlargement of the ventricles and gray or white matter atrophy occurred in Parkinson's disease patients developing cognitive decline. Older nondemented patients with Parkinson's disease (33) and age- and sex-matched controls (39) were recruited and prospectively assessed for the development of significant cognitive decline over 36 months. Magnetic resonance imaging was obtained every 18 months, and ventricular volume and total brain gray and white matter volumes were measured using reliable segmentation of T1-weighted volumetric scans. Subjects with incidental intracranial abnormalities, an atypical course, and stroke as well as dropouts were excluded from a cohort of 52 patients and 50 controls. Among 33 patients and 39 controls, 10 patients and 3 controls developed significant cognitive impairment or dementia. Ventricular change and Parkinson's disease status were significantly associated with dementia. Ventricular change was significantly correlated with change in Mini-Mental Status Examination in the Parkinson's disease with dementia group (r = 0.87, P = .001). Gray matter atrophy was greater in Parkinson's disease with dementia, with similar change over time in both Parkinson's disease and Parkinson's disease with dementia. White matter volumes were not significantly different between Parkinson's disease and Parkinson's disease with dementia; however, the decrease over time might be greater in Parkinson's disease with dementia. Ventricular dilatation occurs early in the course of significant cognitive decline in patients with Parkinson's disease, possibly reflecting both cortical gray and white matter loss.

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

    Science.gov (United States)

    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

  14. [Depression in Parkinson's disease. Assessment and treatment].

    Science.gov (United States)

    Brand, S; Dodel, R; Hautzinger, M; Gründer, G; Althaus, A; Schneider, F

    2007-06-01

    With a prevalence of 40%, depression is the most frequent psychiatric diagnosis in Parkinson's disease. Quality of life in Parkinson's patients is severely restricted. There is still no clear evidence concerning the link between these disorders - findings exist that indicate common neurodegenerative processes. At the same time depression seems to develop as a dysfunctional coping reaction to the motoric, emotional, and social restrictions of Parkinson's disease. The authors point out particular features of the depressive symptom profile in patients with Parkinson's disease and recommend a step-by-step approach to assessing depression: screening, assessment by means of the ICD-10 criteria, quantitative evaluation of depressivity, and assessment of suicidality. A survey of current treatment options is provided: pharmacological, somatic, and psychological approaches are introduced and evaluated with respect to effectiveness in this special group of patients.

  15. Imaging biomarkers in Parkinson's disease.

    Science.gov (United States)

    Brooks, David J; Pavese, Nicola

    2011-12-01

    Parkinson's disease (PD) is characterized by a progressive loss of nigrostriatal dopaminergic neurons associated with intracellular Lewy inclusion bodies. The result is poverty of movement, increased muscle rigidity, and tremor at rest and on posture. Midbrain/nigral structural abnormalities can be demonstrated in vivo with both transcranial sonography (TCS) and diffusion tensor magnetic resonance imaging (DTI) while positron emission tomography (PET) and single photon emission computed tomography (SPECT) ligands exist to demonstrate dopamine terminal dysfunction. These radiotracers are markers of dopamine storage capacity, vesicular monoamine and dopamine transporter availability. While loss of putamen dopaminergic function leads to motor disability, Lewy bodies not only target dopamine neurons but have also been observed in serotoninergic, noradrenergic, and cholinergic neurons. As a consequence, non-dopaminergic neurotransmission is also impaired resulting in non-motor symptoms including sleep disturbance, fatigue, depression, dementia, and autonomic dysfunction. PET and SPECT ligands exist to interrogate the function of monoaminergic and cholinergic neurons. Cortical and limbic Lewy body disease is seen in more advanced PD and this can be detected with FDG PET as abnormal covariance between levels of resting brain metabolism in these regions. Additionally, widespread microglial activation can be detected in PD with PET. This review discusses the role of structural and functional imaging for understanding parkinsonian syndromes and aiding in their diagnosis and management.

  16. Pulmonary function in Parkinson's disease.

    Science.gov (United States)

    Hovestadt, A; Bogaard, J M; Meerwaldt, J D; van der Meché, F G; Stigt, J

    1989-01-01

    Pulmonary function was investigated in 31 consecutive patients with relatively severe Parkinson's disease. Clinical disability was assessed by Hoehn and Yahr scale, Northwestern University Disability Scale and Websterscore. All patients were on levodopa substitution therapy and used anticholinergics. Pulmonary function was investigated by spirography, determination of a maximal inspiratory and expiratory flow-volume curve and, when possible, maximal static mouth pressures were determined. Peak inspiratory and expiratory flow, maximal expiratory flow at 50% and maximal static mouth pressures were significantly below normal values. Vital capacity, forced inspiratory volume in 1 s and the ratio of forced expiratory volume in 1 s and vital capacity were relatively normal. Nine patients had upper airway obstruction (UAO) as judged by abnormal values for peak inspiratory flow, the ratio of forced expiratory volume in 1 s and peak expiratory flow and the ratio of maximal expiratory and inspiratory flow at 50%. Flow-volume curves were normal in eight patients; four patients demonstrated flow decelerations and accelerations (type A) and 16 had a rounded off flow-volume curve (type B). Type A can be explained by UAO and type B by a combination of decreased effective muscle strength and possible UAO. Overall results of pulmonary function tests in patients without any clinical signs or symptoms of pulmonary disease point to subclinical upper airway obstruction and decreased effective muscle strength in a significant proportion of patients. PMID:2926415

  17. Pulmonary function in Parkinson's disease.

    Science.gov (United States)

    Hovestadt, A; Bogaard, J M; Meerwaldt, J D; van der Meché, F G; Stigt, J

    1989-03-01

    Pulmonary function was investigated in 31 consecutive patients with relatively severe Parkinson's disease. Clinical disability was assessed by Hoehn and Yahr scale, Northwestern University Disability Scale and Websterscore. All patients were on levodopa substitution therapy and used anticholinergics. Pulmonary function was investigated by spirography, determination of a maximal inspiratory and expiratory flow-volume curve and, when possible, maximal static mouth pressures were determined. Peak inspiratory and expiratory flow, maximal expiratory flow at 50% and maximal static mouth pressures were significantly below normal values. Vital capacity, forced inspiratory volume in 1 s and the ratio of forced expiratory volume in 1 s and vital capacity were relatively normal. Nine patients had upper airway obstruction (UAO) as judged by abnormal values for peak inspiratory flow, the ratio of forced expiratory volume in 1 s and peak expiratory flow and the ratio of maximal expiratory and inspiratory flow at 50%. Flow-volume curves were normal in eight patients; four patients demonstrated flow decelerations and accelerations (type A) and 16 had a rounded off flow-volume curve (type B). Type A can be explained by UAO and type B by a combination of decreased effective muscle strength and possible UAO. Overall results of pulmonary function tests in patients without any clinical signs or symptoms of pulmonary disease point to subclinical upper airway obstruction and decreased effective muscle strength in a significant proportion of patients.

  18. Current development of acupuncture research in Parkinson's disease.

    Science.gov (United States)

    Zeng, Bai-Yun; Salvage, Sarah; Jenner, Peter

    2013-01-01

    Parkinson's disease is an age-related progressive neurodegenerative disease. The etiology and pathogenetic mechanisms that cause PD are still not fully understood. The available treatments to PD are only symptomatic relief. Acupuncture is used to treat many medical conditions for 1000 years in China and has gained wider and increasing acceptance within both public and medical profession because it has been a very safe and well-tolerated treatment. In this chapter, we reviewed relevant laboratory findings regarding acupuncture mechanism on Parkinson's. We showed that acupuncture stimulation in Parkinson's models had generated valuable mechanistic insight of Parkinson's and showed that acupuncture treatment is in fact a neuroprotective therapy that increase the release of various neuroprotective agents such as brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor, and cyclophilin A. In addition, acupuncture therapy slows cell death process and attenuates oxidative stress to dopaminergic neurons in the substantia nigra. Further, acupuncture therapy modulates neuronal activity of the basal ganglia output structures. These results suggest that early application of acupuncture therapy to Parkinson's patients may be helpful for the best efficacy of acupuncture treatment. It is hopeful that translation of achievement in acupuncture research in Parkinson's models will maximize the potentials of acupuncture treatment.

  19. Neuroanatomical Correlates of Theory of Mind Deficit in Parkinson's Disease: A Multimodal Imaging Study: e0142234

    National Research Council Canada - National Science Library

    María Díez-Cirarda; Natalia Ojeda; Javier Peña; Alberto Cabrera-Zubizarreta; María Ángeles Gómez-Beldarrain; Juan Carlos Gómez-Esteban; Naroa Ibarretxe-Bilbao

    2015-01-01

      Background Parkinson's disease (PD) patients show theory of mind (ToM) deficit since the early stages of the disease, and this deficit has been associated with working memory, executive functions and quality of life impairment...

  20. Structured Regions of Alpha-synuclein Fibrils Include the Early Onset Parkinson's Disease Mutation Sites

    Energy Technology Data Exchange (ETDEWEB)

    Comellas Canal, Gemma; Lemkau, Luisel R.; Nieuwkoop, Andrew J.; Kloepper, Kathryn D.; Ladror, Daniel T.; Ebisu, Reika; Woods, Wendy S.; Lipton, Andrew S.; George, Julia M.; Rienstra, Chad M.

    2011-08-26

    Alpha-Synuclein (AS) fibrils constitute the major proteinaceous component of Lewy bodies (LBs), the pathological hallmark of Parkinson’s disease (PD) and other neurodegenerative diseases. Three single point mutations in the AS gene, as well as multiplication of the wild-type (WT) AS allele, have been previously identified in families with early-onset PD. Although AS fibrils have been the subject of intense study, critical details about their structure including the precise location of the B-strands and the extent of the core, the three-dimensional structure and the effects of the mutations—remain unknown. Here, we have used magic-angle spinning solid-state NMR spectroscopy to present a detailed characterization of the full-length WT AS fibrils. With improved sample preparations, isotopic labeling patterns and NMR experiments, we have confidently assigned more than 90% of the 13C and 15N backbone and sidechain chemical shifts of the detected residues from residue 39 to 97, and quantified the conformational dynamics throughout this region. Our results demonstrate that the core of AS fibrils extends with a repeated motif and that residues 30, 46 and 53-the early-onset PD mutant sites-are located in structured regions of AS fibrils.

  1. How genetics research in Parkinson's disease is enhancing understanding of the common idiopathic forms of the disease.

    Science.gov (United States)

    Cookson, Mark R; Xiromerisiou, Georgia; Singleton, Andrew

    2005-12-01

    Rapid progress in genetics has meant that there are now five genes identified for 'Parkinson's disease'. The detailed phenotypes vary, but generally the dominant genes cause a Lewy body disease spectrum whereas recessive genes cause a milder parkinsonism with variable inclusion body pathology. The subject of this review is to highlight these discoveries and to discuss their relationships to idiopathic Parkinson's disease. In January 2004, mutations in PINK1, coding for a mitochondrial kinase, were found to be causal for recessive parkinsonism. Subsequently, several studies have found additional mutations associated with early onset parkinsonism. Some cases have been described with a phenotype much closer to idiopathic Parkinson's disease, but it does not appear that PINK1 is a major risk factor for the sporadic disease. Later in the same year, the LRRK2 gene was shown to cause a dominant disease with a broader phenotype. The protein product was named dardarin and contains GTPase and kinase domains. Lewy bodies have been reported in LRRK2 cases, potentially linking this gene with sporadic Parkinson's disease. One mutation, G2019S, is found in a significant percentage of cases, including sporadic Parkinson's disease. Mutations in these two genes, along with previously described Mendelian variants, are beginning to yield important information about loss of specific neuronal groups or to protein inclusion pathology. How this relates to sporadic Parkinson's disease, however, is not yet fully defined. There are clear phenotypic overlaps with genetic and sporadic Parkinson's disease, especially for the dominant genes, suggesting that common facets of pathogenesis may exist.

  2. Trajectories of prediagnostic functioning in Parkinson's disease.

    Science.gov (United States)

    Darweesh, Sirwan K L; Verlinden, Vincentius J A; Stricker, Bruno H; Hofman, Albert; Koudstaal, Peter J; Ikram, M Arfan

    2017-02-01

    SEE BREEN AND LANG DOI101093/AWW321 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: At the time of clinical diagnosis, patients with Parkinson's disease already have a wide range of motor and non-motor features that affect their daily functioning. However, the temporal sequence of occurrence of these features remains largely unknown. We studied trajectories of daily functioning and motor and non-motor features in the 23 years preceding Parkinson's disease diagnosis by performing a nested case-control study within the prospective Rotterdam study. Between 1990 and 2013, we repeatedly performed standardized assessments of daily functioning (Stanford Health Assessment Questionnaire, Lawton Instrumental Activities of Daily Living Scale), potential prediagnostic motor (hypo- and bradykinesia, tremor, rigidity, postural imbalance, postural abnormalities) and non-motor features of Parkinson's disease, including cognition (Mini-Mental State Examination, Stroop Test, Letter-Digit-Substitution Test, Word Fluency Test), mood (Center for Epidemiological Studies-Depression Scale, Hamilton Anxiety and Depression Scale), and autonomic function (blood pressure, laxative use). In addition, the cohort was followed-up for the onset of clinical Parkinson's disease using several overlapping modalities, including repeated in-person examinations, as well as complete access to medical records and specialist letters of study participants. During follow-up, 109 individuals were diagnosed with Parkinson's disease, and each case was matched to 10 controls based on age and sex (total n = 1199). Subsequently, we compared prediagnostic trajectories of daily functioning and other features between Parkinson's disease cases and controls. From 7 years before diagnosis onwards, prediagnostic Parkinson's disease cases more commonly had problems in instrumental activities of daily functioning, and more frequently showed signs of movement poverty and slowness, tremor and subtle cognitive deficits. In the

  3. Non-motor features of Parkinson disease.

    Science.gov (United States)

    Schapira, Anthony H V; Chaudhuri, K Ray; Jenner, Peter

    2017-07-01

    Many of the motor symptoms of Parkinson disease (PD) can be preceded, sometimes for several years, by non-motor symptoms that include hyposmia, sleep disorders, depression and constipation. These non-motor features appear across the spectrum of patients with PD, including individuals with genetic causes of PD. The neuroanatomical and neuropharmacological bases of non-motor abnormalities in PD remain largely undefined. Here, we discuss recent advances that have helped to establish the presence, severity and effect on the quality of life of non-motor symptoms in PD, and the neuroanatomical and neuropharmacological mechanisms involved. We also discuss the potential for the non-motor features to define a prodrome that may enable the early diagnosis of PD.

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

    Science.gov (United States)

    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…

  5. CSF neurofilament light chain and tau differentiate multiple system atrophy from Parkinson's disease.

    NARCIS (Netherlands)

    Abdo, W.; Bloem, B.R.; Geel, W.J.A. van; Esselink, R.A.J.; Verbeek, M.M.

    2007-01-01

    BACKGROUND: In early disease stages it can be clinically difficult to differentiate idiopathic Parkinson's disease (IPD) from patients with multiple system atrophy predominated by parkinsonism (MSA-P). METHODS: In CSF of 31 patients with IPD, 19 patients with MSA-P, we analyzed tau, neurofilament

  6. CSF neurofilament light chain and tau differentiate multiple system atrophy from Parkinson's disease.

    NARCIS (Netherlands)

    Abdo, W.; Bloem, B.R.; Geel, W.J.A. van; Esselink, R.A.J.; Verbeek, M.M.

    2007-01-01

    BACKGROUND: In early disease stages it can be clinically difficult to differentiate idiopathic Parkinson's disease (IPD) from patients with multiple system atrophy predominated by parkinsonism (MSA-P). METHODS: In CSF of 31 patients with IPD, 19 patients with MSA-P, we analyzed tau, neurofilament li

  7. Visual Symptoms in Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    R. A. Armstrong

    2011-01-01

    Full Text Available Parkinson's disease (PD is a common disorder of middle-aged and elderly people in which degeneration of the extrapyramidal motor system causes significant movement problems. In some patients, however, there are additional disturbances in sensory systems including loss of the sense of smell and auditory and/or visual problems. This paper is a general overview of the visual problems likely to be encountered in PD. Changes in vision in PD may result from alterations in visual acuity, contrast sensitivity, colour discrimination, pupil reactivity, eye movements, motion perception, visual field sensitivity, and visual processing speeds. Slower visual processing speeds can also lead to a decline in visual perception especially for rapidly changing visual stimuli. In addition, there may be disturbances of visuospatial orientation, facial recognition problems, and chronic visual hallucinations. Some of the treatments used in PD may also have adverse ocular reactions. The pattern electroretinogram (PERG is useful in evaluating retinal dopamine mechanisms and in monitoring dopamine therapies in PD. If visual problems are present, they can have an important effect on the quality of life of the patient, which can be improved by accurate diagnosis and where possible, correction of such defects.

  8. Parkinson's Disease: Hope through Research

    Science.gov (United States)

    ... drug, or in miners exposed to the metal manganese). Other still-unidentified environmental factors may also cause ... severe parkinsonism. This discovery, which showed that a toxic substance could damage the brain and produce parkinsonian ...

  9. POLG1 in idiopathic Parkinson disease.

    Science.gov (United States)

    Tiangyou, W; Hudson, G; Ghezzi, D; Ferrari, G; Zeviani, M; Burn, D J; Chinnery, P F

    2006-11-14

    We studied POLG1 in 140 UK patients with idiopathic Parkinson disease (PD) and 279 Italian patients with PD and compared them to a UK control group (n = 207) and an Italian control group (n = 285). Our observations do not support a role for common POLG1 genetic variants in PD and indicate that dominant POLG1 mutations are a rare cause of parkinsonism in the general population.

  10. Epidemiology of Parkinson's Disease: The Rotterdam Study

    NARCIS (Netherlands)

    M.C. de Rijk (Maarten)

    1997-01-01

    textabstractAt present, Parkinson's disease (PO), after Alzheimer's disease, is generally considered to be the most frequent progressive neurodegenerative disease in the elderly. Due to the growing proportion of elderly in many populations, more and more persons will be affected by this disabling di

  11. [Non-motor symptoms of Parkinson's disease

    NARCIS (Netherlands)

    Weerkamp, N.J.; Nijhof, A.; Tissingh, G.

    2012-01-01

    Parkinson's disease has traditionally been viewed as a disease with only motor features. Nowadays, a wide variety of non-motor symptoms and signs are also recognised as being characteristic of the disease. Non-motor symptoms, most importantly autonomic dysfunction, neuropsychiatric symptoms and slee

  12. Multidimensional exercise for people with Parkinson's disease: a case report.

    Science.gov (United States)

    Kluding, Patricia; McGinnis, Patricia Quinn

    2006-06-01

    The primary impairments associated with Parkinson's disease occur in combination with the secondary, preventable effects of immobility. A community-based fitness program may help increase activity and maintain function in people in the early or middle stages of the disease. This article describes a unique program designed to reduce fall risk and promote independent exercise for people with Parkinson's disease. Two 66-year-old males, both community ambulators and in early or middle stages of Parkinson's disease, participated in 3 months of various physical activities. Group balance classes were held twice weekly during the first month, participants joined a fitness center and self-directed their exercise program during the second month, and group Tai Chi classes were held twice weekly during the third month. At conclusion of the program, participants were given suggestions for continued physical fitness activities. After the 3-month program, improvements were noted for both individuals in functional reach, Timed Up and Go, and Berg Balance scores. Both participants continued to exercise regularly for at least 8 months following the program. Two individuals with Parkinson's disease demonstrated improvement in their balance test performance over a 3-month period. Perhaps most importantly, these participants independently continued exercising after completing this program.

  13. Nutritional therapies in Parkinson's disease.

    Science.gov (United States)

    Evatt, Marian L

    2007-05-01

    Advise patients with Parkinson's disease (PD) to consume a balanced diet, with special attention to adequate intake of dietary fiber, fluids, and macro- and micronutrients. Regularly reassess patients' nutritional history and anthropomorphic measures (height and weight), particularly in patients with advanced disease. PD-related psychosocial as well as physical and cognitive limitations increase susceptibility to subacute and chronic malnutrition. Nutritional requirements may change with PD progression or after surgical therapy for PD. Patients and caregivers may benefit from counseling by a dietician who is knowledgeable about the nutritional risks and needs of PD. Regularly inquire about dysphagia symptoms, and consider speech therapy consultation for clinical and modified barium-swallowing evaluations and management recommendations. Although non-oral delivery options of dopaminergic therapy are increasing, severe dysphagia may warrant percutaneous endoscopic gastrostomy tube placement for nutritional support and more reliable PD medication dosing. Analyze vitamin B(12) and D concentrations at regular intervals. Both vitamins are frequently deficient in elderly persons but may not be routinely checked by primary care physicians. Record over-the-counter and nutritional supplement medications at each visit, and assist patients in periodically re-evaluating their potential benefits, side effects, drug interactions, and costs. To date, clinical trials of antioxidant vitamins and nutritional supplements have provided insufficient evidence to support routine use for PD in the clinic. Data from several clinical trials of antioxidant vitamins/nutritional supplements are expected in the near future. Consider altering medication dosing in relation to meals to help with mild to moderate motor fluctuations. Patients with severe motor fluctuations may benefit from adapting the 5:1 carbohydrate-to-protein ratio in their daily meals and snacks. Following a "protein

  14. Parkinson Disease: An Evolutionary Perspective

    Directory of Open Access Journals (Sweden)

    Pedro J. Garcia-Ruiz

    2017-05-01

    Full Text Available There are two central premises to this evolutionary view of Parkinson disease (PD. First, PD is a specific human disease. Second, the prevalence of PD has increased over the course of human history. Several lines of evidence may explain why PD appears to be restricted to the human species. The major manifestations of PD are the consequence of degeneration in the dopamine-synthesizing neurons of the mesostriatal neuronal pathway. It is of note the enormous expansion of the human dopamine mesencephalic neurons onto the striatum compared with other mammals. Hence, an evolutionary bottle neck was reached with the expansion of the massive nigrostriatal axonal arborization. This peculiar nigral overload may partly explain the selective fragility of the human dopaminergic mesencephalic neurotransmission and the unique presence of PD in humans. On the other hand, several facts may explain the increasing prevalence of PD over the centuries. The apparently low prevalence of PD before the twentieth century may be related to the shorter life expectancy and survival compared to present times. In addition, changes in lifestyle over the course of human history might also account for the increasing burden of PD. Our hunter-gatherers ancestors invested large energy expenditure on a daily basis, a prototypical physical way of life for which our genome remains adapted. Technological advances have led to a dramatic reduction of physical exercise. Since the brain release of neurotrophic factors (including brain-derived neurotrophic factor is partially exercise related, the marked reduction in exercise may contribute to the increasing prevalence of PD.

  15. Parkinson's disease Assessment using Fuzzy Expert System and Nonlinear Dynamics

    Directory of Open Access Journals (Sweden)

    GEMAN, O.

    2013-02-01

    Full Text Available This paper proposes a new screening system for quantitative evaluation and analysis, designed for the early stage detection of Parkinson disease. This has been carried out in the view of improving the diagnosis currently established upon a basis of subjective scores. Parkinson?s disease (PD appears as a result of dopamine loss, a chemical mediator that is responsible for the body?s ability to control movements. The symptoms reflect the loss of nerve cells, due to an unknown. The input parameters of the system are represented by amplitude, frequency, the spectral characteristic and trembling localization. The main symptoms include trembling of hand, arms, movement difficulties, postural instability, disturbance of coordination and equilibrium, sleep disturbance, difficulties in speaking, reducing of voice volume. The medical knowledge in PD field is characterized by imprecision, uncertainty and vagueness. The proposed system (fuzzy expert systems is non-invasive and, easy to use by both physicians and patients at home.

  16. Copper and copper proteins in Parkinson's disease.

    Science.gov (United States)

    Montes, Sergio; 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.

  17. α-Synuclein oligomers and clinical implications for Parkinson disease.

    Science.gov (United States)

    Kalia, Lorraine V; Kalia, Suneil K; McLean, Pamela J; Lozano, Andres M; Lang, Anthony E

    2013-02-01

    Protein aggregation within the central nervous system has been recognized as a defining feature of neurodegenerative diseases since the early 20th century. Since that time, there has been a growing list of neurodegenerative disorders, including Parkinson disease, which are characterized by inclusions of specific pathogenic proteins. This has led to the long-held dogma that these characteristic protein inclusions, which are composed of large insoluble fibrillar protein aggregates and visible by light microscopy, are responsible for cell death in these diseases. However, the correlation between protein inclusion formation and cytotoxicity is inconsistent, suggesting that another form of the pathogenic proteins may be contributing to neurodegeneration. There is emerging evidence implicating soluble oligomers, smaller protein aggregates not detectable by conventional microscopy, as potential culprits in the pathogenesis of neurodegenerative diseases. The protein α-synuclein is well recognized to contribute to the pathogenesis of Parkinson disease and is the major component of Lewy bodies and Lewy neurites. However, α-synuclein also forms oligomeric species, with certain conformations being toxic to cells. The mechanisms by which these α-synuclein oligomers cause cell death are being actively investigated, as they may provide new strategies for diagnosis and treatment of Parkinson disease and related disorders. Here we review the possible role of α-synuclein oligomers in cell death in Parkinson disease and discuss the potential clinical implications.

  18. Physical Equilibrium Evaluation in Parkinson Disease

    Directory of Open Access Journals (Sweden)

    Schmidt, Paula da Silva

    2011-04-01

    Full Text Available Introduction: The Parkinson disease can be among the multiple causes of alterations in the physical equilibrium. Accordingly, this study has the objective to evaluate Parkinson patients' physical equilibrium. Method: Potential study in which 12 Parkinson individuals were evaluated by way of tests of static and dynamic equilibrium, dynamic posturography and vectoelectronystagmograph. To compare the dynamic posturography results a group of gauged control was used. Results: Alterations in Romberg-Barré, Unterberger and Walk tests were found. The vestibular exam revealed 06 normal cases, 04 central vestibular syndrome and 02 cases of peripheral vestibular syndrome. In the dynamic posturography, an equilibrium alteration has been verified, when compared to the control group in all Sensorial Organization Tests, in average and in the utilization of vestibular system. Conclusion: Parkinson patients present a physical equilibrium alteration. The dynamic posturography was more sensitive to detect the equilibrium alterations than vectoelectronystagmograph.

  19. Mortalin inhibition in experimental Parkinson's disease.

    Science.gov (United States)

    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.

  20. Visual hallucinations in Parkinson's disease: theoretical models.

    Science.gov (United States)

    Muller, Alana J; Shine, James M; Halliday, Glenda M; Lewis, Simon J G

    2014-11-01

    One of the most challenging tasks in neuroscience is to be able to meaningfully connect information across the different levels of investigation, from molecular or structural biology to the resulting behavior and cognition. Visual hallucinations are a frequent occurrence in Parkinson's disease and significantly contribute to the burden of the disease. Because of the widespread pathological processes implicated in visual hallucinations in Parkinson's disease, a final common mechanism that explains their manifestation will require an integrative approach, in which consideration is taken across all complementary levels of analysis. This review considers the leading hypothetical frameworks for visual hallucinations in Parkinson's disease, summarizing the key aspects of each in an attempt to highlight the aspects of the condition that such a unifying hypothesis must explain. These competing hypotheses include implications of dream imagery intrusion, deficits in reality monitoring, and impairments in visual perception and attention.

  1. Oral Hygiene in Patients with Parkinson's Disease.

    Science.gov (United States)

    Batista, Leonardo M; Portela de Oliveira, Millena Teles; Magalhaes, Wilrama B; Bastos, Poliana Lima

    2015-11-02

    Parkinson's disease is a chronic progressive neurodegenerative disorder with a multifactorial etiology. The symptoms are characterized by motor disorders - tremor, rigidity, bradykinesia and postural instability, which hinder oral hygiene. Oral and dental health in Parkinson's disease has been under-documented and findings are conflicting. Moreover, a number of dentists have limited experience regarding the management of these patients. This article reviews literature published within the last fifteen years, to better understand the impact of this disease in oral health. A literature search (MEDLINE and PUBMED), using keywords Parkinson Disease and Oral Hygiene, yielded 27 articles, from which 20 were selected. All of the articles were published in English in the last 15 years.

  2. [Placebo effect in Parkinson's disease].

    Science.gov (United States)

    Miwa, Hideto

    2007-02-01

    "Placebo" is Latin for "I shall please". The placebo effect has been widely documented by randomized placebo-controlled drug studies. One of the best examples of placebo effectiveness is that have been shown in clinical trials of anti-parkinsonian drugs. The placebo effect is observable not only in drug trials but also with deep brain stimulation. Recent advances in research on the placebo effect in Parkinson's disease (PD) have suggested that motor symptoms of PD can be essentially improved by placebo. A recent study using positron emission tomography (PET) with raclopride demonstrated that release of endogeneous dopamine in the dorsal striatum occurs in placebo-responsive patients with PD. This suggests that placebo-induced expectation of clinical improvement may activate endogenous dopamine in the striatum, and that placebo effectiveness is thus achieved by endogenous dopamine supplementation. Indeed, decreased neuronal activities in the subthalamic nucleus (STN), that were recorded during surgery to implant deep brain stimulation electrodes, correlated well with placebo-induced clinical improvement in patients with PD. Although the detailed pathophysiological mechanism underlying the placebo effects remains uncertain, theoretically, the placebo effect has generally been explained by two different mechanisms: one is conditioning theory (pavlovian conditioning), and the other is cognitive theory (expectation of clinical improvement). Although both mechanisms may contribute to placebo effects, the placebo effect in PD may be attributed more to cognitive mechanisms such as expectation of improvement, because the placebo effect can be obtained in de novo PD patients. There have been accumulating findings that suggest a functional relationship between dopamine and the expectation of clinical improvement (reward). Further basic studies are required to clarify the complex link between dopamine and the reward system, but such findings will contribute to a better

  3. α-Synuclein oligomers and clinical implications for Parkinson disease

    OpenAIRE

    Kalia, Lorraine V.; Kalia, Suneil K; McLean, Pamela J.; Lozano, Andres M.; Lang, Anthony E

    2012-01-01

    Protein aggregation within the central nervous system has been recognized as a defining feature of neurodegenerative diseases since the early 20th century. Since that time, there has been a growing list of neurodegenerative disorders, including Parkinson disease, which are characterized by inclusions of specific pathogenic proteins. This has led to the long-held dogma that these characteristic protein inclusions, which are composed of large insoluble fibrillar protein aggregates and visible b...

  4. Parkinson Disease: Treating Symptoms Unrelated to Muscle Movement

    Science.gov (United States)

    ... 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 ...

  5. CareMAP: Caring for Someone with Advanced Parkinson Disease

    Science.gov (United States)

    ... Parkinson's There is a lot to know about Parkinson's disease. Learn about symptoms, how it is diagnosed and ... awareness for the 1 million Americans living with Parkinson’s disease. Learn More > Our Impact Our Mission Our Team ...

  6. Exercise May Be Real Medicine for Parkinson's Disease

    Science.gov (United States)

    ... 162698.html Exercise May Be Real Medicine for Parkinson's Disease Physical activity helps improve gait and balance, research ... any exercise is good medicine for someone with Parkinson's disease, a new study confirms. Although physical activity may ...

  7. Pramipexole extended release in Parkinson's disease.

    Science.gov (United States)

    Hametner, Eva-Maria; Seppi, Klaus; Poewe, Werner

    2011-09-01

    Pramipexole extended release (ER) is a new once-daily formulation of pramipexole, a nonergot dopamine agonist, which is available in five dosage strengths: 0.26 (0.375) mg, 0.52 (0.75) mg, 1.05 (1.5) mg, 2.1 (3) mg and 3.15 (4.5) mg (all doses are expressed in terms of pramipexole base and the corresponding dose strengths of pramipexole salt are given in brackets). Pramipexole ER is currently approved as monotherapy in early Parkinson's disease (PD), as well as an adjunct therapy to levodopa in advanced PD. Compared with the immediate release (IR) formulation, the ER formulation offers several advantages, including the potential for improved compliance owing to its simple once-daily dosing regimen and steadier plasma levels over 24 h. Double-blind, randomized, placebo and active comparator controlled trials in early, as well as advanced PD, established the superiority of both pramipexole ER and IR over placebo. The overnight switch from pramipexole IR three times a day to ER once-daily in early PD has been shown to be successful in more than 80% of patients. Pramipexole ER is well tolerated, with a similar adverse event profile to pramipexole IR. The aim of this article is to provide a short review of the most relevant pharmacological and clinical data on pramipexole ER.

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

    Science.gov (United States)

    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

  9. Increased intracranial volume in Parkinson's disease

    DEFF Research Database (Denmark)

    Karlsborg, Merete; Hansen, Andreas; Werdelin, Lene

    2005-01-01

    Parkinson's disease (PD) and multiple system atrophy (MSA) are neurodegenerative diseases that can be difficult to diagnose and distinguish from each other. STUDY AIMS AND METHODS: Patients with PD and MSA and controls were studied with magnetic resonance imaging (MRI) using tissue segmentation...

  10. Chronic, low-dose rotenone reproduces Lewy neurites found in early stages of Parkinson's disease, reduces mitochondrial movement and slowly kills differentiated SH-SY5Y neural cells

    Directory of Open Access Journals (Sweden)

    Liu Lei

    2008-12-01

    Full Text Available Abstract Background Parkinson's disease, the most common adult neurodegenerative movement disorder, demonstrates a brain-wide pathology that begins pre-clinically with alpha-synuclein aggregates ("Lewy neurites" in processes of gut enteric and vagal motor neurons. Rostral progression into substantia nigra with death of dopamine neurons produces the motor impairment phenotype that yields a clinical diagnosis. The vast majority of Parkinson's disease occurs sporadically, and current models of sporadic Parkinson's disease (sPD can utilize directly infused or systemic neurotoxins. Results We developed a differentiation protocol for human SH-SY5Y neuroblastoma that yielded non-dividing dopaminergic neural cells with long processes that we then exposed to 50 nM rotenone, a complex I inhibitor used in Parkinson's disease models. After 21 days of rotenone, ~60% of cells died. Their processes retracted and accumulated ASYN-(+ and UB-(+ aggregates that blocked organelle transport. Mitochondrial movement velocities were reduced by 8 days of rotenone and continued to decline over time. No cytoplasmic inclusions resembling Lewy bodies were observed. Gene microarray analyses showed that the majority of genes were under-expressed. qPCR analyses of 11 mtDNA-encoded and 10 nDNA-encoded mitochondrial electron transport chain RNAs' relative expressions revealed small increases in mtDNA-encoded genes and lesser regulation of nDNA-encoded ETC genes. Conclusion Subacute rotenone treatment of differentiated SH-SY5Y neuroblastoma cells causes process retraction and partial death over several weeks, slowed mitochondrial movement in processes and appears to reproduce the Lewy neuritic changes of early Parkinson's disease pathology but does not cause Lewy body inclusions. The overall pattern of transcriptional regulation is gene under-expression with minimal regulation of ETC genes in spite of rotenone's being a complex I toxin. This rotenone-SH-SY5Y model in a

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

    Science.gov (United States)

    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.

  12. Role of pramipexole in the management of Parkinson's disease.

    Science.gov (United States)

    Antonini, Angelo; Barone, Paolo; Ceravolo, Roberto; Fabbrini, Giovanni; Tinazzi, Michele; Abbruzzese, Giovanni

    2010-10-01

    The non-ergot dopamine agonist pramipexole is currently indicated for the treatment of the signs and symptoms of idiopathic Parkinson's disease and for the treatment of moderate-to-severe primary restless legs syndrome. A new extended-release formulation of pramipexole has now also been launched in Europe and the US to improve ease of use, compliance and provide a more continuous therapeutic effect over 24 hours. Before initiating any treatment, the benefit-risk ratio to the individual patient must be considered. For pramipexole in the treatment of Parkinson's disease, this means taking into account the available evidence regarding its symptomatic efficacy, effect on delaying long-term levodopa-related motor complications, beneficial effect on non-motor symptoms such as depression, and its safety and tolerability profile. Studies have shown that pramipexole is effective as monotherapy in early Parkinson's disease and as adjunctive therapy in advanced disease. Trials further suggest that the benefits of pramipexole may extend beyond the relief of motor symptoms (akinesia, rigidity and tremor at rest) to the amelioration of depressive symptoms in Parkinson's disease. Pramipexole is generally well tolerated; however, compared with levodopa treatment, pramipexole is associated with a higher rate of some dopaminergic adverse effects.

  13. Living Well with Parkinson's Disease Is an Art

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Parkinson's Disease Living Well with Parkinson's Disease is an Art Past Issues / Winter 2014 Table ... Cunningham When did you first get diagnosed with Parkinson's disease? What symptoms led you to go to the ...

  14. [Nature of speech disorders in Parkinson disease].

    Science.gov (United States)

    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.

  15. Can we image premotor Parkinson disease?

    Science.gov (United States)

    Marek, Kenneth; Jennings, Danna

    2009-02-17

    Pathology and imaging studies have shown that patients with Parkinson disease (PD) have a prolonged period of uncertain duration when vulnerable neuronal populations are degenerating, but typical motor symptoms have not yet developed. This provides both an opportunity-it may be best to test new medications and, ultimately, treat PD patients during this early phase of disease--and a challenge--how to find these premotor PD subjects? Imaging biomarkers targeting the premotor period are critical to elucidate both the onset and progression of premotor PD. Widespread data have demonstrated that dopaminergic imaging can detect PD subjects at the motor symptom threshold. Novel strategies combining dopaminergic imaging with known genetic mutations for PD or early clinical signs and PD-associated symptoms, such as olfactory loss and sleep disturbances like REM behavior disorder, have begun to be used to identify individuals at risk for PD before motor symptoms become manifest. Early studies also have used imaging targeting norepinephrine, serotonin, cholinergic, or other neuronal systems to focus on early cardiac, cognitive, and behavioral symptoms. Imaging of nondopaminergic targets such as inflammation or alpha-synuclein deposition may provide further insight into the etiology of PD. Given the multiple genetic etiologies for PD already identified, the marked variability in the loss of dopaminergic markers measured by imaging at motor symptom onset, and the clear heterogeneity of clinical symptoms at PD onset, it is certain that many imaging biomarkers with a focus ranging from clinical symptoms to PD pathobiology to molecular genetic mechanisms, will be necessary to fully map PD risk.

  16. Can Baropodometric Analysis be a Useful Tool in the Early Diagnosis of Atypical Parkinsonism? Preliminary Findings

    Science.gov (United States)

    Furnari, Anna; Imbesi, Donatella; La Fauci Belponer, Francesca; Militi, David; Gervasi, Giuseppe; Pastura, Concetta; Bramanti, Placido

    2014-01-01

    Objective: The differential diagnosis between atypical parkinsonism and Parkinson’s disease is difficult, especially in the early stage. Severe postural instability, falls, and complex gait impairments are usually confined to the later stage of Parkinson’s disease, while atypical parkinsonism patients may present a severe postural instability with consequent falls in the earlier stages. Methods: We retrospectively studied 20 subjects with parkinsonism using clinical and baropodometric tools to give quantitative and objective data on the postural, balance, and gait disturbances. Results: The statistical analysis between atypical parkinsonism and Parkinson’s disease patients showed a significant difference in the frequency of long lead time parameter, foot area, foot load and speed, and, in particular, atypical parkinsonism patients presented a prevalent long lead time impairment (8/8 patients) when compared with Parkinson’s disease patients. Discussion: Beside significant differences in the clinical features between the Parkinson’s disease and atypical parkinsonism, our study showed that baropodometric investigation may a valuable tool for the definition of postural and motor extrapyramidal abnormalities, permitting an earlier differentiation between atypical parkinsonism and Parkinson’s disease. PMID:24653938

  17. Network Analysis Identifies Disease-Specific Pathways for Parkinson's Disease.

    Science.gov (United States)

    Monti, Chiara; Colugnat, Ilaria; Lopiano, Leonardo; Chiò, Adriano; Alberio, Tiziana

    2016-12-21

    Neurodegenerative diseases are characterized by the progressive loss of specific neurons in selected regions of the central nervous system. The main clinical manifestation (movement disorders, cognitive impairment, and/or psychiatric disturbances) depends on the neuron population being primarily affected. Parkinson's disease is a common movement disorder, whose etiology remains mostly unknown. Progressive loss of dopaminergic neurons in the substantia nigra causes an impairment of the motor control. Some of the pathogenetic mechanisms causing the progressive deterioration of these neurons are not specific for Parkinson's disease but are shared by other neurodegenerative diseases, like Alzheimer's disease and amyotrophic lateral sclerosis. Here, we performed a meta-analysis of the literature of all the quantitative proteomic investigations of neuronal alterations in different models of Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis to distinguish between general and Parkinson's disease-specific pattern of neurodegeneration. Then, we merged proteomics data with genetics information from the DisGeNET database. The comparison of gene and protein information allowed us to identify 25 proteins involved uniquely in Parkinson's disease and we verified the alteration of one of them, i.e., transaldolase 1 (TALDO1), in the substantia nigra of 5 patients. By using open-source bioinformatics tools, we identified the biological processes specifically affected in Parkinson's disease, i.e., proteolysis, mitochondrion organization, and mitophagy. Eventually, we highlighted four cellular component complexes mostly involved in the pathogenesis: the proteasome complex, the protein phosphatase 2A, the chaperonins CCT complex, and the complex III of the respiratory chain.

  18. Redistribution of DAT/α-Synuclein Complexes Visualized by “In Situ” Proximity Ligation Assay in Transgenic Mice Modelling Early Parkinson's Disease

    OpenAIRE

    Arianna Bellucci; Laura Navarria; Elisa Falarti; Michela Zaltieri; Federica Bono; Ginetta Collo; Maria Grazia Spillantini; Cristina Missale; Pierfranco Spano

    2011-01-01

    Alpha-synuclein, the major component of Lewy bodies, is thought to play a central role in the onset of synaptic dysfunctions in Parkinson's disease (PD). In particular, α-synuclein may affect dopaminergic neuron function as it interacts with a key protein modulating dopamine (DA) content at the synapse: the DA transporter (DAT). Indeed, recent evidence from our "in vitro" studies showed that α-synuclein aggregation decreases the expression and membrane trafficking of the DAT as the DAT is ret...

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

    Science.gov (United States)

    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.

  20. Glucocerebrosidase mutations in clinical and pathologically proven Parkinson's disease.

    Science.gov (United States)

    Neumann, Juliane; Bras, Jose; Deas, Emma; O'Sullivan, Sean S; Parkkinen, Laura; Lachmann, Robin H; Li, Abi; Holton, Janice; Guerreiro, Rita; Paudel, Reema; Segarane, Badmavady; Singleton, Andrew; Lees, Andrew; Hardy, John; Houlden, Henry; Revesz, Tamas; Wood, Nicholas W

    2009-07-01

    Mutations in the glucocerebrosidase gene (GBA) are associated with Gaucher's disease, the most common lysosomal storage disorder. Parkinsonism is an established feature of Gaucher's disease and an increased frequency of mutations in GBA has been reported in several different ethnic series with sporadic Parkinson's disease. In this study, we evaluated the frequency of GBA mutations in British patients affected by Parkinson's disease. We utilized the DNA of 790 patients and 257 controls, matched for age and ethnicity, to screen for mutations within the GBA gene. Clinical data on all identified GBA mutation carriers was reviewed and analysed. Additionally, in all cases where brain material was available, a neuropathological evaluation was performed and compared to sporadic Parkinson's disease without GBA mutations. The frequency of GBA mutations among the British patients (33/790 = 4.18%) was significantly higher (P = 0.01; odds ratio = 3.7; 95% confidence interval = 1.12-12.14) when compared to the control group (3/257 = 1.17%). Fourteen different GBA mutations were identified, including three previously undescribed mutations, K7E, D443N and G193E. Pathological examination revealed widespread and abundant alpha-synuclein pathology in all 17 GBA mutation carriers, which were graded as Braak stage of 5-6, and had McKeith's limbic or diffuse neocortical Lewy body-type pathology. Diffuse neocortical Lewy body-type pathology tended to occur more frequently in the group with GBA mutations compared to matched Parkinson's disease controls. Clinical features comprised an early onset of the disease, the presence of hallucinations in 45% (14/31) and symptoms of cognitive decline or dementia in 48% (15/31) of patients. This study demonstrates that GBA mutations are found in British subjects at a higher frequency than any other known Parkinson's disease gene. This is the largest study to date on a non-Jewish patient sample with a detailed genotype/phenotype/pathological analyses

  1. Observation on effect of investigation of Parkinson disease depression and early psychological intervention%帕金森病并抑郁调查及早期心理干预的疗效观察

    Institute of Scientific and Technical Information of China (English)

    杨利杰; 李园园; 范丹

    2014-01-01

    目的:观察帕金森病并抑郁的发生率及早期心理干预的临床效果。方法观察112例帕金森病患者,评估非运动症状中抑郁在临床不同分期的发生率。将帕金森病并抑郁分为实验组和对照组,采用Zung氏抑郁自评量表(SDS)评估患者的心理状况,观察早期心理干预的效果。结果帕金森病的非运动症状中,抑郁发生率最高,且早期行心理干预有效,差异有统计学意义(P<0.01)。结论帕金森病并抑郁在非运动症状中发生率较高。患者病后早期行心理干预治疗,能明显改善患者的抑郁症状,提高总体临床疗效。%Objective To investigate clinical effect of early psychological intervention of Parkinson disease depression.Methods To observe 112 cases of patients with Parkinson's disease, and evaluate the depression incidence of non motor symptoms on different clinical stages. The Parkinson disease depression were divided into experimental and control group, and by Zung's Selfrating Depression Scale (SDS) assessed the psychological status of the patients, observed the effect of early psychological intervention.Results Depression was the highest in non motor symptoms of Parkinson disease, and early psychological intervention was effective treatment, with statistically significant (P<0.01).Conclusion Parkinson disease depression has higher incidence in non motor symptoms. Early psychological intervention can significantly improve the patient's symptoms of depression, and improve the overall clinical efficacy.

  2. The characteristic of the visual function of early Parkinson's disease patients%早期帕金森病患者的视觉功能特征

    Institute of Scientific and Technical Information of China (English)

    吴志鹏; 邓如芝; 王苹莉; 赵元琛; 倪渝鲲; 王小同

    2013-01-01

    Objective:To investigate the characteristic of the visual function of early Parkinson's disease (PD) patients and to provide some guidance for clinical diagnosis and treatment.Methods:Fifty-nine subjects were enrolled in this study,including 29 early PD patients in the experimental group and 30 normal subjects in the control group.All subjects didn't receive any anti-Parkinson's disease drugs and ophthalmologic treatment.HoehnYahr stages and Unified Parkinson's Disease Rating Scale (UPDRS) were used to evaluate the PD patient's stage and severity degree.Visual function tests included contrast visual acuity,convergence and accommodative amplitude.ETDRS eyesight chart was used to measure the 100%,25% and 10% contrast visual acuity,respectively.The eyesight function checking was compared to find whether there was a difference between the two groups.Results:There was no significant difference (t=0.16,P=0.8) in 100% high contrast visual acuity between early PD patients and control group,but in 25% and 10% low contrast,the visual acuity of early PD patients was significantly lower than that of control group (t=-2.58,-3.24,P=0.012,0.002,respectively).Near point convergence of early PD patients and control group were (6.4 ± 4.35) cm and (4.7 ± 3.39) cm respectively,but there was no significant difference between the two groups (t=-1.69,P=0.09).Positive fusion convergence of early PD patients was (15.0 ± 5.23)△,significantly lower than that in the control group,which was (19.2 ± 6.97)△ (t=2.60,P=0.01).Convergence insufficiency was diagnosed in 9 early PD patients compared to 2 subjects from the control group (x2=5.78,P=0.016).The accommodative amplitude had no significant difference between early PD patients and control group (t=0.90,P =0.37).Seven early PD patients had visual hallucinations,but nobody in the control group had this symptom (x2 =6.07,P=0.014).Conclusion:There are various kinds of visual dysfunctions that exist in early PD patients

  3. [Speech and voice disorders in Parkinson's disease].

    Science.gov (United States)

    Martnez-Sánchez, Francisco

    2010-11-01

    To examine the voice, speech dysfunction and acoustic parameters typically associated with Parkinson's disease (PD), including the effects on respiration, phonation, articulation and prosody; the effect of treatment with the drug levodopa and deep brain stimulation of the subthalamic nucleus is also examined. One of the features of PD is the alteration of voice and speech. The motor deficits associated with PD adversely affect the major systems that govern speech motor control including respiration, phonation, and articulation. The speech deficits related to PD are often called hypokinetic dysarthria and can be characterized by monopitch, mono-loudness, reduced stress, imprecise consonants, and inappropriate silences. Numerous studies have documented these changes using a wide variety of acoustic measures. Acoustic correlates of PD have a potential to provide useful biomarkers and sensitive methods for the early detection of the onset, progression, and severity of disease states, as well as providing a means to objectively track symptomatic changes and to assess the efficacy of pharmacological and surgical treatments.

  4. [Fatigue and weight loss in Parkinson's disease].

    Science.gov (United States)

    Okuma, Yasuyuki

    2012-04-01

    Fatigue is a common, under recognized, and poorly understood nonmotor symptom in Parkinson's disease (PD). Fatigue frequently presents early in PD, and its prevalence increases with disease progression, affecting up to 60% of patients. Fatigue has a negative impact on quality of life. Fatigue is often associated with other nonmotor symptoms, including sleep disturbance, excessive daytime sleepiness, and depression. Only a few reports have been published on the treatment of fatigue in PD (methylphenidate, levodopa, and pramipexole). Further well-designed studies, including physiotherapy, are necessary to develop more effective treatments for PD-associated fatigue. A number of patients with PD lose weight because of loss of fat. However, the evolution and determinants of weight loss are not well established. Possible determinants of weight loss in PD include loss of appetite, impaired hand-mouth coordination, difficulty in chewing and dysphagia, nausea, intestinal hypomotility, and increased energy requirements because of muscular rigidity and involuntary movements. Noticeable weight gain has repeatedly been reported after subthalamic or pallidal deep brain stimulation. Because low body weight is associated with negative health effects and a poor prognosis, monitoring weight and nutritional status should be part of PD management.

  5. Gastric electromechanical dysfunction in Parkinson's disease.

    Science.gov (United States)

    Krygowska-Wajs, A; Lorens, K; Thor, P; Szczudlik, A; Konturek, S

    2000-01-01

    This study was designed to evaluate gastric myoelectrical and mechanical activities in idiopathic Parkinson's disease (IPD) patients. Twenty patients with IPD (14 male and 6 female, mean age 42 +/- 9 years) were studied. Patients were divided into two groups: group A--early stage of disease (no. = 6) and group B--advanced IPD (no. = 14). Electrogastrography (EGG) was performed in fasting and postprandial conditions (Synectics system). The cross-sectional area of the gastric antrum was measured by sonography (Hitachi EUB-240). The antral area in fasting conditions was 2.1 +/- 0.4 and 4.2 +/- 1.2 cm2 and gastric emptying was 75 +/- 5 and 125 +/- 12 min in groups A and B respectively. EGG showed dysrhythmias (range 1-6 cycles per minute) in about 75% of both groups of IPD patients without increase in signal amplitude after a meal. Our results suggest that gastric motility is particularly impaired in patients with advanced IPD. It may be caused by the primary degenerative process in the autonomic nervous system of the gut.

  6. Cardiovascular autonomic dysfunction in Parkinson's disease.

    Science.gov (United States)

    Ziemssen, Tjalf; Reichmann, Heinz

    2010-02-15

    Symptoms of cardiovascular dysautonomia are a common occurrence in Parkinson's disease (PD). In addition to this dysautonomia as part of PD itself, dysfunction of the autonomic nervous system (ANS) can be triggered as a side-effect of drug treatment interacting with the ANS or - if prominent and early - an indication of a different disease such as multiple system atrophy (MSA). Various diagnostic tests are available to demonstrate autonomic failure. While autonomic function tests can differentiate parasympathetic from sympathetic dysfunction, cardiac imaging can define the pathophysiologically involved site of a lesion. Standard tests such as 24-h ambulatory blood pressure measurements can identify significant autonomic failure which needs treatment. The most frequent and disturbing symptom of cardiovascular autonomic dysfunction is orthostatic hypotension. Symptoms include generalized weakness, light-headiness, mental "clouding" up to syncope. Factors like heat, food, alcohol, exercise, activities which increase intrathoraric pressure (e.g. defecation, coughing) and certain drugs (e.g. vasodilators) can worsen a probably asymptomatic orthostatic hypotension. Non-medical and medical therapies can help the patient to cope with a disabling symptomatic orthostatic hypotension. Supine hypertension is often associated with orthostatic hypotension. The prognostic role of cardiovagal and baroreflex dysfunction is still not yet known.

  7. Parkinson's disease showing progressive conduction aphasia

    OpenAIRE

    Sakai, Kenji; Ono, Kenjiro; Harada, Hiromi; Shima, Keisuke; Notoya, Masako; Yamada, Masahito

    2012-01-01

    Patients with Parkinson's disease (PD) may develop progressive dementia late in their clinical course. Dementia in PD is mostly related to neuropathological findings of extensive Lewy bodies (LBs), with or without the coexistence of Alzheimer's disease (AD) pathology. Aphasia has been reported in patients with LB diseases with AD pathology; however, there have been no reports of typical PD patients developing progressive aphasia during their clinical course. We describe a female PD patient wh...

  8. MDS clinical diagnostic criteria for Parkinson's disease

    NARCIS (Netherlands)

    Postuma, R.B.; Berg, D; Stern, M.; Poewe, W.; Olanow, C.W.; Oertel, W.; Obeso, J.; Marek, K.; Litvan, I.; Lang, A.E.; Halliday, G.; Goetz, C.G.; Gasser, T.; Dubois, B.; Chan, P.; Bloem, B.R.; Adler, C.H.; Deuschl, G.

    2015-01-01

    This document presents the Movement Disorder Society Clinical Diagnostic Criteria for Parkinson's disease (PD). The Movement Disorder Society PD Criteria are intended for use in clinical research but also may be used to guide clinical diagnosis. The benchmark for these criteria is expert clinical di

  9. Benign paroxysmal positional vertigo in Parkinson's disease

    NARCIS (Netherlands)

    Wensen, E. van; Leeuwen, R.B. van; Zaag-Loonen, H.J. van der; Masius-Olthof, S.; Bloem, B.R.

    2013-01-01

    BACKGROUND: Dizziness is a frequent complaint of patients with Parkinson's disease (PD), and orthostatic hypotension (OH) is often thought to be the cause. We studied whether benign paroxysmal positional vertigo (BPPV) could also be an explanation. AIM: To assess the prevalence of benign paroxysmal

  10. Voice Onset Time in Parkinson Disease

    Science.gov (United States)

    Fischer, Emily; Goberman, Alexander M.

    2010-01-01

    Research has found that speaking rate has an effect on voice onset time (VOT). Given that Parkinson disease (PD) affects speaking rate, the purpose of this study was to examine VOT with the effect of rate removed (VOT ratio), along with the traditional VOT measure, in individuals with PD. VOT and VOT ratio were examined in 9 individuals with PD…

  11. Benign paroxysmal positional vertigo in Parkinson's disease

    NARCIS (Netherlands)

    Wensen, E. van; Leeuwen, R.B. van; Zaag-Loonen, H.J. van der; Masius-Olthof, S.; Bloem, B.R.

    2013-01-01

    BACKGROUND: Dizziness is a frequent complaint of patients with Parkinson's disease (PD), and orthostatic hypotension (OH) is often thought to be the cause. We studied whether benign paroxysmal positional vertigo (BPPV) could also be an explanation. AIM: To assess the prevalence of benign paroxysmal

  12. Diurnal and nocturnal drooling in Parkinson's disease.

    NARCIS (Netherlands)

    Kalf, J.G.; Bloem, B.R.; Munneke, M.

    2012-01-01

    Drooling as symptom of Parkinson's disease (PD) has thus far been poorly defined. This uncertainty is reflected by high variations in published prevalence rates. The aim of this study was to investigate the prevalence of saliva loss versus accumulation of saliva as a possible preliminary stage, and

  13. Cyclooxygenase and Neuroinflammation in Parkinson's Disease Neurodegeneration

    NARCIS (Netherlands)

    Bartels, Anna L.; Leenders, Klaus L.

    2010-01-01

    Cyclooxygenase (COX) expression in the brain is associated with pro-inflammatory activities, which are instrumental in neurodegenerative processes such as Parkinson's disease (PD). It is discussed that drugs with the capacity to rescue dopaminergic neurons from microglia toxicity and neuroinflammato

  14. Impulse control disorders in Parkinson's disease

    OpenAIRE

    Stacy, Mark

    2009-01-01

    Since the original descriptions of hedonistic homeostatic dysregulation syndrome and pathological gambling in Parkinson's disease, impulse control disorders, such as compulsive spending, punding, or binge eating, are increasingly recognized. Although the term hedonistic homeostatic dysregulation syndrome has been supplanted by the concept of the dopamine dysregulation syndrome, the features of severe dyskinesias, cyclical mood disorder with hypomania or manic psychosis, and impairment of soci...

  15. Phosphorylated α-synuclein in Parkinson's disease

    DEFF Research Database (Denmark)

    Stewart, Tessandra; Sossi, Vesna; Aasly, Jan O;

    2015-01-01

    INTRODUCTION: α-Synuclein (α-syn) is a key protein in Parkinson's disease (PD), and one of its phosphorylated forms, pS129, is higher in PD patients than healthy controls. However, few studies have examined its levels in longitudinally collected cerebrospinal fluid (CSF) or in preclinical cases. ...

  16. Head injury and risk for Parkinson disease

    DEFF Research Database (Denmark)

    Kenborg, Line; Rugbjerg, Kathrine; Lee, Pei-Chen

    2015-01-01

    OBJECTIVE: To examine the association between head injuries throughout life and the risk for Parkinson disease (PD) in an interview-based case-control study. METHODS: We identified 1,705 patients diagnosed with PD at 10 neurologic centers in Denmark in 1996-2009 and verified their diagnoses...

  17. Nordic walking improves mobility in Parkinson's disease.

    NARCIS (Netherlands)

    Eijkeren, FJ van; Reijmers, R.S.; Kleinveld, M.J.; Minten, A.; Bruggen, J.P.; Bloem, B.R.

    2008-01-01

    Nordic walking may improve mobility in Parkinson's disease (PD). Here, we examined whether the beneficial effects persist after the training period. We included 19 PD patients [14 men; mean age 67.0 years (range 58-76); Hoehn and Yahr stage range 1-3] who received a 6-week Nordic walking exercise pr

  18. Emotion and Object Processing in Parkinson's Disease

    Science.gov (United States)

    Cohen, Henri; Gagne, Marie-Helene; Hess, Ursula; Pourcher, Emmanuelle

    2010-01-01

    The neuropsychological literature on the processing of emotions in Parkinson's disease (PD) reveals conflicting evidence about the role of the basal ganglia in the recognition of facial emotions. Hence, the present study had two objectives. One was to determine the extent to which the visual processing of emotions and objects differs in PD. The…

  19. Voice Onset Time in Parkinson Disease

    Science.gov (United States)

    Fischer, Emily; Goberman, Alexander M.

    2010-01-01

    Research has found that speaking rate has an effect on voice onset time (VOT). Given that Parkinson disease (PD) affects speaking rate, the purpose of this study was to examine VOT with the effect of rate removed (VOT ratio), along with the traditional VOT measure, in individuals with PD. VOT and VOT ratio were examined in 9 individuals with PD…

  20. Occupational risk factors for Parkinson disease

    NARCIS (Netherlands)

    van der Mark, M.|info:eu-repo/dai/nl/322848350

    2014-01-01

    Environmental factors probably play an important role in the etiology of Parkinson disease (PD). However, not many environmental factors have been identified for which unequivocal evidence is available for a relation with PD risk. The main focus of the research described in this thesis was on studyi

  1. Detection of arousals in Parkinson's disease patients

    DEFF Research Database (Denmark)

    Sørensen, Gertrud Laura; Kempfner, Jacob; Jennum, Poul

    2011-01-01

    suffering from Parkinson's disease (PD). The proposed algorithm uses features from EEG, EMG and the manual sleep stage scoring as input to a feed-forward artificial neural network (ANN). The performance of the algorithm has been assessed using polysomnographic (PSG) recordings from a total of 8 patients...

  2. How compensation breaks down in Parkinson's disease

    DEFF Research Database (Denmark)

    Navntoft, Charlotte Amalie; Dreyer, Jakob Kisbye

    2016-01-01

    The bradykinesia and other motor signs of Parkinson's disease (PD) are linked to progressive loss of substantia nigra dopamine (DA) neurons innervating the striatum. However, the emergence of idiopathic PD is likely preceded by a prolonged subclinical phase, which may be masked by a variety of pre...

  3. Nordic walking improves mobility in Parkinson's disease.

    NARCIS (Netherlands)

    Eijkeren, FJ van; Reijmers, R.S.; Kleinveld, M.J.; Minten, A.; Bruggen, J.P.; Bloem, B.R.

    2008-01-01

    Nordic walking may improve mobility in Parkinson's disease (PD). Here, we examined whether the beneficial effects persist after the training period. We included 19 PD patients [14 men; mean age 67.0 years (range 58-76); Hoehn and Yahr stage range 1-3] who received a 6-week Nordic walking exercise

  4. Quality indicators for physiotherapy in Parkinson's disease.

    NARCIS (Netherlands)

    Nijkrake, M.J.; Keus, S.H.J.; Ewalds, H.; Overeem, S.; Braspenning, J.C.C.; Oostendorp, R.A.B.; Hendriks, E.J.; Bloem, B.R.; Munneke, M.

    2009-01-01

    AIM: The aim of this study was to develop quality indicators for physiotherapy in Parkinson's disease (PD) according to international criteria. METHODS: Indicators were based on an evidence-based guideline for physiotherapy in PD. Guideline recommendations were transformed into indicators and rated

  5. Occupational risk factors for Parkinson disease

    NARCIS (Netherlands)

    van der Mark, M.

    2014-01-01

    Environmental factors probably play an important role in the etiology of Parkinson disease (PD). However, not many environmental factors have been identified for which unequivocal evidence is available for a relation with PD risk. The main focus of the research described in this thesis was on studyi

  6. Mortality in patients with Parkinson's disease

    DEFF Research Database (Denmark)

    Wermuth, L; Stenager, E; Boldsen, J

    1995-01-01

    INTRODUCTION: After the introduction of L-dopa the mortality rate in Parkinson's disease (PD) patients has changed, but is still higher than in the background population. MATERIAL & METHODS: Mortality, age at death and cause of death in a group of PD patients compared with the background population...

  7. Hypocretin (orexin) loss in Parkinson's disease.

    NARCIS (Netherlands)

    Fronczek, R.; Overeem, S.; Lee, S.Y.; Hegeman, I.M.; Pelt, J. van; Duinen, S.G. van; Lammers, G.J.; Swaab, D.F.

    2007-01-01

    The hypothalamic hypocretin (orexin) system plays a central role in the regulation of various functions, including sleep/wake regulation and metabolism. There is a growing interest in hypocretin function in Parkinson's disease (PD), given the high prevalence of non-motor symptoms such as sleep distu

  8. Quantitative Motor Performance and Sleep Benefit in Parkinson Disease

    NARCIS (Netherlands)

    Gilst, M.M. van; Mierlo, P. van; Bloem, B.R.; Overeem, S.

    2015-01-01

    STUDY OBJECTIVES: Many people with Parkinson disease experience "sleep benefit": temporarily improved mobility upon awakening. Here we used quantitative motor tasks to assess the influence of sleep on motor functioning in Parkinson disease. DESIGN: Eighteen Parkinson patients with and 20 without sub

  9. Treatment of Parkinson disease: a 64-year-old man with motor complications of advanced Parkinson disease.

    Science.gov (United States)

    Tarsy, Daniel

    2012-06-06

    In early stages, Parkinson disease typically begins with asymmetric or unilateral motor symptoms due to combinations of mild bradykinesia, rigidity, and tremor. In most cases, with progression, signs of more generalized bradykinesia appear, which include facial masking, reduced voice volume, and slowing of activities of daily living. In more advanced Parkinson disease, other disabling manifestations may follow, such as impaired balance, gait freezing, falls, speech disturbance, and cognitive impairment. Levodopa is the most effective medical treatment for Parkinson disease. However, motor complications uniquely related to levodopa treatment may emerge that may be difficult to manage. These include fluctuating levodopa responses and involuntary movements and postures known as dyskinesia and dystonia. Medication adjustments are usually effective, but in some cases surgical intervention with deep brain stimulation becomes necessary to alleviate motor complications. The case of Mr L, a man with an 11-year history of Parkinson disease, illustrates these emerging motor complications and the manner in which they may be managed both medically and surgically.

  10. Nocturnal hypokinesia and sleep quality in Parkinson's disease.

    NARCIS (Netherlands)

    Louter, M.; Munneke, M.; Bloem, B.R.; Overeem, S.

    2012-01-01

    OBJECTIVES: To study the relationship between nocturnal hypokinesia and sleep quality in Parkinson's disease (PD). DESIGN: Questionnaire study using intergroup analysis. SETTING: Parkinson Centre Nijmegen, a tertiary university referral center. PARTICIPANTS: Two hundred forty individuals with

  11. A phenotypic model recapitulating the neuropathology of Parkinson's disease

    OpenAIRE

    Ferris, Craig F.; Marella, Mathieu; Smerkers, Brian; Barchet, Thomas M.; Gershman, Benjamin; Matsuno-Yagi, Akemi; Yagi, Takao

    2013-01-01

    This study was undertaken to develop a phenotypic model recapitulating the neuropathology of Parkinson's disease (PD). Such a model would show loss of dopamine in the basal ganglia, appearance of Lewy bodies, and the early stages of motor dysfunction. The model was developed by subcutaneously injecting biodegradable microspheres of rotenone, a complex I inhibitor in 8–9 month old, ovariectomized Long–Evans rats. Animals were observed for changes in body weight and motor activity. At the end o...

  12. Drugs of abuse and Parkinson's disease.

    Science.gov (United States)

    Mursaleen, Leah R; Stamford, Jonathan A

    2016-01-01

    The term "drug of abuse" is highly contextual. What constitutes a drug of abuse for one population of patients does not for another. It is therefore important to examine the needs of the patient population to properly assess the status of drugs of abuse. The focus of this article is on the bidirectional relationship between patients and drug abuse. In this paper we will introduce the dopaminergic systems of the brain in Parkinson's and the influence of antiparkinsonian drugs upon them before discussing this synergy of condition and medication as fertile ground for drug abuse. We will then examine the relationship between drugs of abuse and Parkinson's, both beneficial and deleterious. In summary we will draw the different strands together and speculate on the future merit of current drugs of abuse as treatments for Parkinson's disease.

  13. Statin use and Parkinson's disease in Denmark

    DEFF Research Database (Denmark)

    Ritz, Beate; Manthripragada, Angelika D; Qian, Lei

    2010-01-01

    The objective of this study was to investigate whether statin (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor) use is associated with risk of Parkinson's disease (PD) in Denmark. We identified 1,931 patients with a first time diagnosis of PD reported in hospital or outpatient clinic...... records between 2001 and 2006. We density matched to these patients 9,651 population controls by birth year and sex relying on the Danish population register. For every participant, we identified pharmacy records of statin and anti-Parkinson drug prescriptions since 1995 and before index date from...... a prescription medication use database for all Danish residents. Whenever applicable, the index dates for cases and their corresponding controls were advanced to the date of first recorded prescription for anti-Parkinson drugs. In our primary analyses, we excluded all statin prescriptions 2-years before PD...

  14. Biomarkers of Parkinson's disease: present and future.

    Science.gov (United States)

    Miller, Diane B; O'Callaghan, James P

    2015-03-01

    Sporadic or idiopathic Parkinson's disease (PD) is an age-related neurodegenerative disorder of unknown origin that ranks only second behind Alzheimer's disease (AD) in prevalence and its consequent social and economic burden. PD neuropathology is characterized by a selective loss of dopaminergic neurons in the substantia nigra pars compacta; however, more widespread involvement of other CNS structures and peripheral tissues now is widely documented. The onset of molecular and cellular neuropathology of PD likely occurs decades before the onset of the motor symptoms characteristic of PD. The hallmark symptoms of PD, resting tremors, rigidity and postural disabilities, are related to dopamine (DA) deficiency. Current therapies treat these symptoms by replacing or boosting existing DA. All current interventions have limited therapeutic benefit for disease progression because damage likely has progressed over an estimated period of ~5 to 15years to a loss of 60%-80% of the nigral DA neurons, before symptoms emerge. There is no accepted definitive biomarker of PD. An urgent need exists to develop early diagnostic biomarkers for two reasons: (1) to intervene at the onset of disease and (2) to monitor the progress of therapeutic interventions that may slow or stop the course of the disease. In the context of disease development, one of the promises of personalized medicine is the ability to predict, on an individual basis, factors contributing to the susceptibility for the development of a given disease. Recent advances in our understanding of genetic factors underlying or contributing to PD offer the potential for monitoring susceptibility biomarkers that can be used to identify at-risk individuals and possibly prevent the onset of disease through treatment. Finally, the exposome concept is new in the biomarker discovery arena and it is suggested as a way to move forward in identifying biomarkers of neurological diseases. It is a two-stage scheme involving a first stage

  15. Prevalence and incidence of Parkinson's disease in The Faroe Islands

    DEFF Research Database (Denmark)

    Wermuth, Lene; Bech, Sara Brynhild Winther; Petersen, Maria Skaalum;

    2008-01-01

    A study in The Faroe Islands in 1995 suggested a high prevalence of idiopathic Parkinson's disease (IPD) and total parkinsonism of 187.6 and 233.4 per 100,000 inhabitants respectively.......A study in The Faroe Islands in 1995 suggested a high prevalence of idiopathic Parkinson's disease (IPD) and total parkinsonism of 187.6 and 233.4 per 100,000 inhabitants respectively....

  16. The coeruleus/subcoeruleus complex in rapid eye movement sleep behaviour disorders in Parkinson's disease.

    Science.gov (United States)

    García-Lorenzo, Daniel; Longo-Dos Santos, Clarisse; Ewenczyk, Claire; Leu-Semenescu, Smaranda; Gallea, Cecile; Quattrocchi, Graziella; Pita Lobo, Patricia; Poupon, Cyril; Benali, Habib; Arnulf, Isabelle; Vidailhet, Marie; Lehericy, Stéphane

    2013-07-01

    In Parkinson's disease, rapid eye movement sleep behaviour disorder is an early non-dopaminergic syndrome with nocturnal violence and increased muscle tone during rapid eye movement sleep that can precede Parkinsonism by several years. The neuronal origin of rapid eye movement sleep behaviour disorder in Parkinson's disease is not precisely known; however, the locus subcoeruleus in the brainstem has been implicated as this structure blocks muscle tone during normal rapid eye movement sleep in animal models and can be damaged in Parkinson's disease. Here, we studied the integrity of the locus coeruleus/subcoeruleus complex in patients with Parkinson's disease using combined neuromelanin-sensitive, structural and diffusion magnetic resonance imaging approaches. We compared 24 patients with Parkinson's disease and rapid eye movement sleep behaviour disorder, 12 patients without rapid eye movement sleep behaviour disorder and 19 age- and gender-matched healthy volunteers. All subjects underwent clinical examination and characterization of rapid eye movement sleep using video-polysomnography and multimodal imaging at 3 T. Using neuromelanin-sensitive imaging, reduced signal intensity was evident in the locus coeruleus/subcoeruleus area in patients with Parkinson's disease that was more marked in patients with than those without rapid eye movement sleep behaviour disorder. Reduced signal intensity correlated with the percentage of abnormally increased muscle tone during rapid eye movement sleep. The results confirmed that this complex is affected in Parkinson's disease and showed a gradual relationship between damage to this structure, presumably the locus subcoeruleus, and abnormal muscle tone during rapid eye movement sleep, which is the cardinal marker of rapid eye movement sleep behaviour disorder. In longitudinal studies, the technique may also provide early markers of non-dopaminergic Parkinson's disease pathology to predict the occurrence of Parkinson's disease.

  17. Catechol-O-methyltransferase and Parkinson's disease.

    OpenAIRE

    Tai CH; Wu RM

    2002-01-01

    Parkinson's disease (PD) is one of the main causes of neurological disability in the elderly. Levodopa is the gold standard for treating this disease, but chronic levodopa therapy is complicated by motor fluctuation and dyskinesia. The catechol-O-methyltransferase (COMT) inhibitors represent a new class of antiparkinsonian drugs. When coadministered with levodopa/decarboxylase inhibitor, 2 COMT inhibitors, tolcapone and entacapone have been shown to improve the clinical benefit of levodopa. C...

  18. Parkinson's disease: carbidopa, nausea, and dyskinesia

    Directory of Open Access Journals (Sweden)

    Hinz M

    2014-11-01

    Full Text Available Marty Hinz,1 Alvin Stein,2 Ted Cole3 1Clinical Research, NeuroResearch Clinics, Cape Coral, FL, 2Stein Orthopedic Associates, Plantation, FL, 3Cole Center for Healing, Cincinnati, OH, USA Abstract: When ʟ-dopa use began in the early 1960s for the treatment of Parkinson's disease, nausea and reversible dyskinesias were experienced as continuing side effects. Carbidopa or benserazide was added to ʟ-dopa in 1975 solely to control nausea. Subsequent to the increasing use of carbidopa has been the recognition of irreversible dyskinesias, which have automatically been attributed to ʟ-dopa. The research into the etiology of these phenomena has identified the causative agent of the irreversible dyskinesias as carbidopa, not ʟ-dopa. The mechanism of action of the carbidopa and benserazide causes irreversible binding and inactivation of vitamin B6 throughout the body. The consequences of this action are enormous, interfering with over 300 enzyme and protein functions. This has the ability to induce previously undocumented profound antihistamine dyskinesias, which have been wrongly attributed to ʟ-dopa and may be perceived as irreversible if proper corrective action is not taken. Keywords: vitamin B6, PLP, irreversible, pyridoxal 5'-phosphate

  19. Postural & striatal deformities in Parkinson`s disease: Are these rare?

    Directory of Open Access Journals (Sweden)

    Sanjay Pandey

    2016-01-01

    Full Text Available Parkinson`s disease (PD is the most common neurodegenerative disease and is characterized by tremor, rigidity and akinesia. Diagnosis is clinical in the majority of the patients. Patients with PD may have stooped posture but some of them develop different types of postural and striatal deformities. Usually these deformities are more common in atypical parkinsonian disorders such as progressive supranuclear palsy and multisystem atrophy. But in many studies it has been highlighted that these may also be present in approximately one third of PD patients leading to severe disability. These include antecollis or dropped head, camptocormia, p0 isa syndrome, scoliosis, striatal hands and striatal toes. The pathogenesis of these deformities is a complex combination of central and peripheral influences such as rigidity, dystonia and degenerative skeletal changes. Duration of parkinsonism symptoms is an important risk factor and in majority of the patients these deformities are seen in advanced statge of the disease. The patients with such symptoms may initially respond to dopaminergic medications but if not intervened they may become fixed and difficult to treat. Pain and restriction of movement are most common clinical manifestations and these may mimick symptoms of musculoskeletal disorders like rheumatoid arthritis. Early diagnosis is important as the patients may respond to adjustment in dopaminergic medications. Recent advances such as deep brain stimulation (DBS and ultrasound guided botulinum toxin injection are helpful in management of these deformities in patients with PD.

  20. Postural & striatal deformities in Parkinson`s disease: Are these rare?

    Science.gov (United States)

    Pandey, Sanjay; Garg, Hitesh

    2016-01-01

    Parkinson`s disease (PD) is the most common neurodegenerative disease and is characterized by tremor, rigidity and akinesia. Diagnosis is clinical in the majority of the patients. Patients with PD may have stooped posture but some of them develop different types of postural and striatal deformities. Usually these deformities are more common in atypical parkinsonian disorders such as progressive supranuclear palsy and multisystem atrophy. But in many studies it has been highlighted that these may also be present in approximately one third of PD patients leading to severe disability. These include antecollis or dropped head, camptocormia, p0 isa syndrome, scoliosis, striatal hands and striatal toes. The pathogenesis of these deformities is a complex combination of central and peripheral influences such as rigidity, dystonia and degenerative skeletal changes. Duration of parkinsonism symptoms is an important risk factor and in majority of the patients these deformities are seen in advanced statge of the disease. The patients with such symptoms may initially respond to dopaminergic medications but if not intervened they may become fixed and difficult to treat. Pain and restriction of movement are most common clinical manifestations and these may mimick symptoms of musculoskeletal disorders like rheumatoid arthritis. Early diagnosis is important as the patients may respond to adjustment in dopaminergic medications. Recent advances such as deep brain stimulation (DBS) and ultrasound guided botulinum toxin injection are helpful in management of these deformities in patients with PD.