Estrogen and early-onset Alzheimer's disease

NARCIS (Netherlands)

A.J.C. Slooter (Arjen); J.B. Bronzova (Juliana); A. Hofman (Albert); C. van Broeckhoven (Christine); C.M. van Duijn (Cornelia); J.C.M. Witteman (Jacqueline)

1999-01-01

textabstractEstrogen use may be protective for Alzheimer's disease with late onset. However, the effects on early onset Alzheimer's disease are unclear. This issue was studied in a population based setting. For each female patient, a female control was matched on age (within 5 years) and place of

The role of early life environmental risk factors in Parkinson disease: what is the evidence?

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Logroscino, Giancarlo

2005-09-01

Parkinson disease (PD) is of unknown but presumably multifactorial etiology. Neuropathologic studies and animal models show that exposure to environmental neurotoxicants can determine progressive damage in the substantia nigra many years before the onset of clinical parkinsonism. Therefore, PD, like other neurologic diseases related to aging, may be determined by exposures present in the environment early during the life span or even during pregnancy. Recent epidemiologic studies have focused on the possible role of environmental risk factors present during adult life or aging. Smoking and coffee drinking have consistently been identified to have protective associations, whereas roles of other risk factors such as pesticide and infections have been reported in some studies but not replicated in others. Both genetic inheritance and sharing of common environment in the same family explain the increased risk of PD of relatives of PD cases compared with relatives of controls in familial aggregation studies. Much evidence indicates that risk factors that have a long latency or a slow effect could be important for late-onset PD. Further epidemiologic studies are warranted in this area.

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

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

2005-07-01

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

Common pathogenic effects of missense mutations in the P-type ATPase ATP13A2 (PARK9) associated with early-onset parkinsonism.

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Podhajska, Agata; Musso, Alessandra; Trancikova, Alzbeta; Stafa, Klodjan; Moser, Roger; Sonnay, Sarah; Glauser, Liliane; Moore, Darren J

2012-01-01

Mutations in the ATP13A2 gene (PARK9) cause autosomal recessive, juvenile-onset Kufor-Rakeb syndrome (KRS), a neurodegenerative disease characterized by parkinsonism. KRS mutations produce truncated forms of ATP13A2 with impaired protein stability resulting in a loss-of-function. Recently, homozygous and heterozygous missense mutations in ATP13A2 have been identified in subjects with early-onset parkinsonism. The mechanism(s) by which missense mutations potentially cause parkinsonism are not understood at present. Here, we demonstrate that homozygous F182L, G504R and G877R missense mutations commonly impair the protein stability of ATP13A2 leading to its enhanced degradation by the proteasome. ATP13A2 normally localizes to endosomal and lysosomal membranes in neurons and the F182L and G504R mutations disrupt this vesicular localization and promote the mislocalization of ATP13A2 to the endoplasmic reticulum. Heterozygous T12M, G533R and A746T mutations do not obviously alter protein stability or subcellular localization but instead impair the ATPase activity of microsomal ATP13A2 whereas homozygous missense mutations disrupt the microsomal localization of ATP13A2. The overexpression of ATP13A2 missense mutants in SH-SY5Y neural cells does not compromise cellular viability suggesting that these mutant proteins lack intrinsic toxicity. However, the overexpression of wild-type ATP13A2 may impair neuronal integrity as it causes a trend of reduced neurite outgrowth of primary cortical neurons, whereas the majority of disease-associated missense mutations lack this ability. Finally, ATP13A2 overexpression sensitizes cortical neurons to neurite shortening induced by exposure to cadmium or nickel ions, supporting a functional interaction between ATP13A2 and heavy metals in post-mitotic neurons, whereas missense mutations influence this sensitizing effect. Collectively, our study provides support for common loss-of-function effects of homozygous and heterozygous missense

Imaging movement-related activity in medicated Parkin-associated and sporadic Parkinson's disease

DEFF Research Database (Denmark)

van Eimeren, Thilo; Binkofski, Ferdinand; Buhmann, Carsten

2010-01-01

Treatment-related motor complications such as dyskinesias are a major problem in the long-term management of Parkinson's disease (PD). In sporadic PD, a relatively early onset of the disease is known to be associated with an early development of dyskinesias. Although linked with early onset...... selected movements. Patients with Parkin-associated and sporadic PD showed no difference in movement-related activation patterns. Moreover, the covariates 'age' and 'disease duration' similarly influenced brain activation in both patient groups. The present finding suggests that a stable long-term motor...

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

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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

Motor and non-motor symptoms in old-age onset Parkinson's disease patients.

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Mendonça, Marcelo D; Lampreia, Tania; Miguel, Rita; Caetano, André; Barbosa, Raquel; Bugalho, Paulo

2017-07-01

Advancing age is a well-known risk factor for Parkinson's disease (PD). With population ageing it is expected that the total number of patients with PD onset at oldage increases. Information on the motor but particularly on non-motor phenotype of this late-onset population is lacking. We recruited 24 patients with PD onset at or over 75 years. Each patient was matched with 1 control patient with PD onset between the ages of 40 and 65 and matched for disease duration. Both groups were assessed with the UPDRS, the Non-motor symptoms scale (NMSS) and other scales to assess non-motor symptoms. Groups were compared with conditional logistic regression analysis. Old-age onset PD was, on average, 80 years at the time of PD onset while middle-age onset were 59. Disease duration was approximately 5 years in both groups. While no difference was observed in the total UPDRS-III scores, old-age onset PD was associated with higher axial symptoms (7.42 vs. 4.63, p = 0.011) and a higher frequency of dementia (7/24 vs. 0/24, p = 0.009). While no difference in the total number of non-motor symptoms was observed (6.79 vs. 6.22, p = 0.310), old-age onset patients had a higher prevalence of gastrointestinal symptoms (20/24 vs. 12/24, p = 0.037). For the same disease duration, older age onset is associated with worse axial motor dysfunction and dementia in PD patients. Beside gastrointestinal symptoms, non-motor symptoms are not associated with age.

Risk factor studies of age-at-onset in a sample ascertained for Parkinson disease affected sibling pairs: a cautionary tale.

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Wilk, Jemma B; Lash, Timothy L

2007-04-04

An association between exposure to a risk factor and age-at-onset of disease may reflect an effect on the rate of disease occurrence or an acceleration of the disease process. The difference in age-at-onset arising from case-only studies, however, may also reflect secular trends in the prevalence of exposure to the risk factor. Comparisons of age-at-onset associated with risk factors are commonly performed in case series enrolled for genetic linkage analysis of late onset diseases. We describe how the results of age-at-onset studies of environmental risk factors reflect the underlying structure of the source population, rather than an association with age-at-onset, by contrasting the effects of coffee drinking and cigarette smoking on Parkinson disease age-at-onset with the effects on age-at-enrollment in a population based study sample. Despite earlier evidence to suggest a protective association of coffee drinking and cigarette smoking with Parkinson disease risk, the age-at-onset results are comparable to the patterns observed in the population sample, and thus a causal inference from the age-at-onset effect may not be justified. Protective effects of multivitamin use on PD age-at-onset are also shown to be subject to a bias from the relationship between age and multivitamin initiation. Case-only studies of age-at-onset must be performed with an appreciation for the association between risk factors and age and ageing in the source population.

Risk factor studies of age-at-onset in a sample ascertained for Parkinson disease affected sibling pairs: a cautionary tale

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Lash Timothy L

2007-04-01

Full Text Available Abstract An association between exposure to a risk factor and age-at-onset of disease may reflect an effect on the rate of disease occurrence or an acceleration of the disease process. The difference in age-at-onset arising from case-only studies, however, may also reflect secular trends in the prevalence of exposure to the risk factor. Comparisons of age-at-onset associated with risk factors are commonly performed in case series enrolled for genetic linkage analysis of late onset diseases. We describe how the results of age-at-onset studies of environmental risk factors reflect the underlying structure of the source population, rather than an association with age-at-onset, by contrasting the effects of coffee drinking and cigarette smoking on Parkinson disease age-at-onset with the effects on age-at-enrollment in a population based study sample. Despite earlier evidence to suggest a protective association of coffee drinking and cigarette smoking with Parkinson disease risk, the age-at-onset results are comparable to the patterns observed in the population sample, and thus a causal inference from the age-at-onset effect may not be justified. Protective effects of multivitamin use on PD age-at-onset are also shown to be subject to a bias from the relationship between age and multivitamin initiation. Case-only studies of age-at-onset must be performed with an appreciation for the association between risk factors and age and ageing in the source population.

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...

Early-onset Alzheimer's Disease Phenotypes: Neuropsychology and Neural Networks

Science.gov (United States)

2017-05-11

Alzheimer Disease, Early Onset; Alzheimer Disease; Alzheimer Disease, Late Onset; Dementia, Alzheimer Type; Logopenic Progressive Aphasia; Primary Progressive Aphasia; Visuospatial/Perceptual Abilities; Posterior Cortical Atrophy; Executive Dysfunction; Corticobasal Degeneration; Ideomotor Apraxia

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

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Christine Petschow

Full Text Available 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.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.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.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 stages of Parkinson's disease.

Early-onset stargardt disease: phenotypic and genotypic characteristics

NARCIS (Netherlands)

Lambertus, S.; Huet, R.A.C. van; Bax, N.M.; Hoefsloot, L.H.; Cremers, F.P.M.; Boon, C.J.F.; Klevering, B.J.; Hoyng, C.B.

2015-01-01

OBJECTIVE: To describe the phenotype and genotype of patients with early-onset Stargardt disease. DESIGN: Retrospective cohort study. PARTICIPANTS: Fifty-one Stargardt patients with age at onset onset, medical history, initial

[Epidemiology and causes of Parkinson's disease].

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Lill, C M; Klein, C

2017-04-01

Parkinson's disease (PD) is the second most common neurodegenerative disease and has a growing socioeconomic impact due to demographic changes in the industrial nations. There are several forms of PD, a fraction of which (parkinsonism including three autosomal dominantly (SNCA, LRRK2, VPS35) and three autosomal recessively inherited ones (Parkin, PINK1, DJ-1). In addition, there are a plethora of genes causing atypical forms of parkinsonism. In contrast, idiopathic PD is of a multifactorial nature. Genome-wide association studies have established a total of 26 genetic loci for this form of the disease; however, for most of these loci the underlying functional genetic variants have not yet been identified and the respective disease mechanisms remain unresolved. Furthermore, there are a number of environmental and life style factors that are associated with idiopathic PD. Exposure to pesticides and possibly a history of head trauma represent genuine risk factors. Other PD-associated factors, such as smoking and intake of coffee and alcohol may not represent risk factors per se and the cause-effect relationship has not yet been elucidated for most of these factors. A patient with a positive family history and/or an early age of disease onset should undergo counseling with respect to a possible monogenic form of the disease. Disease prediction based on genetic, environmental and life style factors is not yet possible for idiopathic PD and potential gene-specific therapies are currently in the development or early testing phase.

Sleepiness in Idiopathic REM Sleep Behavior Disorder and Parkinson Disease.

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Arnulf, Isabelle; Neutel, Dulce; Herlin, Bastien; Golmard, Jean-Louis; Leu-Semenescu, Smaranda; Cochen de Cock, Valérie; Vidailhet, Marie

2015-10-01

To determine whether patients with idiopathic and symptomatic RBD were sleepier than controls, and if sleepiness in idiopathic RBD predicted earlier conversion to Parkinson disease. The Epworth Sleepiness Scale (ESS) and its determinants were compared at the time of a video-polysomnography for an RBD diagnosis in patients with idiopathic RBD, in patients with Parkinson disease, and in controls. Whether sleepiness at time of RBD diagnosis predicted an earlier conversion to neurodegenerative diseases was retrospectively analyzed in the followed-up patients. The 75 patients with idiopathic RBD were sleepier (ESS: 7.8 ± 4.6) at the time of RBD diagnosis than 74 age- and sex-matched controls (ESS: 5.0 ± 3.6, P sleep measures. Among the 69 patients with idiopathic RBD who were followed up for a median 3 years (1-15 years), 16 (23.2%) developed parkinsonism (n = 6), dementia (n = 6), dementia plus parkinsonism (n = 2), and multiple system atrophy (n = 2). An ESS greater than 8 at time of RBD diagnosis predicted a shorter time to phenoconversion to parkinsonism and dementia, from RBD onset, and from RBD diagnosis (when adjusted for age and time between RBD onset and diagnosis). Sleepiness is associated with idiopathic REM sleep behavior disorder and predicts more rapid conversion to parkinsonism and dementia, suggesting it is an early marker of neuronal loss in brainstem arousal systems. © 2015 Associated Professional Sleep Societies, LLC.

Exercise and Early-Onset Alzheimer’s Disease: Theoretical Considerations

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Astrid M. Hooghiemstra

2012-04-01

Full Text Available Background/Aims: Although studies show a negative relationship between physical activity and the risk for cognitive impairment and late-onset Alzheimer’s disease, studies concerning early-onset Alzheimer’s disease (EOAD are lacking. This review aims to justify the value of exercise interventions in EOAD by providing theoretical considerations that include neurobiological processes. Methods: A literature search on key words related to early-onset dementia, exercise, imaging, neurobiological mechanisms, and cognitive reserve was performed. Results/Conclusion: Brain regions and neurobiological processes contributing to the positive effects of exercise are affected in EOAD and, thus, provide theoretical support for exercise interventions in EOAD. Finally, we present the design of a randomized controlled trial currently being conducted in early-onset dementia patients.

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 exo...

Differences in early speech patterns between Parkinson variant of multiple system atrophy and Parkinson's disease.

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Huh, Young Eun; Park, Jongkyu; Suh, Mee Kyung; Lee, Sang Eun; Kim, Jumin; Jeong, Yuri; Kim, Hee-Tae; Cho, Jin Whan

2015-08-01

In Parkinson variant of multiple system atrophy (MSA-P), patterns of early speech impairment and their distinguishing features from Parkinson's disease (PD) require further exploration. Here, we compared speech data among patients with early-stage MSA-P, PD, and healthy subjects using quantitative acoustic and perceptual analyses. Variables were analyzed for men and women in view of gender-specific features of speech. Acoustic analysis revealed that male patients with MSA-P exhibited more profound speech abnormalities than those with PD, regarding increased voice pitch, prolonged pause time, and reduced speech rate. This might be due to widespread pathology of MSA-P in nigrostriatal or extra-striatal structures related to speech production. Although several perceptual measures were mildly impaired in MSA-P and PD patients, none of these parameters showed a significant difference between patient groups. Detailed speech analysis using acoustic measures may help distinguish between MSA-P and PD early in the disease process. Copyright © 2015 Elsevier Inc. All rights reserved.

Cerebrospinal fluid levels of catecholamines and its metabolites in Parkinson's disease

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Dammann Andersen, Andreas; Blaabjerg, Morten; Binzer, Michael

2017-01-01

Levodopa (l-DOPA, l-3,4-dihydroxyphenylalanine) is the most effective drug in the symptomatic treatment of Parkinson's disease (PD), but chronic use initiates a maladaptive process leading to l-DOPA-induced dyskinesia (LID). Risk factors for early onset LID include younger age, more severe diseas...

A controlled, randomized, delayed-start study of rasagiline in early Parkinson disease.

Science.gov (United States)

2004-04-01

Treatment with rasagiline mesylate, an irreversible monoamine oxidase type B inhibitor, improves symptoms of early Parkinson disease (PD). Preclinical studies suggest that this compound may also modify the progression of PD. To compare the effects of early and later initiation of rasagiline on progression of disability in patients with PD. Double-blind, parallel-group, randomized, delayed-start clinical trial. Four hundred four subjects with early PD, not requiring dopaminergic therapy, enrolled at 32 sites in the United States and Canada. Subjects were randomized to receive rasagiline, 1 or 2 mg/d, for 1 year or placebo for 6 months followed by rasagiline, 2 mg/d, for 6 months. Change in total Unified Parkinson's Disease Rating Scale score from baseline to 12 months. Three hundred seventy-one subjects were included in the 1-year efficacy analysis. Subjects treated with rasagiline, 2 mg/d, for 1 year had a 2.29-unit smaller increase in mean adjusted total Unified Parkinson's Disease Rating Scale score compared with subjects treated with placebo for 6 months followed by rasagiline, 2 mg/d, for 6 months (P =.01). The mean adjusted difference between the placebo/rasagiline, 2 mg/d, group and those receiving rasagiline, 1 mg/d, for 1 year was -1.82 unit on the Unified Parkinson's Disease Rating Scale score (P =.05). Subjects treated with rasagiline, 2 and 1 mg/d, for 12 months showed less functional decline than subjects whose treatment was delayed for 6 months.

Gender differences in Parkinson's disease

NARCIS (Netherlands)

Haaxma, Charlotte A.; Bloem, Bastiaan R.; Borm, George F.; Oyen, Wim J. G.; Leenders, Klaus L.; Eshuis, Silvia; Booij, Jan; Dluzen, Dean E.; Horstink, Martin W. I. M.

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 Results: Age at onset

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

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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

Can Biomarkers Help the Early Diagnosis of Parkinson's Disease?

Institute of Scientific and Technical Information of China (English)

Weidong Le; Jie Dong; Song Li; Amos D.Korczyn

2017-01-01

Parkinson's disease (PD) is a complex neurodegenerative disease with progressive loss of dopamine neurons.PD patients usually manifest a series of motor and non-motor symptoms.In order to provide better early diagnosis and subsequent disease-modifying therapies for PD patients,there is an urgent need to identify sensitive and specific biomarkers.Biomarkers can be divided into four categories:clinical,imaging,biochemical,and genetic.Ideal biomarkers not only improve our understanding of PD pathogenesis and progression,but also provide benefits for early risk evaluation and clinical diagnosis of PD.Although many efforts have been made and several biomarkers have been extensively investigated,few if any have been found useful for early diagnosis.Here,we summarize recent developments in the discovered biomarkers of PD and discuss their merits and limitations for the early diagnosis of PD.

Therapies in Parkinson's disease.

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Jankovic, Joseph; Poewe, Werner

2012-08-01

This review examines currently available therapeutic strategies for Parkinson's disease, emphasizing evidence-based data as well as a patient-centered approach to the treatment of motor and nonmotor symptoms. Although clinical trials of disease-modifying approaches have been thus far disappointing, steady advances are being made in the symptomatic treatment of Parkinson's disease. In this review, we focus on recent studies with monoamine oxidase type B inhibitors (selegiline and rasagiline), coenzyme Q10, creatine, and exercise in early Parkinson's disease. We also discuss the relative merits and disadvantages of delaying the initiation of levodopa therapy, the role of dopamine agonists, particularly ropinirole and pramipexole, and management of motor and behavioral complications, such as fluctuations, dyskinesias and impulse-control disorders. Novel formulations and delivery approaches for conventional and new drugs are also discussed. Finally, we review recent studies of surgical treatments of Parkinson's disease, such as deep brain stimulation. Numerous clinical trials have provided evidence that health-related quality of life can be substantially improved with early diagnosis and institution of exercise and other physical measures, appropriate timing of dopaminergic therapy, and strategies to delay and treat levodopa-related motor complications and nonmotor Parkinson's disease-related symptoms.

A controlled trial of rasagiline in early Parkinson disease: the TEMPO Study.

Science.gov (United States)

2002-12-01

Monotherapy with rasagiline mesylate may be useful in early Parkinson disease (PD). To evaluate the safety and efficacy of the selective monoamine oxidase type B inhibitor rasagiline. Multicenter, 26-week, parallel-group, randomized, double-blind, placebo-controlled clinical trial. Academically based movement disorders clinics. Patients with early PD not requiring dopaminergic therapy (n = 404). Research participants were randomized to rasagiline mesylate at dosages of 1 mg or 2 mg per day or matching placebo. A 1-week escalation period was followed by a 25-week maintenance period. The primary prespecified measure of efficacy was the change in the total Unified Parkinson's Disease Rating Scal score between baseline and 26 weeks of treatment, comparing each active treatment group with the placebo group. Monotherapy with rasagiline was effective in this 26-week study. The adjusted effect size for the total Unified Parkinson's Disease Rating Scale was -4.20 units comparing 1 mg of rasagiline and placebo (95% confidence interval, -5.66 to -2.73 units; PRasagiline is effective as monotherapy for patients with early PD. The 2 dosages in this trial were both effective relative to placebo. Further study is warranted to evaluate the longer-term effects of rasagiline in PD.

Analyzing the effectiveness of vocal features in early telediagnosis of Parkinson's disease.

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Betul Erdogdu Sakar

Full Text Available The recently proposed Parkinson's Disease (PD telediagnosis systems based on detecting dysphonia achieve very high classification rates in discriminating healthy subjects from PD patients. However, in these studies the data used to construct the classification model contain the speech recordings of both early and late PD patients with different severities of speech impairments resulting in unrealistic results. In a more realistic scenario, an early telediagnosis system is expected to be used in suspicious cases by healthy subjects or early PD patients with mild speech impairment. In this paper, considering the critical importance of early diagnosis in the treatment of the disease, we evaluate the ability of vocal features in early telediagnosis of Parkinson's Disease (PD using machine learning techniques with a two-step approach. In the first step, using only patient data, we aim to determine the patient group with relatively greater severity of speech impairments using Unified Parkinson's Disease Rating Scale (UPDRS score as an index of disease progression. For this purpose, we use three supervised and two unsupervised learning techniques. In the second step, we exclude the samples of this group of patients from the dataset, create a new dataset consisting of the samples of PD patients having less severity of speech impairments and healthy subjects, and use three classifiers with various settings to address this binary classification problem. In this classification problem, the highest accuracy of 96.4% and Matthew's Correlation Coefficient of 0.77 is obtained using support vector machines with third-degree polynomial kernel showing that vocal features can be used to build a decision support system for early telediagnosis of PD.

Limbic grey matter changes in early Parkinson's disease.

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Li, Xingfeng; Xing, Yue; Schwarz, Stefan T; Auer, Dorothee P

2017-05-02

The purpose of this study was to investigate local and network-related changes of limbic grey matter in early Parkinson's disease (PD) and their inter-relation with non-motor symptom severity. We applied voxel-based morphometric methods in 538 T1 MRI images retrieved from the Parkinson's Progression Markers Initiative website. Grey matter densities and cross-sectional estimates of age-related grey matter change were compared between subjects with early PD (n = 366) and age-matched healthy controls (n = 172) within a regression model, and associations of grey matter density with symptoms were investigated. Structural brain networks were obtained using covariance analysis seeded in regions showing grey matter abnormalities in PD subject group. Patients displayed focally reduced grey matter density in the right amygdala, which was present from the earliest stages of the disease without further advance in mild-moderate disease stages. Right amygdala grey matter density showed negative correlation with autonomic dysfunction and positive with cognitive performance in patients, but no significant interrelations were found with anxiety scores. Patients with PD also demonstrated right amygdala structural disconnection with less structural connectivity of the right amygdala with the cerebellum and thalamus but increased covariance with bilateral temporal cortices compared with controls. Age-related grey matter change was also increased in PD preferentially in the limbic system. In conclusion, detailed brain morphometry in a large group of early PD highlights predominant limbic grey matter deficits with stronger age associations compared with controls and associated altered structural connectivity pattern. This provides in vivo evidence for early limbic grey matter pathology and structural network changes that may reflect extranigral disease spread in PD. Hum Brain Mapp, 2017. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. © 2017 The

Diabetes mellitus and Parkinson disease.

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

2018-05-08

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

parkin mutation dosage and the phenomenon of anticipation: a molecular genetic study of familial parkinsonism

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Schellenberg Gerard D

2005-02-01

Full Text Available Abstract Background parkin mutations are a common cause of parkinsonism. Possessing two parkin mutations leads to early-onset parkinsonism, while having one mutation may predispose to late-onset disease. This dosage pattern suggests that some parkin families should exhibit intergenerational variation in age at onset resembling anticipation. A subset of familial PD exhibits anticipation, the cause of which is unknown. The aim of this study was to determine if anticipation was due to parkin mutation dosage. Methods We studied 19 kindreds that had early-onset parkinsonism in the offspring generation, late-onset parkinsonism in the parent generation, and ≥ 20 years of anticipation. We also studied 28 early-onset parkinsonism cases without anticipation. Patients were diagnosed by neurologists at a movement disorder clinic. parkin analysis included sequencing and dosage analysis of all 12 exons. Results Only one of 19 cases had compound parkin mutations, but contrary to our postulate, the affected relative with late-onset parkinsonism did not have a parkin mutation. In effect, none of the anticipation cases could be attributed to parkin. In contrast, 21% of early-onset parkinsonism patients without anticipation had parkin mutations. Conclusion Anticipation is not linked to parkin, and may signify a distinct disease entity.

Factors contributing to malnutrition in patients with Parkinson's disease.

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Kim, Sung R; Chung, Sun J; Yoo, Sung-Hee

2016-04-01

Our objective in this study was to evaluate the nutritional status and to identify clinical, psychosocial, and nutritional factors contributing to malnutrition in Korean patients with Parkinson's disease. We used a descriptive, cross-sectional study design. Of 102 enrolled patients, 26 (25.5%) were malnourished and 27 (26.5%) were at risk of malnutrition based on Mini-Nutritional Assessment scores. Malnutrition was related to activity of daily living score, Hoehn and Yahr stage, duration of levodopa therapy, Beck Depression Inventory and Spielberger's Anxiety Inventory scores, body weight, body weight at onset of Parkinson's disease, and body mass index. On multiple logistic regression analysis, anxiety score, duration of levodopa therapy, body weight at onset of Parkinson's disease, and loss of body weight were significant factors predicting malnutrition in Parkinson's disease patients. Therefore, nutritional assessment, including psychological evaluation, is required for Parkinson's disease patients to facilitate interdisciplinary nutritional intervention for malnourished patients. © 2014 John Wiley & Sons Australia, Ltd.

Non-invasive assessment determine the swallowing and respiration dysfunction in early Parkinson's disease.

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Wang, Chin-Man; Shieh, Wann-Yun; Weng, Yi-Hsin; Hsu, Yi-Hsuan; Wu, Yih-Ru

2017-09-01

Dysphagia is common among patients with Parkinson's disease. Swallowing and its coordination with respiration is extremely important to achieve safety swallowing. Different tools have been used to assess this coordination, however the results have been inconsistent. We aimed to investigate this coordination in patients with Parkinson's disease using a non-invasive method. Signals of submental muscle activity, thyroid cartilage excursion, and nasal airflow during swallowing were recorded simultaneously. Five different water boluses were swallowed three times, and the data were recorded and analyzed. Thirty-seven controls and 42 patients with early-stage Parkinson's disease were included. The rates of non-expiratory/expiratory pre- and post-swallowing respiratory phase patterns were higher in the patients than in the controls (P Parkinson's disease, and safety compensation mechanisms were used more than efficiency during swallowing. The results of this study may serve as a baseline for further research into new treatment regimens and to improve the management of swallowing in patients with Parkinson's disease. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Early-onset Hirayama disease in a female

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Matthias Baumann

2017-01-01

Full Text Available Objectives: Hirayama disease is a rare myelopathy, occurring predominantly in males with onset in the teens. Methods and results: Here, we report a young female patient who developed the first signs of Hirayama disease at 10.5 years of age. Prior to onset, she had experienced a growth spurt and grew about 8 cm. The disease progressed over 3 years and the typical clinical, electrophysiological, and neuroimaging signs of Hirayama disease were found. After this period and achievement of her final height, no further progression was noticed. Conclusions: This case highlights that pediatric neurologists should be aware of Hirayama disease, which can also occur in girls in early adolescence.

Side-of-onset of Parkinson's disease in relation to neuropsychological measures.

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Modestino, Edward J; Amenechi, Chioma; Reinhofer, AnnaMarie; O'Toole, Patrick

2017-01-01

Parkinson's disease (PD) usually emerges with a unilateral side-of-onset (left-onset: LOPD; right-onset: ROPD; Marinus & van Hilten, 2015) due to an asymmetrical degeneration of striatal dopaminergic neurons (Donnemiller et al., Brain , 135, 2012, 3348). This has led to a body of research exploring the cognitive, neuropsychological, and clinical differences between LOPD and ROPD (e.g., Verreyt et al., Neuropsychology Review , 21, 2011, 405). Thirty ROPD and 14 LOPD cases were drawn from a Boston clinic specializing in PD. Various cognitive and neuropsychological measures were used in an attempt to discover if there were indeed any differences between LOPD and ROPD in this cohort. For LOPD, duration of illness was found to be significantly greater than that of ROPD. However, further testing was able to confirm that despite this difference, it was not the cause of the other significant differences found. Furthermore, this increased duration was consistent with a previous study (Munhoz et al., Parkinsonism and Related Disorders , 19, 2013, 77). Performance on the Digit Span Backward (DSB) was found to be significantly poorer in LOPD than ROPD, suggesting compromised executive function in LOPD. Additionally, LOPD had significantly greater anxiety on the DASS Anxiety scales than ROPD. However, unlike Foster et al ( Cognitive and Behavioral Neurology , 23, 2010, 4), this increased anxiety could not account for the poorer performance on the DSB for LOPD. Finally, ROPD had significantly greater magical ideation than LOPD, which can be explained by the theory put forth by Brugger and Graves ( European Archives of Psychiatry , 247, 1997, 55). Clear and significant differences between LOPD and ROPD were found within our cohort. LOPD showed greater impairment of working memory, greater anxiety, and greater duration of illness-all independent of one another; whereas, those with ROPD had greater magical ideation, also independent of any other variables.

Presymptomatic detection of Parkinson's disease.

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Jenner, P

1993-01-01

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

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

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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

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

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

2010-01-01

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...... sets with previously unknown associations with Parkinson's disease. These gene sets pinpoint defects in mitochondrial electron transport, glucose utilization, and glucose sensing and reveal that they occur early in disease pathogenesis. Genes controlling cellular bioenergetics that are expressed...... in response to peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) are underexpressed in Parkinson's disease patients. Activation of PGC-1α results in increased expression of nuclear-encoded subunits of the mitochondrial respiratory chain and blocks the dopaminergic neuron loss induced...

Olfactory Dysfunction as an Early Biomarker in Parkinson's Disease

Institute of Scientific and Technical Information of China (English)

Michelle E.Fullard; James F.Morley; John E.Duda

2017-01-01

Olfactory dysfunction is common in Parkinson's disease (PD) and often predates the diagnosis by years,reflecting early deposition of Lewy pathology,the histologic hallmark of PD,in the olfactory bulb.Clinical tests are available that allow for the rapid characterization of olfactory dysfunction,including tests of odor identification,discrimination,detection,and recognition thresholds,memory,and tests assessing the build-up of odor intensity across increasing suprathreshold stimulus concentrations.The high prevalence of olfactory impairment,along with the ease and low cost of assessment,has fostered great interest in olfaction as a potential biomarker for PD.Hyposmia may help differentiate PD from other causes of parkinsonism,and may also aid in the identification of "pre-motor" PD due to the early pathologic involvement of olfactory pathways.Olfactory function is also correlated with other non-motor features of PD and may serve as a predictor of cognitive decline.In this article,we summarize the existing literature on olfaction in PD,focusing on the potential for olfaction as a biomarker for early or differential diagnosis and prognosis.

Excessive early-life dietary exposure: a potential source of elevated brain iron and a risk factor for Parkinson's disease.

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Hare, Dominic J; Cardoso, Bárbara Rita; Raven, Erika P; Double, Kay L; Finkelstein, David I; Szymlek-Gay, Ewa A; Biggs, Beverley-Ann

2017-01-01

Iron accumulates gradually in the ageing brain. In Parkinson's disease, iron deposition within the substantia nigra is further increased, contributing to a heightened pro-oxidant environment in dopaminergic neurons. We hypothesise that individuals in high-income countries, where cereals and infant formulae have historically been fortified with iron, experience increased early-life iron exposure that predisposes them to age-related iron accumulation in the brain. Combined with genetic factors that limit iron regulatory capacity and/or dopamine metabolism, this may increase the risk of Parkinson's diseases. We propose to (a) validate a retrospective biomarker of iron exposure in children; (b) translate this biomarker to adults; (c) integrate it with in vivo brain iron in Parkinson's disease; and (d) longitudinally examine the relationships between early-life iron exposure and metabolism, brain iron deposition and Parkinson's disease risk. This approach will provide empirical evidence to support therapeutically addressing brain iron deposition in Parkinson's diseases and produce a potential biomarker of Parkinson's disease risk in preclinical individuals.

INFLAMMATORY BOWEL DISEASE WITH A VERY EARLY ONSET

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E. A. Kornienko

2016-01-01

Full Text Available Inflammatory bowel disease (Crohn's disease and ulcerative colitis has a tendency to manifest at earlier age. In childhood (< 6 years of age it has an especially severe course and is characterized by high grade inflammation, predominantly in the colon, by complication and extra-intestinal autoimmune injury. At younger age, Crohn's disease and ulcerative colitis require more aggressive treatment with frequently poor results. From genetic point of view, monogenic mutations controlling the immune response are characteristic for these diseases with an early onset; therefore, they are frequently associated with primary immunodeficiency. This implies various immunologic deficits, such as breakdown of the epithelial barrier, phagocytic dysfunction and dysfunction of Т and В lymphocytes and regulatory Т cells. Depending on this, a number of primary immunodeficiencies are identified associated with monogenic mutations of more than 50 genes. There some age-related specific features at manifestation. Thus, defects in interleukin 10 and FOXP3 manifest in the first months of life, whereas severe combined immunodeficiencies and phagocytosis defects become evident somewhat later. Virtually all 24 children with very early onset of inflammatory bowel disease, whom we examined, had immunologic defects and one child had a XIAP gene mutation. After identification of a specific immunologic defect, one can understand the mechanism of the disease and suspect one or another genetic defect with subsequent reasonable assessment of mutations in candidate genes. Detection of immunologic and genetic defects in children with a very early onset of inflammatory bowel disease allows for choosing an adequate strategy of non-conventional treatment that may differ depending on the mechanism of the disease.

Early-onset Coronary Artery Disease: Clinical and Hereditary Aspects

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Christiansen, Morten Krogh

2017-01-01

), and to characterize and quantify subclinical atherosclerosis in their relatives. Furthermore, the aim was to explore the impact of common genetic risk variants on the age of onset, familial clustering and disease severity. In study I, 143 patients with early-onset CAD were recruited from the Western Denmark Heart...

Striatal Dopamine Depletion Patterns and Early Non-Motor Burden in Parkinsons Disease.

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Su Jin Chung

Full Text Available The mechanism underlying non-motor symptoms in Parkinson's disease has not yet been elucidated. In this study, we hypothesized that Parkinson patients with more non-motor symptoms have a different pattern of striatal dopamine depletion, particularly in areas other than the sensorimotor striatum, compared to those with fewer non-motor symptoms.We conducted a prospective survey of the degree of non-motor symptoms (using the Korean version of the Non-Motor Symptoms Scale; K-NMSS in 151 patients with early-stage Parkinson's disease who had undergone a dopamine transporter PET scan as an initial diagnostic procedure. We classified the patients into two groups; high non-motor patients (HNM-PD; K-NMSS score ≥ 41 and low non-motor patients (LNM-PD.Patients in the HNM-PD group (n = 71 were older, had longer symptom duration, exhibited more severe motor deficits, and had been prescribed higher levodopa-equivalent doses at follow-up than those in the LNM-PD group. However, dopamine transporter binding to the striatal sub-regions and inter-sub-regional binding ratios were comparable between the two groups. A general linear model showed that the HNM-PD group had significantly more severe motor deficits than the LNM-PD group after controlling for age, gender, symptom duration, and dopamine transporter binding to the sensorimotor striatum.This study demonstrated that the pattern of striatal dopamine depletion does not contribute to early non-motor burden in Parkinson's disease. Our results suggest that LNM-PD patients may have a more benign course of motor symptom progression than HNM-PD patients.

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

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

2018-03-10

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

Estrogen use and early onset Alzheimer's disease: a population-based study

NARCIS (Netherlands)

A.J.C. Slooter (Arjen); J.B. Bronzova (Juliana); J.C.M. Witteman (Jacqueline); C.M. van Duijn (Cornelia); C. van Broeckhoven (Christine); A. Hofman (Albert)

1999-01-01

textabstractEstrogen use may be protective for Alzheimer's disease with late onset. However, the effects on early onset Alzheimer's disease are unclear. This issue was studied in a population based setting. For each female patient, a female control was matched on age (within 5

Loss of VPS13C Function in Autosomal-Recessive Parkinsonism Causes Mitochondrial Dysfunction and Increases PINK1/Parkin-Dependent Mitophagy.

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Lesage, Suzanne; Drouet, Valérie; Majounie, Elisa; Deramecourt, Vincent; Jacoupy, Maxime; Nicolas, Aude; Cormier-Dequaire, Florence; Hassoun, Sidi Mohamed; Pujol, Claire; Ciura, Sorana; Erpapazoglou, Zoi; Usenko, Tatiana; Maurage, Claude-Alain; Sahbatou, Mourad; Liebau, Stefan; Ding, Jinhui; Bilgic, Basar; Emre, Murat; Erginel-Unaltuna, Nihan; Guven, Gamze; Tison, François; Tranchant, Christine; Vidailhet, Marie; Corvol, Jean-Christophe; Krack, Paul; Leutenegger, Anne-Louise; Nalls, Michael A; Hernandez, Dena G; Heutink, Peter; Gibbs, J Raphael; Hardy, John; Wood, Nicholas W; Gasser, Thomas; Durr, Alexandra; Deleuze, Jean-François; Tazir, Meriem; Destée, Alain; Lohmann, Ebba; Kabashi, Edor; Singleton, Andrew; Corti, Olga; Brice, Alexis

2016-03-03

Autosomal-recessive early-onset parkinsonism is clinically and genetically heterogeneous. The genetic causes of approximately 50% of autosomal-recessive early-onset forms of Parkinson disease (PD) remain to be elucidated. Homozygozity mapping and exome sequencing in 62 isolated individuals with early-onset parkinsonism and confirmed consanguinity followed by data mining in the exomes of 1,348 PD-affected individuals identified, in three isolated subjects, homozygous or compound heterozygous truncating mutations in vacuolar protein sorting 13C (VPS13C). VPS13C mutations are associated with a distinct form of early-onset parkinsonism characterized by rapid and severe disease progression and early cognitive decline; the pathological features were striking and reminiscent of diffuse Lewy body disease. In cell models, VPS13C partly localized to the outer membrane of mitochondria. Silencing of VPS13C was associated with lower mitochondrial membrane potential, mitochondrial fragmentation, increased respiration rates, exacerbated PINK1/Parkin-dependent mitophagy, and transcriptional upregulation of PARK2 in response to mitochondrial damage. This work suggests that loss of function of VPS13C is a cause of autosomal-recessive early-onset parkinsonism with a distinctive phenotype of rapid and severe progression. Copyright © 2016 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Metaiodobenzylguanidine (MIBG) uptake in Parkinson's disease also decreases at thyroid

International Nuclear Information System (INIS)

Matsui, Hideaki; Udaka, Fukashi; Oda, Masaya; Tamura, Akiko; Kubori, Tamotsu; Nishinaka, Kazuto; Kameyama, Masakuni

2005-01-01

Decreased cardiac metaiodobenzylguanidine (MIBG) uptake was reported in Parkinson's disease and this contributes to the differential diagnosis between Parkinson's disease and other forms of parkinsonism such as multiple system atrophy. However, decreased MIBG uptake of the thyroid has not been demonstrated. The objective of this study was to compare MIBG uptake of the thyroid among Parkinson's disease, multiple system atrophy and controls. Twenty-six patients with Parkinson's disease, 11 patients with multiple system atrophy and 14 controls were examined in this study. Planar images were taken 15 minutes (early images) and 3 hours (late images) after intravenous injection of 111 MBq 123 I-MIBG. MIBG uptake of the thyroid on early images decreased significantly in Parkinson's disease compared to controls (p<0.0001) and multiple system atrophy (p=0.018). MIBG uptake of the thyroid on early images decreased significantly also in multiple system atrophy compared to controls (p=0.027). On late images, thyroid uptake differed significantly only between Parkinson's disease and controls (p=0.010). Our study is the first to demonstrate decreased MIBG uptake of the thyroid in Parkinson's disease. Sympathetic nervous denervation of Parkinson's disease occurred not only in the heart but also in the thyroid. (author)

Loss of VPS13C Function in Autosomal-Recessive Parkinsonism Causes Mitochondrial Dysfunction and Increases PINK1/Parkin-Dependent Mitophagy

NARCIS (Netherlands)

Lesage, S.; Drouet, V.; Majounie, E.; Deramecourt, V.; Jacoupy, M.; Nicolas, A.; Cormier-Dequaire, F.; Hassoun, S.M.; Pujol, C.; Ciura, S.; Erpapazoglou, Z.; Usenko, T.; Maurage, C.A.; Sahbatou, M.; Liebau, S.; Ding, J.; Bilgic, B.; Emre, M.; Erginel-Unaltuna, N.; Guven, G.; Tison, F.; Tranchant, C.; Vidailhet, M.; Corvol, J.C.; Krack, P.; Leutenegger, A.L.; Nalls, M.A.; Hernandez, D.G.; Heutink, P.; Gibbs, J.R.; Hardy, J.; Wood, N.W.; Gasser, T.; Durr, A.; Deleuze, J.F.; Tazir, M.; Destee, A.; Lohmann, E.; Kabashi, E.; Singleton, A.; Corti, O.; Brice, A.; Scheffer, H.; Bloem, B.R.; et al.,

2016-01-01

Autosomal-recessive early-onset parkinsonism is clinically and genetically heterogeneous. The genetic causes of approximately 50% of autosomal-recessive early-onset forms of Parkinson disease (PD) remain to be elucidated. Homozygozity mapping and exome sequencing in 62 isolated individuals with

Genetics Home Reference: inclusion body myopathy with early-onset Paget disease and frontotemporal dementia

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... Share: Email Facebook Twitter Home Health Conditions IBMPFD Inclusion body myopathy with early-onset Paget disease and ... Javascript to view the expand/collapse boxes. Description Inclusion body myopathy with early-onset Paget disease and ...

Changes in insomnia subtypes in early Parkinson disease.

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Tholfsen, Lena K; Larsen, Jan P; Schulz, Jörn; Tysnes, Ole-Bjørn; Gjerstad, Michaela D

2017-01-24

To examine the development of factors associated with insomnia in a cohort of originally drug-naive patients with incident Parkinson disease (PD) during the first 5 years after diagnosis. One hundred eighty-two drug-naive patients with PD derived from a population-based incident cohort and 202 control participants were assessed for insomnia before treatment initiation and were repeatedly examined after 1, 3, and 5 years. Insomnia was diagnosed according to the Stavanger Sleepiness Questionnaire. The Parkinson's Disease Sleep Scale was used to differentiate sleep initiation problems from problems of sleep maintenance. Generalized estimating equation models were applied for statistical measures. The prevalence of insomnia in general was not higher in patients with PD compared to controls at the 5-year follow-up. There were changes in the prevalence of the different insomnia subtypes over the 5-year follow-up. The prevalence of solitary problems in sleep maintenance increased from 31% (n = 18) in the drug-naive patients at baseline to 49% (n = 29) after 1 year and were associated with the use of dopamine agonists and higher Montgomery-Åsberg Depression Rating Scale scores. The prevalence of solitary sleep initiation problems decreased continuously from 21% (n = 12) at baseline to 7.4% (n = 4) after 5 years; these were associated with less daytime sleepiness. The prevalence rates of the different insomnia subtypes changed notably in patients with early PD. The frequency of sleep maintenance problems increased, and these problems were associated with dopamine agonist use and depressive symptoms, while the total number of patients with insomnia remained stable. Our findings reflect the need for early individual assessments of insomnia subtypes and raise the possibility of intervention to reduce these symptoms in patients with early PD. © 2016 American Academy of Neurology.

Kinesiotherapy of Parkinson`s disease and Parkinson`s syndrom

OpenAIRE

Zechovská, Lenka

2013-01-01

Author: Lenka Zechovská Institution: Rehabilitation Clinic, Faculty of Medicine in Hradec Králové Title: Kinesiotherapy of Parkinson's disease and Parkinson's syndrome Supervisor: Mgr. Ivana Vondráková Number of pages: 115 Number of attachments: 8 Year of defence: 2013 Keywords: Parkinson's disease, basal ganglia, tremor, rigidity, hypokinesia Bachelor thesis deals with the problems of Parkinson's disease and Parkinson's syndrome. The theoretical part includes the basal ganglia pathophysiolog...

"PINK1"-Linked Parkinsonism Is Associated with Lewy Body Pathology

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Samaranch, Lluis; Lorenzo-Betancor, Oswaldo; Arbelo, Jose M.; Ferrer, Isidre; Lorenzo, Elena; Irigoyen, Jaione; Pastor, Maria A.; Marrero, Carmen; Isla, Concepcion; Herrera-Henriquez, Joanna; Pastor, Pau

2010-01-01

Phosphatase and tensin homolog-induced putative kinase 1 gene mutations have been associated with autosomal recessive early-onset Parkinson's disease. To date, no neuropathological reports have been published from patients with Parkinson's disease with both phosphatase and tensin homolog-induced putative kinase 1 gene copies mutated. We analysed…

Accelerated Age-Dependent Hippocampal Volume Loss in Parkinson Disease With Mild Cognitive Impairment.

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Schneider, Christine B; Donix, Markus; Linse, Katharina; Werner, Annett; Fauser, Mareike; Klingelhoefer, Lisa; Löhle, Matthias; von Kummer, Rüdiger; Reichmann, Heinz; Storch, Alexander

2017-09-01

Patients with Parkinson disease are at high risk of developing dementia. During the course of the disease, a substantial number of patients will experience a cognitive decline, indicating the dynamics of the underlying neuropathology. Magnetic resonance imaging (MRI) has become increasingly useful for identifying structural characteristics in radiological brain anatomy existing prior to clinical symptoms. Whether these changes reflect pathology, whether they are aging related, or both often remains unclear. We hypothesized that aging-associated brain structural changes would be more pronounced in the hippocampal region among patients with Parkinson disease having mild cognitive deficits relative to cognitively unimpaired patients. Using MRI, we investigated 30 cognitively healthy patients with Parkinson disease and 33 patients with nondemented Parkinson disease having mild cognitive impairment. All participants underwent structural MRI scanning and extensive clinical and neuropsychological assessments. Irrespective of the study participants' cognitive status, older age was associated with reduced cortical thickness in various neocortical regions. Having mild cognitive impairment was not associated with an increased rate of cortical thinning or volume loss in these regions, except in the hippocampus bilaterally. Patients with Parkinson disease having mild cognitive impairment show an accelerated age-dependent hippocampal volume loss when compared with cognitively healthy patients with Parkinson disease. This may indicate pathological processes in a key region for memory functioning in patients with Parkinson disease at risk of developing dementia. Structural MRI of the hippocampal region could potentially contribute to identifying patients who should receive early treatment aimed at delaying the clinical onset of dementia.

Recent developments in biomarkers in Parkinson disease

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Schapira, Anthony H.V.

2013-01-01

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

Parkinson's disease motor subtypes and mood.

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Burn, David J; Landau, Sabine; Hindle, John V; Samuel, Michael; Wilson, Kenneth C; Hurt, Catherine S; Brown, Richard G

2012-03-01

Parkinson's disease is heterogeneous, both in terms of motor symptoms and mood. Identifying associations between phenotypic variants of motor and mood subtypes may provide clues to understand mechanisms underlying mood disorder and symptoms in Parkinson's disease. A total of 513 patients were assessed using the Hospital Anxiety and Depression Scale, and separately classified into anxious, depressed, and anxious-depressed mood classes based on latent class analysis of a semistructured interview. Motor subtypes assessed related to age-of-onset, rate of progression, presence of motor fluctuations, lateralization of motor symptoms, tremor dominance, and the presence of postural instability and gait symptoms and falls. The directions of observed associations tended to support previous findings with the exception of lateralization of symptoms, for which there were no consistent or significant results. Regression models examining a range of motor subtypes together indicated increased risk of anxiety in patients with younger age-of-onset and motor fluctuations. In contrast, depression was most strongly related to axial motor symptoms. Different risk factors were observed for depressed patients with and without anxiety, suggesting heterogeneity within Parkinson's disease depression. Such association data may suggest possible underlying common risk factors for motor subtype and mood. Combined with convergent evidence from other sources, possible mechanisms may include cholinergic system damage and white matter changes contributing to non-anxious depression in Parkinson's disease, while situational factors related to threat and unpredictability may contribute to the exacerbation and maintenance of anxiety in susceptible individuals. Copyright © 2011 Movement Disorder Society.

Dopaminreceptorscintigraphy in Parkinson's disease - Clinical correlation

International Nuclear Information System (INIS)

Riklund Aahlstroem, K.E.; Hietala, S.-O.; Johansson, F.

2002-01-01

Parkinson's disease is a severe, progressive neuro degenerative disorder which is characterised by a degeneration of the dopamine containing cells and loss of dopamine transporters (DA) in substantia nigra. Earlier 123 I-β-CIT SPECT studies have demonstrated this loss of DA content in Parkinson's disease. Recently a new radioligand 123 I-FP-CIT, with faster kinetics than b-CIT became available for imaging of the DA transporter. The applicability of this radioligand was tested in a large clinical material with early and advanced Parkinson's disease using a one day protocol. 123 I-FP-CIT uptake was decreased in patients with Parkinson's disease and this was seen three hours after injection of the radioligand. In the Parkinson's disease group the uptake in the putamen was reduced more than in the caudate nucleus. Specific to non-specific striatal uptake ratios correlated with the Hoehn and Yahr stage. It appeared that 123 I-FP-CIT SPECT allows a significant discrimination between patients with Parkinson's disease and other movement disorders. The scintigraphic observations were correlated to clinical findings. The results will be presented and discussed

Parkinson's Disease: Leucine-Rich Repeat Kinase 2 and Autophagy, Intimate Enemies

Directory of Open Access Journals (Sweden)

José M. Bravo-San Pedro

2012-01-01

Full Text Available Parkinson's disease is the second common neurodegenerative disorder, after Alzheimer's disease. It is a clinical syndrome characterized by loss of dopamine-generating cells in the substancia nigra, a region of the midbrain. The etiology of Parkinson's disease has long been through to involve both genetic and environmental factors. Mutations in the leucine-rich repeat kinase 2 gene cause late-onset Parkinson's disease with a clinical appearance indistinguishable from Parkinson's disease idiopathic. Autophagy is an intracellular catabolic mechanism whereby a cell recycles or degrades damage proteins and cytoplasmic organelles. This degradative process has been associated with cellular dysfunction in neurodegenerative processes including Parkinson's disease. We discuss the role of leucine-rich repeat kinase 2 in autophagy, and how the deregulations of this degradative mechanism in cells can be implicated in the Parkinson's disease etiology.

Common variants at five new loci associated with early-onset inflammatory bowel disease.

Science.gov (United States)

Imielinski, Marcin; Baldassano, Robert N; Griffiths, Anne; Russell, Richard K; Annese, Vito; Dubinsky, Marla; Kugathasan, Subra; Bradfield, Jonathan P; Walters, Thomas D; Sleiman, Patrick; Kim, Cecilia E; Muise, Aleixo; Wang, Kai; Glessner, Joseph T; Saeed, Shehzad; Zhang, Haitao; Frackelton, Edward C; Hou, Cuiping; Flory, James H; Otieno, George; Chiavacci, Rosetta M; Grundmeier, Robert; Castro, Massimo; Latiano, Anna; Dallapiccola, Bruno; Stempak, Joanne; Abrams, Debra J; Taylor, Kent; McGovern, Dermot; Silber, Gary; Wrobel, Iwona; Quiros, Antonio; Barrett, Jeffrey C; Hansoul, Sarah; Nicolae, Dan L; Cho, Judy H; Duerr, Richard H; Rioux, John D; Brant, Steven R; Silverberg, Mark S; Taylor, Kent D; Barmuda, M Michael; Bitton, Alain; Dassopoulos, Themistocles; Datta, Lisa Wu; Green, Todd; Griffiths, Anne M; Kistner, Emily O; Murtha, Michael T; Regueiro, Miguel D; Rotter, Jerome I; Schumm, L Philip; Steinhart, A Hillary; Targan, Stephen R; Xavier, Ramnik J; Libioulle, Cécile; Sandor, Cynthia; Lathrop, Mark; Belaiche, Jacques; Dewit, Olivier; Gut, Ivo; Heath, Simon; Laukens, Debby; Mni, Myriam; Rutgeerts, Paul; Van Gossum, André; Zelenika, Diana; Franchimont, Denis; Hugot, J P; de Vos, Martine; Vermeire, Severine; Louis, Edouard; Cardon, Lon R; Anderson, Carl A; Drummond, Hazel; Nimmo, Elaine; Ahmad, Tariq; Prescott, Natalie J; Onnie, Clive M; Fisher, Sheila A; Marchini, Jonathan; Ghori, Jilur; Bumpstead, Suzannah; Gwillam, Rhian; Tremelling, Mark; Delukas, Panos; Mansfield, John; Jewell, Derek; Satsangi, Jack; Mathew, Christopher G; Parkes, Miles; Georges, Michel; Daly, Mark J; Heyman, Melvin B; Ferry, George D; Kirschner, Barbara; Lee, Jessica; Essers, Jonah; Grand, Richard; Stephens, Michael; Levine, Arie; Piccoli, David; Van Limbergen, John; Cucchiara, Salvatore; Monos, Dimitri S; Guthery, Stephen L; Denson, Lee; Wilson, David C; Grant, Straun F A; Daly, Mark; Silverberg, Mark S; Satsangi, Jack; Hakonarson, Hakon

2009-12-01

The inflammatory bowel diseases (IBD) Crohn's disease and ulcerative colitis are common causes of morbidity in children and young adults in the western world. Here we report the results of a genome-wide association study in early-onset IBD involving 3,426 affected individuals and 11,963 genetically matched controls recruited through international collaborations in Europe and North America, thereby extending the results from a previous study of 1,011 individuals with early-onset IBD. We have identified five new regions associated with early-onset IBD susceptibility, including 16p11 near the cytokine gene IL27 (rs8049439, P = 2.41 x 10(-9)), 22q12 (rs2412973, P = 1.55 x 10(-9)), 10q22 (rs1250550, P = 5.63 x 10(-9)), 2q37 (rs4676410, P = 3.64 x 10(-8)) and 19q13.11 (rs10500264, P = 4.26 x 10(-10)). Our scan also detected associations at 23 of 32 loci previously implicated in adult-onset Crohn's disease and at 8 of 17 loci implicated in adult-onset ulcerative colitis, highlighting the close pathogenetic relationship between early- and adult-onset IBD.

Assessments of plasma ghrelin levels in the early stages of parkinson's disease.

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Song, Ning; Wang, Weiwei; Jia, Fengjv; Du, Xixun; Xie, Anmu; He, Qing; Shen, Xiaoli; Zhang, Jing; Rogers, Jack T; Xie, Junxia; Jiang, Hong

2017-10-01

Gastrointestinal symptoms are early events in Parkinson's disease (PD). The gastrointestinal hormone ghrelin was neuroprotective in the nigrostriatal dopamine system. The objective of this study was to assess ghrelin levels in the early stages of PD. Plasma was collected in the fasting state in 291 PD patients in stages 1-3 and 303 age- and sex-matched healthy controls. Additional samples were taken in the glucose response test to assess nutrition-related ghrelin levels in 20 PD patients and 20 healthy controls. The enzyme-linked immunosorbent assay was used to measure total and active plasma ghrelin levels. We reported that total and active plasma ghrelin levels were decreased in PD, although there was no difference across progressive PD stages. Postprandial ghrelin suppression and preprandial peak responses were both attenuated in PD. Plasma ghrelin levels were decreased in PD; however, this event might be irrelevant to PD progression. Ghrelin responses to meals were also impaired in PD. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

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

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

2006-07-31

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

Complexity Analysis of Resting-State MEG Activity in Early-Stage Parkinson's Disease Patients

NARCIS (Netherlands)

Gómez, C.; Olde Dubbelink, K.T.E.; Stam, C.J.; Abasolo, D.; Berendse, H.W.; Hornero, R.

2011-01-01

The aim of the present study was to analyze resting-state brain activity in patients with Parkinson's disease (PD), a degenerative disorder of the nervous system. Magnetoencephalography (MEG) signals were recorded with a 151-channel whole-head radial gradiometer MEG system in 18 early-stage

Can patients with Parkinson's disease use dry powder inhalers during off periods?

NARCIS (Netherlands)

Luinstra, M.; Rutgers, A.W.F.; Dijkstra, H.; Grasmeijer, F.; Hagedoorn, P.; Vogelzang, J.M.J.; Frijlink, H.W.; De Boer, A.H.

2015-01-01

Because of its rapid onset of action, pulmonary administration of levodopa is an interesting alternative to oral administration for the rescue treatment of Parkinson's disease patients in an off period. We studied the ability of Parkinson's disease patients to operate a dry powder inhaler (DPI)

Reproductive factors and Parkinson's disease risk in Danish women

DEFF Research Database (Denmark)

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

2014-01-01

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...... and fertile life length, age at menopause or post-menopausal hormone treatment was found. CONCLUSIONS: Reproductive factors related to women's early- to mid-reproductive lives appear to be predictive of subsequent Parkinson's disease risk whereas factors occurring later in life seem less important....

Characteristic Motor and Nonmotor Symptoms Related to Quality of Life in Drug-Naïve Patients with Late-Onset Parkinson Disease.

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Park, Hea Ree; Youn, Jinyoung; Cho, Jin Whan; Oh, Eung-Seok; Kim, Ji Sun; Park, Suyeon; Jang, Wooyoung; Park, Jin Se

2018-01-01

Unlike young-onset Parkinson disease (YOPD), characteristics of late-onset PD (LOPD) have not yet been clearly elucidated. We investigated characteristic features and symptoms related to quality of life (QoL) in LOPD patients. We recruited drug-naïve, early PD patients. The patient cohort was divided into 3 subgroups based on patient age at onset (AAO): the YOPD group (AAO patients, 26 were in the YOPD group, 74 in the MOPD group, and 32 in the LOPD group. Among parkinsonian symptoms, patients in the LOPD group had a lower score on the Korean version of the Montreal Cognitive Assessment than the other groups. Logistic regression analysis showed genitourinary symptoms were related to the LOPD group. Linear regression analysis showed both MS and NMS were correlated with QoL in the MOPD group, but only NMS were correlated with QoL in the LOPD group. Particularly, anxiety and fatigue affected QoL in the LOPD group. LOPD patients showed different characteristic clinical features, and different symptoms were related with QoL for LOPD than YOPD and MOPD patients. © 2018 S. Karger AG, Basel.

Changes in spontaneous brain activity in early Parkinson's disease.

Science.gov (United States)

Yang, Hong; Zhou, Xiaohong Joe; Zhang, Min-Ming; Zheng, Xu-Ning; Zhao, Yi-Lei; Wang, Jue

2013-08-09

Resting state brain activity can provide valuable insights into the pathophysiology of Parkinson's disease (PD). The purpose of the present study was (a) to investigate abnormal spontaneous neuronal activity in early PD patients using resting-state functional MRI (fMRI) with a regional homogeneity (ReHo) method and (b) to demonstrate the potential of using changes in abnormal spontaneous neuronal activity for monitoring the progression of PD during its early stages. Seventeen early PD patients were assessed with the Unified Parkinson's Disease Rating Scale (UPDRS), the Hoehn and Yahr disability scale and the Mini-mental State Examination (MMSE) were compared with seventeen gender- and age-matched healthy controls. All subjects underwent MRI scans using a 1.5T General Electric Signa Excite II scanner. The MRI scan protocol included whole-brain volumetric imaging using a 3D inversion recovery prepared (IR-Prep) fast spoiled gradient-echo pulse sequence and 2D multi-slice (22 axial slices covering the whole brain) resting-state fMRI using an echo planar imaging (EPI) sequence. Images were analyzed in SPM5 together with a ReHo algorithm using the in-house software program REST. A corrected threshold of pbrain regions, including the left cerebellum, left parietal lobe, right middle temporal lobe, right sub-thalamic nucleus areas, right superior frontal gyrus, middle frontal gyrus (MFG), right inferior parietal lobe (IPL), right precuneus lobe, left MFG and left IPL. Additionally, significantly reduced ReHo was also observed in the early PD patients in the following brain regions: the left putamen, left inferior frontal gyrus, right hippocampus, right anterior cingulum, and bilateral lingual gyrus. Moreover, in PD patients, ReHo in the left putamen was negatively correlated with the UPDRS scores (r=-0.69). These results indicate that the abnormal resting state spontaneous brain activity associated with patients with early PD can be revealed by Reho analysis. Copyright �

Parkinson's Disease Dementia

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

Widespread disruption of functional brain organization in early-onset Alzheimer's disease.

Directory of Open Access Journals (Sweden)

Sofie M Adriaanse

Full Text Available Early-onset Alzheimer's disease (AD patients present a different clinical profile than late-onset AD patients. This can be partially explained by cortical atrophy, although brain organization might provide more insight. The aim of this study was to examine functional connectivity in early-onset and late-onset AD patients. Resting-state fMRI scans of 20 early-onset (<65 years old, 28 late-onset (≥65 years old AD patients and 15 "young" (<65 years old and 31 "old" (≥65 years old age-matched controls were available. Resting-state network-masks were used to create subject-specific maps. Group differences were examined using a non-parametric permutation test, accounting for gray-matter. Performance on five cognitive domains were used in a correlation analysis with functional connectivity in AD patients. Functional connectivity was not different in any of the RSNs when comparing the two control groups (young vs. old controls, which implies that there is no general effect of aging on functional connectivity. Functional connectivity in early-onset AD was lower in all networks compared to age-matched controls, where late-onset AD showed lower functional connectivity in the default-mode network. Functional connectivity was lower in early-onset compared to late-onset AD in auditory-, sensory-motor, dorsal-visual systems and the default mode network. Across patients, an association of functional connectivity of the default mode network was found with visuoconstruction. Functional connectivity of the right dorsal visual system was associated with attention across patients. In late-onset AD patients alone, higher functional connectivity of the sensory-motor system was associated with poorer memory performance. Functional brain organization was more widely disrupted in early-onset AD when compared to late-onset AD. This could possibly explain different clinical profiles, although more research into the relationship of functional connectivity and cognitive

Parkinson disease and smoking revisited

DEFF Research Database (Denmark)

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

2014-01-01

patients with PD than controls ever established a smoking habit. Among former smokers, those with greater difficulty quitting or using nicotine substitutes were less likely to develop PD, with the risk being lowest among those reporting "extremely difficult to quit" compared with "easy to quit." Nicotine......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...... substitute usage was strongly associated with quitting difficulty and duration of smoking, i.e., most strongly among current smokers, followed by former smokers who had used nicotine substitutes, and less strongly among former smokers who never used substitutes. CONCLUSIONS: Our data support the notion...

A mathematical model of insulin resistance in Parkinson's disease.

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Braatz, Elise M; Coleman, Randolph A

2015-06-01

This paper introduces a mathematical model representing the biochemical interactions between insulin signaling and Parkinson's disease. The model can be used to examine the changes that occur over the course of the disease as well as identify which processes would be the most effective targets for treatment. The model is mathematized using biochemical systems theory (BST). It incorporates a treatment strategy that includes several experimental drugs along with current treatments. In the past, BST models of neurodegeneration have used power law analysis and simulation (PLAS) to model the system. This paper recommends the use of MATLAB instead. MATLAB allows for more flexibility in both the model itself and in data analysis. Previous BST analyses of neurodegeneration began treatment at disease onset. As shown in this model, the outcomes of delayed, realistic treatment and full treatment at disease onset are significantly different. The delayed treatment strategy is an important development in BST modeling of neurodegeneration. It emphasizes the importance of early diagnosis, and allows for a more accurate representation of disease and treatment interactions. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

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Cesaro, P; Defebvre, L

2014-04-01

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

Recent advances in imaging in Parkinson disease

International Nuclear Information System (INIS)

Baba, Toru; Takeda, Atsushi

2012-01-01

Despite recent knowledge on the pathophysiology of Parkinson disease, the precise and early diagnosis of this condition remains difficult. Advances in imaging techniques have enabled the assessment of in vivo structural, neurometabolic, and neurochemical changes in Parkinson disease, and their role as biomarkers have assumed greater importance in recent years. We presently review the various approaches with these imaging techniques for the study of Parkinson disease. Voxel-based morphometry studies with structural MRI showed a characteristic pattern of gray matter loss, and fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) studies have indicated latent network abnormalities in Parkinson disease. Moreover, radiotracer imaging with dopaminergic markers facilitates the assessment of pre- and postsynaptic nigro-striatal integrity, and other radiotracers have been used in the studies of nondopaminergic neurotransmitter systems, such as the cholinergic, noradrenergic, and serotonergic systems. These imaging techniques can be used to detect presymptomatic disease and to monitor disease progression. Thus, imaging data provide meaningful insights into the pathological process in Parkinson disease. (author)

Cerebral pathological and compensatory mechanisms in the premotor phase of leucine-rich repeat kinase 2 parkinsonism

NARCIS (Netherlands)

Nuenen, B.F.L. van; Helmich, R.C.G.; Ferraye, M.U.; Thaler, A.; Hendler, T.; Orr-Urtreger, A.; Mirelman, A.; Bressman, S.; Marder, K.S.; Giladi, N.; Warrenburg, B.P.C. van de; Bloem, B.R.; Toni, I.

2012-01-01

Compensatory cerebral mechanisms can delay motor symptom onset in Parkinson's disease. We aim to characterize these compensatory mechanisms and early disease-related changes by quantifying movement-related cerebral function in subjects at significantly increased risk of developing Parkinson's

Thiazolidinediones and Parkinson Disease: A Cohort Study.

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

2015-12-01

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

The management of patients with early Parkinson's disease.

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Rascol, O; Payoux, P; Ferreira, J; Brefel-Courbon, C

2002-10-01

A major problem in the management of early Parkinson's disease is to choose the first medication to prescribe. This decision should rely on the level of available clinical evidence, largely based, at least for efficacy, on the results of randomised clinical trials. Safety and costs are also crucial to consider. Other factors like for example pathophysiological concepts, individual experience, marketing pressure, socio-economical environment, patients needs and expectations have, however, also their own influence. Levodopa is efficacious and cheap, but induces long-term motor complications. The early use of dopamine agonists is more and more frequently promoted, because large prospective L-dopa-controlled trials demonstrated that this strategy reduces the risk of such long-term complications. Integrating individual clinical expertise to the best available external clinical evidence (evidence-based medicine) is the best strategy in making decisions about the care of individual patients. Copyright 2002 Elsevier Science Ltd.

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

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

2004-01-01

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

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

Science.gov (United States)

2006-12-01

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

Parkinson's Disease Videos

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Full Text Available ... Expert Briefings: Anxiety in Parkinson's Disease Expert Briefings: Nutrition and Parkinson's Disease NY Nightly News with Chuck ... Briefings: What's in the Parkinson's Pipeline? Expert Briefings: Nutrition and Parkinson's Disease 2010 Expert Briefings: Legal Issues: ...

Parkinson's Disease Videos

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Full Text Available ... Parkinson's Disease: One Voice, Many Listeners Expert Briefings: Medical Therapies: What's in the Parkinson's Pipeline? Expert Briefings: Under-recognized Nonmotor Symptoms of Parkinson's Disease Expert Briefings: Gait, Balance and Falls in Parkinson's Disease Expert Briefings: Coping ...

Edaravone prevents neurotoxicity of mutant L166P DJ-1 in Parkinson's disease.

Science.gov (United States)

Li, Bing; Yu, Dawei; Xu, Zhiying

2013-10-01

Parkinson's disease (PD), which is estimated to affect approximately 1 % of the population over the age of 65, is the second most common neurodegenerative disorder after Alzheimer's disease. It was reported that pathogenic mutations in DJ-1 lead to autosomal recessive early-onset familial Parkinsonism. The L166P mutant of DJ-1 is the most commonly studied loss-of-function mutation in early onset familial PD, but the underlying mechanisms are still unknown. Edaravone is a powerful free radical scavenger used in clinical treatment for cerebral ischemic stroke. In the present study, we investigated the effects of edaravone on the neurotoxicity in PD-induced isoforms of DJ-1 containing the mutation L166P. Our results indicated that edaravone was able to significantly attenuate oxidative stress and improve mitochondrial function. Furthermore, edaravone was found to reduce apoptosis in Neuro2a cells through modulation of mitochondria-dependent apoptosis pathways. Interestingly, our result also demonstrated that edaravone was able to up-regulate VMAT2 expression in N2a cells in a dose-dependent manner. Our findings enhance the understanding of the neuro-protective effects of edaravone in cell models and suggest that edaravone offers significant protection in a PD-related in vitro model.

Cognitive Development in Infantile-Onset Pompe Disease Under Very Early Enzyme Replacement Therapy.

Science.gov (United States)

Lai, Chih-Jou; Hsu, Ting-Rong; Yang, Chia-Feng; Chen, Shyi-Jou; Chuang, Ya-Chin; Niu, Dau-Ming

2016-12-01

Most patients with infantile-onset Pompe disease die in early infancy before beginning enzyme replacement therapy, which has made it difficult to evaluate the impact of Pompe disease on cognitive development. Patients with infantile-onset Pompe disease can survive with enzyme replacement therapy, and physicians can evaluate cognitive development in these patients. We established an effective newborn screening program with quick clinical diagnostic criteria. Cognitive and motor development were evaluated using the Bayley Scales of Infant and Toddler Development-Third Edition at 6, 12, and 24 months of age. The patients who were treated very early demonstrate normal cognitive development with no significant change in cognition during this period (P = .18 > .05). The cognitive development was positively correlated with motor development (r = 0.533, P = .011). The results indicated that very early enzyme replacement therapy could protect cognitive development in patients with infantile-onset Pompe disease up to 24 months of age. © The Author(s) 2016.

Dorsal-to-Ventral Shift in Midbrain Dopaminergic Projections and Increased Thalamic/Raphe Serotonergic Function in Early Parkinson Disease.

Science.gov (United States)

Joutsa, Juho; Johansson, Jarkko; Seppänen, Marko; Noponen, Tommi; Kaasinen, Valtteri

2015-07-01

Loss of nigrostriatal neurons leading to dopamine depletion in the dorsal striatum is the pathologic hallmark of Parkinson disease contributing to the primary motor symptoms of the disease. However, Parkinson pathology is more widespread in the brain, affecting also other dopaminergic pathways and neurotransmitter systems, but these changes are less well characterized. This study aimed to investigate the mesencephalic striatal and extrastriatal dopaminergic projections together with extrastriatal serotonin transporter binding in Parkinson disease. Two hundred sixteen patients with Parkinson disease and 204 control patients (patients without neurodegenerative parkinsonism syndromes and normal SPECT imaging) were investigated with SPECT using the dopamine/serotonin transporter ligand (123)I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane ((123)I-FP-CIT) in the clinical setting. The group differences and midbrain correlations were analyzed voxel by voxel over the entire brain. We found that Parkinson patients had lower (123)I-FP-CIT uptake in the striatum and ventral midbrain but higher uptake in the thalamus and raphe nuclei than control patients. In patients with Parkinson disease, the correlation of the midbrain tracer uptake was shifted from the putamen to widespread corticolimbic areas. All findings were highly significant at the voxel level familywise error-corrected P value of less than 0.05. Our findings show that Parkinson disease is associated not only with the degeneration of the nigrostriatal dopamine neurotransmission, but also with a parallel shift toward mesolimbic and mesocortical function. Furthermore, Parkinson disease patients seem to have upregulation of brain serotonin transporter function at the early phase of the disease. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Comparative efficacy of selegiline versus rasagiline in the treatment of early Parkinson's disease.

Science.gov (United States)

Marconi, S; Zwingers, T

2014-07-01

The monoamine oxidase B inhibitors selegiline and rasagiline have not been compared in head-to-head clinical trials in patients with early Parkinson's disease.  The aim of this review was to compare the efficacy of these two agents in this setting. Randomized, placebo-controlled trials with an endpoint of the mean change from baseline in the Unified Parkinson's Disease Rating Scale (UPDRS) total score were included. Analysis included calculation of the standardized mean differences (SMDs) with 95% confidence intervals (CIs) and Forest Plot analyses for comparisons of pooled results. Five studies with selegiline (n = 1029) and four with rasagiline (n = 820) were included. Treatment duration was 2.5-9 months. Both selegiline and rasagiline showed significant SMDs versus placebo (-0.690, 95% CI -0.811, -0.569 and -1.025, 95% CI -1.230, -0.820; respectively), indicating a significant effect of both drugs on UPDRS. The SMD between selegiline and rasagiline was not significantly different (SMD 0.079; 95% CI -0.010, +0.167). It appears that selegiline and rasagiline have comparable efficacy in improving Parkinsonian symptoms in patients with early stage disease.

Early-Onset Creutzfeldt-Jakob Disease Mimicking Immune-Mediated Encephalitis

Directory of Open Access Journals (Sweden)

Wietse A. Wiels

2018-04-01

Full Text Available ObjectivesThe objective of this study is to explore the clinical, radiological, and pathological manifestations of a rare subtype of prion disease and their implication for differential diagnosis in case of an early onset neuropsychiatric deterioration.MethodsWe discuss a patients’ clinical history, as well as the string of investigations and symptomatological evolution that finally led to a pathological diagnosis.ResultsOur patient had the extremely rare VV1 type sporadic Creutzfeldt-Jakob disease (sCJD. We explain the differential diagnosis of progressive encephalomyelitis with rigidity and myoclonus and its implications for treatment.ConclusionsCJD, especially the VV1 subtype, can present at an early age with an insidious psychiatric onset. Classical findings of prion disease—14-3-3 protein, PSWC on electroencephalography, and magnetic resonance imaging patterns—are not always present. The presence of neural autoantibodies does not always implicate pathogenicity in the presence of other neurological/neurodegenerative conditions.

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

2018-02-01

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.

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

Science.gov (United States)

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

2017-12-01

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

Motor assessment in Parkinson`s disease.

Science.gov (United States)

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

2017-09-21

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

Parkinson Disease Protein DJ-1 Binds Metals and Protects against Metal-induced Cytotoxicity*

Science.gov (United States)

Björkblom, Benny; Adilbayeva, Altynai; Maple-Grødem, Jodi; Piston, Dominik; Ökvist, Mats; Xu, Xiang Ming; Brede, Cato; Larsen, Jan Petter; Møller, Simon Geir

2013-01-01

The progressive loss of motor control due to reduction of dopamine-producing neurons in the substantia nigra pars compacta and decreased striatal dopamine levels are the classically described features of Parkinson disease (PD). Neuronal damage also progresses to other regions of the brain, and additional non-motor dysfunctions are common. Accumulation of environmental toxins, such as pesticides and metals, are suggested risk factors for the development of typical late onset PD, although genetic factors seem to be substantial in early onset cases. Mutations of DJ-1 are known to cause a form of recessive early onset Parkinson disease, highlighting an important functional role for DJ-1 in early disease prevention. This study identifies human DJ-1 as a metal-binding protein able to evidently bind copper as well as toxic mercury ions in vitro. The study further characterizes the cytoprotective function of DJ-1 and PD-mutated variants of DJ-1 with respect to induced metal cytotoxicity. The results show that expression of DJ-1 enhances the cells' protective mechanisms against induced metal toxicity and that this protection is lost for DJ-1 PD mutations A104T and D149A. The study also shows that oxidation site-mutated DJ-1 C106A retains its ability to protect cells. We also show that concomitant addition of dopamine exposure sensitizes cells to metal-induced cytotoxicity. We also confirm that redox-active dopamine adducts enhance metal-catalyzed oxidation of intracellular proteins in vivo by use of live cell imaging of redox-sensitive S3roGFP. The study indicates that even a small genetic alteration can sensitize cells to metal-induced cell death, a finding that may revive the interest in exogenous factors in the etiology of PD. PMID:23792957

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.

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

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Exploring the Association Between Rosacea and Parkinson Disease

DEFF Research Database (Denmark)

Egeberg, Alexander; Hansen, Peter Riis; Gislason, Gunnar H

2016-01-01

Importance: The pathogenesis of rosacea is unclear, but increased matrix metalloproteinase target tissue activity appears to play an important role. Parkinson disease and other neurodegenerative disorders also display increased matrix metalloproteinase activity that contribute to neuronal loss....... Objective: To investigate the risk of incident (new-onset) Parkinson disease in patients with rosacea. Design, Setting, and Participants: A nationwide cohort study of the Danish population was conducted using individual-level linkage of administrative registers. All Danish citizens 18 years or older from...... January 1, 1997, to December 31, 2011 (N = 5 472 745), were included. Data analysis was conducted from June 26 to July 27, 2015. Main Outcomes and Measures: The main outcome was a diagnosis of Parkinson disease. Incidence rates (IRs) per 10 000 person-years were calculated, and incidence rate ratios (IRRs...

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The glucocerobrosidase E326K variant predisposes to Parkinson's disease, but does not cause Gaucher's disease.

Science.gov (United States)

Duran, Raquel; Mencacci, Niccolo E; Angeli, Aikaterini V; Shoai, Maryam; Deas, Emma; Houlden, Henry; Mehta, Atul; Hughes, Derralynn; Cox, Timothy M; Deegan, Patrick; Schapira, Anthony H; Lees, Andrew J; Limousin, Patricia; Jarman, Paul R; Bhatia, Kailash P; Wood, Nicholas W; Hardy, John; Foltynie, Tom

2013-02-01

Heterozygous loss-of-function mutations in the acid beta-glucocerebrosidase (GBA1) gene, responsible for the recessive lysosomal storage disorder, Gaucher's disease (GD), are the strongest known risk factor for Parkinson's disease (PD). Our aim was to assess the contribution of GBA1 mutations in a series of early-onset PD. One hundred and eighty-five PD patients (with an onset age of ≤50) and 283 age-matched controls were screened for GBA1 mutations by Sanger sequencing. We show that the frequency of GBA1 mutations is much higher in this patient series than in typical late-onset patient cohorts. Furthermore, our results reveal that the most prevalent PD-associated GBA1 mutation is E326K, a variant that does not, when homozygous, cause GD. Our results confirm recent reports that the mutation, E326K, predisposes to PD and suggest that, in addition to reduced GBA1 activity, other molecular mechanisms may contribute to the development of the disease. Copyright © 2012 Movement Disorders Society.

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Early Life Stress, Depression And Parkinson's Disease: A New Approach.

Science.gov (United States)

Dallé, Ernest; Mabandla, Musa V

2018-03-19

This review aims to shed light on the relationship that involves exposure to early life stress, depression and Parkinson's disease (PD). A systematic literature search was conducted in Pubmed, MEDLINE, EBSCOHost and Google Scholar and relevant data were submitted to a meta-analysis . Early life stress may contribute to the development of depression and patients with depression are at risk of developing PD later in life. Depression is a common non-motor symptom preceding motor symptoms in PD. Stimulation of regions contiguous to the substantia nigra as well as dopamine (DA) agonists have been shown to be able to attenuate depression. Therefore, since PD causes depletion of dopaminergic neurons in the substantia nigra, depression, rather than being just a simple mood disorder, may be part of the pathophysiological process that leads to PD. It is plausible that the mesocortical and mesolimbic dopaminergic pathways that mediate mood, emotion, and/or cognitive function may also play a key role in depression associated with PD. Here, we propose that a medication designed to address a deficiency in serotonin is more likely to influence motor symptoms of PD associated with depression. This review highlights the effects of an antidepressant, Fluvoxamine maleate, in an animal model that combines depressive-like symptoms and Parkinsonism.

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Digitized Spiral Drawing: A Possible Biomarker for Early Parkinson's Disease.

Science.gov (United States)

San Luciano, Marta; Wang, Cuiling; Ortega, Roberto A; Yu, Qiping; Boschung, Sarah; Soto-Valencia, Jeannie; Bressman, Susan B; Lipton, Richard B; Pullman, Seth; Saunders-Pullman, Rachel

2016-01-01

Pre-clinical markers of Parkinson's Disease (PD) are needed, and to be relevant in pre-clinical disease, they should be quantifiably abnormal in early disease as well. Handwriting is impaired early in PD and can be evaluated using computerized analysis of drawn spirals, capturing kinematic, dynamic, and spatial abnormalities and calculating indices that quantify motor performance and disability. Digitized spiral drawing correlates with motor scores and may be more sensitive in detecting early changes than subjective ratings. However, whether changes in spiral drawing are abnormal compared with controls and whether changes are detected in early PD are unknown. 138 PD subjects (50 with early PD) and 150 controls drew spirals on a digitizing tablet, generating x, y, z (pressure) data-coordinates and time. Derived indices corresponded to overall spiral execution (severity), shape and kinematic irregularity (second order smoothness, first order zero-crossing), tightness, mean speed and variability of spiral width. Linear mixed effect adjusted models comparing these indices and cross-validation were performed. Receiver operating characteristic analysis was applied to examine discriminative validity of combined indices. All indices were significantly different between PD cases and controls, except for zero-crossing. A model using all indices had high discriminative validity (sensitivity = 0.86, specificity = 0.81). Discriminative validity was maintained in patients with early PD. Spiral analysis accurately discriminates subjects with PD and early PD from controls supporting a role as a promising quantitative biomarker. Further assessment is needed to determine whether spiral changes are PD specific compared with other disorders and if present in pre-clinical PD.

Major life events and risk of Parkinson's disease

DEFF Research Database (Denmark)

Rod, Naja Hulvej; Hansen, Johnni; Schernhammer, Eva

2010-01-01

major life events are risk factors for Parkinson's disease. Between 1986 and 2006, we identified 13,695 patients with a (PD) primary diagnosis of PD in the Danish National Hospital Register. Each case was frequency matched by age and gender to five population controls. Information on major life events...... before onset of PD was ascertained from national registries. Among men, number of life events was associated with risk of Parkinson's disease in an inverse dose-response manner (P ....34-0.99). Life events were not associated with PD in women. In contrast, a higher risk of PD was observed among women who had never been married (1.16; 1.04-1.29) and among men (1.47; 1.18-1.82) and women (1.30; 1.05-1.61) who have never been employees. The lower risk of Parkinson's disease among men who had...

The effects of anticholinergic drugs on regional cerebral blood flow, and oxygen metabolism in previously untreated patients with Parkinson`s disease

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Obara, Satoko; Takahashi, Satoshi; Yonezawa, Hisashi; Sato, Yoshitomo [Iwate Medical Univ., Morioka (Japan). School of Medicine

1998-12-01

Regional cerebral blood flow (rCBF) and oxygen metabolism (rCMRO{sub 2}) were measured using the steady-state {sup 15}O technique and positron emission tomography (PET) in six previously untreated patients with Parkinson`s disease before and after trihexyphenidyl (THP) treatment. The patients comprised of 4 men and 2 women with Hoehn-Yahr stage II-III. Their ages at the onset of the study ranged from 46 to 57 years (mean{+-}SD, 51.8{+-}3.7) and the duration of the illness ranged from 10 to 48 months (mean{+-}SD, 28.8{+-}15.5). The PET study, assessments of the disability and cognitive function were undergone twice. The first time assessments were done was when the patients were not receiving any drugs, and the second time was one to three months after administration of 6 mg THP. All patients showed clinical improvement after THP treatment. The mean disability score of Unified Parkinson`s Disease Rating Scale decreased from 35.1 (SD{+-}11.3) to 25.7 (SD{+-}11.6). The cognitive function assessed by Hasegawa`s dementia rating scale-revised, Mini-Mental State Examination, Wechsler Adult Intelligence Scale-Revised, and Wechsler Memory Scale-Revised, were not significantly different before and after the THP treatment. After the THP treatment, rCBF and rCMRO{sub 2} decreased significantly in the striatum (about 15%) and all cerebral cortices (about 10%) on both sides contralateral and ipsilateral to the predominantly symptomatic limbs. We conclude that an anticholinergic THP decreases the rCBF and rCMRO{sub 2} significantly in the cerebral cortices without cognitive impairment in early untreated patients with Parkinson`s disease. (author)

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Full Text Available ... HELPLINE 1-800-4PD-INFO (473-4636) helpline@parkinson.org Search Our Site General Gift Tribute Gift Moving Day Support a Fundraiser Understanding Parkinson's What Is Parkinson's? Causes & Statistics Early Signs Movement ...

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Early- versus Late-Onset Systemic Sclerosis

Science.gov (United States)

Alba, Marco A.; Velasco, César; Simeón, Carmen Pilar; Fonollosa, Vicent; Trapiella, Luis; Egurbide, María Victoria; Sáez, Luis; Castillo, María Jesús; Callejas, José Luis; Camps, María Teresa; Tolosa, Carles; Ríos, Juan José; Freire, Mayka; Vargas, José Antonio; Espinosa, Gerard

2014-01-01

Abstract Peak age at onset of systemic sclerosis (SSc) is between 20 and 50 years, although SSc is also described in both young and elderly patients. We conducted the present study to determine if age at disease onset modulates the clinical characteristics and outcome of SSc patients. The Spanish Scleroderma Study Group recruited 1037 patients with a mean follow-up of 5.2 ± 6.8 years. Based on the mean ± 1 standard deviation (SD) of age at disease onset (45 ± 15 yr) of the whole series, patients were classified into 3 groups: age ≤30 years (early onset), age between 31 and 59 years (standard onset), and age ≥60 years (late onset). We compared initial and cumulative manifestations, immunologic features, and death rates. The early-onset group included 195 patients; standard-onset group, 651; and late-onset, 191 patients. The early-onset group had a higher prevalence of esophageal involvement (72% in early-onset compared with 67% in standard-onset and 56% in late-onset; p = 0.004), and myositis (11%, 7.2%, and 2.9%, respectively; p = 0.009), but a lower prevalence of centromere antibodies (33%, 46%, and 47%, respectively; p = 0.007). In contrast, late-onset SSc was characterized by a lower prevalence of digital ulcers (54%, 41%, and 34%, respectively; p < 0.001) but higher rates of heart conduction system abnormalities (9%, 13%, and 21%, respectively; p = 0.004). Pulmonary hypertension was found in 25% of elderly patients and in 12% of the youngest patients (p = 0.010). After correction for the population effects of age and sex, standardized mortality ratio was shown to be higher in younger patients. The results of the present study confirm that age at disease onset is associated with differences in clinical presentation and outcome in SSc patients. PMID:24646463

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123I-β-CIT SPECT imaging study in early Parkinson's disease

International Nuclear Information System (INIS)

Li Peiyong

1998-01-01

Purpose: To investigate the loss of dopamine transporters in hemi-Parkinson's disease (PD) using 123 I-β-CIT/SPECT. Methods: Seven patients with hemi-Parkinson's disease and 7 age- and sex- matched healthy subjects were studied by 123 I-β-CIT/SPECT. Striatal specific uptake of 123 I-β-CIT was calculated in the ratio of striatal uptake to cerebellar uptake. Results: Mean striatal specific uptake of 123 I-β-CIT in healthy subjects was 3.0 +- 0.5 and 5.5 +- 0.6 at 3h and 18h after injection. Striatal specific uptake in contralateral to the clinical symptom side was 2.0 +- 0.8 and 3.1 +- 0.4; in ipsilateral striatum was 2.3 +- 0.4 and 4.0 +- 0.5. There was a significant reduction of striatal tracer uptake in PD patients compared to the controls. Patient age correlated with the reduction in contralateral striatum but did not correlate with that in ipsilateral striatum. Conclusions: Striatal dopamine transporters bilaterally lost in early PD patients. 123 I-β-CIT uptake in contralateral striatum was reduced more severely than in ipsilateral striatum

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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...

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Medical records documentation of constipation preceding Parkinson disease: A case-control study.

Science.gov (United States)

Savica, R; Carlin, J M; Grossardt, B R; Bower, J H; Ahlskog, J E; Maraganore, D M; Bharucha, A E; Rocca, W A

2009-11-24

Parkinson disease (PD) may affect the autonomic nervous system and may cause constipation; however, few studies have explored constipation preceding the motor onset of PD. We investigated constipation preceding PD using a case-control study design in a population-based sample. Using the medical records-linkage system of the Rochester Epidemiology Project, we identified 196 subjects who developed PD in Olmsted County, MN, from 1976 through 1995. Each incident case was matched by age (+/-1 year) and sex to a general population control. We reviewed the complete medical records of cases and controls in the medical records-linkage system to ascertain the occurrence of constipation preceding the onset of PD (or index year). Constipation preceding PD or the index year was more common in cases than in controls (odds ratio [OR] 2.48; 95% confidence interval [CI] 1.49 to 4.11; p = 0.0005). This association remained significant after adjusting for smoking and coffee consumption (ever vs never), and after excluding constipation possibly induced by drugs. In addition, the association remained significant in analyses restricted to constipation documented 20 or more years before the onset of motor symptoms of PD. Although the association was stronger in women than in men and in patients with PD with rest tremor compared with patients with PD without rest tremor, these differences were not significant. Our findings suggest that constipation occurring as early as 20 or more years before the onset of motor symptoms is associated with an increased risk of Parkinson disease.

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…

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...... purported to be more sensitive than VBM, to test for atrophy in patients with early-stage PD. METHODS: T1-weighted MRI images from 24 early-stage PD patients and 26 age-matched normal control subjects were compared using DBM. Two separate studies were conducted, where two minimally-biased nonlinear...... intensity-average were created; one for all subjects and another for just the PD patients. The DBM technique creates an average population-based MRI-average in an iterative hierarchical fashion. The nonlinear transformations estimated to match each subject to the MRI-average were then analysed. RESULTS...

The use of rasagiline in Parkinson's disease.

Science.gov (United States)

Schapira, A H V

2006-01-01

Rasagiline is a novel, potent, irreversible inhibitor of monoamine oxidative B developed for the symptomatic treatment of Parkinson's disease. The drug has shown efficacy in improving motor features in both early and advanced Parkinson's disease patients. The drug appears to be well tolerated and its once daily fixed dose formulation should make for excellent compliance. Rasagiline has also demonstrated important neuroprotective properties in both in vitro and in vivo laboratory studies. A provisional study of neuroprotection in a delayed start clinical trial of early PD patients has also suggested that this benefit may be translated to the clinic. Additional clinical trials are underway to confirm this.

Different Functional and Microstructural Changes Depending on Duration of Mild Cognitive Impairment in Parkinson Disease.

Science.gov (United States)

Shin, N-Y; Shin, Y S; Lee, P H; Yoon, U; Han, S; Kim, D J; Lee, S-K

2016-05-01

The higher cortical burden of Lewy body and Alzheimer disease-type pathology has been reported to be associated with a faster onset of cognitive impairment of Parkinson disease. So far, there has been a few studies only about the changes of gray matter volume depending on duration of cognitive impairment in Parkinson disease. Therefore, our aim was to evaluate the different patterns of structural and functional changes in Parkinson disease with mild cognitive impairment according to the duration of parkinsonism before mild cognitive impairment. Fifty-nine patients with Parkinson disease with mild cognitive impairment were classified into 2 groups on the basis of shorter (parkinsonism before mild cognitive impairment. Fifteen drug-naïve patients with de novo Parkinson disease with intact cognition were included for comparison. Cortical thickness, Tract-Based Spatial Statistics, and seed-based resting-state functional connectivity analyses were performed. Age, sex, years of education, age at onset of parkinsonism, and levodopa-equivalent dose were included as covariates. The group with shorter duration of parkinsonism before mild cognitive impairment showed decreased fractional anisotropy and increased mean and radial diffusivity values in the frontal areas compared with the group with longer duration of parkinsonism before mild cognitive impairment (corrected P parkinsonism before mild cognitive impairment showed decreased resting-state functional connectivity in the default mode network area when the left or right posterior cingulate was used as a seed, and in the dorsolateral prefrontal areas when the left or right caudate was used as a seed (corrected P parkinsonism before mild cognitive impairment showed decreased resting-state functional connectivity mainly in the medial prefrontal cortex when the left or right posterior cingulate was used as a seed, and in the parieto-occipital areas when the left or right caudate was used as a seed (corrected P Parkinson

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

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

2015-01-01

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

Tc-99m TRODAT-1 and I-123 IBZM SPECT in patients with early Parkinson's disease

International Nuclear Information System (INIS)

Huang, W.S.; Lin, J.C.; Lin, S.Z.; Chen, C.Y.; Ting, G.

2002-01-01

Background: Tc-99m TRODAT-1 and I-123 IBZM are potential agents for dopamine transporter (DAT) and dopamine receptor (DR) SPECT, respectively. Mainly involving pre-synaptic neurons, Parkinson's disease (PD) could be differentiated from other movement disorders such as essential tremor and secondary parkinsonism using TRODAT-1 and IBZM SPECT. This study further investigates the value of TRODAT/ IBZM-specific uptake ratios (SUR) of striatum (ST) and putamrn (PU) in evaluating early PD. Methods and Materials: A total of 13 subjects (8 H and Y stage 1, 5 stage II and 5 age-matched controls) were studied. Tc-99m TRODAT-1 (925 MBq) and then I-123 IBZM (259 MBq) SPECT were performed separately within a month using a dual-head camera equipped with an ultra-high resolution fan beam collimator (Helix SPX, Elscint). Ratios of SURs of TRODAT-1 vs. IBZM (RSUR) were measured. Results: Significant differences in averaged SUR of TRODAT-1 were found among controls and patients with stages I and II (2.03, 1.69 and 1.27, p<0.01 respectively). The averaged SUR of IBZM, however, was significantly decreased only in the contralateral ST of the stage II patients. There was a significant decrease of RSUR of ST and PU in diseased groups especially in the contralateral side. Notably, less overlap in putaminal RSURs between diseased groups, either ipisilaterally or contralaterally, and controls was found. Conclusion: The function of DR might be preserved in early PD. The better discrimination of diseased groups from controls using putaminal RSUR might be due to up-regulated DR, which provided a clue to differentiating idiopathic PD from other parkinsonism at the early stage

Motor subtype changes in early Parkinson's disease.

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Eisinger, Robert S; Hess, Christopher W; Martinez-Ramirez, Daniel; Almeida, Leonardo; Foote, Kelly D; Okun, Michael S; Gunduz, Aysegul

2017-10-01

Distinct motor subtypes of Parkinson's disease (PD) have been described through both clinical observation and through data-driven approaches. However, the extent to which motor subtypes change during disease progression remains unknown. Our objective was to determine motor subtypes of PD using an unsupervised clustering methodology and evaluate subtype changes with disease duration. The Parkinson's Progression Markers Initiative database of 423 newly diagnosed PD patients was utilized to retrospectively identify unique motor subtypes through a data-driven, hierarchical correlational clustering approach. For each patient, we assigned a subtype to each motor assessment at each follow-up visit (time points) and by using published criteria. We examined changes in PD subtype with disease duration using both qualitative and quantitative methods. Five distinct motor subtypes were identified based on the motor assessment items and these included: Tremor Dominant (TD), Axial Dominant, Appendicular Dominant, Rigidity Dominant, and Postural and Instability Gait Disorder Dominant. About half of the patients had consistent subtypes at all time points. Most patients met criteria for TD subtype soon after diagnosis. For patients with inconsistent subtypes, there was an overall trend to shift away from a TD phenotype with disease duration, as shown by chi-squared test, p motor subtypes in PD can shift with increasing disease duration. Shifting subtypes is a factor that should be accounted for in clinical practice or in clinical trials. Copyright © 2017 Elsevier Ltd. All rights reserved.

Reversible Pharmacological Induction of Motor Symptoms in MPTP-Treated Mice at the Presymptomatic Stage of Parkinsonism: Potential Use for Early Diagnosis of Parkinson's Disease.

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Khakimova, Gulnara R; Kozina, Elena A; Kucheryanu, Valerian G; Ugrumov, Michael V

2017-07-01

A crucial event in the pathogenesis of Parkinson's disease is the death of dopaminergic neurons of the nigrostriatal system, which are responsible for the regulation of motor function. Motor symptoms first appear in patients 20-30 years after the onset of the neurodegeneration, when there has been a loss of an essential number of neurons and depletion of compensatory reserves of the brain, which explains the low efficiency of treatment. Therefore, the development of a technology for the diagnosing of Parkinson's disease at the preclinical stage is of a high priority in neurology. In this study, we have developed at an experimental model a fundamentally novel for neurology approach for diagnosis of Parkinson's disease at the preclinical stage. This methodology, widely used for the diagnosis of chronic diseases in the internal medicine, is based on the application of a challenge test that temporarily increases the latent failure of a specific functional system, thereby inducing the short-term appearance of clinical symptoms. The provocation test was developed by a systemic administration of α-methyl-p-tyrosine (αMpT), a reversible inhibitor of tyrosine hydroxylase to MPTP-treated mice at the presymptomatic stage of parkinsonism. For this, we first selected a minimum dose of αMpT, which caused a decrease of the dopamine level in the striatum of normal mice below the threshold at which motor dysfunctions appear. Then, we found the maximum dose of αMpT at which a loss of dopamine in the striatum of normal mice did not reach the threshold level, and motor behavior was not impaired. We showed that αMpT at this dose induced a decrease of the dopamine concentration in the striatum of MPTP-treated mice at the presymptomatic stage of parkinsonism below a threshold level that results in the impairment of motor behavior. Finally, we proved that αMpT exerts a temporal and reversible influence on the nigrostriatal dopaminergic system of MPTP-treated mice with no long

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

Institute of Scientific and Technical Information of China (English)

无

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.

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

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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. Copyright © 2016 Elsevier Ltd. All rights reserved.

Neuromuscular rate of force development deficit in Parkinson disease.

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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.

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

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Rascol, Olivier

2005-10-01

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

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

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Malaty, Irene A; Fernandez, Hubert H

2009-08-01

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

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...

Determination of minimal clinically important change in early and advanced Parkinson's disease.

Science.gov (United States)

Hauser, Robert A; Auinger, Peggy

2011-04-01

Two common primary efficacy outcome measures in Parkinson's disease (PD) are change in Unified Parkinson's Disease Rating Scale (UPDRS) scores in early PD and change in "off" time in patients with motor fluctuations. Defining the minimal clinically important change (MCIC) in these outcome measures is important to interpret the clinical relevance of changes observed in clinical trials and other situations. We analyzed data from 2 multicenter, placebo-controlled, randomized clinical trials of rasagiline; TEMPO studied 404 early PD subjects, and PRESTO studied 472 levodopa-treated subjects with motor fluctuations. An anchor-based approach using clinical global impression of improvement (CGI-I) was used to determine MCIC for UPDRS scores and daily "off" time. MCIC was defined as mean change in actively treated subjects rated minimally improved on CGI-I. Receiver operating characteristic (ROC) curves defined optimal cutoffs discriminating between changed and unchanged subjects. MCIC for improvement in total UPDRS score (parts I-III) in early PD was determined to be -3.5 points based on mean scores and -3.0 points based on ROC curves. In addition, we found an MCIC for reduction in "off" time of 1.0 hours as defined by mean reduction in "off" time in active treated subjects self-rated as minimally improved on CGI-I minus mean reduction in "off" time in placebo-treated subjects self-rated as unchanged (1.9-0.9 hours). We hypothesize that many methodological factors can influence determination of the MCIC, and a range of values is likely to emerge from multiple studies. Copyright © 2011 Movement Disorder Society.

Study of an integrated non-motor symptoms questionnaire for Parkinson's disease

Institute of Scientific and Technical Information of China (English)

YU Bo; XIAO Zhi-ying; LI Jia-zhen; YUAN Jing; LIU Yi-ming

2010-01-01

Background Although the validity of non-motor symptoms screening questionnaire (NMSQuest) for Parkinson's disease has been verified in several recent researches, the specificity of the questionnaire is still in doubt. This study aimed to compare the non-motor symptoms (NMS) in Parkinson's disease (PD) with a medically ill control group.Methods In this study, the first comprehensive clinic-based NMS screening questionnaire for PD developed by the Parkinson's Disease Non-Motor Group (PDNMG) was used. Data from 90 PD patients and 270 sex-and age-matched control subjects, including stroke (n=90), heart disease (n=90) and diabetes (n=90) were analyzed.Results Compared with control group, NMS was more common in PD; on an average, most PD patients reported more than 12 non-motor items. There was a correlation of total NMS score in PD patients with Hoehn & Yahr Staging, but not with age, sex distribution, disease duration, or age at disease onset. Additionally, depression, constipation and impaired olfaction which occurred prior to the motor symptoms of PD were reported in this study.Conclusions NMS are more common in PD patients. There are some NMS that occurred at the preclinical stage of PD and might predict the onset of motor symptoms of PD patients.

Impulse control disorders and depression in Finnish patients with Parkinson's disease.

Science.gov (United States)

Joutsa, Juho; Martikainen, Kirsti; Vahlberg, Tero; Voon, Valerie; Kaasinen, Valtteri

2012-02-01

Impulse control disorders occur frequently in patients with Parkinson's disease. However, the frequencies have been investigated mainly in patients from secondary or tertiary care centers, and thus, the prevalence rates in general community are not known. Our objective was to study the prevalence rates of impulse control disorders and related factors in a large, non-selected sample of Parkinson's disease patients. We conducted a cross-sectional survey among Parkinson's disease patients from Finnish Parkinson Association [n = 575; 365 men, 240 women, median age 64 (range 43-90) years]. Problem and pathological gambling were estimated with the South Oaks Gambling Screen, risk for impulse control disorders with the validated Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease, and depression with the Beck Depression Inventory. The frequency of pathological gambling was 7.0%. The overall frequency of a positive screen for an impulse control disorder was 34.8%, and 12.5% of the patients screened positive for multiple disorders. Depressive symptoms were statistically the most important factor in explaining variance in impulse control disorder risk, even more than sex, age, age of disease onset, alcohol use, or medication. The high proportion of patients screened positive for impulse control disorders in a non-selected sample emphasize the importance of routine screening of these disorders in Parkinson's disease. Pathological gambling prevalence in Parkinson's disease is seven times higher than in the general population in Finland. The results underline the importance of depression in impulse control disorders associated with Parkinson's disease. Copyright © 2011 Elsevier Ltd. All rights reserved.

Diagnostic pitfalls in Parkinson's disease: case report Dificuldades diagnósticas na doença de Parkinson: relato de caso

Directory of Open Access Journals (Sweden)

Flávio Augusto Sekeff-Sallem

2007-06-01

Full Text Available Parkinson's disease (PD is characterized by resting tremor, rigidity and bradykinesia. In 80% of cases, the disorder begins with upper limb resting tremor. However, there are some presenting atypical features that make the diagnosis even more difficult and intriguing. The disorder can have its onset below 40 years old, characterizing early-onset parkinsonism, which differential diagnosis possibilities are varied. Atypical presentations include a pure akinetic-rigid syndrome, the initial manifestations occurring in the lower limbs, and pain as the most important or sole manifestation. These atypical features are unusual, but can be seen in clinical practice. We present a 37 years old woman with early-onset parkinsonism beginning with an akinetic-rigid syndrome in the lower limbs whose first symptom was left leg pain, which diagnosis was made after 4 years of onset and after 16 referrals to several experts in different fields. We discuss these atypical features and the diagnostic pitfalls in PD.A doença de Parkinson (DP caracteriza-se pela tríade de tremor, rigidez e bradicinesia. Em cerca de 80% dos casos inicia-se com tremor em membros superiores. Entretanto, certas atipias na apresentação desta entidade tornam seu diagnóstico ainda mais desafiador. A doença pode iniciar-se abaixo dos 40 anos de idade, caracterizando o parkinsonismo de início precoce. Apresentações atípicas incluem uma síndrome rígido-acinética pura, as manifestações inaugurais ocorrendo em membros inferiores, e uma síndrome dolorosa podendo ser um sintoma inicial proeminente ou o único sintoma. Estas atipias, apesar de infreqüentes, são encontradas na prática clínica diária. Discutimos estas características atípicas ao apresentarmos uma paciente de 37 anos com quadro rígido-acinético de instalação precoce, iniciado em membros inferiores, cujo sintoma predominante era dor, cujo diagnóstico somente foi feito após 4 anos do início e após 16 avalia

Parkinson disease - discharge

Science.gov (United States)

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

Comparison with Parkinson's disease and Parkinsonism in dementia with lewy bodies

International Nuclear Information System (INIS)

Kang, Do Young; Park, Kyung Won; Kim, Jae Woo

2002-01-01

Dementia with lewy bodies (DLB) is recognized as a common cause of dementia in elderly people. It is characterized by Parkinsonism as well as fluctuation cognition and visual hallucination. It is not easy to differentiated DLB with Parkinsonism from Parkinson's disease (PD). We compared clinical features and I-123 IPT SPECT findings between two groups. Ten probable DLB patients and 15 PD patients were included. They were all matched for age (66.9±8.5) vs 65.8±8.5), education period (9.8±4.9 vs 9.1±4.5) and H and Y stage (2.9±0.8). Clinical features were scored. I-123 IPT SPECT were performed. The mean age of disease onset was seen more common in PD, but the severity of rigidity and bradykinesia was not significantly different. We found no significant difference of responsiveness to levodopa measured with decrement of UPDRS scores before and after treatment of levodopa. The mean disease duration reaching same H and Y stage was longer in PD than in DLB. The average K-MMSE score was significantly lower in DLB than in PD. The uptake ratio in the striatum in DLB was comparable to that in PD. In differentiating the two conditions the speed of disease progression and cognitive state were considered to be important. The level of dopamine transporter was not different between two diseases with same H and Y stage

Substantia Nigra Free Water Increases Longitudinally in Parkinson Disease.

Science.gov (United States)

Guttuso, T; Bergsland, N; Hagemeier, J; Lichter, D G; Pasternak, O; Zivadinov, R

2018-02-01

Free water in the posterior substantia nigra obtained from a bi-tensor diffusion MR imaging model has been shown to significantly increase over 1- and 4-year periods in patients with early-stage idiopathic Parkinson disease compared with healthy controls, which suggests that posterior substantia nigra free water may be an idiopathic Parkinson disease progression biomarker. Due to the known temporal posterior-to-anterior substantia nigra degeneration in idiopathic Parkinson disease, we assessed longitudinal changes in free water in both the posterior and anterior substantia nigra in patients with later-stage idiopathic Parkinson disease and age-matched healthy controls for comparison. Nineteen subjects with idiopathic Parkinson disease and 19 age-matched healthy control subjects were assessed on the same 3T MR imaging scanner at baseline and after approximately 3 years. Baseline mean idiopathic Parkinson disease duration was 7.1 years. Both anterior and posterior substantia nigra free water showed significant intergroup differences at baseline ( P Parkinson disease versus healthy controls); however, only anterior substantia nigra free water showed significant longitudinal group × time interaction increases ( P = .021, idiopathic Parkinson disease versus healthy controls). There were no significant longitudinal group × time interaction differences found for conventional diffusion tensor imaging or free water-corrected DTI assessments in either the anterior or posterior substantia nigra. Results from this study provide further evidence supporting substantia nigra free water as a promising disease-progression biomarker in idiopathic Parkinson disease that may help to identify disease-modifying therapies if used in future clinical trials. Our novel finding of longitudinal increases in anterior but not posterior substantia nigra free water is potentially a result of the much longer disease duration of our cohort compared with previously studied cohorts and the known

There is no Parkinson disease.

Science.gov (United States)

Weiner, William J

2008-06-01

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

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.

GATA2 is associated with familial early-onset coronary artery disease.

Directory of Open Access Journals (Sweden)

Jessica J Connelly

2006-08-01

Full Text Available The transcription factor GATA2 plays an essential role in the establishment and maintenance of adult hematopoiesis. It is expressed in hematopoietic stem cells, as well as the cells that make up the aortic vasculature, namely aortic endothelial cells and smooth muscle cells. We have shown that GATA2 expression is predictive of location within the thoracic aorta; location is suggested to be a surrogate for disease susceptibility. The GATA2 gene maps beneath the Chromosome 3q linkage peak from our family-based sample set (GENECARD study of early-onset coronary artery disease. Given these observations, we investigated the relationship of several known and novel polymorphisms within GATA2 to coronary artery disease. We identified five single nucleotide polymorphisms that were significantly associated with early-onset coronary artery disease in GENECARD. These results were validated by identifying significant association of two of these single nucleotide polymorphisms in an independent case-control sample set that was phenotypically similar to the GENECARD families. These observations identify GATA2 as a novel susceptibility gene for coronary artery disease and suggest that the study of this transcription factor and its downstream targets may uncover a regulatory network important for coronary artery disease inheritance.

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.

Effects of deep brain stimulation on rest tremor progression in early stage Parkinson disease.

Science.gov (United States)

Hacker, Mallory L; DeLong, Mahlon R; Turchan, Maxim; Heusinkveld, Lauren E; Ostrem, Jill L; Molinari, Anna L; Currie, Amanda D; Konrad, Peter E; Davis, Thomas L; Phibbs, Fenna T; Hedera, Peter; Cannard, Kevin R; Drye, Lea T; Sternberg, Alice L; Shade, David M; Tonascia, James; Charles, David

2018-06-29

To evaluate whether the progression of individual motor features was influenced by early deep brain stimulation (DBS), a post hoc analysis of Unified Parkinson's Disease Rating Scale-III (UPDRS-III) score (after a 7-day washout) was conducted from the 2-year DBS in early Parkinson disease (PD) pilot trial dataset. The prospective pilot trial enrolled patients with PD aged 50-75 years, treated with PD medications for 6 months-4 years, and no history of dyskinesia or other motor fluctuations, who were randomized to receive optimal drug therapy (ODT) or DBS plus ODT (DBS + ODT). At baseline and 6, 12, 18, and 24 months, all patients stopped all PD therapy for 1 week (medication and stimulation, if applicable). UPDRS-III "off" item scores were compared between the ODT and DBS + ODT groups (n = 28); items with significant between-group differences were analyzed further. UPDRS-III "off" rest tremor score change from baseline to 24 months was worse in patients receiving ODT vs DBS + ODT ( p = 0.002). Rest tremor slopes from baseline to 24 months favored DBS + ODT both "off" and "on" therapy ( p will be tested in the Food and Drug Administration-approved, phase III, pivotal, multicenter clinical trial evaluating DBS in early PD. This study provides Class II evidence that for patients with early PD, DBS may slow the progression of rest tremor. © 2018 American Academy of Neurology.

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Vocal Markers of Motor, Cognitive, and Depressive Symptoms in Parkinson’s Disease

Science.gov (United States)

2017-05-02

Au WL, Tan LC (2015) Prognostic factors for early mortality in Parkinson’s disease . Parkinsonism Relat Disord 21, 226-230. [5] Leroi I, McDonald K...Pantula H, Harbishettar V (2012) Cognitive impairment in Parkinson disease : impact on quality of life, disability, and caregiver burden. J Geriatr...1271. [15] Silbergleit AK, LeWitt PA, Peterson EL, Gardner GM (2015) Quantitative Analysis of Voice in Parkinson Disease Compared to Motor

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Parkinson's disease proteins: Novel mitochondrial targets for cardioprotection

OpenAIRE

Mukherjee, Uma A.; Ong, Sang-Bing; Ong, Sang-Ging; Hausenloy, Derek J.

2015-01-01

Ischemic heart disease (IHD) is the leading cause of death and disability worldwide. Therefore, novel therapeutic targets for protecting the heart against acute ischemia/reperfusion injury (IRI) are required to attenuate cardiomyocyte death, preserve myocardial function, and prevent the onset of heart failure. In this regard, a specific group of mitochondrial proteins, which have been linked to familial forms of Parkinson's disease (PD), may provide novel therapeutic targets for cardioprotect...

[Syndrome of rapid eye movement sleep behavior disorder and nocturia in Parkinson's disease].

Science.gov (United States)

Nodel, M R; Ukraintseva, Yu V; Yakhno, N N

Parasomnia, a syndrome of rapid eye movement sleep behavior disorder (RBD), is a common non-motor impairment in patients with Parkinson's disease (PD). The relationship between RBD with other symptoms of PD affecting night sleep, in particular, nocturia, is understudied. An aim of the study was to determine the symptoms related to night sleep disturbances in PD patients with RBD and assess the dynamics of these disturbances with the disease progression taking into account RBD onset. One hundred and forty patients (72 male and 68 female) with PD without dementia (mean age 61.98±0.79 years, PD stage - 2.35±0.05, duration 5.82±90.65 years) were examined. Motor disorders were assessed with the unified Parkinson's disease rating scale (UPDRS), sleep disturbances and frequent night urinations were evaluated with the Parkinson's Disease Sleep Scale (PDSS). The diagnosis of probable RBD was based on reports of patients or their relatives on the dream-related motor activity and vocalization. Quality-of-life was evaluated with the Parkinson's Disease Questionnaire (PDQ-39). Patients were followed up after 2.5 years. Probable RBD was diagnosed in 46.43% of patients, including 30.77%, who developed the syndrome before the manifestation of motor symptoms, 16.92% patients with simultaneous development of RBD and motor symptoms and 52.31% with RBD development >2 years after motor disorders. Patients with RBD differed from those without parasomnia by the higher severity of nocturia. After 2.5 years of follow-up, the severity of disease was greater in patients with RBD assessed by UPDRS, quality-of-life indices, severity of nocturia and episodes of nocturia. The highest frequency of episodes of nocturia was noted in patients with early onset of RBD before the manifestation of motor symptoms. RBD in patients with PD is associated with the rapid progress of nocturia, higher degree of worsening of daily activities and deterioration of quality of life. The relationship between RBD

The significance of 18F-FP-β-CIT dopamine transporter PET imaging in early diagnosis of Parkinson's disease

International Nuclear Information System (INIS)

Wang Jian; Jiang Yuping; Guo Liping; Yang Liqin; Wu Jianjun; Ding Zhengtong; Guan Yihui; Zhao Jun; Xiang Jingde; Chen Zhengping; Su Huilin

2003-01-01

Objective: To evaluate the 18 F-N-3-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) nortropane ( 18 F-FP-β-CIT) dopamine transporter (DAT) PET imaging in diagnosing Parkinson's disease with early stage and assessing the severity of their disability. Methods: 4 healthy controls, 21 parkinsonian patients with early stage and 10 parkinsonian patients with advanced stage were studied, the ratio of [ region of interest (ROI)-cerebellum]/cerebellum was measured and compared. The correlation between DAT binding in striatum and unified Parkinson's disease rating scale (UPDRS) motor scores was also determined. Results: In patients with early stage (Hoehn and Yahr stage I-II) , the DAT binding uptake in the caudate, anterior putamen and posterior putamen was significantly reduced to 71.8%, 43.8% and 23.6% of the control value respectively, and more pronounced reduction of the uptake was found in the striatum contralateral to the predominant symptoms. Compared with age-matched controls, there was a significant reduction of DAT binding in the ipsilateral (preclinical) striatum of hemi-parkinsonian patients with Hoehn and Yahr stage 1 or 1.5. In the patients with advanced stage, the corresponding figure were further reduced to 51.9%, 31.8%, 15.8%. The DAT binding uptake in striatum of all parkinsonian patients showed significantly negative correlation with UPDRS motor scores, especially in the subregion of posterior putamen. Conclusion: 18 F-FP-β-CIT DAT PET imaging is helpful in diagnosing Parkinson's disease with early stage and assessing the severity of their disability

Parkinson's Disease Videos

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... Nonmotor Symptoms of Parkinson's Disease Expert Briefings: Gait, Balance and Falls in Parkinson's Disease Expert Briefings: Coping Skills for ... Caregivers: Caremap and Caring & Coping CareMAP: Movement and Falls: Part ... There Any Ways to Control the Rate of Progression of the Disease? CareMAP: ...

Daytime Napping, Nighttime Sleeping, and Parkinson Disease

Science.gov (United States)

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

2011-01-01

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

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Pathological gambling and hypersexuality due to dopaminergic treatment in Parkinson' disease.

Science.gov (United States)

Martín Fernández, F; Martín González, T

2009-01-01

Prevalence of psychiatric disorders in patients suffering from Parkinson's disease varies from 12 to 90%. The most common disorder in the natural evolution of Parkinson's disease is depression. However, episodes of psychosis and hypomania are related to treatment with L-dopa and dopaminergic agents. Other recognized, although less frequent, psychiatric disorders are hypersexuality and development of certain addictive behaviors, which is compulsive gambling and overdosing of anti-Parkinson agents. A case is presented of a male patient diagnosed with Parkinson's Disease at an early age who was treated with L-dopa and a combination of dopaminergic agents. During the course of his evolution he manifested symptoms of hypersexuality and pathological gambling which were unrelated to psychotic or mood changes. A number of hospital admissions were needed into order to detect a pattern of abusive consumption of L-dopa as the main factor behind his behavior changes. The possibility of overdosage of L-dopa and dopaminergic drugs should be considered when there is pathological gambling conduct and/or hypersexuality, without psychotic or accompanying affective symptoms, in a male who develops Parkinson's disease at an early age and who undergoes treatment with these drugs and manifests motor fluctuations and dyskinesias. Early detection of the presence of these alterations, included within those described as "dopaminergic dysregulation syndrome", would allow for an early intervention on the cause behind them and would hence avoid the possible medical and social complications.

Nucleus basalis of Meynert degeneration precedes and predicts cognitive impairment in Parkinson's disease.

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Schulz, Jonathan; Pagano, Gennaro; Fernández Bonfante, Juan Alberto; Wilson, Heather; Politis, Marios

2018-05-01

Currently, no reliable predictors of cognitive impairment in Parkinson's disease exist. We hypothesized that microstructural changes at grey matter T1-weighted MRI and diffusion tensor imaging in the cholinergic system nuclei and associated limbic pathways underlie cognitive impairment in Parkinson's disease. We performed a cross-sectional comparison between patients with Parkinson's disease with and without cognitive impairment. We also performed a longitudinal 36-month follow-up study of cognitively intact Parkinson's disease patients, comparing patients who remained cognitively intact to those who developed cognitive impairment. Patients with Parkinson's disease with cognitive impairment showed lower grey matter volume and increased mean diffusivity in the nucleus basalis of Meynert, compared to patients with Parkinson's disease without cognitive impairment. These results were confirmed both with region of interest and voxel-based analyses, and after partial volume correction. Lower grey matter volume and increased mean diffusivity in the nucleus basalis of Meynert was predictive for developing cognitive impairment in cognitively intact patients with Parkinson's disease, independent of other clinical and non-clinical markers of the disease. Structural and microstructural alterations in entorhinal cortex, amygdala, hippocampus, insula, and thalamus were not predictive for developing cognitive impairment in Parkinson's disease. Our findings provide evidence that degeneration of the nucleus basalis of Meynert precedes and predicts the onset of cognitive impairment, and might be used in a clinical setting as a reliable biomarker to stratify patients at higher risk of cognitive decline.

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.

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Maintaining Intestinal Health: The Genetics and Immunology of Very Early Onset Inflammatory Bowel DiseaseSummary

Directory of Open Access Journals (Sweden)

Judith R. Kelsen

2015-09-01

Full Text Available Inflammatory bowel disease (IBD is a multifactoral disease caused by dysregulated immune responses to commensal or pathogenic microbes in the intestine, resulting in chronic intestinal inflammation. An emerging population of patients with IBD younger than 5 years of age represent a unique form of disease, termed very early onset IBD (VEO-IBD, which is phenotypically and genetically distinct from older-onset IBD. VEO-IBD is associated with increased disease severity, aggressive progression, and poor responsiveness to most conventional therapies. Further investigation into the causes and pathogenesis of VEO-IBD will help improve treatment strategies and may lead to a better understanding of the mechanisms that are essential to maintain intestinal health or provoke the development of targeted therapeutic strategies to limit intestinal inflammation and promote tissue repair. Here, we discuss the phenotypic nature of VEO-IBD, the recent identification of novel gene variants associated with disease, and functional immunologic studies interrogating the contribution of specific genetic variants to the development of chronic intestinal inflammation. Keywords: Inflammatory Bowel Disease, Very Early Onset Inflammatory Bowel Disease, Whole Exome Sequencing, Mucosal Immunology

Cerebral hemodynamic difference between early- and late-onset Alzheimer's disease by circumferential profile analysis with 123I-IMP brain SPECT

International Nuclear Information System (INIS)

Arai, Hisayuki; Hanyu, Haruo; Abe, Shinei; Asano, Tetsuichi; Takasaki, Masaru; Suzuki, Takanari; Abe, Kimihiko; Katsunuma, Hideyo.

1992-01-01

We conducted investigation to determine whether early- and late-onset Alzheimer's diseases differ pathophysiologically. Five patients with the early-onset (65 years and under) of the disease and 11 with the late-onset (65 years and over) of the disease were studied by single photon emission CT (SPECT) with N-isopropyl-p-[ 123 I]iodoamphetamine (IMP). Circumferential profile analysis (CPA) was performed to examine differences in the predominant hypoperfusion in the temporoparietal lobe, which is considered to be functionally damaged the most in Alzheimer's disease. The Xm values, calculated from gradients between the motorsensory or occipital cortices and temporoparietal cortex in the circumferential profile curve, were compared in both groups. The Xm values for patients with early- and late-onset Alzheimer's disease were 6.81±2.10 (counts/degree) and 3.28±1.58, respectively, the difference being significant. Our results suggest that functional abnormalities in the temporoparietal area severer in early- than late-onset Alzheimer's disease and that the application of CPA to IMP SPECT is useful to elucidate the pathophysiological difference between each of the disease. (author)

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

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The role of monogenic disease in children with very early onset inflammatory bowel disease.

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Kelsen, Judith R; Baldassano, Robert N

2017-10-01

Inflammatory bowel disease (IBD) is a multifactorial disease caused by dysregulated immune responses to commensal or pathogenic intestinal microbes, resulting in chronic intestinal inflammation. Patients diagnosed with IBD occurring before the age of 5 are a unique population, known as very early onset (VEO)-IBD and can be phenotypically and genetically distinct from older-onset IBD. We aim to review the clinical presentation of children with VEO-IBD and recent discoveries that point to genomic drivers of disease that may impact our therapeutic decisions. VEO-IBD is increasing in incidence and is associated with more severe disease, aggressive progression and poor response to most conventional therapies. This article will review the advances in sequencing technology that have led to identification of novel gene variants associated with disease and potentially new targeted therapeutic options. Children with VEO-IBD may present with a different phenotype and more severe disease than older children and adults. Identification of the causal gene or pathways, these children may allow for true precision medicine with targeted therapy and improved disease course.

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Double-blind, randomized, controlled trial of rasagiline as monotherapy in early Parkinson's disease patients.

Science.gov (United States)

Stern, Matthew B; Marek, Kenneth L; Friedman, Joseph; Hauser, Robert A; LeWitt, Peter A; Tarsy, Daniel; Olanow, C Warren

2004-08-01

Rasagiline (N-propargyl-1(R)-aminoindan) mesylate is a potent, selective, and irreversible monoamine oxidase-B inhibitor. This study was designed to evaluate the safety, tolerability, and preliminary efficacy of rasagiline monotherapy in early Parkinson's disease (PD) patients not receiving levodopa. The study was performed as a multicenter, parallel-group, double-blind, randomized, placebo-controlled, 10-week study. Fifty-six PD patients were randomly assigned to rasagiline mesylate 1, 2, or 4 mg once daily, or placebo. A 3-week dose-escalation period was followed by a 7-week maintenance phase. At week 10, the mean (+/-SE) changes from baseline in total Unified Parkinson's Disease Rating Scale (UPDRS) score were -1.8 (+/-1.3), -3.6 (+/-1.7), -3.6 (+/-1.2), and -0.5 (+/-0.8) in the rasagiline 1, 2, and 4 mg/day and placebo groups, respectively. Analysis of responders showed that 28% of patients (12 of 43) receiving rasagiline had an improvement in total UPDRS score of greater than 30%, compared with none of the patients receiving placebo (P rasagiline-treated and placebo-treated patients were similar. These results suggest that rasagiline monotherapy is well tolerated and efficacious in early PD. Copyright 2004 Movement Disorder Society

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

Science.gov (United States)

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

2017-01-01

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

Nonmotor symptoms in patients with Parkinson disease

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Zhang, Tie-mei; Yu, Shu-yang; Guo, Peng; Du, Yang; Hu, Yang; Piao, Ying-shan; Zuo, Li-jun; Lian, Teng-hong; Wang, Rui-dan; Yu, Qiu-jin; Jin, Zhao; Zhang, Wei

2016-01-01

Abstract Parkinson disease (PD) is usually accompanied by numerous nonmotor symptoms (NMS), such as neuropsychiatric symptoms, sleep disorders, autonomic dysfunctions, and sensory disturbances. However, it is not clear that the factors influencing the occurrence of NMS and its sequence with motor symptoms (MS). We conducted comprehensive assessments of NMS by using 13 scales in 1119 PD patients. A total of 70.8% PD patients present NMS. Olfactory dysfunction tends to occur in PD patients with older age, more severe depression, sleep problems, and autonomic dysfunctions. Older patients are more likely to have olfactory dysfunction before MS than younger patients. Rapid eye movement behavior disorder is more prone to happen in patients with older age, older onset age, more severe depression, sleep problems, and autonomic dysfunctions. Patients with rapid eye movement behavior disorder before MS are older in onset age than after group. Olfactory dysfunction, constipation, rapid eye movement behavior disorder, and depression, as early warning NMSs of PD, connected to each other. There is a clinical heterogeneity that older patients are more likely to have NMS before MS, while younger patients are opposite. PMID:27977578

Parkinson's Disease Videos

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The relevance of pre-motor symptoms in Parkinson's disease.

Science.gov (United States)

Visanji, Naomi; Marras, Connie

2015-10-01

Parkinson's disease (PD) has a wide range of non-motor symptoms including; constipation, sleep disturbance, deficits in vision and olfaction, mood disorders and cardiac autonomic dysfunction. Several of these non-motor symptoms can manifest prior to the onset of motor symptoms. Recognizing these pre-motor symptoms may enable early diagnosis of PD. Currently, no single pre-motor symptom is able to predict the development of PD with 100% sensitivity or specificity. Ongoing studies in several independent at-risk cohorts should reveal the potential of combinations of pre-motor symptoms and multi-stage screening strategies to identify individuals at increased risk of PD. PD progression may be governed by a prion-like spread of a-syn throughout the nervous system. Identifying individuals at the earliest stage will likely be critical to preventing the pathological progression of PD, highlighting the relevance of pre-motor symptoms in the future treatment of the disease.

Evaluation of 99Tcm-trodat-1 SPECT/CT imaging in the diagnosis of parkinson's disease in early stage

International Nuclear Information System (INIS)

Liu Xiaohua; Tai Jian; Zhang Fuhai; Xiao Qian; Jia Qiang; Dong Feng

2004-01-01

Parkinson's disease is a progressive neurodegenerative disorder characterized by a selective loss of dopamine in the striatum with age. At present, the diagnosis of Parkinson's disease is mainly remained in clinical standard. According to the clinical symptoms and the response to DOPA treatment, it is not difficult to diagnose typical PD. But it is difficult to diagnose early stage PD, which lacks the typical clinical symptoms and signs. A 99Tcm -labeled tropane derivative that binds to dopamine transporter with high selectivity is [2- [ [2- [ [ [3- (4-chlorophenyl)- 8-methyl- 8-azabicyclo [3,2,1 ] oct-2-yl]methyl] (2-mercaptoethyl)amino] eth yl]amino]ethanethiolato(3-)-N2,N2',S2,S2'] oxo-[1R-(exo-exo)] (TRODAT-1). Objective: The purpose of this study is to evaluate the clinical application of 99Tcm-TRODAT-1 SPECT/CT imaging in the diagnosis of Parkinson's disease (PD) in early stage. Methods: Twenty-four patients with early-stage idiopathic Parkinson's disease were recruited. For all patients, the severity was assessed by the Hoehnand Yahrscale. Twenty-four early stage PD patients (15 Hoehn Yahr stage I and 9 Hoehn Yahr stage II), eight advanced PD patients and ten healthy volunteers (five men, five women) were studied by 99Tcm-TRODAT-1 SPECT/CT imaging. 99Tcm-TRODAT-1 was prepared from a lyophilized kit. Brain SPECT imaging was performed 2 hours after injection, using GE Discovery VH equipped with FanBeam collimators. Data were obtained using energy window of 20% centered on 140 KEV for 99Tcm. The brain SPECT data were acquired after Hawkeye CT acquisition. Regions of interest were delineated over the striata and the cerebella, and the ratios of striatum-to-cerebellum (ST/CB) were calculated. Specific uptake in the striatum and its subregions, including the putamen and caudate nucleus, was calculated and compared with that of the other side as well as that of healthy volunteers. Results: Dopamine transporter (DAT) imaging of the 10 healthy volunteers showed

Psychiatric Symptomatology in Early-Onset Binswanger’s Disease: Two Case Reports

Directory of Open Access Journals (Sweden)

R. M. Lawrence

1995-01-01

Full Text Available We describe two cases of Binswanger's disease of pre-senile onset which presented with affective and psychotic symptoms well before the appearance of cognitive deterioration and neurological signs, initially evading an accurate diagnosis. Psychiatrists should be aware of white matter disease and its role in the pathogenesis of psychiatric illness. Particular attention should be given to a history of hypertension as a risk factor in the early identification of these cases.

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Genetics Home Reference: Parkinson disease

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... Email Facebook Twitter Home Health Conditions Parkinson disease Parkinson disease Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Parkinson disease is a progressive disorder of the nervous ...

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Association of coffee consumption and non-motor symptoms in drug-naïve, early-stage Parkinson's disease.

Science.gov (United States)

Cho, Bang-Hoon; Choi, Seong-Min; Kim, Joon-Tae; Kim, Byeong C

2018-02-09

Coffee consumption has an inverse association with the risk of Parkinson's disease (PD). The aim of this study was to investigate the association between coffee consumption and non-motor symptoms (NMSs) in patients with PD. In this cross-sectional study, we included 196 early-stage, treatment-naïve PD patients. Coffee consumption history was obtained via semi-structured interviews. NMSs were assessed using the Non-Motor Symptom assessment scale (NMSS). Of the 196 patients with PD, 136 (69.3%) were categorized as coffee drinkers and 60 (30.6%) were non-drinkers. Coffee drinkers were younger, predominantly male, were younger in age at symptom onset, had lower Unified Parkinson's Disease Rating Scale motor and Beck Depression Inventory scores, and higher Mini-Mental State Examination scores than non-coffee drinkers. After adjustment, coffee drinking was significantly inversely associated with the prevalence of lack of motivation, anhedonia, and lack of pleasure, which were less frequent in coffee drinkers. Total NMSS scores were lower in coffee drinkers than in non-drinkers (p = 0.047). In particular, coffee drinking was significantly associated with a reduced severity of the mood/cognition domain of NMSS (p = 0.003). After correcting for multiple testing, there were no significant differences in the prevalence of NMSs, but there were significant differences in the severity of NMSs between coffee drinkers and non-drinkers. There is a negative association between coffee consumption and the severity of the mood/cognition domain of NMSS in patients with PD. Clinicians should consider the history of coffee consumption in the assessment of NMSs in PD. Copyright © 2018 Elsevier Ltd. All rights reserved.

Functional and morphological assessment of ocular structures and follow-up of patients with early-stage Parkinson's disease.

Science.gov (United States)

Hasanov, Samir; Demirkilinc Biler, Elif; Acarer, Ahmet; Akkın, Cezmi; Colakoglu, Zafer; Uretmen, Onder

2018-05-09

To evaluate and follow-up of functional and morphological changes of the optic nerve and ocular structures prospectively in patients with early-stage Parkinson's disease. Nineteen patients with a diagnosis of early-stage Parkinson's disease and 19 age-matched healthy controls were included in the study. All participants were examined minimum three times at the intervals of at least 6 month following initial examination. Pattern visually evoked potentials (VEP), contrast sensitivity assessments at photopic conditions, color vision tests with Ishihara cards and full-field visual field tests were performed in addition to measurement of retinal nerve fiber layer (RNFL) thickness of four quadrants (top, bottom, nasal, temporal), central and mean macular thickness and macular volumes. Best corrected visual acuity was observed significantly lower in study group within all three examinations. Contrast sensitivity values of the patient group were significantly lower in all spatial frequencies. P100 wave latency of VEP was significantly longer, and amplitude was lower in patient group; however, significant deterioration was not observed during the follow-up. Although average peripapillary RNFL thickness was not significant between groups, RNFL thickness in the upper quadrant was thinner in the patient group. While there was no difference in terms of mean macular thickness and total macular volume values between the groups initially, a significant decrease occurred in the patient group during the follow-up. During the initial and follow-up process, a significant deterioration in visual field was observed in the patient group. Structural and functional disorders shown as electro-physiologically and morphologically exist in different parts of visual pathways in early-stage Parkinson's disease.

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Impulse control disorders in advanced Parkinson's disease with dyskinesia: The ALTHEA study.

Science.gov (United States)

Biundo, Roberta; Weis, Luca; Abbruzzese, Giovanni; Calandra-Buonaura, Giovanna; Cortelli, Pietro; Jori, Maria Cristina; Lopiano, Leonardo; Marconi, Roberto; Matinella, Angela; Morgante, Francesca; Nicoletti, Alessandra; Tamburini, Tiziano; Tinazzi, Michele; Zappia, Mario; Vorovenci, Ruxandra Julia; Antonini, Angelo

2017-11-01

Impulse control disorders and dyskinesia are common and disabling complications of dopaminergic treatment in Parkinson's disease. They may coexist and are possibly related. The objectives of this study were to assess the frequency and severity of impulse control disorders in Parkinson's disease patients with dyskinesia. The ALTHEA study enrolled 251 Parkinson's disease patients with various degrees of dyskinesia severity from 11 movement disorders centers in Italy. Each patient underwent a comprehensive assessment including Unified Dyskinesia Rating Scale and the Questionnaire for Impulsive Compulsive Disorders in Parkinson Disease-Rating Scale. There was an overall 55% frequency of impulse control disorder and related behaviors (36% were clinically significant). The positive patients were younger at disease diagnosis and onset and had higher Unified Dyskinesia Rating Scale historical and total score (P = 0.001 and P = 0.02, respectively, vs negative). There was an increased frequency of clinically significant impulse control disorders in patients with severe dyskinesia (P = 0.013), a positive correlation between the questionnaire total score and dopamine agonist dose (P = 0.018), and a trend with levodopa dose. More than half of Parkinson's disease patients with dyskinesia have impulse control disorders and related behaviors, which are frequently clinically significant. Dopaminergic therapy total dose is associated with their severity. Clinicians should carefully assess patients with maladaptive behaviors and dyskinesia because they do not properly evaluate their motor and nonmotor status. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

Young-Onset Parkinson's

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... the entire Parkinson's community. Learn more Get Involved Moving Day Walk Parkinson's Champions Create Your Own Fundraiser Advocate With Us Local Resources Find an Event My PD Story Volunteer ... Support a Moving Day Walker Support a Parkinson's Champion Bequests & Planned ...

Subcortical grey matter changes in untreated, early stage Parkinson's disease without dementia.

Science.gov (United States)

Lee, Hye Mi; Kwon, Kyum-Yil; Kim, Min-Jik; Jang, Ji-Wan; Suh, Sang-Il; Koh, Seong-Beom; Kim, Ji Hyun

2014-06-01

Previous MRI studies have investigated cortical or subcortical grey matter changes in patients with Parkinson's disease (PD), yielding inconsistent findings between the studies. We therefore sought to determine whether focal cortical or subcortical grey matter changes may be present from the early disease stage. We recruited 49 untreated, early stage PD patients without dementia and 53 control subjects. Voxel-based morphometry was used to evaluate cortical grey matter changes, and automated volumetry and shape analysis were used to assess volume changes and shape deformation of the subcortical grey matter structures, respectively. Voxel-based morphometry showed neither reductions nor increases in grey matter volume in patients compared to controls. Compared to controls, PD patients had significant reductions in adjusted volumes of putamen, nucleus accumbens, and hippocampus (corrected p grey matter and clinical variables representing disease duration and severity. Our results suggest that untreated, early stage PD without dementia is associated with volume reduction and shape deformation of subcortical grey matter, but not with cortical grey matter reduction. Our findings of structural changes in the posterolateral putamen and ventromedial putamen/nucleus accumbens could provide neuroanatomical basis for the involvement of motor and limbic striatum, further implicating motor and non-motor symptoms in PD, respectively. Early hippocampal involvement might be related to the risk for developing dementia in PD patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

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Is PIGD a legitimate motor subtype in Parkinson disease?

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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.

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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

1 S.I. : Genetic pathways to Neurodegeneration Parkinson's Disease ...

Indian Academy of Sciences (India)

Dorit Trudler

Parkinson's Disease: What the Model Systems Have Taught Us So Far? .... triggered by the finding that the protein α-synuclein (encoded by the SNCA gene) is a ... lower dopamine levels in the GI tract in severely constipated PD patients ..... related genetic defects even in healthy carriers, as well as the variable age of onset ...

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

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. Copyright © 2014 the American Physiological Society.

Early-onset Alzheimer's disease: nonamnestic subtypes and type 2 AD.

Science.gov (United States)

Mendez, Mario F

2012-11-01

Patients with Alzheimer's disease (AD), the most prevalent neurodegenerative dementia, are usually elderly; however, ∼4-5% develop early-onset AD (EOAD) with onset before age 65. Most EOAD is sporadic, but about 5% of patients with EOAD have an autosomal dominant mutation such as Presenilin 1, Presenilin 2, or alterations in the Amyloid Precursor Protein gene. Although most Alzheimer's research has concentrated on older, late-onset AD (LOAD), there is much recent interest and research in EOAD. These recent studies indicate that EOAD is a heterogeneous disorder with significant differences from LOAD. From 22-64% of EOAD patients have a predominant nonamnestic syndrome presenting with deficits in language, visuospatial abilities, praxis, or other non-memory cognition. These nonamnestic patients may differ in several ways from the usual memory or amnestic patients. Patients with nonamnestic EOAD compared to typical amnestic AD have a more aggressive course, lack the apolipoprotein Eɛ4 (APOE ɛ4) susceptibility gene for AD, and have a focus and early involvement of non-hippocampal areas of brain, particularly parietal neocortex. These differences in the EOAD subtypes indicate differences in the underlying amyloid cascade, the prevailing pathophysiological theory for the development of AD. Together the results of recent studies suggest that nonamnestic subtypes of EOAD constitute a Type 2 AD distinct from the usual, typical disorder. In sum, the study of EOAD can reveal much about the clinical heterogeneity, predisposing factors, and neurobiology of this disease. Copyright © 2012 IMSS. Published by Elsevier Inc. All rights reserved.

Impulsive and compulsive behaviors among Danish patients with Parkinson's disease: prevalence, depression, and personality.

Science.gov (United States)

Callesen, M B; Weintraub, D; Damholdt, M F; Møller, A

2014-01-01

Dopaminergic medication administered to ameliorate motor symptoms of Parkinson's disease is associated with impulse control disorders, such as pathological gambling, hypersexuality, compulsive buying, and binge eating. Studies indicate a prevalence of impulse control disorders in Parkinson's disease of 6-16%. To estimate the prevalence of impulsive and compulsive behaviors among Danish patients with Parkinson's disease and to explore the relation of such behavioral disorders to depression and personality. 490 patients with Parkinson's disease (303 males), identified through the National Danish Patient Registry, were evaluated with: 1) the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease; 2) the Geriatric Depression Scale; and 3) the NEO-Personality Inventory. 176 (35.9%) patients reported impulsive and compulsive behaviors sometime during Parkinson's disease (current symptoms in 73, 14.9%). Hereof, 114 (23.3%) reported multiple behavioral symptoms. Patients with behavioral symptoms were significantly younger, were younger at PD onset, had longer disease duration, displayed more motor symptoms, and received higher doses of dopaminergic medication than patients without behavioral symptoms. Furthermore, they reported significantly more depressive symptoms and scored significantly higher on neuroticism and lower on both agreeableness and conscientiousness than patients without behavioral symptoms. A history of impulsive and compulsive behaviors are common in Danish patients with Parkinson's disease and have clinical correlates that may allow identification of patients at risk for developing these behaviors. Copyright © 2013 Elsevier Ltd. All rights reserved.

Parkinson's disease and anxiety

OpenAIRE

Walsh, K; Bennett, G

2001-01-01

There has been a recent surge of interest in the subject of anxiety in patients with Parkinson's disease. Up to 40% of patients with Parkinson's disease experience clinically significant anxiety. This anxiety may be a psychological reaction to the stress of the illness or may be related to the neurochemical changes of the disease itself. Antiparkinsonian drugs may have a role in the pathogenesis of the anxiety. The anxiety disorders in Parkinson's disease patients appear to be clustered in th...

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.

Progressive dopamine and hypocretin deficiencies in Parkinson's disease: is there an impact on sleep and wakefulness?

Science.gov (United States)

Wienecke, Miriam; Werth, Esther; Poryazova, Rositsa; Baumann-Vogel, Heide; Bassetti, Claudio L; Weller, Michael; Waldvogel, Daniel; Storch, Alexander; Baumann, Christian R

2012-12-01

Sleep-wake disturbances are frequent in patients with Parkinson's disease, but prospective controlled electrophysiological studies of sleep in those patients are surprisingly sparse, and the pathophysiology of sleep-wake disturbances in Parkinson's disease remains largely elusive. In particular, the impact of impaired dopaminergic and hypocretin (orexin) signalling on sleep and wakefulness in Parkinson's disease is still unknown. We performed a prospective, controlled electrophysiological study in patients with early and advanced Parkinson's disease, e.g. in subjects with presumably different levels of dopamine and hypocretin cell loss. We compared sleep laboratory tests and cerebrospinal fluid levels with hypocretin-deficient patients with narcolepsy with cataplexy, and with matched controls. Nocturnal sleep efficiency was most decreased in advanced Parkinson patients, and still lower in early Parkinson patients than in narcolepsy subjects. Excessive daytime sleepiness was most severe in narcolepsy patients. In Parkinson patients, objective sleepiness correlated with decrease of cerebrospinal fluid hypocretin levels, and repeated hypocretin measurements in two Parkinson patients revealed a decrease of levels over years. This suggests that dopamine and hypocretin deficiency differentially affect sleep and wakefulness in Parkinson's disease. Poorer sleep quality is linked to dopamine deficiency and other disease-related factors. Despite hypocretin cell loss in Parkinson's disease being only partial, disturbed hypocretin signalling is likely to contribute to excessive daytime sleepiness in Parkinson patients. © 2012 European Sleep Research Society.

Predictive Big Data Analytics: A Study of Parkinson?s Disease Using Large, Complex, Heterogeneous, Incongruent, Multi-Source and Incomplete Observations

OpenAIRE

Dinov, Ivo D.; Heavner, Ben; Tang, Ming; Glusman, Gustavo; Chard, Kyle; Darcy, Mike; Madduri, Ravi; Pa, Judy; Spino, Cathie; Kesselman, Carl; Foster, Ian; Deutsch, Eric W.; Price, Nathan D.; Van Horn, John D.; Ames, Joseph

2016-01-01

Background A unique archive of Big Data on Parkinson?s Disease is collected, managed and disseminated by the Parkinson?s Progression Markers Initiative (PPMI). The integration of such complex and heterogeneous Big Data from multiple sources offers unparalleled opportunities to study the early stages of prevalent neurodegenerative processes, track their progression and quickly identify the efficacies of alternative treatments. Many previous human and animal studies have examined the relationsh...

Adult-onset phenylketonuria with rapidly progressive dementia and parkinsonism.

Science.gov (United States)

Tufekcioglu, Zeynep; Cakar, Arman; Bilgic, Basar; Hanagasi, Hasmet; Gurvit, Hakan; Emre, Murat

2016-06-01

Phenylketonuria (PKU) is an autosomal recessive metabolic disorder due to mutations in the phenylalanine hydroxylase (PAH) gene, which converts phenylalanine (PHE) to tyrosine. Although it is principally a childhood disorder, in rare cases, the first signs of PKU may develop in late adulthood resembling common neurological diseases. Here we report a 59-year-old, previously normal functioning man who was admitted with blurred vision, cognitive problems, and gait difficulty that began 8 months before. He had brisk reflexes and left side dominant parkinsonism. His Mini-Mental State Examination (MMSE) score was 25/30, and neuropsychological evaluation revealed a dysexecutive syndrome with simultanagnosia and constructional apraxia. His Clinical Dementia Rating score (CDR) was 1. Cranial MRI revealed bilateral diffuse hyperintense lesions in parietal and occipital white matter in T2, fluid-attenuated inversion recovery, and diffusion weighted images. Diagnostic workup for rapidly progressive dementias was all normal except PHE level which was found to be highly elevated (1075 μmol/L, normal 39-240 μmol/L) with normal tyrosine level (61.20 μmol/L, normal 35-100 μmol/L). Three months after PHE-restricted diet, his cognitive impairment and signs of parkinsonism significantly improved, with MRI scan unchanged. This case demonstrates that late-onset PKU is a rare, treatable cause of rapidly progressive dementia and parkinsonism with certain constellations such as consanguinity and white matter abnormalities (WMAs) in imaging.

Strong family history and early onset of schizophrenia: about 2 ...

African Journals Online (AJOL)

Schizophrenia is a highly heritable psychotic disorder and high genetic loading is associated with early onset of the disease. The outcome of schizophrenia has also been linked with the age of onset as well as the presence of family history of the disease. Therefore families with patients with early onset Schizophrenia are ...

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[Parkinson's disease(s): recent insight into genetic factors

NARCIS (Netherlands)

Warrenburg, B.P.C. van de; Scheffer, H.; Heutink, P.; Bloem, B.R.

2007-01-01

In recent years, 5 genes have been identified that are unambiguously associated with genetic forms of Parkinson's disease. These genes probably explain less than 10% of all cases of Parkinson's disease. Clinically, these genetic forms can closely resemble idiopathic Parkinson's disease. Mutation

Cellular and Molecular Basis of Neurodegeneration in Parkinson Disease

Directory of Open Access Journals (Sweden)

Xian-Si Zeng

2018-04-01

Full Text Available It has been 200 years since Parkinson disease (PD was described by Dr. Parkinson in 1817. The disease is the second most common neurodegenerative disease characterized by a progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Although the pathogenesis of PD is still unknown, the research findings from scientists are conducive to understand the pathological mechanisms. It is well accepted that both genetic and environmental factors contribute to the onset of PD. In this review, we summarize the mutations of main seven genes (α-synuclein, LRRK2, PINK1, Parkin, DJ-1, VPS35 and GBA1 linked to PD, discuss the potential mechanisms for the loss of dopaminergic neurons (dopamine metabolism, mitochondrial dysfunction, endoplasmic reticulum stress, impaired autophagy, and deregulation of immunity in PD, and expect the development direction for treatment of PD.

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An Evaluation of Neuropsychiatric Symptoms in Parkinson's Disease ...

African Journals Online (AJOL)

2016-08-22

Aug 22, 2016 ... KEYWORDS: Depression, Parkinson's disease, psychosis. An Evaluation ... depression, hallucination, anxiety, sleep disorders, and psychosis .... relationship was the same in early and late stage PD. .... giver stress. J Neurol ...

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

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

2018-06-19

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

Early life exposure to permethrin: a progressive animal model of Parkinson's disease.

Science.gov (United States)

Nasuti, Cinzia; Brunori, Gloria; Eusepi, Piera; Marinelli, Lisa; Ciccocioppo, Roberto; Gabbianelli, Rosita

Oxidative stress, alpha-synuclein changes, mitochondrial complex I defects and dopamine loss, observed in the striatum of rats exposed to the pesticide permethrin in early life, could represent neuropathological hallmarks of Parkinson's disease (PD). Nevertheless, an animal model of PD should also fulfill criteria of face and predictive validities. This study was designed to: 1) verify dopaminergic status in the striatum and substantia nigra pars compacta; 2) recognize non-motor symptoms; 3) investigate the time-course development of motor disabilities; 4) assess L-Dopa effectiveness on motor symptoms in rats previously exposed to permethrin in early life. The permethrin-treated group received 34mg/kg daily of permethrin from postnatal day 6 to 21, whereas the age-matched control group was administered with the vehicle only. At adolescent age, the permethrin-treated group showed decreased levels of dopamine in the striatum, loss of dopaminergic neurons in the substantia nigra pars compacta and cognitive impairments. Motor coordination defects appeared at adult age (150days old) in permethrin-treated rats on rotarod and beam walking tasks, whereas no differences between the treated and control groups were detected on the foot print task. Predictive validity was evaluated by testing the ability of L-Dopa (5, 10 or 15mg/kg, os) to restore the postural instability in permethrin-treated rats (150days old) tested in a beam walking task. The results revealed full reversal of motor deficits starting from 10mg/kg of L-Dopa. The overall results indicate that this animal model replicates the progressive, time-dependent nature of the neurodegenerative process in Parkinson's disease. Copyright © 2016 Elsevier Inc. All rights reserved.

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Early Identification and Treatment of Communication and Swallowing Deficits in Parkinson Disease

Science.gov (United States)

Ciucci, Michelle R.; Grant, Laura M.; Paul Rajamanickam, Eunice S.; Hilby, Breanna L.; Blue, Katherine V.; Jones, Corinne A.; Kelm-Nelson, Cynthia A.

2015-01-01

Parkinson disease (PD) is a complex, progressive, neurodegenerative disorder that leads to a wide range of deficits including fine and gross sensorimotor impairment, autonomic dysfunction, mood disorders, and cognitive decline. Traditionally, the focus for diagnosis and treatment has been on sensorimotor impairment related to dopamine depletion. It is now widely recognized, however, that PD-related pathology affects multiple central nervous system neurotransmitters and pathways. Communication and swallowing functions can be impaired even in the early stages, significantly affecting health and quality of life. The purpose of this article is to review the literature on early intervention for communication and swallowing impairment in PD. Overarching themes were that (1) studies and interpretation of data from studies in early PD are limited; (2) best therapy practices have not been established, in part due to the heterogeneous nature of PD; and (3) as communication and swallowing problems are pervasive in PD, further treatment research is essential. PMID:24166192

Parkinson's Disease: Diagnosis and Treatment

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... of this page please turn JavaScript on. Feature: Parkinson's Disease Parkinson's Disease: Diagnosis and Treatment Past Issues / Winter 2014 ... live productive lives and maintain mobility. How is Parkinson's Diagnosed? There are no blood or laboratory tests ...

Detection of preclinical Parkinson's disease with PET

International Nuclear Information System (INIS)

Brooks, D.J.

1991-01-01

Putamen 18F-dopa uptake of patients with Parkinson's disease (PD) is reduced by at least 35% at onset of symptoms; therefore, positron-emission tomography (PET) can be used to detect preclinical disease in clinically unaffected twins and relatives of patients with PD. Three out of 6 monozygotic and 2 out of 3 dizygotic unaffected PD co-twins have shown reduced putamen 18F-dopa uptake to date. In addition, an intact sibling and a daughter of 1 of 4 siblings with PD both had low putamen 18F-dopa uptake. These preliminary findings suggest there may be a familial component to the etiology of PD. PET can also be used to detect underlying nigral pathology in patients with isolated tremor and patients who become rigid taking dopamine-receptor blocking agents (DRBAs). Patients with familial essential tremor have normal, and those with isolated rest tremor have consistently low, putamen 18F-dopa uptake. Drug-induced parkinsonism is infrequently associated with underlying nigral pathology

Cheaper, simpler, and better: tips for treating seniors with Parkinson disease.

Science.gov (United States)

Ahlskog, J Eric

2011-12-01

Treatment of seniors with Parkinson disease is within the domain of primary care physicians and internists. A good working knowledge of carbidopa/levodopa principles should allow excellent care of most patients, at least during the early years of the disease. Even later, when levodopa responses become more complicated (eg, dyskinesias, motor fluctuations, insomnia, anxiety), levodopa adjustments may be all that is necessary. A dozen tips for optimizing treatment of Parkinson disease are discussed herein.

Early onset of coronary artery disease after prenatal exposure to the Dutch famine

NARCIS (Netherlands)

Painter, Rebecca C.; de Rooij, Susanne R.; Bossuyt, Patrick M.; Simmers, Timothy A.; Osmond, Clive; Barker, David J.; Bleker, Otto P.; Roseboom, Tessa J.

2006-01-01

BACKGROUND: Limited evidence suggests that maternal undernutrition at the time of conception is associated with increased cardiovascular disease risk in adult offspring. OBJECTIVE: We investigated whether persons conceived during the Dutch famine of World War II had an early onset of coronary artery

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

Directory of Open Access Journals (Sweden)

Roberta Biundo

Full Text Available 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.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.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.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.

Longitudinal CSF biomarkers in patients with early Parkinson disease and healthy controls.

Science.gov (United States)

Mollenhauer, Brit; Caspell-Garcia, Chelsea J; Coffey, Christopher S; Taylor, Peggy; Shaw, Leslie M; Trojanowski, John Q; Singleton, Andy; Frasier, Mark; Marek, Kenneth; Galasko, Douglas

2017-11-07

To analyze longitudinal levels of CSF biomarkers in drug-naive patients with Parkinson disease (PD) and healthy controls (HC), examine the extent to which these biomarker changes relate to clinical measures of PD, and identify what may influence them. CSF α-synuclein (α-syn), total and phosphorylated tau (t- and p-tau), and β-amyloid 1-42 (Aβ42) were measured at baseline and 6 and 12 months in 173 patients with PD and 112 matched HC in the international multicenter Parkinson's Progression Marker Initiative. Baseline clinical and demographic variables, PD medications, neuroimaging, and genetic variables were evaluated as potential predictors of CSF biomarker changes. CSF biomarkers were stable over 6 and 12 months, and there was a small but significant increase in CSF Aβ42 in both patients with patients with PD and HC from baseline to 12 months. The t-tau remained stable. The p-tau increased marginally more in patients with PD than in HC. α-syn remained relatively stable in patients with PD and HC. Ratios of p-tau/t-tau increased, while t-tau/Aβ42 decreased over 12 months in patients with PD. CSF biomarker changes did not correlate with changes in Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale motor scores or dopamine imaging. CSF α-syn levels at 12 months were lower in patients with PD treated with dopamine replacement therapy, especially dopamine agonists. These core CSF biomarkers remained stable over 6 and 12 months in patients with early PD and HC. PD medication use may influence CSF α-syn. Novel biomarkers are needed to better profile progressive neurodegeneration in PD. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Natural History of Parkinson's Disease in the Province of Segovia: Disability in a 20 Years Longitudinal Study.

Science.gov (United States)

Duarte, Jacinto; García Olmos, Luis Miguel; Mendoza, Amelia; Martínez Pueyo, Ángel; Clavería, Luis Erik

2015-01-01

Parkinson's disease mainly affects the elderly population causing a progressive functional disability with motor, psychic, and cognitive deterioration. This study was carried out to evaluate disability caused by Parkinson's disease by analyzing the median time to reach Hoehn and Yahr stage III and to investigate predictor variables based on a 20-year longitudinal follow-up study. We examined 273 patients with Parkinson's disease recruited between 1978 and 1998. We performed a survival analysis using the Kaplan-Meier method to determine the time to disability and we used a Cox regression model to adjust prognosis factors. The median time to reach Hoehn and Yahr stage III was 7.73 years (95% CI: 5.95-8.05). Independent predictors of disability were: age at onset, the hazard ratio (HR) = 1.10, 95% CI: 1.08-1.12; UPDRS II (activities of daily living) HR = 1.08, 95% CI: 1.03-1.14; and akinesia and rigidity at onset HR = 1.55, 95% CI: 1.07-2.24. Patients with Parkinson's disease evolve gradually toward disability, and prognostic factors of this evolution were identified. © 2015 S. Karger AG, Basel.

The genetic basis of Parkinson's disease

Directory of Open Access Journals (Sweden)

A. A. Tappakhov

2017-01-01

Full Text Available Parkinson's disease (PD is a multifactorial disease that develops in the presence of both genetic and environmental factors. In recent years, there has been sufficient information on the role of genetic predisposition in the development of not only familial cases, but also sporadic ones. A hereditary burden in PD may not be traced in cases of recessive inheritance with a low gene penetrance, as well as in a patient's death before the onset of the disease. Active introduction of molecular genetic methods, including next generation sequencing, can annually identify new gene mutations that underlie sporadic PD cases. This paper provides an overview of the current literature on the genetic aspects of PD with emphasis on the ethnic characteristics of the disease.

Current Experimental Studies of Gene Therapy in Parkinson's Disease

Directory of Open Access Journals (Sweden)

Jing-ya Lin

2017-05-01

Full Text Available Parkinson's disease (PD was characterized by late-onset, progressive dopamine neuron loss and movement disorders. The progresses of PD affected the neural function and integrity. To date, most researches had largely addressed the dopamine replacement therapies, but the appearance of L-dopa-induced dyskinesia hampered the use of the drug. And the mechanism of PD is so complicated that it's hard to solve the problem by just add drugs. Researchers began to focus on the genetic underpinnings of Parkinson's disease, searching for new method that may affect the neurodegeneration processes in it. In this paper, we reviewed current delivery methods used in gene therapies for PD, we also summarized the primary target of the gene therapy in the treatment of PD, such like neurotrophic factor (for regeneration, the synthesis of neurotransmitter (for prolong the duration of L-dopa, and the potential proteins that might be a target to modulate via gene therapy. Finally, we discussed RNA interference therapies used in Parkinson's disease, it might act as a new class of drug. We mainly focus on the efficiency and tooling features of different gene therapies in the treatment of PD.

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Early diagnosis of Parkinson's disease: neurospect by trodat-1Tc99m, dopamine transporter marker

International Nuclear Information System (INIS)

Mena, Ismael; Diaz, Fernando; Gomez, Ariel

2001-01-01

Information: We have recently preliminarily reported that NeuroSPECT (NSP) of the Dopamine Transporter (DAT) is a highly sensitive method for early diagnosis of Parkinson disease (27). Objectives: To evaluate the sensitivity of NSP of DAT in patients with de novo hemiparkinsonism and compare the contralateral Vs ipsilateral to the symptomatic side results and also Vs. normal controls, in order to assess the sensitivity to detect pre symptomatic and symptomatic impairment of concentration of DAT (Au)

Laterality Influences Brain Atrophy in Parkinson's Disease - a Voxel-based Morphometry Study

Directory of Open Access Journals (Sweden)

Maria Cristina Arci Santos

2016-09-01

Full Text Available Background: Several neuroimaging studies revealed widespread neurodegeneration in Parkinson's disease but only few considered the asymmetrical clinical presentation. Objective: To investigate gray matter (GM atrophy in Parkinson Disease considering the side of motor symptom onset. Methods: Sixty patients (57.87± 10.27 years diagnosed according to the Brain Bank criteria, 26 with right-sided disease onset (RDO and 34 with left-sided disease onset (LDO, were compared to 80 healthy controls (HC (57.1± 9.47 years. T1-weighted images were acquired on a 3T scanner. VBM8 (SPM8/Dartel on Matlab R2012b platform processed and analyzed the images. Statistics included a two-sample test (FWE p<0.05 with extent threshold of 20 voxels. In a secondary analysis, we used MRIcro software to flip the images right/left of 25 patients, which had a RDO, so that all images had the contralateral side of disease onset at the right hemisphere. Thirty-five HC images were flipped, as the hemispheres are not completely equivalent. Results: Compared to HC, GM atrophy in LDO was identified in the insula, putamen, anterior cingulate, frontotemporal cortex and right caudate. For the RDO group, anterior cingulate, insula, frontotemporal and occipital cortex. VBM of total brain-flipped images showed GM loss mainly in the left putamen, left olfactory cortex, amygdala, parahipocampal gyrus and in the rectus gyrus, insula, frontotemporal cortex, cuneus, precuneus and calcarine fissure bilaterally. (p<0.05 FWE corrected. Conclusions: The study revealed widespread GM atrophy in PD, predominantly in the left hemisphere. Future investigations should also consider handedness and side of onset to better characterize cerebral involvement and its progression in PD.

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

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Malnutrition in a sample of community-dwelling people with Parkinson's disease.

Directory of Open Access Journals (Sweden)

Jamie M Sheard

Full Text Available OBJECTIVE: Malnutrition results in poor health outcomes, and people with Parkinson's disease may be more at risk of malnutrition. However, the prevalence of malnutrition in Parkinson's disease is not yet well defined. The aim of this study is to provide an estimate of the extent of malnutrition in community-dwelling people with Parkinson's disease. METHODS: This is a cross-sectional study of people with Parkinson's disease residing within a 2 hour driving radius of Brisbane, Australia. The Subjective Global Assessment (SGA and scored Patient Generated Subjective Global Assessment (PG-SGA were used to assess nutritional status. Body weight, standing or knee height, mid-arm circumference and waist circumference were measured. RESULTS: Nineteen (15% of the participants were moderately malnourished (SGA-B. The median PG-SGA score of the SGA-B group was 8 (4-15, significantly higher than the SGA-A group, U = 1860.5, p<.05. The symptoms most influencing intake were loss of appetite, constipation, early satiety and problems swallowing. CONCLUSIONS: As with other populations, malnutrition remains under-recognised and undiagnosed in people with Parkinson's disease. Regular screening of nutritional status in people with Parkinson's disease by health professionals with whom they have regular contact should occur to identify those who may benefit from further nutrition assessment and intervention.

Impulsive-compulsive behaviors in parkin-associated Parkinson disease.

Science.gov (United States)

Morgante, Francesca; Fasano, Alfonso; Ginevrino, Monia; Petrucci, Simona; Ricciardi, Lucia; Bove, Francesco; Criscuolo, Chiara; Moccia, Marcello; De Rosa, Anna; Sorbera, Chiara; Bentivoglio, Anna Rita; Barone, Paolo; De Michele, Giuseppe; Pellecchia, Maria Teresa; Valente, Enza Maria

2016-10-04

The aim of this multicenter, case-control study was to investigate the prevalence and severity of impulsive-compulsive behaviors (ICBs) in a cohort of patients with parkin-associated Parkinson disease (PD) compared to a group of patients without the mutation. We compared 22 patients with biallelic parkin mutations (parkin-PD) and 26 patients negative for parkin, PINK1, DJ-1, and GBA mutations (PD-NM), matched for age at onset, disease duration, levodopa, and dopamine agonist equivalent daily dose. A semistructured interview was used to diagnose each of the following ICBs: compulsive sexual behavior, compulsive buying, binge eating, punding, hobbyism, and compulsive medication use. The Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) was adopted to rate ICB severity. Frequency of patients with at least one ICB was comparable between parkin-PD and PD-NM. Nevertheless, when analyzing the distribution of specific ICBs, a higher frequency of compulsive shopping, binge eating, and punding/hobbyism was found in the parkin-PD group. Compared to PD-NM, parkin-PD patients with ICB had younger onset age and higher frequency of smokers; in 5 patients, ICB had predated PD onset. Total and partial (compulsive buying, compulsive sexual behavior, binge eating, hobbyism/punding) QUIP-RS scores were higher in patients with parkin-PD compared to patients with PD-NM. Logistic regression analysis showed that the presence of parkin mutations was associated with smoking status and higher QUIP-RS total score. Our data expand the parkin-associated phenotypic spectrum demonstrating higher frequency and severity of specific ICBs, and suggesting an association between the parkin genotype, smoking status, and ICB severity. © 2016 American Academy of Neurology.

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

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

Science.gov (United States)

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

2013-01-01

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. 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. Our findings indicate that testing odor identification can be a supportive diagnostic tool for Parkinson's disease. The application of only three odors performed well in discriminating Parkinson patients from controls, which can facilitate a wider application of this method as a point-of-care test.

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Rasagiline ameliorates olfactory deficits in an alpha-synuclein mouse model of Parkinson's disease.

Directory of Open Access Journals (Sweden)

Géraldine H Petit

Full Text Available Impaired olfaction is an early pre-motor symptom of Parkinson's disease. The neuropathology underlying olfactory dysfunction in Parkinson's disease is unknown, however α-synuclein accumulation/aggregation and altered neurogenesis might play a role. We characterized olfactory deficits in a transgenic mouse model of Parkinson's disease expressing human wild-type α-synuclein under the control of the mouse α-synuclein promoter. Preliminary clinical observations suggest that rasagiline, a monoamine oxidase-B inhibitor, improves olfaction in Parkinson's disease. We therefore examined whether rasagiline ameliorates olfactory deficits in this Parkinson's disease model and investigated the role of olfactory bulb neurogenesis. α-Synuclein mice were progressively impaired in their ability to detect odors, to discriminate between odors, and exhibited alterations in short-term olfactory memory. Rasagiline treatment rescued odor detection and odor discrimination abilities. However, rasagiline did not affect short-term olfactory memory. Finally, olfactory changes were not coupled to alterations in olfactory bulb neurogenesis. We conclude that rasagiline reverses select olfactory deficits in a transgenic mouse model of Parkinson's disease. The findings correlate with preliminary clinical observations suggesting that rasagiline ameliorates olfactory deficits in Parkinson's disease.

Molecular genetics of early-onset Alzheimer's disease revisited.

Science.gov (United States)

Cacace, Rita; Sleegers, Kristel; Van Broeckhoven, Christine

2016-06-01

As the discovery of the Alzheimer's disease (AD) genes, APP, PSEN1, and PSEN2, in families with autosomal dominant early-onset AD (EOAD), gene discovery in familial EOAD came more or less to a standstill. Only 5% of EOAD patients are carrying a pathogenic mutation in one of the AD genes or a apolipoprotein E (APOE) risk allele ε4, most of EOAD patients remain unexplained. Here, we aimed at summarizing the current knowledge of EOAD genetics and its role in ongoing approaches to understand the biology of AD and disease symptomatology as well as developing new therapeutics. Next, we explored the possible molecular mechanisms that might underlie the missing genetic etiology of EOAD and discussed how the use of massive parallel sequencing technologies triggered novel gene discoveries. To conclude, we commented on the relevance of reinvestigating EOAD patients as a means to explore potential new avenues for translational research and therapeutic discoveries. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Early- and late-onset Alzheimer disease: Are they the same entity?

Science.gov (United States)

Tellechea, P; Pujol, N; Esteve-Belloch, P; Echeveste, B; García-Eulate, M R; Arbizu, J; Riverol, M

2018-05-01

Early-onset Alzheimer disease (EOAD), which presents in patients younger than 65 years, has frequently been described as having different features from those of late-onset Alzheimer disease (LOAD). This review analyses the most recent studies comparing the clinical presentation and neuropsychological, neuropathological, genetic, and neuroimaging findings of both types in order to determine whether EOAD and LOAD are different entities or distinct forms of the same entity. We observed consistent differences between clinical findings in EOAD and in LOAD. Fundamentally, the onset of EOAD is more likely to be marked by atypical symptoms, and cognitive assessments point to poorer executive and visuospatial functioning and praxis with less marked memory impairment. Alzheimer-type features will be more dense and widespread in neuropathology studies, with structural and functional neuroimaging showing greater and more diffuse atrophy extending to neocortical areas (especially the precuneus). In conclusion, available evidence suggests that EOAD and LOAD are 2 different forms of a single entity. LOAD is likely to be influenced by ageing-related processes. Copyright © 2015 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

[Early-onset and late-onset male hypogonadotropic hypogonadism and osteoporosis].

Science.gov (United States)

Okada, Hiroshi; Shin, Takeshi; Kobori, Yoshitomo

2016-07-01

Hypogonadism is classified into two major clinical entities, namely early-onset hypogonadism and late-onset hypogonadism. The former is characterized by the malfunction of hypothalamo-pituitary-gonadal(testicular)axis or by the primary hypofunction of testes(e.g. Klinefelter's syndrome). The latter is summarized as LOH syndrome which is attributed to the dropped level of bioavailable testosterone. In these diseases testosterone is the key molecule which may cause various symptoms relating not only to physical health but also to mental or psychologic health. In this review issues concerning bone health in these disease are described.

Western equine encephalitis with rapid onset of parkinsonism.

Science.gov (United States)

Schultz, D R; Barthal, J S; Garrett, G

1977-11-01

A patient with confirmed western equine encephalitis had the rapid onset of postencephalitic parkinsonian sequelae. This observation corroborates similar previous but rare reports. Response to therapy with levodopa, dopa decarboxylase inhibitor, and trihexyphenidyl was dramatic. However, remission maintained for 12 months without medication suggests that the parkinsonism would have remitted spontaneously. In either case, this has not previously been reported with the western equine togavirus.

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Mutations in the Na+/K+-ATPase alpha 3 gene ATP1A3 are associated with rapid-onset dystonia parkinsonism

NARCIS (Netherlands)

Aguiar, PD; Sweadner, KJ; Penniston, JT; Zaremba, J; Liu, L; Caton, M; Linazasoro, G; Borg, M; Tijssen, MAJ; Bressman, SB; Dobyns, WB; Brashear, A; Ozelius, LJ

2004-01-01

Rapid-onset dystonia-parkinsonism (RDP, DYT12) is a distinctive autosomal-dominant movement disorder with variable expressivity and reduced penetrance characterized by abrupt onset of dystonia, usually accompanied by signs of parkinsonism. The sudden onset of symptoms over hours to a few weeks,

Mutations in the Na+/K+ -ATPase alpha3 gene ATP1A3 are associated with rapid-onset dystonia parkinsonism

NARCIS (Netherlands)

de Carvalho Aguiar, Patricia; Sweadner, Kathleen J.; Penniston, John T.; Zaremba, Jacek; Liu, Liu; Caton, Marsha; Linazasoro, Gurutz; Borg, Michel; Tijssen, Marina A. J.; Bressman, Susan B.; Dobyns, William B.; Brashear, Allison; Ozelius, Laurie J.

2004-01-01

Rapid-onset dystonia-parkinsonism (RDP, DYT12) is a distinctive autosomal-dominant movement disorder with variable expressivity and reduced penetrance characterized by abrupt onset of dystonia, usually accompanied by signs of parkinsonism. The sudden onset of symptoms over hours to a few weeks,

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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.

Comparison of the Psychological Symptoms and Disease-Specific Quality of Life between Early- and Typical-Onset Parkinson’s Disease Patients

Directory of Open Access Journals (Sweden)

Seyed-Mohammad Fereshtehnejad

2014-01-01

Full Text Available The impact of Parkinson’s disease (PD on psychological status and quality of life (QoL may vary depending on age of disease onset. The aim of this study was to compare psychological symptoms and disease-specific QoL between early onset versus the rest of the PD patients. A total number of 140 PD patients with the mean current age of 61.3 (SD=10.4 yr were recruited in this study. PD patients with the onset age of ≤50 yr were defined as “early-onset” (EOPD group (n=45, while the ones with >50 yr at the time of diagnosis were categorized as the “typical-onset” (TOPD patients (n=95. Different questionnaires and scales were used for between-group comparisons including PDQ39, HADS (hospital anxiety and depression scale, FSS (fatigue severity scale, MNA (mininutritional assessment, and the UPDRS. Depression score was significantly higher in EOPD group (6.3 (SD=4.5 versus 4.5 (SD=4.2, P=0.02. Among different domains of QoL, emotion score was also significantly higher in the EOPD group (32.3 (SD=21.6 versus 24.4 (SD=22.7, P=0.05. Our findings showed more severe depression and more impaired emotional domain of QoL in early-onset PD patients. Depression and anxiety play an important role to worsen QoL among both EOPD and TOPD patients, while no interaction was observed in the efficacy of these two psychiatric symptoms and the onset age of PD patients.

Bipolar affective disorder and Parkinson's disease: a rare, insidious and often unrecognized association.

Science.gov (United States)

Cannas, A; Spissu, A; Floris, G L; Congia, S; Saddi, M V; Melis, M; Mascia, M M; Pinna, F; Tuveri, A; Solla, P; Milia, A; Giagheddu, M; Tacconi, P

2002-09-01

Five patients (4 women) with Parkinson's disease (PD) and primary major psychiatric disorder (PMPD) meeting DSM-IV criteria for the diagnosis of bipolar affective disorder (BAD) were studied. Four patients had early onset PD. Four developed a severe psychiatric disorder a few years after starting dopaminergic therapy in presence of a mild motor disability and a mild cognitive impairment, with no evidence of cerebral atrophy at CT or MRI. Two patients developed a clear manic episode; the other three presented a severe depressive episode (in one case featuring a Cotard syndrome). None showed previous signs of long term L-dopa treatment syndrome (LTS), hallucinosis or other minor psychiatric disorders. The two manic episodes occurred shortly after an increase of dopaminergic therapy and in one case rapid cyclic mood fluctuations were observed. At the onset of psychiatric symptoms, all patients had an unspecific diagnosis of chronic delusional hallucinatory psychosis (CDHP).

Regional cerebral blood flow in SPECT pattern in Parkinson's disease

International Nuclear Information System (INIS)

Lenart-Jankowska, D.; Junik, R.; Sowinski, J.; Gembicki, M.; Wender, M.

1997-01-01

The purpose of our work was to compare the regional cerebral blood flow (rCBF) in SPECT examination in Parkinson's disease with (17 cases) and without (7 cases) dementia and in various clinical stages of the disease. The patients underwent SPECT examination 5-40 min after intravenous application of HMPAO (Ceretec, Amersham) with 740 Mbq (20 mCi) pertechnate 99m Tc. SPECT was performed with a Siemens Diacam single-head rotating gamma camera coupled to a high resolution collimator and Icon computer system provided by the manufacturer. The results were defined in relative values of ROI in relation to cerebellum. Patients with Parkinson's disease showed hypoperfusion in cerebral lobes and in deep cerebral structures including the basal ganglia. Regional perfusion deficit in SPECT was seen with and without associated dementia and already in early stage of the disease. Parkinson's disease is provoked by the lesions of dopaminergic neurons of the central nervous system leading to domination of extrapyramidal symptoms. There are many indications that also the neurotransmitters associated with cognitive functions as acetylcholine demonstrate some abnormalities. However, only in some cases of Parkinson's disease dementia is the dominating symptom. Our results of regional cerebral blood flow testify that in Parkinson's disease the dysfunction of the central nervous system is more diffuse than has previously been suggested. (author)

Incident impulse control disorder symptoms and dopamine transporter imaging in Parkinson disease.

Science.gov (United States)

Smith, Kara M; Xie, Sharon X; Weintraub, Daniel

2016-08-01

To describe the incidence of, and clinical and neurobiological risk factors for, new-onset impulse control disorder (ICD) symptoms and related behaviours in early Parkinson disease (PD). The Parkinson's Progression Markers Initiative is an international, multicenter, prospective study of de novo patients with PD untreated at baseline and assessed annually, including serial dopamine transporter imaging (DAT-SPECT) and ICD assessment (Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease short form, QUIP). Participants were included if they screened negative on the QUIP at baseline. Kaplan-Meier curves and generalised estimating equations examined frequency and predictors of incident ICD symptoms. Participants were seen at baseline (n=320), year 1 (n=284), year 2 (n=217) and year 3 (n=96). Estimated cumulative incident rates of ICD symptoms and related behaviours were 8% (year 1), 18% (year 2) and 25% (year 3) and increased each year in those on dopamine replacement therapy (DRT) and decreased in those not on DRT. In participants on DRT, risk factors for incident ICD symptoms were younger age (OR=0.97, p=0.05), a greater decrease in right caudate (OR=4.03, p=0.01) and mean striatal (OR=6.90, p=0.04) DAT availability over the first year, and lower right putamen (OR=0.06, p=0.01) and mean total striatal (OR=0.25, p=0.04) DAT availability at any post-baseline visit. The rate of incident ICD symptoms increases with time and initiation of DRT in early PD. In this preliminary study, a greater decrease or lower DAT binding over time increases risk of incident ICD symptoms, conferring additional risk to those taking DRT. NCT01141023. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

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Early-onset childhood sarcoidosis: a case report

Directory of Open Access Journals (Sweden)

Lai-San Wong

2011-12-01

Full Text Available Sarcoidosis is a multisystemic granulomatous disease of unknown etiology and it most commonly affects young adults. Childhood sarcoidosis is relatively rare; older children usually present a picture similar to that of adults, with frequent hilar lymphadenopathy and pulmonary infiltration. Early-onset (<4 years of age childhood sarcoidosis is a unique disease and has a different presentation. It is characterized by arthritis, uveitis, and cutaneous involvement. The prognosis of early-onset childhood sarcoidosis varies in different studies due to the rarity of the disease. The treatment of choice in systemic involvement of childhood sarcoidosis is corticosteroids. Methotrexate can also be considered in the long-term treatment due to its safety, effectiveness, and steroid-sparing effect in children.

Driving in Parkinson's disease: mobility, accidents, and sudden onset of sleep at the wheel.

Science.gov (United States)

Meindorfner, Charlotte; Körner, Yvonne; Möller, Jens Carsten; Stiasny-Kolster, Karin; Oertel, Wolfgang Hermann; Krüger, Hans-Peter

2005-07-01

Only few studies have addressed driving ability in Parkinson's disease (PD) to date. However, studies investigating accident proneness of PD patients are urgently needed in the light of motor disability in PD and--particularly--the report of "sleep attacks" at the wheel. We sent a questionnaire about sudden onset of sleep (SOS) and driving behavior to 12,000 PD patients. Subsequently, of 6,620 complete data sets, 361 patients were interviewed by phone. A total of 82% of those 6,620 patients held a driving license, and 60% of them still participated in traffic. Of the patients holding a driving license, 15% had been involved in and 11% had caused at least one accident during the past 5 years. The risk of causing accidents was significantly increased for patients who felt moderately impaired by PD, had an increased Epworth Sleepiness Scale (ESS) score, and had experienced SOS while driving. Sleep attacks at the wheel usually occurred in easy driving situations and resulted in typical fatigue-related accidents. Those having retired from driving had a more advanced (subjective) disease severity, higher age, more frequently female gender, an increased ESS score, and a longer disease duration. The study revealed SOS and daytime sleepiness as critical factors for traffic safety in addition to motor disabilities of PD patients. The results suggest that real sleep attacks without any prior sleepiness are rare. However, our data underline the importance of mobility for patients and the need for further studies addressing the ability to drive in PD. Copyright 2005 Movement Disorder Society.

Speech disorders did not correlate with age at onset of Parkinson’s disease

Directory of Open Access Journals (Sweden)

Alice Estevo Dias

2016-02-01

Full Text Available ABSTRACT Speech disorders are common manifestations of Parkinson´s disease. Objective To compare speech articulation in patients according to age at onset of the disease. Methods Fifty patients was divided into two groups: Group I consisted of 30 patients with age at onset between 40 and 55 years; Group II consisted of 20 patients with age at onset after 65 years. All patients were evaluated based on the Unified Parkinson’s Disease Rating Scale scores, Hoehn and Yahr scale and speech evaluation by perceptual and acoustical analysis. Results There was no statistically significant difference between the two groups regarding neurological involvement and speech characteristics. Correlation analysis indicated differences in speech articulation in relation to staging and axial scores of rigidity and bradykinesia for middle and late-onset. Conclusions Impairment of speech articulation did not correlate with age at onset of disease, but was positively related with disease duration and higher scores in both groups.

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Impulse control disorders in Chinese Parkinson's disease patients: the effect of ergot derived dopamine agonist.

Science.gov (United States)

Auyeung, M; Tsoi, T H; Tang, W K; Cheung, C M; Lee, C N; Li, R; Yeung, Eric

2011-09-01

We studied the prevalence and related risk factors of impulse control disorders in Chinese Parkinson's disease patients. We screened all non-demented Parkinson's disease patients attending our Parkinson's disease clinic from August 2009 to March 2010. The clinical characteristics of patients with impulse control disorders and those without were compared. Of the 213 PD subjects screened, 15 (7.0%) with impulse control disorders were identified. Fourteen of these subjects were on both a dopamine agonist and Levodopa, and one was on Levodopa alone. Of the fourteen subjects on both a dopamine agonist and Levodopa, eleven were on bromocriptine and Levodopa; 10.5% of the subjects exposed to bromocriptine had impulse control disorder. Upon multivariate analysis, dose of dopamine agonist used, young age at onset of Parkinson's disease and a history of anxiety or depression were independent predictors for developing impulse control disorders. 7% of our Chinese PD subjects had impulse control disorders. When young Parkinson's disease patients with a history of anxiety or depression are treated with high dose of DA, they are at risk of developing impulse control disorders. Copyright © 2011 Elsevier Ltd. All rights reserved.

A Multicenter Comparative Study of Impulse Control Disorder in Latin American Patients With Parkinson Disease.

Science.gov (United States)

Ramírez Gómez, Carolina Candelaria; Serrano Dueñas, Marcos; Bernal, Oscar; Araoz, Natalia; Sáenz Farret, Michel; Aldinio, Victoria; Montilla, Verónica; Micheli, Federico

Impulse control disorder (ICD) is a common adverse effect in patients with Parkinson disease who receive dopamine agonists; however, other factors are involved in its manifestations. To study the frequency and factors involved in the development of this adverse effect in a Latin American population, we conducted a cross-sectional multicenter study. Two hundred fifty-five patients in 3 Latin American centers were evaluated by examination and application of scales (Unified Parkinson's Disease Rating Scale, Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale, Hoehn and Yahr, Clinical Impression of Severity Index for Parkinson's Disease). Of the patients, 27.4% had ICD, most of whom were on dopamine agonists. Other associated risk factors included a younger age at onset of Parkinson disease, moderate symptoms, a shorter evolution of the clinical manifestations, rapid eye movement (REM) sleep disorder behavior, and the consumption of tea, mate, and alcohol. The frequency of ICD is higher in Latin America than in Anglo-Saxon populations. Consuming tea and mate, in addition to the use of dopamine agonists, is a factor that may demonstrate a genetic link that predisposes patients to the establishment of an ICD.

[A case of Neuro-Behçet's disease with early onset of bipolar mood disorder].

Science.gov (United States)

Nakano, Yuko; Hatanaka, Yuki; Ikebuchi, Emi; Shimizu, Teruo; Nanko, Shinichiro; Utsumii, Takeshi

2004-01-01

In this report, we describe a case of Neuro-Behçet's disease with early onset of bipolar mood disorder. A 53-year-old man with neuropathy including dysphasia and dyslalia developed bipolar mood disorder with anxiety, agitation, depressive mood, talkativeness, hyperkinesias, and appetite rise, and soon exhibited severe personality deterioration. Oral aphthae, cell proliferation and elevated IL-6 levels in spinal fluid, and the patient's clinical downhill course with remission and relapse in spite of good reaction to steroid preparation indicated the possibility of Neuro-Behçet's disease. Brain MRI showed clear swelling of the brain stem area, especially in the pons, in the active phase with low signal in T1-weighted images contrasting with clear high signal in T2-weighted images and FLAIR. At the time of remission, atrophy of the brain stem was shown. These findings were consistent with the view reported in recent years concerning the brain image of Neuro-Behçet's disease, which seemed to be useful for the differential diagnosis. This case manifested two outstanding clinical features. First, it showed bipolar mood swing or mixed state distinguishable from disinhibition or euphoria in deteriorated personality, which is common in this condition. A clear bipolar mood disorder has not been described until now in Neuro-Behçet's disease. Second, subclinical dysthymia or hypomanic phase occurred before clear onset of the disease. In Neuro-Behçet's disease, it is currently considered that psychiatric symptoms may appear in the early stage, but there is controversy as to whether they can precede the other symptoms. Our case indicated very early onset of psychiatric symptoms in this condition.

Tiny But Mighty: Promising Roles of MicroRNAs in the Diagnosis and Treatment of Parkinson's Disease

Institute of Scientific and Technical Information of China (English)

Ying Wang; Zhaofei Yang; Weidong Le

2017-01-01

Parkinson's disease (PD) is the second most common age-related neurodegenerative disorder after Alzheimer's disease.To date,the clinical diagnosis of PD is primarily based on the late onset of motor impairments.Unfortunately,at this stage,most of the dopaminergic neurons may have already been lost,leading to the limited clinical benefits of current therapeutics.Therefore,early identification of PD,especially at the prodromal stage,is still a main challenge in the diagnosis and management of this disease.Recently,microRNAs (miRNAs) in cerebrospinal fluid or peripheral blood have been proposed as putative biomarkers to assist in PD diagnosis and therapy.In this review,we systematically summarize the changes of miRNA expression profiles in PD patients,and highlight their putative roles in the diagnosis and treatment of this devastating disease.

Precuneus atrophy in early-onset Alzheimer's disease: a morphometric structural MRI study

International Nuclear Information System (INIS)

Karas, Giorgos; Scheltens, Philip; Jones, Bethany; Rombouts, Serge; Schijndel, Ronald van; Klein, Martin; Flier, Wiesje van der; Vrenken, Hugo; Barkhof, Frederik

2007-01-01

Alzheimer's disease (AD) usually first presents in elderly patients, but may also develop at an earlier age. Patients with an early age at onset tend to present with complaints other than memory impairment, such as visuospatial problems or apraxia, which may reflect a different distribution of cortical involvement. In this study we set out to investigate whether age at onset in patients with AD determines the pattern of atrophy on cerebral MRI scans. We examined 55 patients with AD over a wide age range and analyzed their 3-D T1-weighted structural MRI scans in standard space using voxel-based morphometry (VBM). Regression analysis was performed to estimate loss of grey matter as a function of age, corrected for mini-mental state examination (MMSE) scores and sex. The VBM analyses identified multiple areas (including the temporal and parietal lobes), showing more atrophy with advancing age. By contrast, a younger age at onset was found to be associated with lower grey matter density in the precuneus. Regionalized volumetric analysis of this region confirmed the existence of disproportionate atrophy in the precuneus in patients with early-onset AD. Application of a multivariate model with precuneus grey matter density as input, showed that precuneal and hippocampal atrophy are independent from each other. Additionally, we found that a smaller precuneus is associated with impaired visuospatial functioning. Our findings support the notion that age at onset modulates the distribution of cortical involvement, and that disproportionate precuneus atrophy is more prominent in patients with a younger age of onset. (orig.)

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.

Gait Rather Than Cognition Predicts Decline in Specific Cognitive Domains in Early Parkinson's Disease.

Science.gov (United States)

Morris, Rosie; Lord, Sue; Lawson, Rachael A; Coleman, Shirley; Galna, Brook; Duncan, Gordon W; Khoo, Tien K; Yarnall, Alison J; Burn, David J; Rochester, Lynn

2017-11-09

Dementia is significant in Parkinson's disease (PD) with personal and socioeconomic impact. Early identification of risk is of upmost importance to optimize management. Gait precedes and predicts cognitive decline and dementia in older adults. We aimed to evaluate gait characteristics as predictors of cognitive decline in newly diagnosed PD. One hundred and nineteen participants recruited at diagnosis were assessed at baseline, 18 and 36 months. Baseline gait was characterized by variables that mapped to five domains: pace, rhythm, variability, asymmetry, and postural control. Cognitive assessment included attention, fluctuating attention, executive function, visual memory, and visuospatial function. Mixed-effects models tested independent gait predictors of cognitive decline. Gait characteristics of pace, variability, and postural control predicted decline in fluctuating attention and visual memory, whereas baseline neuropsychological assessment performance did not predict decline. This provides novel evidence for gait as a clinical biomarker for PD cognitive decline in early disease. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America.

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.

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 by light microscopy, are responsible for cell death in these diseases. However, the correlation between protein inclusion formation and cytotoxicity is inconsistent suggesting 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. PMID:23225525

Early Freezing of Gait: Atypical versus Typical Parkinson Disorders

Directory of Open Access Journals (Sweden)

Abraham Lieberman

2015-01-01

Full Text Available In 18 months, 850 patients were referred to Muhammad Ali Parkinson Center (MAPC. Among them, 810 patients had typical Parkinson disease (PD and 212 had PD for ≤5 years. Among the 212 patients with early PD, 27 (12.7% had freezing of gait (FOG. Forty of the 850 had atypical parkinsonism. Among these 40 patients, all of whom had symptoms for ≤5 years, 12 (30.0% had FOG. FOG improved with levodopa in 21/27 patients with typical PD but did not improve in the 12 patients with atypical parkinsonism. FOG was associated with falls in both groups of patients. We believe that FOG unresponsive to levodopa in typical PD resembles FOG in atypical parkinsonism. We thus compared the 6 typical PD patients with FOG unresponsive to levodopa plus the 12 patients with atypical parkinsonism with the 21 patients with typical PD responsive to levodopa. We compared them by tests of locomotion and postural stability. Among the patients with FOG unresponsive to levodopa, postural stability was more impaired than locomotion. This finding leads us to believe that, in these patients, postural stability, not locomotion, is the principal problem underlying FOG.

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

Science.gov (United States)

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

2013-01-01

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

I-123 IMP SPECT in Parkinson's disease

International Nuclear Information System (INIS)

Kawabata, Keita; Tachibana, Kyudai; Sugita, Minoru

1990-01-01

To examine semiquantitatively regional cerebral blood flow, SPECT with N-isopropyl-p-[I-123]iodoamphetamine (I-123 IMP) was undertaken in 17 patients with Parkinson's disease. Seven patients with Alzheimer's disease and 9 senile control subjects were also imaged for comparison. Both the Parkinson's disease group and the Alzheimer's disease group had a decreased uptake of I-123 IMP in the frontal lobe, in comparison with the control group. A remarkably decreased uptake was seen in the lateral and parietal lobes in the group of Parkinson's disease associated with dementia, as well as in the Alzheimer's disease group. A significantly decreased uptake was observed in the frontal lobe, lateral lobe, thalamus, and basal ganglia in the Parkinson's disease group, irrespective of the presence or absence of dementia. For Parkinson's disease associated with dementia, there was much more significant decrease in I-123 IMP uptake. The pattern of regional cerebral blood flow in the Alzheimer's disease group was analogous to that in the Parkinson's disease group associated with dementia. This supports the hypothesis that Alzheimer's disease may be somewhat involved in the occurrence of dementia for Parkinson's disease. (N.K.)

Pre- and postsynaptic dopamine SPECT in the early phase of idiopathic parkinsonism: a population-based study

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Jakobson, Mo Susanna; Riklund, Katrine [Umeaa University, Department of Radiation Sciences, Diagnostic Radiology, Umeaa (Sweden); Linder, Jan; Forsgren, Lars [Umeaa University, Department of Pharmacology and Clinical Neuroscience, Neurology, Umeaa (Sweden); Larsson, Anne; Johansson, Lennart [Umeaa University, Department of Radiation Sciences, Radiation Physics, Umeaa (Sweden)

2010-11-15

The aim of this study was to assess the diagnostic contribution of pre- and postsynaptic dopamine SPECT in drug-naive patients with early idiopathic parkinsonism and to investigate possible differences between idiopathic Parkinson's disease (PD) and atypical parkinsonian syndromes (APS) and possible differences in motor subtypes of parkinsonism. A group of 128 newly diagnosed idiopathic parkinsonian patients and 48 healthy controls was studied. Presynaptic baseline SPECT with {sup 123}I-FP-CIT was performed in all patients and in 120 patients also a baseline postsynaptic SPECT with {sup 123}I-IBZM. Clinical diagnoses were reassessed after 12 months. Presynaptic uptake in the putamen and caudate was significantly reduced in patients compared to controls. Presynaptic uptake ratios were not different between PD patients and patients with APS, and postsynaptic uptake in APS was not significantly reduced compared to PD or controls. In half of the APS patients both pre- and postsynaptic uptake ratios were reduced on the same side in the striatum. Impaired motor performance was associated with decreased presynaptic uptake in the putamen in PD. The postural instability and gait difficulty (PIGD) subtype of PD had lower presynaptic uptake ratios than patients with tremor-dominated (TD) symptoms. Not only presynaptic putamen uptake ratios, but also caudate ratios were reduced in a majority of the patients in our study. At baseline scan, i.e. in an early stage of the disease, the accuracy of excluding APS in the whole study population was 85% using a combination of pre- and postsynaptic SPECT. Already at baseline, lower presynaptic SPECT ratios were seen in PD with PIGD at onset compared to those with TD subtype. (orig.)

Monamine oxidase inhibitors: current and emerging agents for Parkinson disease.

Science.gov (United States)

Fernandez, Hubert H; Chen, Jack J

2007-01-01

Monoamine oxidase type B (MAO-B) is the predominant isoform responsible for the metabolic breakdown of dopamine in the brain. Selective inhibition of brain MAO-B results in elevation of synaptosomal dopamine concentrations. Data have been reported regarding the selective MAO-B inhibitors, rasagiline and selegiline, for the symptomatic treatment of Parkinson disease (PD). Selegiline has demonstrated efficacy as monotherapy in patients with early PD (Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism study), but evidence of selegiline efficacy as adjunctive treatment in levodopa-treated PD patients with motor fluctuations is equivocal. A new formulation of selegiline (Zydis selegiline) has been evaluated in 2 small, placebo-controlled studies as adjunctive therapy to levodopa. The Zydis formulation allows pregastric absorption of selegiline, minimizing first-pass metabolism, and thereby increasing selegiline bioavailability and reducing the concentration of amphetamine metabolites. Rasagiline is a selective, second-generation, irreversible MAO-B inhibitor, with at least 5 times the potency of selegiline in vitro and in animal models. Rasagiline has demonstrated efficacy in 1 large, randomized, double-blind, placebo-controlled trial (TVP-1012 in Early Monotherapy for Parkinson's Disease Outpatients) as initial monotherapy in patients with early PD, and in 2 large, controlled trials (Parkinson's Rasagiline: Efficacy and Safety in the Treatment of "Off," Lasting Effect in Adjunct Therapy With Rasagiline Given Once Daily) as adjunctive treatment in levodopa-treated PD patients with motor fluctuations. Unlike selegiline, rasagiline is an aminoindan derivative with no amphetamine metabolites. A randomized clinical trial is underway to confirm preclinical and preliminary clinical data suggesting rasagiline has disease-modifying effects.

Very early onset inflammatory bowel disease: Investigation of the IL-10 signaling pathway in Iranian children

NARCIS (Netherlands)

Nemati, Shahram; Teimourian, Shahram; Tabrizi, Mina; Najafi, Mehri; Dara, Naghi; Imanzadeh, Farid; Ahmadi, Mitra; Aghdam, Maryam Kazemi; Tavassoli, Mohmoud; Rohani, Pejman; Madani, Seyyed Ramin; de Boer, Martin; Kuijpers, T. W.; Roos, Dirk

2017-01-01

Background & aim: Comparing to adult inflammatory bowel disease (IBD), those with early onset manifestations have different features in terms of the underlying molecular pathology, the course of disease and the response to therapy. We investigated the IL-10 signaling pathway previously reported as

Efficacy of rasagiline in early Parkinson's disease: a meta-analysis of data from the TEMPO and ADAGIO studies.

Science.gov (United States)

Hauser, Robert A; Abler, Victor; Eyal, Eli; Eliaz, Rom E

2016-10-01

To evaluate the efficacy of rasagiline versus placebo in a pooled population of patients with early Parkinson's disease (PD). TEMPO and ADAGIO were Phase III studies that evaluated the symptomatic efficacy of rasagiline versus placebo in patients with early PD. This meta-analysis included Unified Parkinson's Disease Rating Scale (UPDRS) observations from weeks 12, 24 and 36 in ADAGIO and from weeks 14 and 26 in TEMPO; TEMPO visits were recoded to weeks 12 and 24, respectively. The present analysis includes all patients who received rasagiline 1 mg/day, 2 mg/day or placebo, and had ≥1 post-baseline observations and a subgroup of patients whose baseline UPDRS Total scores were ≥27 (Upper Quartile population). Change from baseline in UPDRS scores were evaluated using mixed models repeated measures analyses. Of the 1578 patients randomized to the two studies, 1546 patients met criteria for inclusion in the meta-analysis. Effects on UPDRS Total, motor and activities of daily living scores were significantly better for both doses of rasagiline compared with placebo at all time periods. The Upper Quartile population included 402 patients with a UPDRS Total score ≥27 at baseline. These patients generally demonstrated a larger magnitude of treatment effect than was seen in the full population. This meta-analysis confirms the efficacy of rasagiline monotherapy over 36 weeks. Although TEMPO and ADAGIO are considered studies of "very early" PD, both contained a sizeable pool of patients with more severe disease. In addition, the meta-analysis showed a larger magnitude of effect in patients with more severe baseline disease.

Validity of Montreal Cognitive Assessment in non-english speaking patients with Parkinson's disease.

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Krishnan, Syam; Justus, Sunitha; Meluveettil, Radhamani; Menon, Ramshekhar N; Sarma, Sankara P; Kishore, Asha

2015-01-01

The Montreal Cognitive Assessment is a brief and easy screening tool for accurately testing cognitive dysfunction in Parkinson's disease. We tested its validity for use in non-English (Malayalam) speaking patients with Parkinson's disease. We developed a Malayalam (a south-Indian language) version of Montreal Cognitive Assessment and applied to 70 patients with Parkinson's disease and 60 age- and education-matched healthy controls. Metric properties were assessed, and the scores were compared with the performance in validated Malayalam versions of Mini Mental Status Examination and Addenbrooke's Cognitive Examination. The Montreal Cognitive Assessment-Malayalam showed good internal consistency and test-retest reliability and its scores correlated with Mini Mental Status Examination (patients: R = 0.70; P speaking Parkinson's disease patients for early screening and potential future interventions for cognitive dysfunction.

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 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.

Parkinson's Disease Videos

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Full Text Available ... Nursing Solutions: Improving Parkinson's Care Everywhere CareMAP: La Alimentación y la Deglución, Parte 1 CareMAP: El Baño, ... How Does Parkinson's Disease Affect Memory? CareMAP: La Alimentación y la Deglución, Parte 2 Caregiver Summit 2016: ...

Slowing of oscillatory brain activity is a stable characteristic of Parkinson's disease without dementia

NARCIS (Netherlands)

Stoffers, D.; Bosboom, JL; Deijen, J.B.; Wolters, E.C.M.J.; Berendse, H.W.; Stam, L.

2007-01-01

Extensive changes in resting-state oscillatory brain activity have recently been demonstrated using magnetoencephalography (MEG) in moderately advanced, non-demented Parkinson's disease patients relative to age-matched controls. The aim of the present study was to determine the onset and evolution

Mitochondrial serine protease HTRA2 p.G399S in a kindred with essential tremor and Parkinson disease.

Science.gov (United States)

Unal Gulsuner, Hilal; Gulsuner, Suleyman; Mercan, Fatma Nazli; Onat, Onur Emre; Walsh, Tom; Shahin, Hashem; Lee, Ming K; Dogu, Okan; Kansu, Tulay; Topaloglu, Haluk; Elibol, Bulent; Akbostanci, Cenk; King, Mary-Claire; Ozcelik, Tayfun; Tekinay, Ayse B

2014-12-23

Essential tremor is one of the most frequent movement disorders of humans and can be associated with substantial disability. Some but not all persons with essential tremor develop signs of Parkinson disease, and the relationship between the conditions has not been clear. In a six-generation consanguineous Turkish kindred with both essential tremor and Parkinson disease, we carried out whole exome sequencing and pedigree analysis, identifying HTRA2 p.G399S as the allele likely responsible for both conditions. Essential tremor was present in persons either heterozygous or homozygous for this allele. Homozygosity was associated with earlier age at onset of tremor (P relationship to Parkinson disease.

The increasing role of monoamine oxidase type B inhibitors in Parkinson's disease therapy.

Science.gov (United States)

Elmer, Lawrence W; Bertoni, John M

2008-11-01

The role of monoamine oxidase type B inhibitors in the treatment of Parkinson's disease has expanded with the new monoamine oxidase B inhibitor rasagiline and a new formulation, selegiline oral disintegrating tablets. As primary therapy in early disease monoamine oxidase B inhibitors reduce motor disability and delay the need for levodopa. In more advanced disease requiring levodopa, adjunctive monoamine oxidase B inhibitors reduce 'off' time and may improve gait and freezing. Rasagiline and selegiline oral disintegrating tablets may reduce the safety risks associated with the amfetamine and methamfetamine metabolites of conventional oral selegiline while retaining or improving therapeutic efficacy. Articles were identified by searches of PubMed and searches on the Internet and reviewed. All articles and other referenced materials were retrieved using the keywords 'Parkinson's disease', 'treatment' and 'monoamine oxidase B inhibitor' and were published between 1960 and 2007, with older references selected for historical significance. Only papers published in English were reviewed. Accumulating data support the use of monoamine oxidase B inhibitors as monotherapy for early and mild Parkinson's disease and as adjunctive therapy for more advanced Parkinson's disease with levodopa-associated motor fluctuations. The recently released monoamine oxidase B inhibitor rasagiline and a new formulation, selegiline oral disintegrating tablets, have potential advantages over conventional oral selegiline.

Regulation of motor proteins, axonal transport deficits and adult-onset neurodegenerative diseases.

Science.gov (United States)

Brady, Scott T; Morfini, Gerardo A

2017-09-01

Neurons affected in a wide variety of unrelated adult-onset neurodegenerative diseases (AONDs) typically exhibit a "dying back" pattern of degeneration, which is characterized by early deficits in synaptic function and neuritic pathology long before neuronal cell death. Consistent with this observation, multiple unrelated AONDs including Alzheimer's disease, Parkinson's disease, Huntington's disease, and several motor neuron diseases feature early alterations in kinase-based signaling pathways associated with deficits in axonal transport (AT), a complex cellular process involving multiple intracellular trafficking events powered by microtubule-based motor proteins. These pathogenic events have important therapeutic implications, suggesting that a focus on preservation of neuronal connections may be more effective to treat AONDs than addressing neuronal cell death. While the molecular mechanisms underlying AT abnormalities in AONDs are still being analyzed, evidence has accumulated linking those to a well-established pathological hallmark of multiple AONDs: altered patterns of neuronal protein phosphorylation. Here, we present a short overview on the biochemical heterogeneity of major motor proteins for AT, their regulation by protein kinases, and evidence revealing cell type-specific AT specializations. When considered together, these findings may help explain how independent pathogenic pathways can affect AT differentially in the context of each AOND. Copyright © 2017 Elsevier Inc. All rights reserved.

[Neuroprotective subthalamotomy in Parkinson's disease. The role of magnetic resonance-guided focused ultrasound in early surgery].

Science.gov (United States)

Guridi, Jorge; Marigil, Miguel; Becerra, Victoria; Parras, Olga

Subthalamic nucleus hyperactivity in Parkinson's disease may be a very early phenomenon. Its start is not well known, and it may occur during the pre-symptomatic disease stage. Glutamatergic hyperactivity may be neurotoxic over the substantia nigra compacta dopaminergic neurons. If this occurred, the excitatory neurotransmitter, glutamate, should affect the neurons that maintain a high turnover as a compensatory mechanism. Would a subthalamic nucleus lesion decrease this hyperactivity and thus be considered as a neuroprotective mechanism for dopaminergic neurons? The authors hypothesise about the possibility to perform surgery on a subthalamic nucleus lesion at a very early stage in order to avoid the neurotoxic glutamatergic effect over the dopaminergic neurons, and therefore be considered as a neuroprotective surgery able to alter the progress of the disease during early motor symptoms. In this regard, magnetic resonance-guided focused ultrasound techniques open a new window in the stereotactic armamentarium. Copyright © 2016 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.

Imaging biomarkers in Parkinson?s disease and Parkinsonian syndromes: current and emerging concepts

OpenAIRE

Saeed, Usman; Compagnone, Jordana; Aviv, Richard I.; Strafella, Antonio P.; Black, Sandra E.; Lang, Anthony E.; Masellis, Mario

2017-01-01

Two centuries ago in 1817, James Parkinson provided the first medical description of Parkinson?s disease, later refined by Jean-Martin Charcot in the mid-to-late 19th century to include the atypical parkinsonian variants (also termed, Parkinson-plus syndromes). Today, Parkinson?s disease represents the second most common neurodegenerative disorder with an estimated global prevalence of over 10 million. Conversely, atypical parkinsonian syndromes encompass a group of relatively heterogeneous d...

Maintaining intestinal health: the genetics and immunology of very early onset inflammatory bowel disease.

Science.gov (United States)

Kelsen, Judith R; Baldassano, Robert N; Artis, David; Sonnenberg, Gregory F

2015-09-01

Inflammatory bowel disease (IBD) is a multifactoral disease caused by dysregulated immune responses to commensal or pathogenic microbes in the intestine, resulting in chronic intestinal inflammation. An emerging population of patients with IBD occurring before the age of 5 represent a unique form of disease, termed Very Early Onset (VEO)-IBD, which is phenotypically- and genetically-distinct from older-onset IBD. VEO-IBD is associated with increased disease severity, aggressive progression and poor responsiveness to most conventional therapies. Further investigation into the causes and pathogenesis of VEO-IBD will help improve treatment strategies, and may lead to a better understanding of the mechanisms that are essential to maintain intestinal health or provoke the development of targeted therapeutic strategies to limit intestinal disease. Here we discuss the phenotypic nature of VEO-IBD, the recent identification of novel gene variants associated with disease, and functional immunologic studies interrogating the contribution of specific genetic variants to the development of chronic intestinal inflammation.

Cue-induced striatal dopamine release in Parkinson's disease-associated impulsive-compulsive behaviours.

Science.gov (United States)

O'Sullivan, Sean S; Wu, Kit; Politis, Marios; Lawrence, Andrew D; Evans, Andrew H; Bose, Subrata K; Djamshidian, Atbin; Lees, Andrew J; Piccini, Paola

2011-04-01

Impulsive-compulsive behaviours are a significant source of morbidity for patients with Parkinson's disease receiving dopaminergic therapy. The development of these behaviours may reflect sensitization of the neural response to non-drug rewards, similar to that proposed for sensitization to drug rewards in addiction. Here, by using (11)C-raclopride positron emission tomography imaging, we investigated the effects of reward-related cues and L-dopa challenge in patients with Parkinson's disease with and without impulsive-compulsive behaviours on striatal levels of synaptic dopamine. Eighteen patients (11 with and seven without impulsive-compulsive behaviours) underwent three (11)C-raclopride positron emission tomography scans. The impulsive-compulsive behaviours included hypersexuality, binge eating, punding, compulsive use of dopamine replacement therapy, compulsive buying and pathological gambling, with eight patients exhibiting more than one impulsive-compulsive behaviour. There were no significant differences in baseline dopamine D2 receptor availability between the Parkinson's disease groups. No differences were found when comparing the percentage change of raclopride binding potential between the two Parkinson's disease groups following L-dopa challenge with neutral cues. The group with Parkinson's disease with impulsive-compulsive behaviours had a greater reduction of ventral striatum (11)C-raclopride binding potential following reward-related cue exposure, relative to neutral cue exposure, following L-dopa challenge (16.3% compared with 5.8% in Parkinson's disease controls, P = 0.016). The heightened response of striatal reward circuitry to heterogeneous reward-related visual cues among a group of patients with different impulsive-compulsive behaviours is consistent with a global sensitization to appetitive behaviours with dopaminergic therapy in vulnerable individuals. Our findings are relevant for the broader debate on the relation between impulsive

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Does early-onset multiple sclerosis differ from adult-onset form in Iranian people

Directory of Open Access Journals (Sweden)

Fereshteh Ashtari

2010-01-01

Full Text Available Background: Few studies have attempted to delineate the clinical profile of multiple Sclerosis (MS among people of Asia. This study sought to identify the characteristics of early-onset Multiple Sclerosis (EOMS comparison to adult-onset form (AOMS in Isfahan, IRAN. Methods: This prospective study was conducted on 104 youths with multiple sclerosis beginning before the age of 16 years and 123 patients with adult-onset multiple sclerosis. Patients were observed for a mean period of 5 years. The common presenting symptoms, MRI finding, course of disease and disability score were compared between the two groups. Results: The mean onset age of disease in youths and adults were 14 ± 1.9 and 27.7 ± 8.06 years, respectively. Female/male ratio was 4.47:1 in EOMS and 3.92:1 in AOMS, this ratio was 7:1 in early childhood MS (≤ 10 year. The most common presenting symptom was optic neuritis in the EOMS group and paresthesia in AOMS. Optic neuritis was common in AOMS too, but brainstem/cerebellar signs were more common in EOMS than AOMS. Seizure occurred more frequently in EOMS than in the AOMS group (12.6% vs. 1.6%, respectively, p < 0.001. MRI showed that brainstem plaques were more prevalent in the EOMS compared with the AOMS group. Conclusions: It was concluded that early-onset MS does not significantly differ from adult form in terms of major clinical manifestation and course of disease, however Seizure is more common in EOMS, and brainstem and cerebellar symptoms as presenting symptom are more common.

Comparative study of CT scan findings and intellectual function between Parkinson's disease and vascular Parkinsonism

International Nuclear Information System (INIS)

Indo, Toshikatsu

1986-01-01

Comparative study of CT scan findings and intellectual function between 64 cases with Parkinson's disease and 25 cases with vascular Parkinsonism was carried out. The rate of abnormality of CT scan findings, either ventricular dilatation or widening of sulci, in vascular Parkinsonism was strikingly high compared with Parkinson's disease. Patients could be divided into three groups according to the degree of overall abnormalities of CT scan findings (group A: markedly abnormal, group B: mildly abnormal, group C: normal). Incidences of group A were 9.4 % in Parkinson's disease and 52 % in vascular Parkinsonism, whereas those of group C were 56 % in the former and 28 % in the latter. All patients of group A were over 65 years of age in Parkinson's disease, but one-third of patients in group A were under 59 years of age in vascular Parkinsonism. Moreover, in vascular Parkinsonism, the level of disability was directly proportional to the abnormality of CT scan findings. The rate of predementia and dementia classified by Hasegawa's intelligence scale was 12.5 % in Parkinson's disease and 48 % in vascular Parkinsonism. No difference was found between the mean values of intelligence scale and background factors in Parkinson's disease. On the other hand, the mean value was significantly low in proportion to the poverty of L-dopa effect in vascular Parkinsonism. From these results, the abnormality of CT scan findings and intellectual impairment were probably related to the cerebral pathological process in vascular Parkinsonism, but these relationship was absent in Parkinson's disease. (author)

Comparative study of CT scan findings and intellectual function between Parkinson's disease and vascular Parkinsonism

Energy Technology Data Exchange (ETDEWEB)

Indo, Toshikatsu

1986-01-01

Comparative study of CT scan findings and intellectual function between 64 cases with Parkinson's disease and 25 cases with vascular Parkinsonism was carried out. The rate of abnormality of CT scan findings, either ventricular dilatation or widening of sulci, in vascular Parkinsonism was strikingly high compared with Parkinson's disease. Patients could be divided into three groups according to the degree of overall abnormalities of CT scan findings (group A: markedly abnormal, group B: mildly abnormal, group C: normal). Incidences of group A were 9.4 % in Parkinson's disease and 52 % in vascular Parkinsonism, whereas those of group C were 56 % in the former and 28 % in the latter. All patients of group A were over 65 years of age in Parkinson's disease, but one-third of patients in group A were under 59 years of age in vascular Parkinsonism. Moreover, in vascular Parkinsonism, the level of disability was directly proportional to the abnormality of CT scan findings. The rate of predementia and dementia classified by Hasegawa's intelligence scale was 12.5 % in Parkinson's disease and 48 % in vascular Parkinsonism. No difference was found between the mean values of intelligence scale and background factors in Parkinson's disease. On the other hand, the mean value was significantly low in proportion to the poverty of L-dopa effect in vascular Parkinsonism. From these results, the abnormality of CT scan findings and intellectual impairment were probably related to the cerebral pathological process in vascular Parkinsonism, but these relationship was absent in Parkinson's disease.

Olfactory disfunction and its relation olfactory bulb volume in Parkinson's disease.

Science.gov (United States)

Altinayar, S; Oner, S; Can, S; Kizilay, A; Kamisli, S; Sarac, K

2014-01-01

Olfactory dysfunction is the most frequently seen non-motor symptom of Idiopathic Parkinson's disease (IPD). The aim of this study is to analyze selective olfactory dysfunction, and olfactory bulb volume (OBV) in subtypes of IPD, and compare them with those of the healthy controls. Our study included 41 patients with IPD and age and gender matched 19 healthy controls. IPD patients were either tremor dominant (65.9%; TDPD) or non-tremor dominant (34.1%; NTDPD) type. All patients underwent neurological, ear, nose, and throat examinations, and orthonasal olfaction testing. Magnetic resonance imaging (MRI) technique was used to measure the volume of the olfactory bulb. A significant decrease in olfactory identification scores was found in the patient group. The patients had difficulty in discriminating between odors of mothballs, chocolate, Turkish coffee and soap. OBV did not differ between the patient, and the control groups. In the TDPD group, odor identification ability was decreased when compared to the control group. However, odor test results of NTDPD, control and TDPD groups were similar. OBV estimates of the TDPD group were not different from those of the control group, while in the NTDPD group OBVs were found to be decreased. In all patients with Parkinson's disease OBV values did not vary with age of the patients, duration of the disease, age at onset of the disease, and Unified Parkinson's Disease Rating Scale motor scores (UPDRS-m). Olfactory function is a complex process involving olfactory, and cortical structures as well. In Idiopathic Parkinson's disease, changes in OBV do not seem to be directly related to olfactory dysfunction.

Attenuated heart rate response in REM sleep behavior disorder and Parkinson's disease

DEFF Research Database (Denmark)

Sorensen, Gertrud Laura; Kempfner, Jacob; Zoetmulder, Marielle

2012-01-01

The objective of this study was to determine whether patients with Parkinson's disease with and without rapid‐eye‐movement sleep behavior disorder and patients with idiopathic rapid‐eye‐movement sleep behavior disorder have an attenuated heart rate response to arousals or to leg movements during...... sleep compared with healthy controls. Fourteen and 16 Parkinson's patients with and without rapid‐eye‐movement sleep behavior disorder, respectively, 11 idiopathic rapid‐eye‐movement sleep behavior disorder patients, and 17 control subjects underwent 1 night of polysomnography. The heart rate response...... associated with arousal or leg movement from all sleep stages was analyzed from 10 heartbeats before the onset of the sleep event to 15 heartbeats following onset of the sleep event. The heart rate reponse to arousals was significantly lower in both parkinsonian groups compared with the control group...

Lumbar Spine Surgery in Patients with Parkinson Disease.

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

2015-10-21

Parkinson disease is the second most common neurodegenerative condition. The literature on patients with Parkinson disease and spine surgery is limited, but increased complications have been reported. All patients with Parkinson disease undergoing lumbar spine surgery between 2002 and 2012 were identified. Patients' charts, radiographs, and outcome questionnaires were reviewed. Parkinson disease severity was assessed with use of the modified Hoehn and Yahr staging scale. Complications and subsequent surgeries were analyzed. Risk for reoperation was assessed. Ninety-six patients underwent lumbar spine surgery. The mean patient age was 63.0 years. The mean follow-up duration was 30.1 months. The Parkinson disease severity stage was Parkinson disease severity stage of ≥3 (p Parkinson disease is good, with improvement of spine-related pain. A larger prospective study is warranted. Copyright © 2015 by The Journal of Bone and Joint Surgery, Incorporated.

Neuropsychological profile of Parkinson's disease patients selected for deep brain stimulation surgery

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Flavia Amaral Machado

Full Text Available ABSTRACT Background: Parkinson's disease (PD shows symptoms involving motor and non-motor complications, including cognitive and behavioral changes, such changes might to contraindicate deep brain stimulation surgery (DBS. Objective: The aim of study was to investigate the neuropsychological profile of patients with PD in a waiting list for DBS. Methods: The neuropsychological evaluation was held in 30 patients of the ISCMPA Movement Disorders Clinic, with surgical indication based on the criteria of the responsible neurologists, in the period of 12 months. Instruments used: MMSE, FAB, MoCA, BDI, Semantic Verbal Fluency, PDQ-39, PDSS; and the UPDRS and Hoehn-Yahr scale. Results: The patients were mostly male (66.7% with a mean age of 59.37 (SD 10.60 and disease duration 9.33 (SD 4.08. There was cognitive impairment in 56.7% of patients by FAB and 76.7% by MoCA. Conclusion: Even in the earliest stages of the disease, there is the incidence of non-motor symptoms, especially in those subjects who had an early onset of the disease.

The Clinical Findings Useful for Driving Safety Advice for Parkinson's Disease Patients.

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Ando, Rina; Iwaki, Hirotaka; Tsujii, Tomoaki; Nagai, Masahiro; Nishikawa, Noriko; Yabe, Hayato; Aiba, Ikuko; Hasegawa, Kazuko; Tsuboi, Yoshio; Aoki, Masashi; Nakashima, Kenji; Nomoto, Masahiro

2018-02-28

Objective We conducted a study to obtain information that could be used to provide Parkinson's disease (PD) patients with appropriate advice on safe driving. Methods Consecutive PD patients who visited our office were studied. Among these patients, those who had experienced driving after being diagnosed with PD were interviewed by neurologists and a trained nurse to investigate their previous car accidents, motor function, cognitive function, sleepiness, levodopa equivalent dose (LED), and emotional dysregulation. The rates of major car accidents before and after the onset of PD were compared. Results Fifteen patients had experienced a major car accident resulting in human injury or serious property damage since the onset of PD. When the rates of major car accidents before and after the onset of PD were compared, the ratio was 4.3 (95% CI 1.9-9.7). The incidence of accidents after the onset of PD was correlated with age, disease duration, LED, the cognitive function (MMSE, MoCA-J), but not the motor symptom score (UPDRS part III at the time of the study). The Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP) score was also higher in patients with major car accidents. Conclusion The severity of symptoms (Hoehn-Yahr classification), cognitive function, and disease duration were expected to be risk factors for car accidents. However, the motor symptom score (UPDRS part III) was not associated with the incidence of major car accidents. In addition to a low cognitive function and the severity of symptoms, the QUIP score might be an independent factor that can be referenced when advising PD patients to refrain from driving.

Relationship Between Voice and Motor Disabilities of Parkinson's Disease.

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Majdinasab, Fatemeh; Karkheiran, Siamak; Soltani, Majid; Moradi, Negin; Shahidi, Gholamali

2016-11-01

To evaluate voice of Iranian patients with Parkinson's disease (PD) and find any relationship between motor disabilities and acoustic voice parameters as speech motor components. We evaluated 27 Farsi-speaking PD patients and 21 age- and sex-matched healthy persons as control. Motor performance was assessed by the Unified Parkinson's Disease Rating Scale part III and Hoehn and Yahr rating scale in the "on" state. Acoustic voice evaluation, including fundamental frequency (f0), standard deviation of f0, minimum of f0, maximum of f0, shimmer, jitter, and harmonic to noise ratio, was done using the Praat software via /a/ prolongation. No difference was seen between the voice of the patients and the voice of the controls. f0 and its variation had a significant correlation with the duration of the disease, but did not have any relationships with the Unified Parkinson's Disease Rating Scale part III. Only limited relationship was observed between voice and motor disabilities. Tremor is an important main feature of PD that affects motor and phonation systems. Females had an older age at onset, more prolonged disease, and more severe motor disabilities (not statistically significant), but phonation disorders were more frequent in males and showed more relationship with severity of motor disabilities. Voice is affected by PD earlier than many other motor components and is more sensitive to disease progression. Tremor is the most effective part of PD that impacts voice. PD has more effect on voice of male versus female patients. Copyright © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Sleep disturbances in Parkinson's disease patients and management options

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Claassen DO

2011-12-01

Full Text Available Daniel O Claassen, Scott J KutscherDepartment of Neurology, Vanderbilt University, Nashville, TN, USAAbstract: Sleep disturbances are among the most common nonmotor complaints of patients with Parkinson's disease (PD, and can have a great impact on quality of life. These disturbances manifest in a variety of ways; for instance, insomnia, sleep fragmentation, and excessive daytime sleepiness. Sleep-related movement disorders such as restless legs syndrome and periodic leg movements may share a common pathophysiology, and occurrence of rapid eye movement behavior disorder may predate the onset of PD or other synucleinopathies by several years. Medications for PD can have a significant impact on sleep, representing a great challenge to the treating physician. Awareness of the complex relationship between PD and sleep disorders, as well as the varied way in which sleep disturbances appear, is imperative for successful long-term management.Keywords: sleep disorders, insomnia, restless legs syndrome, Parkinson disease, fatigue, REM behavior disorder