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Sample records for parkinson disease association

  1. Parkinson disease

    MedlinePlus

    American Parkinson Disease Association. Parkinson's Disease Handbook: A Guide for Patients and Their Families. Revised 2009. Available at: www.apdaparkinson.org/uploads/files/MP51919AmParkinsonHBK-vaU.pdf . Accessed September 15, ...

  2. Association between Parkinson's Disease and Helicobacter Pylori

    PubMed Central

    Oğuz, Sıdıka

    2016-01-01

    Helicobacter pylori (HP) is a common infection of the gastrointestinal system that is usually related to peptic ulcers. However, recent studies have revealed relationships between HP and many other diseases. Although the exact mechanism is unknown, HP can prevent the absorption of certain drugs. A high prevalence of HP has been found in patients with Parkinson's disease, and this bacterium causes motor fluctuations by affecting the absorption of levodopa, which is the main drug used to treat Parkinson's disease. Eradicating HP from patients with Parkinson's disease by applying antibiotic treatment will increase the absorption of levodopa and decrease their motor fluctuations. PMID:26932258

  3. Association between Parkinson's Disease and Helicobacter Pylori.

    PubMed

    Çamcı, Gülşah; Oğuz, Sıdıka

    2016-04-01

    Helicobacter pylori (HP) is a common infection of the gastrointestinal system that is usually related to peptic ulcers. However, recent studies have revealed relationships between HP and many other diseases. Although the exact mechanism is unknown, HP can prevent the absorption of certain drugs. A high prevalence of HP has been found in patients with Parkinson's disease, and this bacterium causes motor fluctuations by affecting the absorption of levodopa, which is the main drug used to treat Parkinson's disease. Eradicating HP from patients with Parkinson's disease by applying antibiotic treatment will increase the absorption of levodopa and decrease their motor fluctuations. PMID:26932258

  4. Associations between B Vitamins and Parkinson's Disease.

    PubMed

    Shen, Liang

    2015-09-01

    B vitamins may correlate with Parkinson's disease (PD) through regulating homocysteine level. However, there is no comprehensive assessment on the associations between PD and B vitamins. The present study was designed to perform a meta-analytic assessment of the associations between folate, vitamin B6, and vitamin B12 and PD, including the status of B vitamins in PD patients compared with controls, and associations of dietary intakes of B vitamins and risk of PD. A literature search using Medline database obtained 10 eligible studies included in the meta-analyses. Stata 12.0 statistical software was used to perform the meta-analysis. Pooled data revealed that there was no obvious difference in folate level between PD patients and healthy controls, and PD patients had lower level of vitamin B12 than controls. Available data suggested that higher dietary intake of vitamin B6 was associated with a decreased risk of PD (odds ratio (OR) = 0.65, 95% confidence intervals (CI) = (0.30, 1.01)), while no significant association was observed for dietary intake of folate and vitamin B12 and risk of PD. PD patients had lower level of vitamin B12 and similar level of folate compared with controls. Dietary intake of vitamin B6 exhibited preventive effect of developing PD based on the available data. As the number of included studies is limited, more studies are needed to confirm the findings and elucidate the underpinning underlying these associations. PMID:26343714

  5. Inverse Association of Parkinson Disease With Systemic Lupus Erythematosus

    PubMed Central

    Liu, Feng-Cheng; Huang, Wen-Yen; Lin, Te-Yu; Shen, Chih-Hao; Chou, Yu-Ching; Lin, Cheng-Li; Lin, Kuen-Tze; Kao, Chia-Hung

    2015-01-01

    Abstract The effects of the inflammatory mediators involved in systemic lupus erythematous (SLE) on subsequent Parkinson disease have been reported, but no relevant studies have focused on the association between the 2 diseases. This nationwide population-based study evaluated the risk of Parkinson disease in patients with SLE. We identified 12,817 patients in the Taiwan National Health Insurance database diagnosed with SLE between 2000 and 2010 and compared the incidence rate of Parkinson disease among these patients with that among 51,268 randomly selected age and sex-matched non-SLE patients. A Cox multivariable proportional-hazards model was used to evaluate the risk factors of Parkinson disease in the SLE cohort. We observed an inverse association between a diagnosis of SLE and the risk of subsequent Parkinson disease, with the crude hazard ratio (HR) being 0.60 (95% confidence interval 0.45–0.79) and adjusted HR being 0.68 (95% confidence interval 0.51–0.90). The cumulative incidence of Parkinson disease was 0.83% lower in the SLE cohort than in the non-SLE cohort. The adjusted HR of Parkinson disease decreased as the follow-up duration increased and was decreased among older lupus patients with comorbidity. We determined that patients with SLE had a decreased risk of subsequent Parkinson disease. Further research is required to elucidate the underlying mechanism. PMID:26579824

  6. Association Between Tuberculosis and Parkinson Disease

    PubMed Central

    Shen, Chih-Hao; Chou, Chung-Hsing; Liu, Feng-Cheng; Lin, Te-Yu; Huang, Wen-Yen; Wang, Yu-Chiao; Kao, Chia-Hung

    2016-01-01

    Abstract Few studies have investigated the association between tuberculosis (TB) and Parkinson disease (PD). This nationwide, population-based, retrospective cohort study investigated the risk of PD in patients with TB. We selected patients newly diagnosed with TB (International Classification of Diseases, Ninth Revision, Clinical Modification: 011) from 2000 to 2009 in the Taiwan National Health Insurance Database as the TB cohort. The comparison cohort (the non-TB cohort) was frequency matched to the TB cohort at a ratio of 4:1 by sex, age, and the index date. We analyzed the risks of PD by using Cox proportional hazard regression models. A total of 121,951 patients with TB and 487,800 non-TB controls were enrolled in this study. The TB cohort had a 1.38-fold risk of PD compared with the non-TB cohort after adjustment for age, sex, and comorbidities (aHR, 95% CI: 1.30–1.46). The adjusted risk of PD in the TB and non-TB cohorts increased in subgroups regardless of age, sex, and comorbidities. Combined effect of TB and comorbidities on the risk of PD were significant in patients with TB who had diabetes (aHR: 2.26, 95% CI: 2.02–2.52), hypertension (aHR: 2.23, 95% CI: 2.04–2.44), head injury (aHR: 2.32, 95% CI: 1.95–2.77), chronic kidney disease (aHR: 2.02, 95% CI: 1.49–2.72), chronic obstructive pulmonary disease (aHR: 1.84, 95% CI: 1.66–2.05), depression (aHR: 4.66, 95% CI: 3.59–6.05), dementia (aHR: 3.70, 95% CI: 2.99–4.59), and stroke (aHR: 2.56, 95% CI: 2.28–2.87). The risk of PD was higher in a follow-up within 1 year (aHR: 1.78, 95% CI: 1.58–2.00) and decreased with the follow-up period in the TB cohort. Patients with TB have an independently 1.38-fold risk of PD. The risk of PD decreased with the follow-up period in the TB cohort. Physicians should be aware of the risk of PD in patients with TB when treating such patients. PMID:26937925

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

    SciTech Connect

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

    1994-12-15

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

  8. Why psychosis is frequently associated with Parkinson's disease?

    PubMed Central

    Zhong, Jingmei; Wu, Shaoyuan; Zhao, Ying; Chen, Hui; Zhao, Naiwei; Zheng, Kunwen; Zhao, Zhong; Chen, Wenli; Wang, Bo; Wu, Kunhua

    2013-01-01

    Psychosis is a common non-motor symptom of Parkinson's disease whose pathogenesis remains poorly understood. Parkinson's disease in conjunction with psychosis has been shown to induce injury to extracorticospinal tracts as well as within some cortical areas. In this study, Parkinson's disease patients with psychosis who did not receive antipsychotic treatment and those without psychosis underwent diffusion tensor imaging. Results revealed that in Parkinson's disease patients with psychosis, damage to the left frontal lobe, bilateral occipital lobe, left cingulated gyrus, and left hippocampal white-matter fibers were greater than damage to the substantia nigra or the globus pallidus. Damage to white-matter fibers in the right frontal lobe and right cingulate gyrus were also more severe than in the globus pallidus, but not the substantia nigra. Damage to frontal lobe and cingulate gyrus white-matter fibers was more apparent than that to occipital or hippocampal fiber damage. Compared with Parkinson's disease patients without psychosis, those with psychosis had significantly lower fractional anisotropy ratios of left frontal lobe, bilateral occipital lobe, left cingu-lated gyrus, and left hippocampus to ipsilateral substantia nigra or globus pallidus, indicating more severe damage to white-matter fibers. These results suggest that psychosis associated with Par-kinson's disease is probably associated with an imbalance in the ratio of white-matter fibers be-tween brain regions associated with psychiatric symptoms (frontal lobe, occipital lobe, cingulate gyrus, and hippocampus) and those associated with the motor symptoms of Parkinson's disease (the substantia nigra and globus pallidus). The relatively greater damage to white-matter fibers in psychiatric symptom-related brain regions than in extracorticospinal tracts might explain why chosis often occurs in Parkinson's disease patients. PMID:25206565

  9. Parkinson's Disease

    MedlinePlus

    ... about 5 to 10 percent of people with Parkinson's have "early-onset" disease which begins before the age of 50. Early-onset forms of Parkinson's are often inherited, though not always, and some ...

  10. Parkinson's Disease

    MedlinePlus

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

  11. Parkinson disease

    MedlinePlus

    Nerve cells use a brain chemical called dopamine to help control muscle movement. With Parkinson disease, the brain cells that make dopamine slowly die. Without dopamine, the cells that control movement ...

  12. Parkinson's Disease

    MedlinePlus

    ... cells make and use a brain chemical called dopamine (say: DOH-puh-meen) to send messages to ... coordinate body movements. When someone has Parkinson's disease, dopamine levels are low. So, the body doesn't ...

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

    PubMed

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

    2016-06-01

    The development of biomarkers to predict the progression of Parkinson's disease (PD) from its earliest stage through its heterogeneous course is critical for research and therapeutic development. The Parkinson's Progression Markers Initiative (PPMI) study is an ongoing international multicenter, prospective study to validate biomarkers in drug-naïve PD patients and matched healthy controls (HC). We quantified cerebrospinal fluid (CSF) alpha-synuclein (α-syn), amyloid-beta1-42 (Aβ1-42), total tau (t-tau), and tau phosphorylated at Thr181 (p-tau) in 660 PPMI subjects at baseline, and correlated these data with measures of the clinical features of these subjects. We found that CSF α-syn, t-tau and p-tau levels, but not Aβ1-42, were significantly lower in PD compared with HC, while the diagnostic value of the individual CSF biomarkers for PD diagnosis was limited due to large overlap. The level of α-syn, but not other biomarkers, was significantly lower in PD patients with non-tremor-dominant phenotype compared with tremor-dominant phenotype. In addition, in PD patients the lowest Aβ1-42, or highest t-tau/Aβ1-42 and t-tau/α-syn quintile in PD patients were associated with more severe non-motor dysfunction compared with the highest or lowest quintiles, respectively. In a multivariate regression model, lower α-syn was significantly associated with worse cognitive test performance. APOE ε4 genotype was associated with lower levels of Aβ1-42, but neither with PD diagnosis nor cognition. Our data suggest that the measurement of CSF biomarkers in early-stage PD patients may relate to disease heterogeneity seen in PD. Longitudinal observations in PPMI subjects are needed to define their prognostic performance. PMID:27021906

  14. Parkinson Disease.

    PubMed

    Capriotti, Teri; Terzakis, Kristina

    2016-06-01

    Parkinson disease (PD) is a progressive neurodegenerative disease that affects one million people in the United States. This article reviews the etiology and pathophysiology of PD, risk factors, clinical manifestations, diagnostic criteria, and treatment of this common disease. Implications for home care clinicians are included. PMID:27243427

  15. Strong association between glucocerebrosidase mutations and Parkinson's disease in Sweden.

    PubMed

    Ran, Caroline; Brodin, Lovisa; Forsgren, Lars; Westerlund, Marie; Ramezani, Mehrafarin; Gellhaar, Sandra; Xiang, Fengqing; Fardell, Camilla; Nissbrandt, Hans; Söderkvist, Peter; Puschmann, Andreas; Ygland, Emil; Olson, Lars; Willows, Thomas; Johansson, Anders; Sydow, Olof; Wirdefeldt, Karin; Galter, Dagmar; Svenningsson, Per; Belin, Andrea Carmine

    2016-09-01

    Several genetic studies have demonstrated an association between mutations in glucocerebrosidase (GBA), originally implicated in Gaucher's disease, and an increased risk of Parkinson's disease (PD). We have investigated the possible involvement of genetic GBA variations in PD in the Swedish population. Three GBA variants, E326K, N370S, and L444P were screened in the largest Swedish Parkinson cohort reported to date; 1625 cases and 2025 control individuals. We found a significant association with high effect size of the rare variant L444P with PD (odds ratio 8.17; 95% confidence interval: 2.51-26.23; p-value = 0.0020) and a significant association of the common variant E326K (odds ratio 1.60; 95% confidence interval: 1.16-2.22; p-value = 0.026). The rare variant N370S showed a trend for association. Most L444P carriers (68%) were found to reside in northern Sweden, which is consistent with a higher prevalence of Gaucher's disease in this part of the country. Our findings support the role of GBA mutations as risk factors for PD and point to lysosomal dysfunction as a mechanism contributing to PD etiology. PMID:27255555

  16. Advances in GBA-associated Parkinson's disease--Pathology, presentation and therapies.

    PubMed

    Barkhuizen, Melinda; Anderson, David G; Grobler, Anne F

    2016-02-01

    GBA mutations are to date the most common genetic risk factor for Parkinson's disease. The GBA gene encodes the lysomal hydrolase glucocerebrosidase. Whilst bi-allelic GBA mutations cause Gaucher disease, both mono- and bi-allelic mutations confer risk for Parkinson's disease. Clinically, Parkinson's disease patients with GBA mutations resemble idiopathic Parkinson's disease patients. However, these patients have a modest reduction in age-of-onset of disease and a greater incidence of cognitive decline. In some cases, GBA mutations are also responsible for familial Parkinson's disease. The accumulation of α-synuclein into Lewy bodies is the central neuropathological hallmark of Parkinson's disease. Pathologic GBA mutations reduce enzymatic function. A reduction in glucocerebrosidase function increases α-synuclein levels and propagation, which in turn inhibits glucocerebrosidase in a feed-forward cascade. This cascade is central to the neuropathology of GBA-associated Parkinson's disease. The lysosomal integral membrane protein type-2 is necessary for normal glucocerebrosidase function. Glucocerebrosidase dysfunction also increases in the accumulation of β-amyloid and amyloid-precursor protein, oxidative stress, neuronal susceptibility to metal ions, microglial and immune activation. These factors contribute to neuronal death. The Mendelian Parkinson's disease genes, Parkin and ATP13A2, intersect with glucocerebrosidase. These factors sketch a complex circuit of GBA-associated neuropathology. To clinically interfere with this circuit, central glucocerebrosidase function must be improved. Strategies based on reducing breakdown of mutant glucocerebrosidase and increasing the fraction that reaches the lysosome has shown promise. Breakdown can be reduced by interfering with the ability of heat-shock proteins to recognize mutant glucocerebrosidase. This underlies the therapeutic efficacy of certain pharmacological chaperones and histone deacetylase inhibitors. These

  17. Association Between Autonomic Impairment and Structural Deficit in Parkinson Disease

    PubMed Central

    Chen, Meng-Hsiang; Lu, Cheng-Hsien; Chen, Pei-Chin; Tsai, Nai-Wen; Huang, Chih-Cheng; Chen, Hsiu-Ling; Yang, I-Hsiao; Yu, Chiun-Chieh; Lin, Wei-Che

    2016-01-01

    Abstract Patients with Parkinson disease (PD) have impaired autonomic function and altered brain structure. This study aimed to evaluate the relationship of gray matter volume (GMV) determined by voxel-based morphometry (VBM) to autonomic impairment in patients with PD. Whole-brain VBM analysis was performed on 3-dimensional T1-weighted images in 23 patients with PD and 15 sex- and age-matched healthy volunteers. The relationship of cardiovascular autonomic function (determined by survey) to baroreflex sensitivity (BRS) (determined from changes in heart rate and blood pressure during the early phase II of the Valsalva maneuver) was tested using least-squares regression analysis. The differences in GMV, autonomic parameters, and clinical data were correlated after adjusting for age and sex. Compared with controls, patients with PD had low BRS, suggesting worse cardiovascular autonomic function, and smaller GMV in several brain locations, including the right amygdala, left hippocampal formation, bilateral insular cortex, bilateral caudate nucleus, bilateral cerebellum, right fusiform, and left middle frontal gyri. The decreased GMVs of the selected brain regions were also associated with increased presence of epithelial progenitor cells (EPCs) in the circulation. In patients with PD, decrease in cardiovascular autonomic function and increase in circulating EPC level are associated with smaller GMV in several areas of the brain. Because of its possible role in the modulation of the circulatory EPC pool and baroreflex control, the left hippocampal formation may be a bio-target for disease-modifying therapy and treatment monitoring in PD. PMID:26986144

  18. Association Between Autonomic Impairment and Structural Deficit in Parkinson Disease.

    PubMed

    Chen, Meng-Hsiang; Lu, Cheng-Hsien; Chen, Pei-Chin; Tsai, Nai-Wen; Huang, Chih-Cheng; Chen, Hsiu-Ling; Yang, I-Hsiao; Yu, Chiun-Chieh; Lin, Wei-Che

    2016-03-01

    Patients with Parkinson disease (PD) have impaired autonomic function and altered brain structure. This study aimed to evaluate the relationship of gray matter volume (GMV) determined by voxel-based morphometry (VBM) to autonomic impairment in patients with PD.Whole-brain VBM analysis was performed on 3-dimensional T1-weighted images in 23 patients with PD and 15 sex- and age-matched healthy volunteers. The relationship of cardiovascular autonomic function (determined by survey) to baroreflex sensitivity (BRS) (determined from changes in heart rate and blood pressure during the early phase II of the Valsalva maneuver) was tested using least-squares regression analysis. The differences in GMV, autonomic parameters, and clinical data were correlated after adjusting for age and sex.Compared with controls, patients with PD had low BRS, suggesting worse cardiovascular autonomic function, and smaller GMV in several brain locations, including the right amygdala, left hippocampal formation, bilateral insular cortex, bilateral caudate nucleus, bilateral cerebellum, right fusiform, and left middle frontal gyri. The decreased GMVs of the selected brain regions were also associated with increased presence of epithelial progenitor cells (EPCs) in the circulation.In patients with PD, decrease in cardiovascular autonomic function and increase in circulating EPC level are associated with smaller GMV in several areas of the brain. Because of its possible role in the modulation of the circulatory EPC pool and baroreflex control, the left hippocampal formation may be a bio-target for disease-modifying therapy and treatment monitoring in PD. PMID:26986144

  19. Association between antidepressants and falls in Parkinson's disease.

    PubMed

    Martinez-Ramirez, Daniel; Giugni, Juan C; Almeida, Leonardo; Walz, Roger; Ahmed, Bilal; Chai, Fiona A; Rundle-Gonzalez, Valerie; Bona, Alberto R; Monari, Erin; Wagle Shukla, Aparna; Hess, Christopher W; Hass, Chris J; Okun, Michael S

    2016-01-01

    Parkinson's disease (PD) patients have an increased risk of falls resulting in important social and economical consequences. Risk factors for falls include the use of psychotropic drugs, which are used for the treatment of PD neuropsychiatric symptoms. We aimed to determine the association between psychotropic drug use and falls in a PD cohort. A cross-sectional study from the NPF QII study UF site was conducted. Subjects reported presence and frequency of falls in the prior year. Frequency was scored from 0 (no falls) to 4 (falling daily). Antidepressants, antipsychotics, cognitive enhancers/stimulants, and benzodiazepines were considered psychotropics. Forty percent of the 647 subjects included had a fall in the previous year. Fallers were found to have clinical signs of a more advanced disease. After adjusting for confounding variables, the regression analysis showed that use of antidepressants alone (adjusted OR 2.2, CI 95 % 1.3-3.8, p = 0.04), benzodiazepines alone (adjusted OR 2.0, CI 95 % 1.1-3.5, p = 0.02), and the combination of antidepressants with benzodiazepines (adjusted OR 4.1, CI 95 % 2.0-8.3, p < 0.0001) were independently associated with the presence of falls. When comparing to those not on psychotropics, subjects on antidepressants alone had a significantly higher mean frequency of falls score (1.07 vs. 0.44, p < 0.0001). The use of antidepressants was independently associated with falls in our PD cohort after considering for confounding variables such as age and measures of disease progression. Other factors related to disease progression should be considered before claiming the use of psychotropic drugs as causative. PMID:26514836

  20. Parkinson's Disease

    MedlinePlus

    ... results in reduction of a critical neurotransmitter called dopamine, a chemical responsible for transmitting messages to parts ... that coordinate muscle movement. Parkinson's patients have less dopamine. Studies have shown that the symptoms of Parkinson's ...

  1. The treatment of cognitive impairment associated with Parkinson's disease.

    PubMed

    Burn, David J

    2010-05-01

    Cognitive impairment and dementia associated with Parkinson's disease (PD) are common and often have devastating effects upon the patient and their family. Early cognitive impairment in PD is frequent, and the functional impact may be underestimated. Optimal management will rely upon better identification of the predominant symptoms and greater knowledge of their pathophysiological basis. The management of dementia in PD (PD-D) also has to consider the significant neuropsychiatric burden that frequently accompanies the cognitive decline, as well as fluctuations in attention. Atypical anti-psychotics have a limited role at present in treating PD-D, although new drugs are under development. The mainstay of drug management for people with PD-D is cholinesterase inhibitors, although recent trials have suggested that the N-methyl-D aspartate antagonist memantine may also have some benefit. Disease modification remains the ultimate goal for preventing the inexorable decline in PD-D, although effective interventions are still some way off. Limited benefit may, however, be possible through exercise programmes and so-called "medical foods", although randomised trials are required to confirm largely anecdotal observations. PMID:20522093

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

    PubMed

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

    2014-08-01

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

  3. Parkinson's Disease Foundation

    MedlinePlus

    ... Parkinson’s View All News PDF at the 4th World Parkinson Congress Tuesday, September 20-Friday, September 23 ... the Parkinson's Disease Foundation (PDF) at the 4th World Parkinson Congress, a gathering of the international Parkinson’s ...

  4. Parkinson disease - discharge

    MedlinePlus

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

  5. Parkinson disease - discharge

    MedlinePlus

    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 ...

  6. Val66Met BDNF polymorphism is associated with Parkinson's disease cognitive impairment.

    PubMed

    Altmann, Vivian; Schumacher-Schuh, Artur F; Rieck, Mariana; Callegari-Jacques, Sidia M; Rieder, Carlos R M; Hutz, Mara H

    2016-02-26

    Parkinson's disease (PD) is one of the most common neurodegenerative diseases worldwide. Besides characteristic PD motor features, the disease has important non-motor characteristics such as cognitive impairment. The role of genetic factors in cognitive impairment associated with PD is still unclear. In this study, we examined whether BDNF Val66Met was associated with impaired cognition in Parkinson's disease. One hundred and seventy five patients with a clinical diagnosis of Parkinson's disease were included. Global cognitive abilities of the patients were measured by the Mini-Mental State Examination (MMSE). Poisson Regression models were used to test for association between 66Met carriers and cognitive impairment controlling for covariates. Carriers of at least one BDNF 66Met allele presented a higher prevalence of cognitive impairment (p=0.005 RR=1.45 IC=95% [1.1-1.8]). These results suggest a role for BDNF Val66Met polymorphism on cognitive impairment in PD. PMID:26806863

  7. Parkinson disease - resources

    MedlinePlus

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

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

    PubMed

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

    2015-09-01

    There are no cures for neurodegenerative diseases and this is partially due to the difficulty of monitoring pathogenic molecules in patients during life. The Parkinson's disease gene α-synuclein (SNCA) is selectively expressed in blood cells and neurons. Here we show that SNCA transcripts in circulating blood cells are paradoxically reduced in early stage, untreated and dopamine transporter neuroimaging-supported Parkinson's disease in three independent regional, national, and international populations representing 500 cases and 363 controls and on three analogue and digital platforms with P < 0.0001 in meta-analysis. Individuals with SNCA transcripts in the lowest quartile of counts had an odds ratio for Parkinson's disease of 2.45 compared to individuals in the highest quartile. Disease-relevant transcript isoforms were low even near disease onset. Importantly, low SNCA transcript abundance predicted cognitive decline in patients with Parkinson's disease during up to 5 years of longitudinal follow-up. This study reveals a consistent association of reduced SNCA transcripts in accessible peripheral blood and early-stage Parkinson's disease in 863 participants and suggests a clinical role as potential predictor of cognitive decline. Moreover, the three independent biobank cohorts provide a generally useful platform for rapidly validating any biological marker of this common disease. PMID:26220939

  9. Association analysis of a polymorphism of the monoamine oxidase B gene with Parkinson`s disease in a Japanese population

    SciTech Connect

    Morimoto, Yuji; Murayama, Nobuhiro; Kuwano, Akira; Kondo, Ikuko

    1995-12-18

    The polymorphic allele of the monoamine oxidase B (MAO-B) gene detected by polymerase chain reaction (PCR) and single-stranded conformation polymorphism (SSCP) was associated with Parkinson`s disease (PD) in Caucasians. We characterized this polymorphic allele, allele 1, of the MAO-B gene using direct sequencing of PCR products. A single DNA substitution (G-A), resulting gain of Mae III restriction site was detected in intron 13 of the MAO-B gene. The allele associated with PD in Caucasians was twice as frequent as in healthy Japanese, but the association of the allele of the MAO-B gene was not observed in Japanese patients with PD. 7 refs., 2 figs., 1 tab.

  10. Loss of phosphodiesterase 10A expression is associated with progression and severity in Parkinson's disease.

    PubMed

    Niccolini, Flavia; Foltynie, Thomas; Reis Marques, Tiago; Muhlert, Nils; Tziortzi, Andri C; Searle, Graham E; Natesan, Sridhar; Kapur, Shitij; Rabiner, Eugenii A; Gunn, Roger N; Piccini, Paola; Politis, Marios

    2015-10-01

    pallidal loss of PDE10A expression, which is associated with Parkinson's duration and severity of motor symptoms and complications. PDE10A is an enzyme that could be targeted with novel pharmacotherapy, and this may help improve dopaminergic signalling and striatal output, and therefore alleviate symptoms and complications of Parkinson's disease. PMID:26210536

  11. Intonation Contrast in Cantonese Speakers with Hypokinetic Dysarthria Associated with Parkinson's Disease

    ERIC Educational Resources Information Center

    Ma, Joan K.-Y.; Whitehill, Tara L.; So, Susanne Y.-S.

    2010-01-01

    Purpose: Speech produced by individuals with hypokinetic dysarthria associated with Parkinson's disease (PD) is characterized by a number of features including impaired speech prosody. The purpose of this study was to investigate intonation contrasts produced by this group of speakers. Method: Speech materials with a question-statement contrast…

  12. Methamphetamine and Parkinson's Disease

    PubMed Central

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

    2013-01-01

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

  13. Cognitive impairment in Parkinson's disease.

    PubMed

    Ransmayr, Gerhard

    2015-12-01

    Parkinson's disease is the second most frequent neurodegenerative disorder. There is significantly elevated risk of cognitive decline and associated neuropsychiatric symptoms. Dementia may develop insidiously several years after manifestation of Parkinson motor symptoms (dementia associated with Parkinson's disease; Parkinson's disease dementia) or in close temporal relationship (within one year) after onset of motor symptoms (Dementia with Lewy bodies). There are clinical, pathophysiological and therapeutic similarities between these two conditions. Men are more frequently affected than women. Risk factor or indicators are advanced age at disease onset, disease duration, rigidity, akinesia and posture and gait impairment and falls as opposed to tremor dominance, and associated neuropsychiatric symptoms (depression, apathy, hallucinosis, delirium). Dementia is treatable with cholinesterase inhibitors (rivastigmine, donepezil), memantine, and adjustment of the pharmacological regimen of parkinsonian motor symptoms. Concomitant autonomic nervous system symptoms and neuropsychiatric complications warrant early clinical awareness and are accessible to pharmacological therapy. PMID:26609664

  14. Parkinson's disease with camptocormia

    PubMed Central

    Bloch, F; Houeto, J L; du Montcel, S Tezenas; Bonneville, F; Etchepare, F; Welter, M L; Rivaud‐Pechoux, S; Hahn‐Barma, V; Maisonobe, T; Behar, C; Lazennec, J Y; Kurys, E; Arnulf, I; Bonnet, A M; Agid, Y

    2006-01-01

    Background Camptocormia is defined as an abnormal flexion of the trunk that appears when standing or walking and disappears in the supine position. The origin of the disorder is unknown, but it is usually attributed either to a primary or a secondary paravertebral muscle myopathy or a motor neurone disorder. Camptocormia is also observed in a minority of patients with parkinsonism. Objective To characterise the clinical and electrophysiological features of camptocormia and parkinsonian symptoms in patients with Parkinson's disease and camptocormia compared with patients with Parkinson's disease without camptocormia. Methods Patients with parkinsonism and camptocormia (excluding patients with multiple system atrophy) prospectively underwent a multidisciplinary clinical (neurological, neuropsychological, psychological, rheumatological) and neurophysiological (electromyogram, ocular movement recording) examination and were compared with age‐matched patients with Parkinson's disease without camptocormia. Results The camptocormia developed after 8.5 (SD 5.3) years of parkinsonism, responded poorly to levodopa treatment (20%) and displayed features consistent with axial dystonia. Patients with camptocormia were characterised by prominent levodopa‐unresponsive axial symptoms (ie, axial rigidity, gait disorder and postural instability), along with a tendency for greater error in the antisaccade paradigm. Conclusion We suggest that (1) the salient features of parkinsonism observed in patients with camptocormia are likely to represent a specific form of Parkinson's disease and camptocormia is an axial dystonia and (2) both camptocormia and parkinsonism in these patients might result from additional, non‐dopaminergic neuronal dysfunction in the basal ganglia. PMID:16754693

  15. [Depression in Parkinson's disease].

    PubMed

    Murata, Miho; Okamoto, Tomoko

    2013-01-01

    The frequency of depression in patients with Parkinson's disease is approximately 30-40%. Depression has a significantly negative impact on the QOL in Parkinson's disease patients. It leads to the worsening of tremors and frozen gait without disease progression and decreases the patient's motivation to participate in rehabilitation. The distinguishing feature of depression in patients with Parkinson's disease is that guilt, self-blame and suicidal ideation are rarely seen compared to that observed in patients with major depression. Depression can occur in the pre-motor, diagnostic and advanced stages of Parkinson's disease. In particular, patients with wearing-off symptoms are apt to develop anxiety. As for treatment, it is very important to optimize dopamine replacement therapy. Antiparkinsonian drugs may have beneficial effects not only on the motor symptoms of the disease, but also the patient's mood. Cognitive behavioral therapy (CBT) and peer counseling may also be beneficial. PMID:24622217

  16. Glutathione as a Biomarker in Parkinson's Disease: Associations with Aging and Disease Severity

    PubMed Central

    Mischley, Laurie K.; Standish, Leanna J.; Weiss, Noel S.; Padowski, Jeannie M.; Kavanagh, Terrance J.; White, Collin C.; Rosenfeld, Michael E.

    2016-01-01

    Objectives. Oxidative stress contributes to Parkinson's disease (PD) pathophysiology and progression. The objective was to describe central and peripheral metabolites of redox metabolism and to describe correlations between glutathione (Glu) status, age, and disease severity. Methods. 58 otherwise healthy individuals with PD were examined during a single study visit. Descriptive statistics and scatterplots were used to evaluate normality and distribution of this cross-sectional sample. Blood tests and magnetic resonance spectroscopy (MRS) were used to collect biologic data. Spearman's rank-order correlation coefficients were used to evaluate the strength and direction of the association. The Unified PD Rating Scale (UPDRS) and the Patient-Reported Outcomes in PD (PRO-PD) were used to rate disease severity using regression analysis. Results. Blood measures of Glu decreased with age, although there was no age-related decline in MRS Glu. The lower the blood Glu concentration, the more severe the UPDRS (P = 0.02, 95% CI: −13.96, −1.14) and the PRO-PD (P = 0.01, 95% CI: −0.83, −0.11) scores. Discussion. These data suggest whole blood Glu may have utility as a biomarker in PD. Future studies should evaluate whether it is a modifiable risk factor for PD progression and whether Glu fortification improves PD outcomes.

  17. Early-onset Parkinson's Disease Associated with Chromosome 22q11.2 Deletion Syndrome.

    PubMed

    Oki, Mitsuaki; Hori, Shin-ichiro; Asayama, Shinya; Wate, Reika; Kaneko, Satoshi; Kusaka, Hirofumi

    2016-01-01

    We herein report the case of a 43-year-old man with a 4-year history of resting tremor and akinesia. His resting tremor and rigidity were more prominent on the left side. He also presented retropulsion. His symptoms responded to the administration of levodopa. The patient also had a cleft lip and palate, cavum vergae, and hypoparathyroidism. A chromosome analysis disclosed a hemizygous deletion in 22q11.2, and he was diagnosed with early-onset Parkinson's disease associated with 22q11.2 deletion syndrome. However, the patient lacked autonomic nerve dysfunction, and his cardiac uptake of (123)I-metaiodobenzylguanidine was normal, indicating an underlying pathological mechanism that differed to that of sporadic Parkinson's disease. PMID:26831029

  18. FMR1 Gray Zone Alleles: Association with Parkinson Disease in Women?

    PubMed Central

    Hall, Deborah A; Berry-Kravis, Elizabeth; Zhang, Wenting; Tassone, Flora; Spector, Elaine; Zerbe, Gary; Hagerman, Paul J; Ouyang, Bichun; Leehey, Maureen A

    2014-01-01

    Purpose Carriers of fragile X mental retardation 1 (FMR1) repeat expansions in the premutation range (55–200 CGG repeats), especially males, often develop tremor, ataxia, and parkinsonism.1–2 These neurological signs are believed to be due to elevated levels of expanded CGG repeat FMR1 mRNA. The purpose of this study was to determine the prevalence of FMR1 repeat expansions in a movement disorder population, comprised of all types of tremor, ataxia or parkinsonism subjects. Methods We screened 335 consecutive movement disorders patients with tremor, ataxia, or parkinsonism and 273 controls confirmed to have no movement disorders. Results There was no difference in FMR1 premutation size expansions in the cases compared to controls. Eleven percent of the women with Parkinson disease (PD) had FMR1 gray zone expansions compared to 4.4% of female controls, odds ratio of 3.2 (95% CI 1.2–8.7). Gray zone expansions in patients with other phenotypes were not overrepresented in comparison with controls. Conclusions FMR1 premutation range expansions are not more common in a mixed movement disorder population compared to controls. Our results, however, suggest that FMR1 gray zone alleles may be associated with PD in women. PMID:21567456

  19. Distinct effects of dopamine vs STN stimulation therapies in associative learning and retention in Parkinson disease.

    PubMed

    Ventre-Dominey, Jocelyne; Mollion, Hélène; Thobois, Stephane; Broussolle, Emmanuel

    2016-04-01

    Evidence has been provided in Parkinson's disease patients of cognitive impairments including visual memory and learning which can be partially compensated by dopamine medication or subthalamic nucleus stimulation. The effects of these two therapies can differ according to the learning processes involving the dorsal vs ventral part of the striatum. Here we aimed to investigate and compare the outcomes of dopamine vs stimulation treatment in Parkinson patient's ability to acquire and maintain over successive days their performance in visual working memory. Parkinson patients performed conditional associative learning embedded in visual (spatial and non spatial) working memory tasks over two consecutive days either ON or OFF dopaminergic drugs or STN stimulation depending on the group of patients studied. While Parkinson patients were more accurate and faster in memory tasks ON vs OFF stimulation independent of the day of testing, performance in medicated patients differed depending on the medication status during the initial task acquisition. Patients who learnt the task ON medication the first day were able to maintain or even improve their memory performance both OFF and ON medication on the second day after consolidation. These effects were observed only in patients with dopamine replacement with or without motor fluctuations. This enhancement in memory performance after having learnt under dopamine medication and not under STN stimulation was mostly significant in visuo-spatial working memory tasks suggesting that dopamine replacement in the depleted dorsal striatum is essential for retention and consolidation of learnt skill. PMID:26778783

  20. Parkinson's Disease Foundation Newsletter

    MedlinePlus

    ... Newsletters These include monthly e-newsletters and quarterly science-specific e-newsletters. Read the latest issue below or browse the archives. National Parkinson Foundation and the Parkinson’s Disease Foundation Complete Merger to ...

  1. Identification of four novel potentially Parkinson's disease associated LRRK2 variations among Iranian patients.

    PubMed

    Shojaee, Seyedmehdi; Fazlali, Zeinab; Ghazavi, Farzaneh; Banihosseini, Setareh Sadat; Kazemi, Mohammad Hossein; Parsa, Khosro; Sadeghi, Homa; Sina, Farzad; Shahidi, Gholam-Ali; Ronaghi, Mostafa; Elahi, Elahe

    2009-12-25

    The results of mutation screening of 24 exons of LRRK2 in 60 Iranian Parkinson's Disease patients are presented. The Iranian cohort represents a novel population and was notably young (average age at onset of disease: 36.0 years). Fifty sequence variations were found, seventeen of which are novel. Variations considered possibly associated with disease were screened in available family members, 145 additional patients and 220 control individuals. It was surmised that four novel sequence variations (IVS49+178A>G, p.R1725Q, p.Q1823K, and p.D2175H) may be associated with PD status, albeit they may be very rare non-disease associated variations. The four variations were all observed in the heterozygous state in early onset cases. If one or more of the variations do indeed contribute to disease status, their penetrance is expected to be low. PMID:19800393

  2. Dopamine gene therapy for Parkinson's disease in a nonhuman primate without associated dyskinesia.

    PubMed

    Jarraya, Béchir; Boulet, Sabrina; Ralph, G Scott; Jan, Caroline; Bonvento, Gilles; Azzouz, Mimoun; Miskin, James E; Shin, Masahiro; Delzescaux, Thierry; Drouot, Xavier; Hérard, Anne-Sophie; Day, Denise M; Brouillet, Emmanuel; Kingsman, Susan M; Hantraye, Philippe; Mitrophanous, Kyriacos A; Mazarakis, Nicholas D; Palfi, Stéphane

    2009-10-14

    In Parkinson's disease, degeneration of specific neurons in the midbrain can cause severe motor deficits, including tremors and the inability to initiate movement. The standard treatment is administration of pharmacological agents that transiently increase concentrations of brain dopamine and thereby discontinuously modulate neuronal activity in the striatum, the primary target of dopaminergic neurons. The resulting intermittent dopamine alleviates parkinsonian symptoms but is also thought to cause abnormal involuntary movements, called dyskinesias. To investigate gene therapy for Parkinson's disease, we simulated the disease in macaque monkeys by treating them with the complex I mitochondrial inhibitor 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, which induces selective degeneration of dopamine-producing neurons. In this model, we demonstrated that injection of a tricistronic lentiviral vector encoding the critical genes for dopamine synthesis (tyrosine hydroxylase, aromatic L-amino acid decarboxylase, and guanosine 5'-triphosphate cyclohydrolase 1) into the striatum safely restored extracellular concentrations of dopamine and corrected the motor deficits for 12 months without associated dyskinesias. Gene therapy-mediated dopamine replacement may be able to correct Parkinsonism in patients without the complications of dyskinesias. PMID:20368163

  3. [Parkinson's disease associated with a mutation in the PARK2 gene].

    PubMed

    Kaasinen, Valtteri; Hietala, Marja; Kuoppamäki, Mikko

    2015-01-01

    The most common cause of monogenic hereditary Parkinson's disease is a mutation in the PARK2 gene. Early onset, slow progression, dystonia, and good response to levodopa are typical of the disease phenotype. Finnish PARK2 patients have not been described previously. We describe two patients, in whom pathogenic mutations in the PARK2 gene were the cause of parkinsonism. PMID:26245049

  4. Parkinson's disease and insomnia.

    PubMed

    Ylikoski, Ari; Martikainen, Kirsti; Sieminski, Mariusz; Partinen, Markku

    2015-11-01

    There is a broad spectrum of sleep disturbances observed in Parkinson's disease (PD). The prevalence of symptoms of insomnia and chronic inability to sleep and their association with other sleep disorders were studied. Altogether 1447 randomly selected Parkinson patients, aged 43-89 years, participated in a questionnaire study. A structured questionnaire with 207 items was based on the Basic Nordic Sleep questionnaire. Questions on demographics, PD, REM Sleep Behavior Disorder, and other issues were included. The response rate was 59 % (N = 854), and of these 81 % returned fully answered questionnaire (N = 689). Prevalence of chronic inability to sleep was 36.9 % (95 % CI 33.3-40.5). Difficulty of initiating sleep was 18.0 % (95 % CI 15.1-20.9), disrupted sleep 81.54 % (78.5-84.4), awakenings during night 31.3 % (27.8-34.8), early morning awakenings 40.4 % (36.8-44.1) and non-restorative sleep 38.5 % (34.8-42.1). In the logistic regression models, poor quality of life and restless legs syndrome correlated significantly with chronic insomnia disorder. Disrupted sleep and early morning awakenings were the most common insomnia symptoms. PD patients do not seem to have difficulties in sleep initiation. Insomnia symptoms including disruptive sleep and non-restorative sleep are common in patients with Parkinson's disease. Inability to sleep is more common as comorbidity than a single sleep problem. PMID:26099862

  5. Prolidase-Associated Trace Elements (Mn, Zn, Co, and Ni) in the Patients with Parkinson's Disease.

    PubMed

    Verma, Akhilesh Kumar; Keshari, Anand Kumar; Raj, Janak; Kumari, Renu; Kumar, Tarun; Sharma, Vivek; Singh, Tej Bali; Srivastava, Shalabh; Srivastava, Ragini

    2016-05-01

    Micronutrients and trace elements have been identified to play an important role in the development of Parkinson's disease (PD). In our previous study, we observed that prolidase activity is associated with oxidative stress and progression of PD. In present study, we aimed to study the association of prolidase-associated trace elements, such as Co, Mn, Ni, and Zn in the plasma of patients with PD by inductively coupled plasma spectrometry. Plasma levels of Co, Mn, and Ni were significantly increased, whereas plasma levels of Zn was significantly decreased (all P < 0.05) in the patients with PD than healthy controls. Plasma prolidase activity was not correlated to its associated trace elements in PD. A positive, linear, and significant correlation was observed between age and Co, and Mn, and Ni while negative and non-significant between age and status of Zn in the patients. Co, Mn, and Ni were continually elevated with increase in age as well as duration of disease in the patients with PD, whereas status of Zn was continually decreased. Thus, the study concluded that trace elements Co, Ni, and Mn status were increased and Zn status was decreased in the plasma of patients with PD. It is also concluded that elevated Co, Mn, and Ni has been associated with progression of Parkinson's disease. PMID:26364956

  6. [Parkinson's disease and psychoses].

    PubMed

    Bizzarri, Jacopo Vittoriano; Giupponi, Giancarlo; Maniscalco, Ignazio; Schroffenegger, Patrizia; Conca, Andreas; Kapfhammer, Hans Peter

    2015-01-01

    Psychotic symptoms are common in Parkinson's disease (PD) and are associated with increased disability, worsened quality of life, and poor long-term prognosis. In this article, clinical features, hypotheses on pathogenesis, and current treatment strategies for Parkinson's disease psychosis (PDP) are reviewed. According to epidemiological studies, the prevalence of PDP is between 20 to 40 %. Complex visual hallucinations are the most common psychotic symptoms and are present in 17-72 % of the patients. Other sensory disturbances encompass tactile hallucinations and minor hallucinatory phenomena, such as sense of presence and visual illusions. Hallucinations are often accompanied by delusions, whose most frequent themes are persecution and jealousy. The pathophysiology of PDP remains unclear. Different factors have been implicated, including Levo-dopa and dopaminergic medications, neurotransmitter imbalances, neuroanatomic alterations, abnormal visuospatial processes, and genetic predisposition. The first-line strategy in the treatment of persistent and problematic PDP is represented by reduction in anti-PD medications. Second-generation antipsychotics are the treatment of choice, with clozapine being demonstrated as the most effective and tolerable drug for PD patients. PMID:25586068

  7. Association of depressive symptoms with circadian blood pressure alterations in Parkinson's disease.

    PubMed

    Vetrano, Davide L; Pisciotta, Maria S; Lo Monaco, Maria R; Onder, Graziano; Laudisio, Alice; Brandi, Vincenzo; La Carpia, Domenico; Guglielmo, Mauro; Nacchia, Antonio; Fusco, Domenico; Ricciardi, Diego; Bentivoglio, Anna R; Bernabei, Roberto; Zuccalà, Giuseppe

    2015-11-01

    To assess whether among patients with Parkinson's disease (PD) depression, a common non-motor symptom associated with reduced survival, is associated with cardiovascular dysautonomia. We enrolled 125 subjects with PD consecutively admitted to a geriatric day hospital. All participants underwent comprehensive evaluation, fasting blood sampling, and 24-h ambulatory blood pressure monitoring. The percent reduction in nocturnal blood pressure (dipping) was calculated. Depressive symptoms were assessed through the 15-item Geriatric Depression Scale (GDS); a score ≥5 identified moderate to severe symptoms. Among participants (mean age 72.7 ± 7.8 years, 32 % women) 61 subjects (49 %) presented with a GDS score ≥ 5. When compared with other participants, subjects with a GDS score ≥ 5 had reduced adjusted levels of percent systolic (-2.6 ± 2.7 vs. 4.7 ± 2.5; p = 0.003), diastolic (0.6 ± 2.8 vs. 7.4 ± 2.6; p = 0.007), and mean blood pressure dipping (-0.7 ± 2.6 vs. 6.8 ± 2.5; p = 0.002). In separate logistic regression models, depressive symptoms were associated with reduced systolic (OR 0.94; 95 % CI 0.89; 0.98), diastolic (OR 0.94; 95 % CI 0.90; 0.99), and mean blood pressure dipping (OR 0.93; 95 % CI 0.89; 0.98), after adjusting for potential confounders. Depressive symptoms are prevalent, and independently associated with cardiovascular dysautonomia among patients with Parkinson's disease. This might explain the remarkable incidence of sudden death, as well as the association of depressive symptoms with reduced survival reported in these patients. The finding of depressive symptoms in subjects with Parkinson's disease should therefore prompt assessment of cardiovascular autonomic function. PMID:26338815

  8. Hereditary Parkinson s Disease Natural History Protocol

    ClinicalTrials.gov

    2016-08-31

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

  9. Medical management of levodopa-associated motor complications in patients with Parkinson's disease.

    PubMed

    Jankovic, Joseph; Stacy, Mark

    2007-01-01

    Parkinson's disease is a neurodegenerative disorder that affects approximately 1% of people over the age of 60 years. Levodopa is standard, and often initial, therapy for patients with this condition; however, with continued treatment and as the disease progresses, up to 80% of patients experience 'wearing-off' symptoms, dyskinesias and other motor complications. These levodopa-associated problems may become disabling and profoundly affect quality of life. Medications commonly used to manage these symptoms include monoamine oxidase type B (MAO-B) inhibitors, catechol-O-methyltransferase (COMT) inhibitors, the NMDA receptor antagonist amantadine and dopamine receptor agonists. Agents that block MAO-B, such as rasagiline and selegiline, are used as both initial and adjunctive therapy in patients with Parkinson's disease. These medications increase concentrations of dopamine in the brain by blocking its reuptake from the synaptic cleft, a mechanism that can slow motor decline, increase 'on' time and improve symptoms of Parkinson's disease. Adverse events with these agents can include confusion, hallucination and orthostatic hypotension. MAO-B inhibition may elicit drug-drug interactions if administered with TCAs, SSRIs or SNRIs. Conventional oral selegiline is associated with potentially harmful plasma concentrations of three major amphetamine metabolites, although metabolite concentrations are significantly lower with a new orally disintegrating tablet (ODT) selegiline formulation. Selegiline ODT is also absorbed more efficiently and shows less pharmacokinetic variability than conventional oral selegiline.COMT mediates peripheral catabolism of levodopa. Therefore, agents that block COMT, such as tolcapone and entacapone, increase the elimination half-life of levodopa. Given adjunctively with levodopa, COMT inhibitors can decrease 'off' time and increase 'on' time, as well as lower the daily levodopa dose. Although more potent than entacapone, tolcapone requires

  10. Deletions at 22q11.2 in idiopathic Parkinson's disease: a combined analysis of genome-wide association data

    PubMed Central

    Mok, Kin Y; Sheerin, Una; Simón-Sánchez, Javier; Salaka, Afnan; Chester, Lucy; Escott-Price, Valentina; Mantripragada, Kiran; Doherty, Karen M; Noyce, Alastair J; Mencacci, Niccolo E; Lubbe, Steven J; Williams-Gray, Caroline H; Barker, Roger A; van Dijk, Karin D; Berendse, Henk W; Heutink, Peter; Corvol, Jean-Christophe; Cormier, Florence; Lesage, Suzanne; Brice, Alexis; Brockmann, Kathrin; Schulte, Claudia; Gasser, Thomas; Foltynie, Thomas; Limousin, Patricia; Morrison, Karen E; Clarke, Carl E; Sawcer, Stephen; Warner, Tom T; Lees, Andrew J; Morris, Huw R; Nalls, Mike A; Singleton, Andrew B; Hardy, John; Abramov, Andrey Y; Plagnol, Vincent; Williams, Nigel M; Wood, Nicholas W

    2016-01-01

    Summary Background Parkinson's disease has been reported in a small number of patients with chromosome 22q11.2 deletion syndrome. In this study, we screened a series of large, independent Parkinson's disease case-control studies for deletions at 22q11.2. Methods We used data on deletions spanning the 22q11.2 locus from four independent case-control Parkinson's disease studies (UK Wellcome Trust Case Control Consortium 2, Dutch Parkinson's Disease Genetics Consortium, US National Institute on Aging, and International Parkinson's Disease Genomics Consortium studies), which were independent of the original reports of chromosome 22q11.2 deletion syndrome. We did case-control association analysis to compare the proportion of 22q11.2 deletions found, using the Fisher's exact test for the independent case-control studies and the Mantel-Haenszel test for the meta-analyses. We retrieved clinical details of patients with Parkinson's disease who had 22q11.2 deletions from the medical records of these patients. Findings We included array-based copy number variation data from 9387 patients with Parkinson's disease and 13 863 controls. Eight patients with Parkinson's disease and none of the controls had 22q11.2 deletions (p=0·00082). In the 8451 patients for whom age at onset data were available, deletions at 22q11.2 were associated with Parkinson's disease age at onset (Mann-Whitney U test p=0·001). Age at onset of Parkinson's disease was lower in patients carrying a 22q11.2 deletion (median 37 years, 95% CI 32·0–55·5; mean 42·1 years [SD 11·9]) than in those who did not carry a deletion (median 61 years, 95% CI 60·5–61·0; mean 60·3 years [SD 12·8]). A 22q11.2 deletion was present in more patients with early-onset (p<0·0001) and late-onset Parkinson's disease (p=0·016) than in controls, and in more patients with early-onset than late-onset Parkinson's disease (p=0·005). Interpretation Clinicians should be alert to the possibility of 22q11.2 deletions in

  11. Protagonists with Parkinson's disease.

    PubMed

    Haan, Joost

    2013-01-01

    Parkinson's disease is a complex disorder with many fascinating features. Its onset is creeping, the progression is slow but inevitable. There are motor symptoms, such as a tremor, rigidity, bradykinesia, mask-like facial expression, and postural abnormalities, but also hallucinations, cognitive deterioration, and depression. In many novels, fictive patients with Parkinson's disease play a role. It seems that authors have used many aspects of the disease to emphasize their messages. Their narratives include themes such as rigidity, petrifaction, confusion, dementia, and hallucinations. In this chapter, as examples, several protagonists with Parkinson's disease will be described from works of John Updike, Jonathan Franzen, Sue Miller, J.M. Coetzee, and John Harding, among others. PMID:23485900

  12. BDNF genetic variants are associated with onset age of familial Parkinson disease: GenePD Study.

    PubMed

    Karamohamed, S; Latourelle, J C; Racette, B A; Perlmutter, J S; Wooten, G F; Lew, M; Klein, C; Shill, H; Golbe, L I; Mark, M H; Guttman, M; Nicholson, G; Wilk, J B; Saint-Hilaire, M; DeStefano, A L; Prakash, R; Tobin, S; Williamson, J; Suchowersky, O; Labell, N; Growdon, B N J; Singer, C; Watts, R; Goldwurm, S; Pezzoli, G; Baker, K B; Giroux, M L; Pramstaller, P P; Burn, D J; Chinnery, P; Sherman, S; Vieregge, P; Litvan, I; Gusella, J F; Myers, R H; Parsian, A

    2005-12-13

    Brain-derived neurotrophic factor (BDNF) stimulates neuronal growth and protects nigral dopamine neurons in animal models of Parkinson disease (PD). Therefore, BDNF is a candidate gene for PD. The authors investigated five single-nucleotide polymorphisms in 597 cases of familial PD. Homozygosity for the rare allele of the functional BDNF G196A (Val66Met) variant was associated with a 5.3-year older onset age (p = 0.0001). These findings suggest that BDNF may influence PD onset age. PMID:16344533

  13. Reevaluation of Phosphorylation Sites in the Parkinson Disease-associated Leucine-rich Repeat Kinase 2*

    PubMed Central

    Li, Xiaojie; Moore, Darren J.; Xiong, Yulan; Dawson, Ted M.; Dawson, Valina L.

    2010-01-01

    Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene have been identified as an important cause of late-onset, autosomal dominant familial Parkinson disease and contribute to sporadic Parkinson disease. LRRK2 is a large complex protein with multiple functional domains, including a Roc-GTPase, protein kinase, and multiple protein-protein interaction domains. Previous studies have suggested an important role for kinase activity in LRRK2-induced neuronal toxicity and inclusion body formation. Disease-associated mutations in LRRK2 also tend to increase kinase activity. Thus, enhanced kinase activity may therefore underlie LRRK2-linked disease. Similar to the closely related mixed-lineage kinases, LRRK2 can undergo autophosphorylation in vitro. Three putative autophosphorylation sites (Thr-2031, Ser-2032, and Thr-2035) have been identified within the activation segment of the LRRK2 kinase domain based on sequence homology to mixed-lineage kinases. Phosphorylation at one or more of these sites is critical for the kinase activity of LRRK2. Sensitive phopho-specific antibodies to each of these three sites have been developed and validated by ELISA, dot-blot, and Western blot analysis. Using these antibodies, we have found that all three putative sites are phosphorylated in LRRK2, and Ser-2032 and Thr-2035 are the two important sites that regulate LRRK2 kinase activity. PMID:20595391

  14. Parkinson's disease and the skin.

    PubMed

    Gregory, Ralph; Miller, Sarah

    2015-08-01

    The concept that the skin is a mirror of Parkinson's disease dates to the start of the last century. Despite dermatological disorders being recognised as a common non-motor symptom of Parkinson's disease, they are often overlooked. This article reviews the various skin disorders seen in Parkinson's disease and addresses the other dermatological questions that are frequently raised by those attending Parkinson's disease clinics. PMID:25862733

  15. Parkinson Disease and Dementia.

    PubMed

    Garcia-Ptacek, Sara; Kramberger, Milica G

    2016-09-01

    Dementia is a frequent complication of Parkinson disease (PD) with a yearly incidence of around 10% of patients with PD. Lewy body pathology is the most important factor in the development of Parkinson disease dementia (PDD) and there is evidence for a synergistic effect with β-amyloid. The clinical phenotype in PDD extends beyond the dysexecutive syndrome that is often present in early PD and encompasses deficits in recognition memory, attention, and visual perception. Sleep disturbances, hallucinations, neuroleptic sensitivity, and fluctuations are often present. This review provides an update on current knowledge of PDD including aspects of epidemiology, pathology, clinical presentation, management, and prognosis. PMID:27502301

  16. HLA-DRA is associated with Parkinson's disease in Iranian population.

    PubMed

    Jamshidi, J; Movafagh, A; Emamalizadeh, B; Zare Bidoki, A; Manafi, A; Ghasemi Firouzabadi, S; Shahidi, G-A; Kazeminasab, S; Petramfar, P; Fazeli, A; Motallebi, M; Mortazavi-Tabatabaei, S A; Kowsari, A; Jafarian, Z; Darvish, H

    2014-12-01

    The rs3129882, a noncoding variant in HLA-DR, was found to be associated with Parkinson's disease (PD) using several genome-wide association studies. The aim of this replication study was to explore the relationship between this variant and PD in Iranian population. Genomic DNA was extracted from peripheral blood samples, and the rs3129882 SNP was genotyped using a PCR-RFLP method in 520 PD patients and 520 healthy Iranian controls. Significant differences were found in allele frequencies between patients and controls (χ(2) = 4.64, P = 0.031). Under additive and dominant models, the association of the SNP with PD risk is significant, where the A allele was observed to be protective. The results suggest that rs3129882 polymorphism may be a risk factor for PD in Iranian. This is the first study reporting such an association in this population. More replication studies are needed to confirm this data. PMID:25319953

  17. Aldehyde dehydrogenase variation enhances effect of pesticides associated with Parkinson disease

    PubMed Central

    Fitzmaurice, Arthur G.; Rhodes, Shannon L.; Cockburn, Myles; Ritz, Beate

    2014-01-01

    Objective: The objective of this study was to determine whether environmental and genetic alterations of neuronal aldehyde dehydrogenase (ALDH) enzymes were associated with increased Parkinson disease (PD) risk in an epidemiologic study. Methods: A novel ex vivo assay was developed to identify pesticides that can inhibit neuronal ALDH activity. These were investigated for PD associations in a population-based case-control study, the Parkinson's Environment & Genes (PEG) Study. Common variants in the mitochondrial ALDH2 gene were genotyped to assess effect measure modification (statistical interaction) of the pesticide effects by genetic variation. Results: All of the metal-coordinating dithiocarbamates tested (e.g., maneb, ziram), 2 imidazoles (benomyl, triflumizole), 2 dicarboxymides (captan, folpet), and 1 organochlorine (dieldrin) inhibited ALDH activity, potentially via metabolic byproducts (e.g., carbon disulfide, thiophosgene). Fifteen screened pesticides did not inhibit ALDH. Exposures to ALDH-inhibiting pesticides were associated with 2- to 6-fold increases in PD risk; genetic variation in ALDH2 exacerbated PD risk in subjects exposed to ALDH-inhibiting pesticides. Conclusion: ALDH inhibition appears to be an important mechanism through which environmental toxicants contribute to PD pathogenesis, especially in genetically vulnerable individuals, suggesting several potential interventions to reduce PD occurrence or slow or reverse its progression. PMID:24491970

  18. Structural Brain Alterations Associated with Rapid Eye Movement Sleep Behavior Disorder in Parkinson's Disease.

    PubMed

    Boucetta, Soufiane; Salimi, Ali; Dadar, Mahsa; Jones, Barbara E; Collins, D Louis; Dang-Vu, Thien Thanh

    2016-01-01

    Characterized by dream-enactment motor manifestations arising from rapid eye movement (REM) sleep, REM sleep behavior disorder (RBD) is frequently encountered in Parkinson's disease (PD). Yet the specific neurostructural changes associated with RBD in PD patients remain to be revealed by neuroimaging. Here we identified such neurostructural alterations by comparing large samples of magnetic resonance imaging (MRI) scans in 69 PD patients with probable RBD, 240 patients without RBD and 138 healthy controls, using deformation-based morphometry (p < 0.05 corrected for multiple comparisons). All data were extracted from the Parkinson's Progression Markers Initiative. PD patients with probable RBD showed smaller volumes than patients without RBD and than healthy controls in the pontomesencephalic tegmentum, medullary reticular formation, hypothalamus, thalamus, putamen, amygdala and anterior cingulate cortex. These results demonstrate that RBD is associated with a prominent loss of volume in the pontomesencephalic tegmentum, where cholinergic, GABAergic and glutamatergic neurons are located and implicated in the promotion of REM sleep and muscle atonia. It is additionally associated with more widespread atrophy in other subcortical and cortical regions whose loss also likely contributes to the altered regulation of sleep-wake states and motor activity underlying RBD in PD patients. PMID:27245317

  19. Advanced Parkinson's disease effect on goal-directed and habitual processes involved in visuomotor associative learning

    PubMed Central

    Hadj-Bouziane, Fadila; Benatru, Isabelle; Brovelli, Andrea; Klinger, Hélène; Thobois, Stéphane; Broussolle, Emmanuel; Boussaoud, Driss; Meunier, Martine

    2013-01-01

    The present behavioral study re-addresses the question of habit learning in Parkinson's disease (PD). Patients were early onset, non-demented, dopa-responsive, candidates for surgical treatment, similar to those we found earlier as suffering greater dopamine depletion in the putamen than in the caudate nucleus. The task was the same conditional associative learning task as that used previously in monkeys and healthy humans to unveil the striatum involvement in habit learning. Sixteen patients and 20 age- and education-matched healthy control subjects learned sets of 3 visuo-motor associations between complex patterns and joystick displacements during two testing sessions separated by a few hours. We distinguished errors preceding vs. following the first correct response to compare patients' performance during the earliest phase of learning dominated by goal-directed actions with that observed later on, when responses start to become habitual. The disease significantly retarded both learning phases, especially in patients under 60 years of age. However, only the late phase deficit was disease severity-dependent and persisted on the second testing session. These findings provide the first corroboration in Parkinson patients of two ideas well-established in the animal literature. The first is the idea that associating visual stimuli to motor acts is a form of habit learning that engages the striatum. It is confirmed here by the global impairment in visuo-motor learning induced by PD. The second idea is that goal-directed behaviors are predominantly caudate-dependent whereas habitual responses are primarily putamen-dependent. At the advanced PD stages tested here, dopamine depletion is greater in the putamen than in the caudate nucleus. Accordingly, the late phase of learning corresponding to the emergence of habitual responses was more vulnerable to the disease than the early phase dominated by goal-directed actions. PMID:23386815

  20. Microstructural changes in white matter associated with freezing of gait in Parkinson's disease.

    PubMed

    Vercruysse, Sarah; Leunissen, Inge; Vervoort, Griet; Vandenberghe, Wim; Swinnen, Stephan; Nieuwboer, Alice

    2015-04-01

    In Parkinson's disease (PD), freezing of gait (FOG) is associated with widespread functional and structural gray matter changes throughout the brain. Previous study of freezing-related white matter changes was restricted to brainstem and cerebellar locomotor tracts. This study was undertaken to determine the spatial distribution of white matter damage associated with FOG by combining whole brain and striatofrontal seed-based diffusion tensor imaging. Diffusion-weighted images were collected in 26 PD patients and 16 age-matched controls. Parkinson's disease groups with (n = 11) and without freezing of gait (n = 15) were matched for age and disease severity. We applied tract-based spatial statistics to compare fractional anisotropy and mean diffusivity of white matter structure across the whole brain between groups. Probabilistic tractography was used to evaluate fractional anisotropy and mean diffusivity of key subcortico-cortical tracts. Tract-based spatial statistics revealed decreased fractional anisotropy in PD with FOG in bilateral cerebellar and superior longitudinal fascicle clusters. Increased mean diffusivity values were apparent in the right internal capsule, superior frontal cortex, anterior corona radiata, the left anterior thalamic radiation, and cerebellum. Tractography showed consistent white matter alterations in striatofrontal tracts through the putamen, caudate, pallidum, subthalamic nucleus, and in connections of the cerebellar peduncle with subthalamic nucleus and pedunculopontine nucleus bilaterally. We conclude that FOG is associated with diffuse white matter damage involving major cortico-cortical, corticofugal motor, and several striatofrontal tracts in addition to previously described cerebello-pontine connectivity changes. These distributed white matter abnormalities may contribute to the motor and non-motor correlates of FOG. PMID:25640958

  1. [Parkinson disease and communication].

    PubMed

    Barat, M; Daverat, P; Mazaux, J M

    1992-01-01

    Communication abilities imply multifactorial analysis. These disorders in Parkinson's disease involve speech, graphism, functional and paraverbal gestures. The patient's isolation in a major form of disease is dramatic. Functional study requires an analysis of each factor; progress should be realized for an objective approach. With a therapeutic objective in view, the most impaired features, and the patients real situation and way of life must be evaluated. Some training measures are useful especially for social adjustment and motivational reinforcement. PMID:1344546

  2. History of falls in Parkinson disease is associated with reduced cholinergic activity

    PubMed Central

    Bohnen, N I.; Müller, M L.T.M.; Koeppe, R A.; Studenski, S A.; Kilbourn, M A.; Frey, K A.; Albin, R L.

    2009-01-01

    Objective: To investigate the relationships between history of falls and cholinergic vs dopaminergic denervation in patients with Parkinson disease (PD). Background: There is a need to explore nondopaminergic mechanisms of gait control as the majority of motor impairments associated with falls in PD are resistant to dopaminergic treatment. Alterations in cholinergic neurotransmission in PD may be implicated because of evidence that gait control depends on cholinergic system–mediated higher-level cortical and subcortical processing, including pedunculopontine nucleus (PPN) function. Methods: In this cross-sectional study, 44 patients with PD (Hoehn & Yahr stages I–III) without dementia and 15 control subjects underwent a clinical assessment and [11C]methyl-4-piperidinyl propionate (PMP) acetylcholinesterase (AChE) and [11C]dihydrotetrabenazine (DTBZ) vesicular monoamine transporter type 2 (VMAT2) brain PET imaging. Results: Seventeen patients (38.6%) reported a history of falls and 27 patients had no falls. Analysis of covariance of the cortical AChE hydrolysis rates demonstrated reduced cortical AChE in the PD fallers group (−12.3%) followed by the PD nonfallers (−6.6%) compared to control subjects (F = 7.22, p = 0.0004). Thalamic AChE activity was lower only in the PD fallers group (−11.8%; F = 4.36, p = 0.008). There was no significant difference in nigrostriatal dopaminergic activity between PD fallers and nonfallers. Conclusions: Unlike nigrostriatal dopaminergic denervation, cholinergic hypofunction is associated with fall status in Parkinson disease (PD). Thalamic AChE activity in part represents cholinergic output of the pedunculopontine nucleus (PPN), a key node for gait control. Our results are consistent with other data indicating that PPN degeneration is a major factor leading to impaired postural control and gait dysfunction in PD. GLOSSARY AChE = acetylcholinesterase; ANCOVA = analysis of covariance; MMSE = Mini-Mental State Examination; PD

  3. Drivers with Parkinson's disease: are the symptoms of PD associated with restricted driving practices?

    PubMed

    Crizzle, Alexander M; Myers, Anita M; Roy, Eric A; Almeida, Quincy J

    2013-10-01

    This study examined whether symptoms (motor, cognitive, vision, sleepiness, depression) of Parkinson's disease (PD) were associated with restricted driving practices. To quantify driving practices, electronic devices were installed in the vehicles of 27 drivers with PD (78 % men; M = 71.6, SD = 6.6; Unified Parkinson's Disease Rating Scale (UPDRS) motor score M = 30.1, SD = 8.6; disease duration M = 3.9, SD = 2.8 years) and 20 controls (80 % men; M = 70.6, SD = 7.9) for 2 weeks. Participants completed measures of sleepiness, depression, quality of life, and assessments of motor, cognitive and visual functions. The PD group had significantly slower brake response times (p < 0.05), poorer cognitive and quality of life scores (p < 0.01) and greater depression (p < 0.05) compared to controls. Slower reaction time was significantly related to reduced driving; specifically, fewer trips (r = -0.46; p < 0.05), distance (r = -0.54, p < 0.01) and duration at night (r = -0.58, p < 0.01). Better cognitive scores were associated with driving less often in difficult situations such as bad weather and rush hour (p < 0.05), as well as reduced speed on city streets, but only for the control group. While most drivers with PD rated their overall health as good or excellent, the five PD drivers who rated their health more poorly had significantly worse clinical symptoms (UPDRS motor scores, contrast sensitivity, depression, brake response time) and more restricted driving patterns. These findings show that drivers with PD who perceive their health poorly have greater symptomatology and were more likely to restrict their driving, possibly due to noticeable declines in multiple driving-related abilities. PMID:23821027

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

    PubMed

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

    2013-01-01

    The role of inflammation in Parkinson's Disease (PD) is well appreciated, but its underlying mechanisms are still unclear. Our objective was to determine whether dendritic cells (DC), a unique type of migratory immune cells that regulate immunological response and inflammation have an impact on PD. In a case-control study including 80 PD patients and 80 age- and gender-matched healthy control subjects, the two main blood subsets of plasmacytoid and myeloid DC were defined by flow cytometry analysis. Clinical evaluation of subjects consisting of cognition and depression assessment was performed using the Mini Mental State Examination and the Beck Depression Inventory. The severity of motor symptoms was measured using the Unified Parkinson's Disease Rating Scale-Part III. Comparison between patient and control DC measures and their relationships with clinical assessments were evaluated.The following main results were obtained: 1) the level of circulating DC (mainly the myeloid subset) was significantly reduced in PD patients in comparison with healthy controls; 2) after controlling for depressive and cognitive characteristics, the frequency of myeloid DC was confirmed as one of the independent determinants of PD; 3) the number of both myeloid and plasmacytoid DC was negatively associated with motor symptom severity. Overall, the decline of blood DC, perhaps due to the recruitment of immune cells to the site of disease-specific lesions, can be considered a clue of the immune alteration that characterizes PD, suggesting innovative exploitations of DC monitoring as a clinically significant tool for PD treatment. Indeed, this study suggests that reduced peripheral blood DC are a pathologically-relevant factor of PD and also displays the urgency to better understand DC role in PD for unraveling the immune system contribution to disease progression and thus favoring the development of innovative therapies ideally based on immunomodulation. PMID:23776473

  5. Orthostatic hypotension and cognitive impairment in Parkinson's disease: Causation or association?

    PubMed

    McDonald, Claire; Newton, Julia L; Burn, David J

    2016-07-01

    Orthostatic hypotension and cognitive impairment are common in Parkinson's disease (PD) and significantly impair quality of life. Orthostatic hypotension and cognitive impairment appear to be interrelated. Whether the relationship is causative or associative remains unclear. The vascular hypothesis proposes that recurrent episodic hypotension results in cerebral hypoperfusion, in turn causing anoxic damage to vulnerable areas of the brain and impaired cognitive function. Support for this hypothesis has come from brain MRI studies showing an association between white matter hyperintensities and a postural drop in blood pressure among PD patients. Alternatively, the association between orthostatic hypotension and cognitive decline in PD may reflect shared underlying synuclein-related pathology affecting common neuroanatomical and neurochemical substrates. Cardiac imaging studies demonstrate noradrenergic denervation early in PD, and cardiac denervation has been associated with poorer cognition. Neurogenic orthostatic hypotension occurs as a result of defective norepinephrine release from sympathetic terminals upon standing. Neuropathological studies have also demonstrated Lewy body pathology in the locus coeruleus; the main source of noradrenaline in the brain. Locus coeruleus norepinephrine levels are reduced in PD patients with dementia when compared with PD patients without. In this review, we examine the evidence for an association between orthostatic hypotension and cognitive impairment in PD. We evaluate the literature supporting the hypothesis that progressive noradrenergic denervation underlies both orthostatic hypotension and cognitive impairment, and we examine studies suggesting that recurrent cerebral hypoperfusion results in cognitive decline in PD. Finally, we explore how modulation of blood pressure and the noradrenergic nervous system may improve cognition in PD. © 2016 International Parkinson and Movement Disorder Society. PMID:27091624

  6. Speech and Pause Characteristics Associated with Voluntary Rate Reduction in Parkinson's Disease and Multiple Sclerosis

    ERIC Educational Resources Information Center

    Tjaden, Kris; Wilding, Greg

    2011-01-01

    The primary purpose of this study was to investigate how speakers with Parkinson's disease (PD) and Multiple Sclerosis (MS) accomplish voluntary reductions in speech rate. A group of talkers with no history of neurological disease was included for comparison. This study was motivated by the idea that knowledge of how speakers with dysarthria…

  7. Imaging in Parkinson's disease.

    PubMed

    Pagano, Gennaro; Niccolini, Flavia; Politis, Marios

    2016-08-01

    The clinical presentation of Parkinson's disease (PD) is heterogeneous and overlaps with other conditions, including the parkinsonian variant of multiple system atrophy (MSA-P), progressive supranuclear palsy (PSP) and essential tremor. Imaging of the brain in patients with parkinsonism has the ability to increase the accuracy of differential diagnosis. Magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT) and positron emission tomography (PET) allow brain imaging of structural, functional and molecular changes in vivo in patients with PD. Structural MRI is useful to differentiate PD from secondary and atypical forms of parkinsonism. 123I-ioflupane (DaTSCAN(TM)) SPECT is a valid tool in the differential diagnosis between PD and non-degenerative tremors, while cardiac 123I-metaiodobenzylguanidine SPECT and 18F-fluorodeoxyglucose PET are valid in the differential diagnosis between PD and atypical parkinsonism (MSA-P, PSP). However, despite significant evidence for the utility of neuroimaging in assessing parkinsonian patients, none of the neuroimaging techniques are specifically recommended for routine use in clinical practice. Hopefully, future larger trials will help to demonstrate additional evidence for the clinical utility of neuroimaging and will include an analysis of the financial benefits for the NHS in the longer term management of the patients. PMID:27481384

  8. [Genetics and present therapy options in Parkinson's disease: a review].

    PubMed

    Bereznai, Benjamin; Molnar, Mária Judit

    2009-05-30

    In the past years, six monogenic forms of Parkinson disease have clearly been associated with this movement disorder. The most frequent forms are LRRK2- and Parkin-associated Parkinson disease. Currently, a genetic diagnosis does not change the therapy, the genes involved in genetic Parkinson disease help to understand the underlying pathophysiologic mechanisms of Parkinson disease. Beside the overview of the molecular-genetic basis, we give a review about genetic testing, pharmacological and other multidisciplinary treatment options. PMID:19579663

  9. Micrographia in Parkinson's disease.

    PubMed

    Contreras-Vidal, J L; Teulings, H L; Stelmach, G E

    1995-10-23

    A computational neural model of movement production in normal and Parkinson's disease (PD) is used to provide a neural account for the source of micrographia in PD handwriting. It is hypothesized that smaller than normal pallido-thalamic signals, due to dopamine depletion, are responsible for the observed overall smallness, slowness and variability in PD handwriting. Experimental data from PD patients that show micrographia support this hypothesis and imply the functional segregation of basal ganglia neural populations. PMID:8580447

  10. Hallucinations in Parkinson disease.

    PubMed

    Diederich, Nico J; Fénelon, Gilles; Stebbins, Glenn; Goetz, Christopher G

    2009-06-01

    Patients with Parkinson disease (PD) can experience hallucinations (spontaneous aberrant perceptions) and illusions (misinterpretations of real perceptual stimuli). Of such phenomena, visual hallucinations (VHs) and illusions are the most frequently encountered, although auditory, olfactory and tactile hallucinations can also occur. In cross-sectional studies, VHs occur in approximately one-third of patients, but up to three-quarters of patients might develop VHs during a 20-year period. Hallucinations can have substantial psychosocial effects and, historically, were the main reason for placing patients in nursing homes. Concomitant or overlapping mechanisms are probably active during VHs, and these include the following: central dopaminergic overactivity and an imbalance with cholinergic neurotransmission; dysfunction of the visual pathways, including specific PD-associated retinopathy and functional alterations of the extrastriate visual pathways; alterations of brainstem sleep-wake and dream regulation; and impaired attentional focus. Possible treatments include patient-initiated coping strategies, a reduction of antiparkinson medications, atypical neuroleptics and, potentially, cholinesterase inhibitors. Evidence-based studies, however, only support the use of one atypical neuroleptic, clozapine, and only in patients without dementia. Better phenomenological discrimination, combined with neuroimaging tools, should refine therapeutic options and improve prognosis. The aim of this Review is to present epidemiological, phenomenological, pathophysiological and therapeutic aspects of hallucinations in PD. PMID:19498436

  11. Association between MAPT haplotype and memory function in patients with Parkinson's disease and healthy aging individuals

    PubMed Central

    Winder-Rhodes, Sophie E.; Hampshire, Adam; Rowe, James B.; Peelle, Jonathan E.; Robbins, Trevor W.; Owen, Adrian M.; Barker, Roger A.

    2015-01-01

    Genetic variation is associated with differences in the function of the brain as well as its susceptibility to disease. The common H1 haplotypic variant of the microtubule-associated protein tau gene (MAPT) has been related to an increased risk for Parkinson's disease (PD). Furthermore, among PD patients, H1 homozygotes have an accelerated progression to dementia. We investigated the neurocognitive correlates of MAPT haplotypes using functional magnetic resonance imaging. Thirty-seven nondemented patients with PD (19 H1/H1, 18 H2 carriers) and 40 age-matched controls (21 H1/H1, 19 H2 carriers) were scanned during performance of a picture memory encoding task. Behaviorally, H1 homozygosity was associated with impaired picture recognition memory in PD patients and control subjects. These impairments in the H1 homozygotes were accompanied by an altered blood-oxygen level-dependent response in the medial temporal lobe during successful memory encoding. Additional age-related differences in blood-oxygen level-dependent response were observed in the medial temporal lobes of H1 homozygotes with PD. These results suggest that common variation in MAPT is not only associated with the dementia of PD but also differences in the neural circuitry underlying aspects of cognition in normal aging. PMID:25577413

  12. Dysphagia in Parkinson's Disease.

    PubMed

    Suttrup, Inga; Warnecke, Tobias

    2016-02-01

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

  13. Progression of Parkinson's Disease

    MedlinePlus

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

  14. Inverse association between yerba mate consumption and idiopathic Parkinson's disease. A case-control study.

    PubMed

    Gatto, Emilia Mabel; Melcon, Carlos; Parisi, Virginia L; Bartoloni, Leonardo; Gonzalez, Claudio D

    2015-09-15

    Yerba mate tea is a very common beverage in some countries of South America. We conducted a case-control study on an individual basis using hospital records to investigate the association between Parkinson's disease (PD) and yerba mate intake. A case was defined as an age of ≥ 40 years with ≥ 1 year of PD. Each case was individually matched by two controls. Exposure was measured by yerba mate consumption, coffee, tea, and alcohol intake and smoking status. The sample consisted of 223 PD patients (mean age 68 years and mean disease duration 7.3 years) and 406 controls. There was an inverse association between yerba mate "bombilla" consumption and PD (OR 0.64, 95% CI: 0.54-0.76, p=0.00001). A multivariate analysis with a logistic regression adjusted by sex, alcohol intake and smoking provided the following results: yerba mate (OR 0.63, 95% CI: 0.53-0.76), tea (OR 0.60, 95% CI: 0.42-0.86), coffee (OR 0.51, 95% CI: 0.35-0.73). We found an inverse association between yerba mate consumption and PD. These results led us to hypothesize that yerba mate may have a potential protective role in the development of PD. PMID:26148934

  15. [Effect of high dose pergolide mesilate on restless legs syndrome associated with Parkinson disease].

    PubMed

    Imamura, Akiko; Tsuboi, Yoshio; Tanaka, Miki; Obata, Toyoshi; Yamada, Tatsuo

    2007-04-01

    Restless legs syndrome (RLS) is one of the common nocturnal disturbance seen in Parkinson's disease (PD) patients. The prevalence of RLS with PD is greater than that of general populations; however, etiology of RLS in patients with PD is still controversial. We report a 63-year-old man with PD, who was admitted to our hospital with uncontrollable unpleasant feeling in both legs leading to sleep disturbance. At age 59, he experienced numbness and nocturnal myoclonus in his right foot. One year later, he developed resting tremor and bradykinesia in his right hand, and was diagnosed as PD. Levodopa was initiated with favorable response for his resting tremor and bradykinesia, however, his dysesthesia of the legs spread to both side and associated with an urge to move which occurs at rest and was ameliorated by walking. On admission, his parkinsonism was well controlled by 400 mg/ day of levodopa/benserazide. Polysomnography (PSG) revealed periodic limb movements in sleep (PLMS). Secondary RLS such as drug-induced, iron deficiency and uraemia, was excluded in this patient. Because levodopa did not improve his RLS, additional symptomatic RLS treatment was initiated. Oral dosage with 150 microg pergolide did not have any effect on his RLS symptoms. An increase up to 750 microg pergolide led to a marked reduction of symptoms. Repeated PSG showed significant reduction of PLMS and improved sleep efficacy. Usually, low dose of dopamine agonist is enough to treat RLS occurred in general populations. However, moderate to high dose of dopamine agonists were needed for our patient with RLS, indicating that pharmacological responses might be different between RLS in general and that associated with PD. It is important to consider that PD-related RLS can be treated with high dose dopamine agonist to obtain favorable management of nocturnal disturbances. PMID:17511286

  16. Association of Common Variants in the Glucocerebrosidase Gene with High Susceptibility to Parkinson's Disease among Chinese.

    PubMed

    Zhang, Xiong; Bao, Qiong-Qiong; Zhuang, Xiao-Sai; Gan, Shi-Rui; Zhao, Dan; Liu, Yun; Hu, Qiao; Chen, Ying; Zhu, Feiyan; Wang, Lian; Wang, Ning

    2012-12-31

    The genetic variants in glucocerebrosidase (GBA) gene have been previously examined as potential susceptibility factors for Parkinson's disease (PD). Although of great interest, possible role of GBA gene in PD has not been well investigated in eastern Chinese population. To explore this association, we conducted a genetic screen of three common GBA variants (p.L444P, p.N370S, and p.R120W) in a casecontrol cohort comprised of 638 subjects of Chinese ethnicity. In order to provide a more precise estimate of this association, a meta-analysis was performed. We found that the GBA p.L444P allele was significantly more frequent (P = 0.001) in the PD patients (6/195 = 3.08%) than in the controls (0/443). The p.L444P mutation, but not p.N370S and p.R120W, was found to be associated with PD. Combined analysis including all previously published ancestral Chinese data yielded a highly significant association between the GBA gene and an increased risk for PD (OR = 8.13, 95% CI, 4.43-14.92, P < 0.00001). Our study suggests that the GBA gene may be a susceptibility gene for PD in the Chinese population. Efforts to elucidate in detail this interesting and biologically plausible genetic association are warranted. PMID:23286447

  17. Impaired Finger Dexterity in Parkinson's Disease Is Associated with Praxis Function

    ERIC Educational Resources Information Center

    Vanbellingen, T.; Kersten, B.; Bellion, M.; Temperli, P.; Baronti, F.; Muri, R.; Bohlhalter, S.

    2011-01-01

    A controversial concept suggests that impaired finger dexterity in Parkinson's disease may be related to limb kinetic apraxia that is not explained by elemental motor deficits such as bradykinesia. To explore the nature of dexterous difficulties, the aim of the present study was to assess the relationship of finger dexterity with ideomotor praxis…

  18. Parkinson's Disease Is Associated with Goal Setting Deficits during Task Switching

    ERIC Educational Resources Information Center

    Meiran, Nachshon; Friedman, Gilad; Yehene, Eynat

    2004-01-01

    Ten Parkinson's Disease (PD) patients and 10 control participants were tested using a task-switching paradigm in which there was a random task sequence, and the task was cued in every trial. Five PD patients showed a unique error profile. Their performance approximated guessing when accuracy was dependent on correct task identification, and was…

  19. The rs3857059 variant of the SNCA gene is associated with Parkinson's disease in Mexican Mestizos.

    PubMed

    García, S; Chavira-Hernández, G; Gallegos-Arreola, M P; Dávila-Maldonado, L; García Martínez, F; Montes Almanza, L A; Palma-Flores, C; Mondragón-Terán, P; Alcaraz Estrada, S L; López-Hernández, L B

    2016-06-01

    Among the candidate genes for Parkinson's disease (PD), SNCA has replicated association in different populations. Besides other known mutations in the SNCA gene, the rs3857059 variant has also been linked to various neurodegenerative disorders. Therefore, the aim of the present study was to search for association of this variant and sporadic PD in Mexican Mestizo patients. A case-control study was performed including 241 individuals, 106 patients, and 135 healthy controls. Genotyping was performed using real-time PCR. The rs3857059 variant demonstrated an association with PD in Mexican Mestizos (OR = 2.40, CI, 1.1 to 5.1, p = 0.02) under the recessive model. In addition, a gender effect was found for the GG genotype in females (OR = 1.31, CI, 1.01 to 1.7, p = 0.037). This is the first study to confirm an association of the rs3857059 variant with PD and also to show a gender effect. Our data contribute to the elucidation of the link between rs3857059 and susceptibility to PD observed in the Mexican Mestizo population. PMID:27332068

  20. The association between alterations of eye movement control and cerebral intrinsic functional connectivity in Parkinson's disease.

    PubMed

    Gorges, Martin; Müller, Hans-Peter; Lulé, Dorothée; Pinkhardt, Elmar H; Ludolph, Albert C; Kassubek, Jan

    2016-03-01

    Patients with Parkinson's disease (PD) present with eye movement disturbances that accompany the cardinal motor symptoms. Previous studies have consistently found evidence that large-scale functional networks are critically involved in eye movement control. We challenged the hypothesis that altered eye movement control in patients with PD is closely related to alterations of whole-brain functional connectivity in association with the neurodegenerative process. Saccadic and pursuit eye movements by video-oculography and 'resting-state' functional MRI (3 Tesla) were recorded from 53 subjects, i.e. 31 patients with PD and 22 matched healthy controls. Video-oculographically, a broad spectrum of eye movement impairments was demonstrated in PD patients vs. controls, including interrupted smooth pursuit, hypometric saccades, and a high distractibility in anti-saccades. Significant correlations between altered oculomotor parameters and functional connectivity measures were observed, i.e. the worse the oculomotor performance was, the more the regional functional connectivity in cortical, limbic, thalamic, cerebellar, and brainstem areas was decreased. Remarkably, decreased connectivity between major nodes of the default mode network was tightly correlated with the prevalence of saccadic intrusions as a measure for distractability. In conclusion, dysfunctional eye movement control in PD seems to be primarily associated with (cortical) executive deficits, rather than being related to the ponto-cerebellar circuits or the oculomotor brainstem nuclei. Worsened eye movement performance together with the potential pathophysiological substrate of decreased intrinsic functional connectivity in predominantly oculomotor-associated cerebral functional networks may constitute a behavioral marker in PD. PMID:25749936

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

    MedlinePlus

    ... Find People About NINDS Parkinson's Disease Research Web - Information for Patients & Caregivers Parkinson's Disease Highlights for Patients & ... and progression biomarkers for PD. NINDS Parkinson's Disease Information Parkinson's Disease Information Page Parkinson's Disease: Hope Through ...

  2. An association study between Heme oxygenase-1 genetic variants and Parkinson's disease.

    PubMed

    Ayuso, Pedro; Martínez, Carmen; Pastor, Pau; Lorenzo-Betancor, Oswaldo; Luengo, Antonio; Jiménez-Jiménez, Félix J; Alonso-Navarro, Hortensia; Agúndez, José A G; García-Martín, Elena

    2014-01-01

    The blood-brain barrier (BBB) supplies brain tissues with nutrients, filters harmful compounds from the brain back to the bloodstream, and plays a key role in iron homeostasis in the human brain. Disruptions of the BBB are associated with several neurodegenerative conditions including Parkinson's disease (PD). Oxidative stress, iron deposition and mitochondrial impaired function are considered as risk factors for degeneration of the central nervous system. Heme oxygenase (HMOX) degrades heme ring to biliverdin, free ferrous iron and carbon monoxide being the rate-limiting activity in heme catabolism. The isoform HMOX1 is highly inducible in response to reactive oxygen species, which induce an increase in BBB permeability and impair its pathophysiology. Consequently, an over- expression of this enzyme may contribute to the marked iron deposition found in PD. We analyzed the HMOX1 SNPs rs2071746, rs2071747, and rs9282702, a microsatellite (GT) n polymorphism and copy number variations in 691 patients suffering from PD and 766 healthy control individuals. Copy number variations in the HMOX1 gene exist, but these do not seem to be associated with PD risk. In contrast two polymorphisms that modify the transcriptional activity of the gene, namely a VNTR (GT) n and the SNP rs2071746, are strongly associated with PD risk, particularly with the classic PD phenotype and with early onset of the disease. This study indicates that HMOX1 gene variants are associated to the risk of developing some forms of PD, thus adding new information that supports association of HMOX gene variations with PD risk. PMID:25309329

  3. An association study between Heme oxygenase-1 genetic variants and Parkinson's disease

    PubMed Central

    Ayuso, Pedro; Martínez, Carmen; Pastor, Pau; Lorenzo-Betancor, Oswaldo; Luengo, Antonio; Jiménez-Jiménez, Félix J.; Alonso-Navarro, Hortensia; Agúndez, José A. G.; García-Martín, Elena

    2014-01-01

    The blood-brain barrier (BBB) supplies brain tissues with nutrients, filters harmful compounds from the brain back to the bloodstream, and plays a key role in iron homeostasis in the human brain. Disruptions of the BBB are associated with several neurodegenerative conditions including Parkinson's disease (PD). Oxidative stress, iron deposition and mitochondrial impaired function are considered as risk factors for degeneration of the central nervous system. Heme oxygenase (HMOX) degrades heme ring to biliverdin, free ferrous iron and carbon monoxide being the rate-limiting activity in heme catabolism. The isoform HMOX1 is highly inducible in response to reactive oxygen species, which induce an increase in BBB permeability and impair its pathophysiology. Consequently, an over- expression of this enzyme may contribute to the marked iron deposition found in PD. We analyzed the HMOX1 SNPs rs2071746, rs2071747, and rs9282702, a microsatellite (GT)n polymorphism and copy number variations in 691 patients suffering from PD and 766 healthy control individuals. Copy number variations in the HMOX1 gene exist, but these do not seem to be associated with PD risk. In contrast two polymorphisms that modify the transcriptional activity of the gene, namely a VNTR (GT)n and the SNP rs2071746, are strongly associated with PD risk, particularly with the classic PD phenotype and with early onset of the disease. This study indicates that HMOX1 gene variants are associated to the risk of developing some forms of PD, thus adding new information that supports association of HMOX gene variations with PD risk. PMID:25309329

  4. Neuropsychological Characteristics and Their Association with Higher-Level Functional Capacity in Parkinson's Disease

    PubMed Central

    Miura, Kayoko; Matsui, Mie; Takashima, Shutaro; Tanaka, Kortaro

    2015-01-01

    Background/Aims Little is known about the relationship between cognitive functions and higher-level functional capacity (e.g. intellectual activity, social role, and social participation) in Parkinson's disease (PD). The purpose of this study was to clarify neuropsychological characteristics and their association with higher-level functional capacity in PD patients. Methods Participants were 31 PD patients and 23 demographically matched healthy controls. Neuropsychological tests were conducted. One year later, a questionnaire survey evaluated higher-level functional capacity in daily living. Results The PD group scored significantly lower than the control group in all cognitive domains, particularly executive function and processing. Executive function, processing speed, language, and memory were significantly correlated with higher-level functional capacity in PD patients. Stepwise regression showed that only executive function (Trail Making Test-B), together with disease severity (HY stage), predicted the higher-level functional capacity. Conclusion Our findings provide evidence of a relationship between executive function and higher-level functional capacity in patients with PD. PMID:26273243

  5. Association Between Early-Onset Parkinson Disease and 22q11.2 Deletion Syndrome

    PubMed Central

    Butcher, Nancy J.; Kiehl, Tim-Rasmus; Hazrati, Lili-Naz; Chow, Eva W. C.; Rogaeva, Ekaterina; Lang, Anthony E.; Bassett, Anne S.

    2015-01-01

    IMPORTANCE Clinical case reports of parkinsonism co-occurring with hemizygous 22q11.2 deletions and the associated multisystem syndrome, 22q11.2 deletion syndrome (22q11.2DS), suggest that 22q11.2 deletions may lead to increased risk of early-onset Parkinson disease (PD). The frequency of PD and its neuropathological presentation remain unknown in this common genetic condition. OBJECTIVE To evaluate a possible association between 22q11.2 deletions and PD. DESIGN, SETTING, AND PARTICIPANTS An observational study of the occurrence of PD in the world’s largest cohort of well-characterized adults with a molecularly confirmed diagnosis of 22q11.2DS (n = 159 [6 with postmortem tissue]; age range, 18.1–68.6 years) was conducted in Toronto, Ontario, Canada. Rare postmortem brain tissue from individuals with 22q11.2DS and a clinical history of PD was investigated for neurodegenerative changes and compared with that from individuals with no history of a movement disorder. MAIN OUTCOMES AND MEASURES A clinical diagnosis of PD made by a neurologist and neuropathological features of PD. RESULTS Adults with 22q11.2DS had a significantly elevated occurrence of PD compared with standard population estimates (standardized morbidity ratio = 69.7; 95% CI, 19.0–178.5). All cases showed early onset and typical PD symptom pattern, treatment response, and course. All were negative for family history of PD and known pathogenic PD-related mutations. The common use of antipsychotics in patients with 22q11.2DS to manage associated psychiatric symptoms delayed diagnosis of PD by up to 10 years. Postmortem brain tissue revealed classic loss of midbrain dopaminergic neurons in all 3 postmortem 22q11.2DS-PD cases. Typical α-synuclein–positive Lewy bodies were present in the expected distribution in 2 cases but absent in another. CONCLUSIONS AND RELEVANCE These findings suggest that 22q11.2 deletions represent a novel genetic risk factor for early-onset PD with variable neuropathological

  6. Patterns of cortical thickness associated with impulse control disorders in Parkinson's disease.

    PubMed

    Biundo, Roberta; Weis, Luca; Facchini, Silvia; Formento-Dojot, Patrizia; Vallelunga, Annamaria; Pilleri, Manuela; Weintraub, Daniel; Antonini, Angelo

    2015-04-15

    Previous functional neuroimaging studies in Parkinson's disease (PD) patients with impulse control disorders (ICDs) demonstrated dysfunction of the reward network, although the extent of anatomical changes is unclear. The aim of this study was to measure brain cortical thickness and subcortical volumes, and to assess their relationship with presence and severity of symptoms, in PD patients with and without ICDs. We studied 110 PD patients (N=58 with ICDs) and 33 healthy controls (all negative for ICDs) who underwent an extensive neurological, neuropsychological, and behavioral assessment as well as structural 1.5 Tesla magnetic resonance imaging (MRI). Between-group differences in brain cortical thickness and subcortical volumes, assessed with the FreeSurfer 5.1 tool, were analyzed. In patients with ICDs, we found significant cortical thinning in fronto-striatal circuitry, specifically in the right superior orbitofrontal, left rostral middle frontal, bilateral caudal middle frontal region, and corpus callosum, as well as volume reduction in the right accumbens and increase in the left amygdala. Finally, we observed a positive association relationship between severity of impulsive symptoms and left rostral middle frontal, inferior parietal, and supramarginal areas. These results support the involvement of both reward and response inhibition networks in PD patients with ICDs. Moreover, their severity is associated with alterations in brain regions linked with reward and top-down control networks. Increased understanding of the mechanisms underlying impulsive and compulsive behaviors might help improve therapeutic strategies for these important disorders. PMID:25649923

  7. Clinical and imaging findings in Parkinson disease associated with the A53E SNCA mutation

    PubMed Central

    Päivärinta, Markku; Hietala, Marja; Kaasinen, Valtteri

    2015-01-01

    Objective: To describe the clinical features and brain imaging findings of autosomal dominant Parkinson disease (PD) associated with a recently reported mutation in SNCA. Methods: A Finnish family with PD in 3 successive generations, in accordance with an autosomal dominant inheritance pattern, was identified. We examined 2 available members of the family, the female proband and her daughter (both with early-onset PD), clinically and using dopamine transporter imaging ([123I]FP-CIT SPECT). A possible causative genetic defect was investigated by molecular genetic analyses. Results: A heterozygous c.158C>A (p.A53E) point mutation in SNCA was revealed in both patients. The patients presented with PD clinically characterized by severe bradykinesia but with very little tremor and early onset of levodopa-induced dyskinesia. No cognitive decline or dysautonomic features have emerged during more than 5 years of follow-up. Both patients presented with a severe striatal binding defect in dopamine transporter SPECT imaging. Conclusions: The results of this observational study add evidence to the suggestion that the p.A53E mutation in SNCA is indeed pathogenic and results in autosomal dominant PD. Bradykinesia and early onset of levodopa-induced dyskinesia are the characteristic clinical features associated with the A53E mutation, but the patients did not exhibit dementia or dysautonomia. The [123I]FP-CIT SPECT findings indicated a profound, symmetric dopaminergic defect, in contrast to those observed in patients with idiopathic PD. PMID:27066564

  8. Parkinson disease-associated mutant VPS35 causes mitochondrial dysfunction by recycling DLP1 complexes

    PubMed Central

    Fujioka, Hisashi; Hoppel, Charles; Whone, Alan L.; Caldwell, Maeve A.; Cullen, Peter J.; Liu, Jun; Zhu, Xiongwei

    2015-01-01

    Mitochondrial dysfunction represents a critical step during the pathogenesis of Parkinson disease (PD) and increasing evidence suggests abnormal mitochondrial dynamics and quality control as important underlying mechanisms. The VPS35 gene, encoding a key component of the retromer complex, is the third autosomal-dominant gene associated with PD. However, how VPS35 mutations may lead to neurodegeneration remains unclear. Here we demonstrate that PD-associated VPS35 mutations caused mitochondrial fragmentation and cell death in cultured neurons in vitro, in mouse substantia nigra neurons in vivo, and in human fibroblasts from PD patient bearing the D620N mutation. VPS35-induced mitochondrial deficits and neuronal dysfunction could be prevented by inhibition of mitochondrial fission. VPS35 mutation caused increased interactions with DLP1 which enhanced mitochondrial DLP1 complex turnover via mitochondria-derived vesicles-dependent trafficking to lysosomes for degradation. Importantly, oxidative stress increased the VPS35–DLP1 interaction which was also increased in the brains of sporadic PD cases. These results revealed a novel cellular mechanism for the involvement of VPS35 in mitochondrial fission, dysregulation of which is likely involved in the pathogenesis of familial, and possibly sporadic, PD. PMID:26618722

  9. Association of TLR9 polymorphisms with sporadic Parkinson's disease in Chinese Han population.

    PubMed

    Zhu, Konghua; Teng, Jijun; Zhao, Jing; Liu, Hongxin; Xie, Anmu

    2016-07-01

    Previous studies have acknowledged that inflammatory reaction has implicated in Parkinson's disease (PD) pathogenesis nowadays. Toll-like receptors (TLRs), as key players in the inflammatory reaction, play a pivotal role in the PD pathogenesis and accumulating evidences have shown that TLRs are increased in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of PD. Therefore, the present study aimed to identify the role of the polymorphisms of rs187084 and rs352140 in TLR9 gene with PD. The genotypes were detected by polymerase chain reaction and restriction fragment length polymorphism analysis in 380 PD patients and 380 healthy matched individuals in Chinese Han population. For rs352140, our data revealed a significant difference in allele distribution in female PD group and its healthy matched control (P = 0.040). Moreover, rs352140 T allele carriers of female group were associated with a reduced risk of PD (TT + TC vs. CC, P = 0.018). However, no significant differences in genotype and allele distribution were found between the age and gender subgroups for rs187084. Therefore, our studies indicate that the rs352140 gene polymorphism may be associated with the susceptibility of female PD in Chinese Han population. PMID:26000920

  10. BDNF polymorphism associates with decline in set shifting in Parkinson's disease.

    PubMed

    van der Kolk, Nicolien M; Speelman, Arlene D; van Nimwegen, Marlies; Kessels, Roy P C; IntHout, Joanna; Hakobjan, Marina; Munneke, Marten; Bloem, Bastiaan R; van de Warrenburg, Bart P

    2015-03-01

    Parkinson's disease (PD) is a neurodegenerative disorder caused by nigrostriatal dopaminergic degeneration. Brain-derived neurotrophic factor (BDNF) is a key protein in brain plasticity and is particularly important for survival of dopaminergic neurons. The Val66Met polymorphism of BDNF (rs6265) has been associated with functional differences (mainly cognitive) between healthy adults and also with differences in the clinical expression of several other neuropsychiatric illnesses including PD. However, these studies used different outcome measures, have not been replicated, and were cross sectional, making it difficult to establish the role of BDNF in the clinical variability of PD. Here, a large cohort of 384 PD patients were followed up for 2 years, and associations between BDNF genotype and various clinical characteristics were examined. The BDNF Met-allele carriers showed a significantly smaller decline in set shifting during follow-up compared with the homozygous BDNF Val-allele carriers. Contrary to previous assumptions, these results indicate that mental flexibility is one of the cognitive processes that may benefit from the BDNF Met allele in PD patients. PMID:25444596

  11. Mild cognitive impairment in patients with Parkinson's disease is associated with increased cortical degeneration.

    PubMed

    Hanganu, Alexandru; Bedetti, Christophe; Jubault, Thomas; Gagnon, Jean-Francois; Mejia-Constain, Béatriz; Degroot, Clotilde; Lafontaine, Anne-Louise; Chouinard, Sylvain; Monchi, Oury

    2013-09-01

    Mild cognitive impairment (MCI) can occur early in the course of Parkinson's disease (PD), and its presence increases the risk of developing dementia. Determining the cortical changes associated with MCI in PD, thus, may be useful in predicting the future development of dementia. To address this objective, 37 patients with PD, divided into 2 groups according to the presence or absence MCI (18 with and 19 without) and 16 matched controls, underwent anatomic magnetic resonance imaging. Corticometry analyses were performed to measure the changes in cortical thickness and surface area as well as their correlation with disease duration. Compared with healthy controls, the PD-MCI group exhibited increased atrophy and changes of local surface area in the bilateral occipital, left temporal, and frontal cortices; whereas the PD non-MCI group exhibited only unilateral thinning and decreased surface area in the occipital lobe and in the frontal cortex. In addition, a comparison between the PD-MCI and PD non-MCI groups revealed increased local surface area in the occipital lobe, temporal lobe, and postcentral gyrus for the cognitively impaired patients. It is noteworthy that, in the PD-MCI group, cortical thickness had a significant negative correlation with disease duration in the precentral, supramarginal, occipital, and superior temporal cortices; whereas, in the PD non-MCI group, such a correlation was absent. The findings from this study reveal that, at the same stage of PD evolution, the presence of MCI is associated with a higher level of cortical changes, suggesting that cortical degeneration is increased in patients with PD because of the presence of MCI. PMID:23801590

  12. Parkinson's disease tremor: pathophysiology.

    PubMed

    Hallett, Mark

    2012-01-01

    There are a number of tremors that may affect patients with Parkinson's disease, but the classic is tremor-at-rest. The tremor is also seen during postural action after a short pause, and is often called re-emergent tremor although it appears that the physiology is the same. As a manifestation of Parkinson's disease, it is separate from bradykinesia and rigidity as the magnitude of tremor is not related to dopamine deficiency nor does it respond readily to dopamine treatment. Cellular activity in the different basal ganglia nuclei can be coherent with tremor, but cellular activity in the VIM nucleus of the thalamus, a cerebellar relay nucleus, is more coherent than cellular activity in basal ganglia. It is also notable that different body parts may have similar tremor frequencies, but are generally not exactly the same and are not phase locked. This suggests that each body part has a separate tremor generator. The ability to stay separate may be due to the somatotopic segregation of basal ganglia loops. Analysis of cellular behavior in the thalamus shows that the thalamus is not the generator of tremor. New data suggest that the basal ganglia trigger a cerebellar circuit to produce the tremor. PMID:22166464

  13. Nonmotor Features in Parkinson's Disease: What Are the Most Important Associated Factors?

    PubMed Central

    Kadastik-Eerme, Liis; Muldmaa, Mari; Lilles, Stella; Rosenthal, Marika; Taba, Nele; Taba, Pille

    2016-01-01

    Introduction. The purpose of this study was to demonstrate the frequency and severity of nonmotor symptoms and their correlations with a wide range of demographic and clinical factors in a large cohort of patients with Parkinson's disease (PD). Methods. 268 PD patients were assessed using the validated Movement Disorders Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS), the Beck Depression Inventory (BDI), Parkinson's Disease Questionnaire (PDQ-39), the Hoehn and Yahr scale (HY), the Schwab and England Activities of Daily Living (SE-ADL) Scale, and the Minimental State Examination (MMSE). Results. Nonmotor symptoms had a strong positive relationship with depression and lower quality of life. Also, age, duration and severity of PD, cognitive impairment, daily dose, and duration of levodopa treatment correlated with the burden of nonmotor symptoms. Patients with postural instability and gait disorder (PIGD) dominance or with the presence of motor complications had higher MDS-UPDRS Part I scores expressing the load of nonmotor features, compared to participants with other disease subtypes or without motor complications. Conclusions. Though the severity of individual nonmotor symptoms was generally rated by PD patients as “mild” or less, we found a significant cumulative effect of nonmotor symptoms on patients' mood, daily activities, and quality of life. PMID:27195172

  14. Nonmotor Features in Parkinson's Disease: What Are the Most Important Associated Factors?

    PubMed

    Kadastik-Eerme, Liis; Muldmaa, Mari; Lilles, Stella; Rosenthal, Marika; Taba, Nele; Taba, Pille

    2016-01-01

    Introduction. The purpose of this study was to demonstrate the frequency and severity of nonmotor symptoms and their correlations with a wide range of demographic and clinical factors in a large cohort of patients with Parkinson's disease (PD). Methods. 268 PD patients were assessed using the validated Movement Disorders Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS), the Beck Depression Inventory (BDI), Parkinson's Disease Questionnaire (PDQ-39), the Hoehn and Yahr scale (HY), the Schwab and England Activities of Daily Living (SE-ADL) Scale, and the Minimental State Examination (MMSE). Results. Nonmotor symptoms had a strong positive relationship with depression and lower quality of life. Also, age, duration and severity of PD, cognitive impairment, daily dose, and duration of levodopa treatment correlated with the burden of nonmotor symptoms. Patients with postural instability and gait disorder (PIGD) dominance or with the presence of motor complications had higher MDS-UPDRS Part I scores expressing the load of nonmotor features, compared to participants with other disease subtypes or without motor complications. Conclusions. Though the severity of individual nonmotor symptoms was generally rated by PD patients as "mild" or less, we found a significant cumulative effect of nonmotor symptoms on patients' mood, daily activities, and quality of life. PMID:27195172

  15. Thyroid hormone level is associated with motor symptoms in de novo Parkinson's disease.

    PubMed

    Umehara, Tadashi; Matsuno, Hiromasa; Toyoda, Chizuko; Oka, Hisayoshi

    2015-07-01

    Sympathetic denervation has been observed not only in the myocardium but also in the thyroid of patients with Parkinson's disease (PD). We investigated whether sympathetic denervation as indicated by decreased cardiac (123)I-meta-iodobenzylguanidine uptake is associated with the levels of thyroid hormones and whether the levels of thyroid hormones affect clinical manifestations in patients with PD. The subjects were 75 patients with de novo PD and 20 age-matched healthy controls. We examined the levels of thyroid-stimulating hormone, free triiodothyronine, and free thyroxine, and evaluated the associations of these levels with cardiac (123)I-meta-iodobenzylguanidine uptake and motor symptoms. The results showed that the free triiodothyronine level was below the normal range in 29 patients (approximately 40 %) and was significantly lower in the patients with PD than in the controls. The decreased free triiodothyronine level was associated with akinetic-rigid motor subtype and washout ratio of cardiac (123)I-meta-iodobenzylguanidine scintigraphy. The free triiodothyronine level negatively correlated with disease severity. Thyroid-stimulating hormone level was within normal range. However, its level was lower in patients with tremor-dominant type or mixed type than in those with akinetic-rigid type. All correlations of these variables with the levels of thyroid hormones remained statistically significant on multiple regression analysis. Our results suggest that the thyroid hormone level, especially the free triiodothyronine level, is closely related to motor symptoms in patients with de novo PD. Further studies are needed to clarify whether the decreased hormone levels have functional roles in motor and non-motor symptoms. PMID:25987207

  16. Managing Your Parkinson's Disease

    MedlinePlus

    ... Team Finding Resources Parkinson's HelpLine Learn More Educational Materials Do you want to know more about Parkinson's? PDF's materials provide information about symptoms, medications, resources & more. Order ...

  17. Associations between Anticholinergic Burden and Adverse Health Outcomes in Parkinson Disease

    PubMed Central

    Crispo, James A. G.; Willis, Allison W.; Thibault, Dylan P.; Fortin, Yannick; Hays, Harlen D.; McNair, Douglas S.; Bjerre, Lise M.; Kohen, Dafna E.; Perez-Lloret, Santiago; Mattison, Donald R.; Krewski, Daniel

    2016-01-01

    Background Elderly adults should avoid medications with anticholinergic effects since they may increase the risk of adverse events, including falls, delirium, and cognitive impairment. However, data on anticholinergic burden are limited in subpopulations, such as individuals with Parkinson disease (PD). The objective of this study was to determine whether anticholinergic burden was associated with adverse outcomes in a PD inpatient population. Methods Using the Cerner Health Facts® database, we retrospectively examined anticholinergic medication use, diagnoses, and hospital revisits within a cohort of 16,302 PD inpatients admitted to a Cerner hospital between 2000 and 2011. Anticholinergic burden was computed using the Anticholinergic Risk Scale (ARS). Primary outcomes were associations between ARS score and diagnosis of fracture and delirium. Secondary outcomes included associations between ARS score and 30-day hospital revisits. Results Many individuals (57.8%) were prescribed non-PD medications with moderate to very strong anticholinergic potential. Individuals with the greatest ARS score (≥4) were more likely to be diagnosed with fractures (adjusted odds ratio (AOR): 1.56, 95% CI: 1.29–1.88) and delirium (AOR: 1.61, 95% CI: 1.08–2.40) relative to those with no anticholinergic burden. Similarly, inpatients with the greatest ARS score were more likely to visit the emergency department (adjusted hazard ratio (AHR): 1.32, 95% CI: 1.10–1.58) and be readmitted (AHR: 1.16, 95% CI: 1.01–1.33) within 30-days of discharge. Conclusions We found a positive association between increased anticholinergic burden and adverse outcomes among individuals with PD. Additional pharmacovigilance studies are needed to better understand risks associated with anticholinergic medication use in PD. PMID:26939130

  18. Risk and protective haplotypes of the alpha-synuclein gene associated with Parkinson's disease differentially affect cognitive sequence learning.

    PubMed

    Kéri, S; Nagy, H; Myers, C E; Benedek, G; Shohamy, D; Gluck, M A

    2008-02-01

    Alpha-synuclein (SNCA) is a key factor in the regulation of dopaminergic transmission and is related to Parkinson's disease. In this study, we investigated the effects of risk and protective SNCA haplotypes associated with Parkinson's disease on cognitive sequence learning in 204 healthy volunteers. We found that the 3'-block risk SNCA haplotypes are associated with less effective stimulus-reward learning of sequences and with superior context representation of sequences. In contrast, participants with protective haplotypes exhibit better stimulus-reward learning and worse context representation, which suggest that these functions are inversely affected by risk and protective haplotypes. The Rep1 promoter polymorphism does not influence cognitive sequence learning. Because stimulus-reward learning may be mediated by the basal ganglia and context learning may be related to the medial temporal lobe, our data raise the possibility that dopaminergic signals regulated by SNCA inversely affect these memory systems. PMID:17451452

  19. Association of the MTHFR rs1801131 and rs1801133 variants in sporadic Parkinson's disease patients.

    PubMed

    Yuan, Lamei; Song, Zhi; Deng, Xiong; Xiong, Wei; Yang, Zhijian; Deng, Hao

    2016-03-11

    Parkinson's disease (PD) is a common age-dependent neurodegenerative movement disorder related to multiple factors, and genetic factors play an important role in the pathogenesis of PD. Variants in the methylenetetrahydrofolate reductase gene (MTHFR), a gene encoding a folate-dependent enzyme that is involved in homocysteine metabolism, have been reported to be associated with PD. To explore the role of the MTHFR gene in the development of PD in Chinese Han population, we analyzed two MTHFR variants (rs1801131 and rs1801133) in a patient cohort consisting of 512 patients with PD from mainland China and a control cohort consisting of 512 age, gender and ethnicity matched normal subjects. Statistically significant differences in genotypic and allelic frequencies were detected in the MTHFR variant rs1801133 (P=0.022 and 0.007, respectively; odds ratio=0.780, 95% confidence interval=0.651-0.934). In addition, the A-T haplotype of rs1801131-rs1801133 showed a protective role against PD development (P=0.007, odds ratio=0.779, 95% confidence interval=0.650-0.933). Our results suggested that the T allele of rs1801133 variant and A-T haplotype of rs1801131-rs1801133 in the MTHFR gene may decrease the risk of developing PD in Chinese Han population from mainland China. PMID:26806866

  20. Caspase-1 causes truncation and aggregation of the Parkinson's disease-associated protein α-synuclein.

    PubMed

    Wang, Wei; Nguyen, Linh T T; Burlak, Christopher; Chegini, Fariba; Guo, Feng; Chataway, Tim; Ju, Shulin; Fisher, Oriana S; Miller, David W; Datta, Debajyoti; Wu, Fang; Wu, Chun-Xiang; Landeru, Anuradha; Wells, James A; Cookson, Mark R; Boxer, Matthew B; Thomas, Craig J; Gai, Wei Ping; Ringe, Dagmar; Petsko, Gregory A; Hoang, Quyen Q

    2016-08-23

    The aggregation of α-synuclein (aSyn) leading to the formation of Lewy bodies is the defining pathological hallmark of Parkinson's disease (PD). Rare familial PD-associated mutations in aSyn render it aggregation-prone; however, PD patients carrying wild type (WT) aSyn also have aggregated aSyn in Lewy bodies. The mechanisms by which WT aSyn aggregates are unclear. Here, we report that inflammation can play a role in causing the aggregation of WT aSyn. We show that activation of the inflammasome with known stimuli results in the aggregation of aSyn in a neuronal cell model of PD. The insoluble aggregates are enriched with truncated aSyn as found in Lewy bodies of the PD brain. Inhibition of the inflammasome enzyme caspase-1 by chemical inhibition or genetic knockdown with shRNA abated aSyn truncation. In vitro characterization confirmed that caspase-1 directly cleaves aSyn, generating a highly aggregation-prone species. The truncation-induced aggregation of aSyn is toxic to neuronal culture, and inhibition of caspase-1 by shRNA or a specific chemical inhibitor improved the survival of a neuronal PD cell model. This study provides a molecular link for the role of inflammation in aSyn aggregation, and perhaps in the pathogenesis of sporadic PD as well. PMID:27482083

  1. The Parkinson's Disease-Associated Protein Kinase LRRK2 Modulates Notch Signaling through the Endosomal Pathway.

    PubMed

    Imai, Yuzuru; Kobayashi, Yoshito; Inoshita, Tsuyoshi; Meng, Hongrui; Arano, Taku; Uemura, Kengo; Asano, Takeshi; Yoshimi, Kenji; Zhang, Chang-Liang; Matsumoto, Gen; Ohtsuka, Toshiyuki; Kageyama, Ryoichiro; Kiyonari, Hiroshi; Shioi, Go; Nukina, Nobuyuki; Hattori, Nobutaka; Takahashi, Ryosuke

    2015-09-01

    Leucine-rich repeat kinase 2 (LRRK2) is a key molecule in the pathogenesis of familial and idiopathic Parkinson's disease (PD). We have identified two novel LRRK2-associated proteins, a HECT-type ubiquitin ligase, HERC2, and an adaptor-like protein with six repeated Neuralized domains, NEURL4. LRRK2 binds to NEURL4 and HERC2 via the LRRK2 Ras of complex proteins (ROC) domain and NEURL4, respectively. HERC2 and NEURL4 link LRRK2 to the cellular vesicle transport pathway and Notch signaling, through which the LRRK2 complex promotes the recycling of the Notch ligand Delta-like 1 (Dll1)/Delta (Dl) through the modulation of endosomal trafficking. This process negatively regulates Notch signaling through cis-inhibition by stabilizing Dll1/Dl, which accelerates neural stem cell differentiation and modulates the function and survival of differentiated dopaminergic neurons. These effects are strengthened by the R1441G ROC domain-mutant of LRRK2. These findings suggest that the alteration of Notch signaling in mature neurons is a component of PD etiology linked to LRRK2. PMID:26355680

  2. Orthostatic hypotension is associated with decreased cerebrospinal fluid levels of chromogranin A in early stage of Parkinson disease.

    PubMed

    Kaiserova, Michaela; Prikrylova Vranova, Hana; Galuszka, Jan; Stejskal, David; Mensikova, Katerina; Zapletalova, Jana; Mares, Jan; Kanovsky, Petr

    2015-10-01

    An association between the CSF chromogranin A (CgA) and orthostatic blood pressure changes was investigated in 20 patients in the early stage of Parkinson disease (PD). There was a positive correlation between the CSF CgA and diastolic blood pressure change, when CSF CgA levels were lower in patients with orthostatic hypotension (OH). Decreased CSF CgA may be useful in predicting OH in the early stage of PD. PMID:26359267

  3. Associations between neuropsychiatric symptoms and cognition in Chinese idiopathic Parkinson's disease patients.

    PubMed

    Guo, Xiaoyan; Song, Wei; Chen, Ke; Chen, XuePing; Zheng, Zhenzhen; Cao, Bei; Huang, Rui; Zhao, Bi; Wu, Ying; Shang, Hui-Fang

    2015-03-01

    The associations between neuropsychiatric symptoms and cognition, frontal lobe function and frontal behavioral changes in the Chinese idiopathic Parkinson's disease (PD) population are largely unknown. This study included 348 idiopathic PD patients from southwest China. Neuropsychiatric symptoms were investigated using the Neuropsychiatric Inventory Questionnaire (NPI), and cognition was assessed using Addenbrooke's Cognitive Examination-Revised (ACE-R). The Frontal Assessment Battery (FAB) was used to evaluate frontal function and the Frontal Behavior Inventory (FBI) was used to assess frontal behavioral changes. The mean (± standard deviation) age of the PD patients was 60.24 ± 12.07 years, and the mean disease duration was 3.88 ± 3.34 years. The mean NPI score was 3.49 ± 4.00. The mean score of ACE-R was 76.82 ± 16.73. The mean score of FAB was 15.27 ± 2.90, and the mean score of FBI was 3.18 ± 5.17. Weak negative correlations between the NPI and ACE-R scores as well as FAB score were found in the total sample, the male patient subgroup, the early onset PD subgroup and the late onset PD subgroup. Strong positive correlations were found between the NPI and FBI scores in the total sample (r=0.661, p<0.001), the male patient subgroup (r=0.789, p<0.001) and the late onset PD subgroup (r=0.749, p<0.001). Moderate positive correlations were found between the NPI and FBI scores in the female patient subgroup (r=0.536, p<0.001) and the early onset PD subgroup (r=0.462, p<0.001). Neuropsychiatric symptoms were closely associated with frontal behavioral changes but were not closely related with worse cognition and frontal lobe function in the Chinese idiopathic PD population. PMID:25582976

  4. Genetic comorbidities in Parkinson's disease.

    PubMed

    Nalls, Mike A; Saad, Mohamad; Noyce, Alastair J; Keller, Margaux F; Schrag, Anette; Bestwick, Jonathan P; Traynor, Bryan J; Gibbs, J Raphael; Hernandez, Dena G; Cookson, Mark R; Morris, Huw R; Williams, Nigel; Gasser, Thomas; Heutink, Peter; Wood, Nick; Hardy, John; Martinez, Maria; Singleton, Andrew B

    2014-02-01

    Parkinson's disease (PD) has a number of known genetic risk factors. Clinical and epidemiological studies have suggested the existence of intermediate factors that may be associated with additional risk of PD. We construct genetic risk profiles for additional epidemiological and clinical factors using known genome-wide association studies (GWAS) loci related to these specific phenotypes to estimate genetic comorbidity in a systematic review. We identify genetic risk profiles based on GWAS variants associated with schizophrenia and Crohn's disease as significantly associated with risk of PD. Conditional analyses adjusting for SNPs near loci associated with PD and schizophrenia or PD and Crohn's disease suggest that spatially overlapping loci associated with schizophrenia and PD account for most of the shared comorbidity, while variation outside of known proximal loci shared by PD and Crohn's disease accounts for their shared genetic comorbidity. We examine brain methylation and expression signatures proximal to schizophrenia and Crohn's disease loci to infer functional changes in the brain associated with the variants contributing to genetic comorbidity. We compare our results with a systematic review of epidemiological literature, while the findings are dissimilar to a degree; marginal genetic associations corroborate the directionality of associations across genetic and epidemiological data. We show a strong genetically defined level of comorbidity between PD and Crohn's disease as well as between PD and schizophrenia, with likely functional consequences of associated variants occurring in brain. PMID:24057672

  5. Genetic comorbidities in Parkinson's disease

    PubMed Central

    Nalls, Mike A.; Saad, Mohamad; Noyce, Alastair J.; Keller, Margaux F.; Schrag, Anette; Bestwick, Jonathan P.; Traynor, Bryan J.; Gibbs, J. Raphael; Hernandez, Dena G.; Cookson, Mark R.; Morris, Huw R.; Williams, Nigel; Gasser, Thomas; Heutink, Peter; Wood, Nick; Hardy, John; Martinez, Maria; Singleton, Andrew B.

    2014-01-01

    Parkinson's disease (PD) has a number of known genetic risk factors. Clinical and epidemiological studies have suggested the existence of intermediate factors that may be associated with additional risk of PD. We construct genetic risk profiles for additional epidemiological and clinical factors using known genome-wide association studies (GWAS) loci related to these specific phenotypes to estimate genetic comorbidity in a systematic review. We identify genetic risk profiles based on GWAS variants associated with schizophrenia and Crohn's disease as significantly associated with risk of PD. Conditional analyses adjusting for SNPs near loci associated with PD and schizophrenia or PD and Crohn's disease suggest that spatially overlapping loci associated with schizophrenia and PD account for most of the shared comorbidity, while variation outside of known proximal loci shared by PD and Crohn's disease accounts for their shared genetic comorbidity. We examine brain methylation and expression signatures proximal to schizophrenia and Crohn's disease loci to infer functional changes in the brain associated with the variants contributing to genetic comorbidity. We compare our results with a systematic review of epidemiological literature, while the findings are dissimilar to a degree; marginal genetic associations corroborate the directionality of associations across genetic and epidemiological data. We show a strong genetically defined level of comorbidity between PD and Crohn's disease as well as between PD and schizophrenia, with likely functional consequences of associated variants occurring in brain. PMID:24057672

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

    PubMed

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

    2016-01-01

    General medical problems and complications have a major impact on the quality of life in all stages of Parkinson's disease. To introduce an effective treatment, a comprehensive analysis of the various clinical symptoms must be undertaken. One must distinguish between (1) diseases which arise independently of Parkinson's disease, and (2) diseases which are a direct or indirect consequence of Parkinson's disease. Medical comorbidity may induce additional limitations to physical strength and coping strategies, and may thus restrict the efficacy of the physical therapy which is essential for treating hypokinetic-rigid symptoms. In selecting the appropriate medication for the treatment of any additional medical symptoms, which may arise, its limitations, contraindications and interactions with dopaminergic substances have to be taken into consideration. General medical symptoms and organ manifestations may also arise as a direct consequence of the autonomic dysfunction associated with Parkinson's disease. As the disease progresses, additional non-parkinsonian symptoms can be of concern. Furthermore, the side effects of Parkinson medications may necessitate the involvement of other medical specialists. In this review, we will discuss the various general medical aspects of Parkinson's disease. PMID:26298728

  7. Homotaurine in Parkinson's disease.

    PubMed

    Ricciardi, Lucia; De Nigris, Francesca; Specchia, Alessandro; Fasano, Alfonso

    2015-09-01

    Homotaurine is a natural compound of red algae, which has been demonstrated to have a neuroprotective effect and has been evaluated as a possible therapeutic agent for Alzheimer's disease. This was a single blind, randomized, controlled study to evaluate the safety and efficacy of homotaurine in patients with Parkinson's disease (PD) and cognitive impairment. Patients were evaluated at baseline and 6 months later. Assessments included, the evaluation of: motor and non-motor conditions and complications (Unified Parkinson's Disease Rating Scale, UPDRS); disability and quality of life; depression; excessive daytime sleepiness and fatigue. An extensive neuropsychological tests battery was administered evaluating specific cognitive domains: memory, phonemic verbal fluency, executive functions and selective visual attention. After baseline testing, patients were allocated to one of the two groups: (A) treatment group: patients treated with homotaurine 100 mg; (B) control group: patients not treated with homotaurine. Forty-seven patients were evaluated at baseline, 24 (51 %) completed the study (PD-homotaurine: n = 11; 44 % and PD-controls: n = 13; 59 %); discontinuation rate was similar across subjects (p = 1.0). Intention to treat analyses to evaluate homotaurine safety showed mild side effects (gastrointestinal upsetting) in 3 patients. Per protocol analyses of homotaurine efficacy showed no difference between groups. Within group analyses showed that PD-homotaurine patients had better score at UPDRS-I at the end of the study compared to baseline (p = 0.017) and at Epworth Sleepiness Scale (p = 0.01). No other differences were found. No significant difference arose for the PD-ctrl group. Homotaurine is a safe drug. Our data suggest a beneficial effect of homotaurine on excessive sleepiness. Future studies are encouraged to confirm this promising role of homotaurine in promoting the sleep/awake cycle in patients with PD. PMID:25894843

  8. Association of AKT1 gene polymorphisms with sporadic Parkinson's disease in Chinese Han population.

    PubMed

    Li, Xiao-Yuan; Teng, Ji-Jun; Liu, Yang; Wu, Yu-Bin; Zheng, Yu; Xie, An-Mu

    2016-08-26

    Genetic variants of AKT1 have been shown to influence brain function of Parkinson's disease (PD) patients, and in this paper our aim is to investigate the association between the three single-nucleotide polymorphisms (rs2498799; rs2494732; rs1130214) and PD in Han Chinese. 413 Han Chinese PD patients and 450 healthy age and gender-matched controls were genotyped using the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. Both the patient and control groups show similar genotype frequencies at the three loci: rs2498799, rs2494732 and rs1130214. We are able to identify a significant difference in the frequencies of genotype (p=0.019) and G allele (OR=0.764, 95% CI=0.587-0.995, p=0.045) both at rs2498799 between the patient and control groups. Furthermore, the association of subjects with GG genotypes versus those with GA+AA genotype remain significant after adjusting for age in the Han Chinese female cohort (OR=0.538, 95%CI=0.345-0.841, p=0.006), which is especially evident in the late-onset cohort (OR=0.521, 95%CI=0.309-0.877, p=0.012). In contrast, allele frequencies at rs2494732 and rs1130214 were similar between patients and controls in all subgroup analyses. These results suggest that polymorphism of AKT1 locus is associated with risk of PD and that the G allele at rs2498799 may decrease the risk of PD in the North-eastern part of Han Chinese female population. PMID:27353512

  9. Association of RAGE gene polymorphisms with sporadic Parkinson's disease in Chinese Han population.

    PubMed

    Gao, Jing; Teng, Jijun; Liu, Hongxin; Han, Xun; Chen, Biao; Xie, Anmu

    2014-01-24

    Previous studies have corroborated receptor for advanced glycation end-products (RAGE) ablation had a protective effect on nigral dopaminergic neurons in the MPTP model of Parkinson's disease (PD). Genetic variation of RAGE gene may be associated with the development of onset of sporadic PD. The present study aimed to explore the possible association of RAGE gene polymorphisms namely -374T/A,-429T/C, and G82S with PD. A total of 285 PD patients and 285 healthy-matched individuals in Chinese Han population were enrolled. Genotype analyses were performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Only the -429T/C polymorphism denoted a significant difference between PD patients and controls (P=0.015) of the three examined single nucleotide polymorphisms (SNPs). Our data also revealed that -429C allele carriers seem to have a decreased risk of PD (OR=0.617, P=0.007). Moreover, there were significant differences in genotype distribution in female PD group and its healthy-matched control subgroup (P=0.014), as well as between late-onset PD (LOPD) and the controls subgroup (P=0.016). However, for -374T/A and 82GS polymorphisms, there was no significant difference in the genotype and allele frequencies between PD patients and the controls, as well as gender- and age-related differences. Our present findings indicate that the RAGE -429T/C polymorphism may be associated with the susceptibility of PD and the CC genotype of -429T/C may be a protective factor for PD in Chinese Han population. PMID:24304868

  10. Erectile function and risk of Parkinson's disease.

    PubMed

    Gao, Xiang; Chen, Honglei; Schwarzschild, Michael A; Glasser, Dale B; Logroscino, Giancarlo; Rimm, Eric B; Ascherio, Alberto

    2007-12-15

    Erectile dysfunction is common among individuals with Parkinson's disease, but it is unknown whether it precedes the onset of the classic features of Parkinson's disease. To address this question, the authors examined whether erectile dysfunction was associated with Parkinson's disease risk in the Health Professionals Follow-up Study. Analyses included 32,616 men free of Parkinson's disease at baseline in 1986 who in 2000 completed a retrospective questionnaire with questions on erectile dysfunction in different time periods. Relative risks were computed using Cox proportional hazards models adjusting for age, smoking, caffeine intake, history of diabetes, and other covariates. Among men who reported their erectile function before 1986, 200 were diagnosed with Parkinson's disease during 1986-2002. Men with erectile dysfunction before 1986 were 3.8 times more likely to develop Parkinson's disease during the follow-up than were those with very good erectile function (relative risk = 3.8, 95% confidence interval: 2.4, 6.0; p < 0.0001). Multivariate-adjusted relative risks of Parkinson's disease were 2.7, 3.7, and 4.0 (95% confidence interval: 1.4, 11.1; p = 0.008) for participants with first onset of erectile dysfunction (before 1986) at 60 or more, 50-59, and less than 50 years of age, respectively, relative to those without erectile dysfunction. In conclusion, in this retrospective analysis in a large cohort of men, the authors observed that erectile dysfunction was associated with a higher risk of developing Parkinson's disease. PMID:17875583

  11. Associations of Matrix Metalloproteinase-9 and Tissue Inhibitory Factor-1 Polymorphisms With Parkinson Disease in Taiwan

    PubMed Central

    Chen, Yi-Chun; Wu, Yih-Ru; Mesri, Mina; Chen, Chiung-Mei

    2016-01-01

    Abstract Matrix metalloproteinases (MMPs) function in the degradation of extracellular matrix and are considered to play a role in the pathogenesis of neurodegenerative diseases including Parkinson disease (PD). MMPs activities are modulated by tissue inhibitors of metalloproteinases (TIMPs). This study examined whether the genetic polymorphisms of MMP-3, gelatinase (MMP-2 and MMP-9), TIMP-2, and TIMP-1 were associated with PD in Taiwan. A total of 359 PD patients and 332 controls were enrolled. The candidate genetic variants included MMP-2 rs2285053 (−735 C > T), MMP-3 rs3025058 (−1171 5A > 6A), MMP-9 rs3918241 (−1831 T > A), rs17576 (G > A, R279Q), and rs3787268 (G > A, intron), TIMP-1 rs4898 (T > C, F124F), and TIMP-2 rs7503607 (−269 G > T). Associations were tested by logistic regression, adjusted with gender and age at onset. Minor allele frequency of TIMP-1 rs4898 (36.0%) was significantly lower in the male PD patients than in the male controls (51.2%) (χ2 test, P = 0.004). When adjusted with gender and age at onset, MMP-9 rs17576 AA genotype was associated with PD susceptibility in a recessive fashion (odds ratios [OR] = 2.28, 95% confidence intervals [95% CI] = 1.12–4.62, P = 0.02). In males, TIMP-1 rs4898 C allele was associated with a protective effect on PD (OR = 0.75, 95% CI = 0.60–0.94, P = 0.014). We did not find association between the examined genetic variants of MMP-2, MMP-3, and TIMP-2 and PD susceptibility. This is the first study that demonstrated a protective effect of TIMP-1 rs4898 C allele on male PD and a modest association of MMP-9 rs17576 AA genotype with PD susceptibility in the Taiwan population. Further replication is needed for confirmation. PMID:26844501

  12. Associations of Matrix Metalloproteinase-9 and Tissue Inhibitory Factor-1 Polymorphisms With Parkinson Disease in Taiwan.

    PubMed

    Chen, Yi-Chun; Wu, Yih-Ru; Mesri, Mina; Chen, Chiung-Mei

    2016-02-01

    Matrix metalloproteinases (MMPs) function in the degradation of extracellular matrix and are considered to play a role in the pathogenesis of neurodegenerative diseases including Parkinson disease (PD). MMPs activities are modulated by tissue inhibitors of metalloproteinases (TIMPs). This study examined whether the genetic polymorphisms of MMP-3, gelatinase (MMP-2 and MMP-9), TIMP-2, and TIMP-1 were associated with PD in Taiwan.A total of 359 PD patients and 332 controls were enrolled. The candidate genetic variants included MMP-2 rs2285053 (-735 C > T), MMP-3 rs3025058 (-1171 5A > 6A), MMP-9 rs3918241 (-1831 T > A), rs17576 (G > A, R279Q), and rs3787268 (G > A, intron), TIMP-1 rs4898 (T > C, F124F), and TIMP-2 rs7503607 (-269 G > T). Associations were tested by logistic regression, adjusted with gender and age at onset.Minor allele frequency of TIMP-1 rs4898 (36.0%) was significantly lower in the male PD patients than in the male controls (51.2%) (χ test, P = 0.004). When adjusted with gender and age at onset, MMP-9 rs17576 AA genotype was associated with PD susceptibility in a recessive fashion (odds ratios [OR] = 2.28, 95% confidence intervals [95% CI] = 1.12-4.62, P = 0.02). In males, TIMP-1 rs4898 C allele was associated with a protective effect on PD (OR = 0.75, 95% CI = 0.60-0.94, P = 0.014). We did not find association between the examined genetic variants of MMP-2, MMP-3, and TIMP-2 and PD susceptibility.This is the first study that demonstrated a protective effect of TIMP-1 rs4898 C allele on male PD and a modest association of MMP-9 rs17576 AA genotype with PD susceptibility in the Taiwan population. Further replication is needed for confirmation. PMID:26844501

  13. [Biotherapies and Parkinson's disease].

    PubMed

    Cesaro, P; Fenelon, G; Remy, P

    2009-11-01

    In the last years, several experimental biotherapies have been developed to treat Parkinson's disease. Initially, fetal dopaminergic transplants were proposed. Although a proof of concept and encouraging results have been provided, limitations of this treatment emerged over the years and the failure of controlled trials have conducted to a pause in the development of strategies based on fetal cells. Alternative approaches such as the use of retinal pigmented cells recently provided disappointing results in patients and much hope has now been reported on other sources of dopaminergic neurons such as those originating from stem cells. This strategy is however not yet ready for clinical trials in patients. Eventually, gene therapy is a new original experimental technique which has elicited several trials in the last few years some of them being promising. PMID:19487002

  14. Vitamin D from different sources is inversely associated with Parkinson disease

    PubMed Central

    Wang, Liyong; Evatt, Marian L.; Maldonado, Lizmarie G.; Perry, William R.; Ritchie, James C.; Beecham, Gary W.; Martin, Eden R.; Haines, Jonathan L.; Pericak-Vance, Margaret A.; Vance, Jeffery M.; Scott, William K.

    2014-01-01

    Background An inverse association between Parkinson disease (PD) and total vitamin D levels has been reported but it is unknown whether vitamin D from different sources, i.e. 25(OH)D2 (from diet and supplements) and 25(OH)D3 (mainly from sunlight exposure), all contribute to the association. Methods Plasma total 25(OH)D, 25(OH)D2, and 25(OH)D3 levels were measured by liquid chromatography-tandem mass spectrometry in PD patients (N=478) and controls (N=431). Total 25(OH)D was categorized by clinical insufficiency or deficiency, 25(OH)D2 and 25(OH)D3 were analyzed in quartiles. Results Vitamin D deficiency (total 25(OH)D < 20 ng/mL) and vitamin D insufficiency (total 25(OH)D < 30 ng/mL) are associated with PD risk [Odds Ratio (OR)=2.6 (deficiency) and 2.1 (insufficiency), P<0.0001], adjusting for age, sex and sampling season. Both 25(OH)D2 and 25(OH)D3 levels are inversely associated with PD (Ptrend<0.0001). The association between 25(OH)D2 and PD risk is largely confined to individuals with low 25(OH)D3 levels (Ptrend=0.0008 and 0.12 in individuals with 25(OH)D3 < 20 ng/mL and 25(OH)D3 >= 20 ng/mL, respectively) Conclusions Our data confirm the association between vitamin D deficiency and PD, and for the first time demonstrate an inverse association of 25(OH)D2 with PD. Given that 25(OH)D2 concentration is independent of sunlight exposure, this new finding suggests that the inverse association between vitamin D levels and PD is not simply due to lack of sunlight exposure PD patients with impaired mobility. The current study, however, cannot exclude the possibility that gastrointestinal dysfunction, a non-motor PD symptom, contributes to the lower vitamin D2 levels in PD patients. PMID:25545356

  15. Association of Dopamine Beta-Hydroxylase (DBH) Polymorphisms with Susceptibility to Parkinson's Disease.

    PubMed

    Shao, Peng; Yu, Yun-Xia; Bao, Jing-Xi

    2016-01-01

    BACKGROUND The purpose of this study was to explore the association between 2 single-nucleotide polymorphisms (SNPs) in the dopamine β-hydroxylase (DBH) gene (rs1611115 and rs732833) and the susceptibility to Parkinson's disease (PD). MATERIAL AND METHODS Polymerase chain reaction direct sequencing (PCR-DS) was used to test the genotypes of DBH polymorphisms in 95 PD patients and 100 healthy examinees frequency-matched with the former by age and sex. The genotype and allele distribution differences between the case and control groups were analyzed by chi-square test, and the relative risk of PD in southern Chinese populations was expressed by odds ratio (OR) and 95% confidence interval (CI). Hardy-Weinberg equilibrium (HWE) was also checked by chi-square test. RESULTS The genotype and allele distribution frequencies in rs1611115 were obviously different between PD patients and the healthy control group (P<0.05). The TT genotype may lead to a 2.95 times higher risk of PD occurrence compared with the common genotype CC (OR=2.95, 95%CI=1.02-8.51), and the C allele increased risk of onset of PD (OR=1.81, 95%CI=1.17-2.82). Cognition of the PD patients was different between CC and CT+TT genotypes of rs1611115 (P=0.047). CONCLUSIONS DBH rs1611115 polymorphism was likely to be associated with the susceptibility to PD, but we did not find that rs732833 is a susceptibility marker for PD. PMID:27177268

  16. Parkinsonism Associated with Glucocerebrosidase Mutation

    PubMed Central

    Sunwoo, Mun-Kyung; Kim, Seung-Min; Lee, Sarah

    2011-01-01

    Background Gaucher's disease is an autosomal recessive, lysosomal storage disease caused by mutations of the β-glucocerebrosidase gene (GBA). There is increasing evidence that GBA mutations are a genetic risk factor for the development of Parkinson's disease (PD). We report herein a family of Koreans exhibiting parkinsonism-associated GBA mutations. Case Report A 44-year-old woman suffering from slowness and paresthesia of the left arm for the previous 1.5years, visited our hospital to manage known invasive ductal carcinoma. During a preoperative evaluation, she was diagnosed with Gaucher's disease and double mutations of S271G and R359X in GBA. Parkinsonian features including low amplitude postural tremors, rigidity, bradykinesia and shuffling gait were observed. Genetic analysis also revealed that her older sister, who had also been diagnosed with PD and had been taking dopaminergic drugs for 8-years, also possessed a heterozygote R359X mutation in GBA. 18F-fluoropropylcarbomethoxyiodophenylnortropane positron-emission tomography in these patients revealed decreased uptake of dopamine transporter in the posterior portion of the bilateral putamen. Conclusions This case study demonstrates Korean familial cases of PD with heterozygote mutation of GBA, further supporting the association between PD and GBA mutation. PMID:21779299

  17. Association between MDR1 gene polymorphisms and Parkinson's disease in Asian and Caucasian populations: a meta-analysis.

    PubMed

    Ahmed, Shiek S S J; Husain, R S Akram; Kumar, Suresh; Ramakrishnan, V

    2016-09-15

    Parkinson's disease (PD) is a complex neurodegenerative disease, its etiology is largely unknown. Studies demonstrate the association of genetic and environment factors in causing neuronal degeneration. Reports suggest that the multi-drug resistance gene (MDR1) plays a vital role in preventing the toxic substance in entering the brain, which is associated with PD. However, the association between the MDR1 polymorphisms (C1236T and C3435T) and its susceptibility to PD is inconclusive. Meta analysis was carried by retrieving literatures from databases to search the case-control studies on the associations between the MRD1 polymorphisms and PD. The pooled odds ratios (ORs) and its 95% confidence intervals (CIs) were calculated using fixed and random model to determine the association between the polymorphisms and PD susceptibility. Significant association was noticed for C1236T polymorphism and PD risk in the recessive model OR=0.80, 95% CI=0.66-0.97. Further, ethnicity based analysis showed significant association for C1236T in allelic model of Asian population and also in the recessive models of both Asian and Caucasian populations. However, insignificant associations were noticed for C3435T in all the four models. Overall, the analysis suggested that MDR1 C1236T polymorphism substantially contribute to Parkinson's disease in the recessive genetic model. PMID:27538645

  18. Oxidative Stress in Genetic Mouse Models of Parkinson's Disease

    PubMed Central

    Varçin, Mustafa; Bentea, Eduard; Michotte, Yvette; Sarre, Sophie

    2012-01-01

    There is extensive evidence in Parkinson's disease of a link between oxidative stress and some of the monogenically inherited Parkinson's disease-associated genes. This paper focuses on the importance of this link and potential impact on neuronal function. Basic mechanisms of oxidative stress, the cellular antioxidant machinery, and the main sources of cellular oxidative stress are reviewed. Moreover, attention is given to the complex interaction between oxidative stress and other prominent pathogenic pathways in Parkinson's disease, such as mitochondrial dysfunction and neuroinflammation. Furthermore, an overview of the existing genetic mouse models of Parkinson's disease is given and the evidence of oxidative stress in these models highlighted. Taken into consideration the importance of ageing and environmental factors as a risk for developing Parkinson's disease, gene-environment interactions in genetically engineered mouse models of Parkinson's disease are also discussed, highlighting the role of oxidative damage in the interplay between genetic makeup, environmental stress, and ageing in Parkinson's disease. PMID:22829959

  19. Association Between Tuberculosis and Parkinson Disease: A Nationwide, Population-Based Cohort Study.

    PubMed

    Shen, Chih-Hao; Chou, Chung-Hsing; Liu, Feng-Cheng; Lin, Te-Yu; Huang, Wen-Yen; Wang, Yu-Chiao; Kao, Chia-Hung

    2016-02-01

    Few studies have investigated the association between tuberculosis (TB) and Parkinson disease (PD). This nationwide, population-based, retrospective cohort study investigated the risk of PD in patients with TB.We selected patients newly diagnosed with TB (International Classification of Diseases, Ninth Revision, Clinical Modification: 011) from 2000 to 2009 in the Taiwan National Health Insurance Database as the TB cohort. The comparison cohort (the non-TB cohort) was frequency matched to the TB cohort at a ratio of 4:1 by sex, age, and the index date. We analyzed the risks of PD by using Cox proportional hazard regression models.A total of 121,951 patients with TB and 487,800 non-TB controls were enrolled in this study. The TB cohort had a 1.38-fold risk of PD compared with the non-TB cohort after adjustment for age, sex, and comorbidities (aHR, 95% CI: 1.30-1.46). The adjusted risk of PD in the TB and non-TB cohorts increased in subgroups regardless of age, sex, and comorbidities. Combined effect of TB and comorbidities on the risk of PD were significant in patients with TB who had diabetes (aHR: 2.26, 95% CI: 2.02-2.52), hypertension (aHR: 2.23, 95% CI: 2.04-2.44), head injury (aHR: 2.32, 95% CI: 1.95-2.77), chronic kidney disease (aHR: 2.02, 95% CI: 1.49-2.72), chronic obstructive pulmonary disease (aHR: 1.84, 95% CI: 1.66-2.05), depression (aHR: 4.66, 95% CI: 3.59-6.05), dementia (aHR: 3.70, 95% CI: 2.99-4.59), and stroke (aHR: 2.56, 95% CI: 2.28-2.87). The risk of PD was higher in a follow-up within 1 year (aHR: 1.78, 95% CI: 1.58-2.00) and decreased with the follow-up period in the TB cohort.Patients with TB have an independently 1.38-fold risk of PD. The risk of PD decreased with the follow-up period in the TB cohort. Physicians should be aware of the risk of PD in patients with TB when treating such patients. PMID:26937925

  20. Parkinson disease and exercise.

    PubMed

    Earhart, Gammon M; Falvo, Michael J

    2013-04-01

    Parkinson disease (PD) is a progressive, neurodegenerative movement disorder. PD was originally attributed to neuronal loss within the substantia nigra pars compacta, and a concomitant loss of dopamine. PD is now thought to be a multisystem disorder that involves not only the dopaminergic system, but other neurotransmitter systems whose role may become more prominent as the disease progresses (189). PD is characterized by four cardinal symptoms, resting tremor, rigidity, bradykinesia, and postural instability, all of which are motor. However, PD also may include any combination of a myriad of nonmotor symptoms (195). Both motor and nonmotor symptoms may impact the ability of those with PD to participate in exercise and/or impact the effects of that exercise on those with PD. This article provides a comprehensive overview of PD, its symptoms and progression, and current treatments for PD. Among these treatments, exercise is currently at the forefront. People with PD retain the ability to participate in many forms of exercise and generally respond to exercise interventions similarly to age-matched subjects without PD. As such, exercise is currently an area receiving substantial research attention as investigators seek interventions that may modify the progression of the disease, perhaps through neuroprotective mechanisms. PMID:23720332

  1. Genetics Home Reference: Parkinson disease

    MedlinePlus

    ... Many Parkinson disease symptoms occur when nerve cells (neurons) in the substantia nigra die or become impaired. ... produce smooth physical movements. When these dopamine-producing neurons are damaged or die, communication between the brain ...

  2. [Initial symptomatology of Parkinson disease].

    PubMed

    Fuhr, P; Maritz, D; Bernatik, J; Steck, A J

    1995-01-01

    The early diagnosis of Parkinson's disease (idiopathic parkinsonism) is important for two reasons. Some never drugs possibly have a neuroprotective effect, which can be utilized maximally only with early onset of treatment. Moreover, diagnostic mistakes may occur early in the course of the disease. Although the hallmark of Parkinson's disease is a syndrome of movement disorders, slight cognitive deficits, depression, or pain with or without paresthesias can be present at an early stage. Therefore, symptoms at the time of the first diagnosis and at the beginning of the first clinical manifestation of Parkinson's disease are often not identical. The diagnosis can be made only clinically, since no biological marker is available up to now. However, in unclear cases pharmacological tests constitute a valuable extension of the clinical examination. PMID:8533059

  3. Polyneuropathy associated with duodenal infusion of levodopa in Parkinson's disease: features, pathogenesis and management.

    PubMed

    Uncini, Antonino; Eleopra, Roberto; Onofrj, Marco

    2015-05-01

    Patients with Parkinson's disease (PD) treated with oral levodopa have a higher prevalence of chronic, prevalently sensory, usually mild axonal polyneuropathy (PNP). Several studies showed a positive association among PNP, cumulative levodopa dosage, low serum B12 and high-homocysteine and methylmalonic acid level. Anecdotal severe acute or subacute PNPs thought to be Guillain-Barré syndrome have been reported in patients receiving continuous intraduodenal infusion of levodopa/carbidopa intestinal gel (LCIG). We report an additional acute case and by a systematic literature search we also reviewed the clinical and laboratory features of 13 other acute and 21 subacute PNP cases occurring during LCIG treatment. In series with at least nine patients, the mean frequency of acute and subacute PNP is 13.6% and the mortality rate at 6 months in acute cases is 14%. The great majority of PNP cases displayed axonal sensory-motor and reduced vitamin B12 levels, and alterations of metabolites of 1-carbon pathway were found in most patients. We discuss the possible role of high-levodopa dosage, vitamin B12, B6 and folate deficiency and accumulation of homocysteine and methylmalonic acid in the pathogenesis to conclude that there is enough, although circumstantial, evidence that alterations of 1-carbon pathway are implicated also in acute and subacute PNP during LCIG usage. There is no solid proof for a dysimmune pathogenesis and in our opinion acute, subacute and chronic PNP, either after oral levodopa or LCIG, represent a continuum. Finally, we propose recommendations for prevention and management of PNP occurring during LCIG treatment. PMID:25168395

  4. Free and cued recall memory in Parkinson's disease associated with amnestic mild cognitive impairment.

    PubMed

    Costa, Alberto; Monaco, Marco; Zabberoni, Silvia; Peppe, Antonella; Perri, Roberta; Fadda, Lucia; Iannarelli, Francesca; Caltagirone, Carlo; Carlesimo, Giovanni A

    2014-01-01

    The hypothesis has been advanced that memory disorders in individuals with Parkinson's disease (PD) are related to either retrieval or consolidation failure. However, the characteristics of the memory impairments of PD patients with amnestic mild cognitive impairment have not been clarified. This study was aimed at investigating whether memory deficits in PD patients with amnestic mild cognitive impairment (PDaMCI) are due to failure of retrieval or consolidation processes. Sixteen individuals with PDaMCI, 20 with amnestic mild cognitive impairment without PD (aMCINPD), and 20 healthy controls were recruited. Participants were administered the Free and Cued Selective Reminding Test. An index of cueing was computed for each subject to capture the advantage in retrieval of cued compared to free recall. Individuals with PDaMCI performed worse than healthy controls on the free recall (p<0.01) but not the cued recall (p>0.10) task, and they performed better than aMCINPD subjects on both recall measures (p<0.01). The index of cueing of subjects with PD was comparable to that of healthy controls (p>0.10) but it was significantly higher than that of the aMCINPD sample (p<0.01). Moreover, PD patients' performance on free recall trials was significantly predicted by scores on a test investigating executive functions (i.e., the Modified Card Sorting Test; p = 0.042). Findings of the study document that, in subjects with amnestic mild cognitive impairment associated to PD, episodic memory impairment is related to retrieval rather than to consolidation failure. The same data suggest that, in these individuals, memory deficits might be due to altered frontal-related executive functioning. PMID:24465977

  5. What can rodent models tell us about apathy and associated neuropsychiatric symptoms in Parkinson's disease?

    PubMed Central

    Magnard, R; Vachez, Y; Carcenac, C; Krack, P; David, O; Savasta, M; Boulet, S; Carnicella, S

    2016-01-01

    In addition to classical motor symptoms, Parkinson's disease (PD) patients display incapacitating neuropsychiatric manifestations, such as apathy, anhedonia, depression and anxiety. These hitherto generally neglected non-motor symptoms, have gained increasing interest in medical and scientific communities over the last decade because of the extent of their negative impact on PD patients' quality of life. Although recent clinical and functional imaging studies have provided useful information, the pathophysiology of apathy and associated affective impairments remains elusive. Our aim in this review is to summarize and discuss recent advances in the development of rodent models of PD-related neuropsychiatric symptoms using neurotoxin lesion-based approaches. The data collected suggest that bilateral and partial lesions of the nigrostriatal system aimed at inducing reliable neuropsychiatric-like deficits while avoiding severe motor impairments that may interfere with behavioral evaluation, is a more selective and efficient strategy than medial forebrain bundle lesions. Moreover, of all the different classes of pharmacological agents, D2/D3 receptor agonists such as pramipexole appear to be the most efficient treatment for the wide range of behavioral deficits induced by dopaminergic lesions. Lesion-based rodent models, therefore, appear to be relevant tools for studying the pathophysiology of the non-motor symptoms of PD. Data accumulated so far confirm the causative role of dopaminergic depletion, especially in the nigrostriatal system, in the development of behavioral impairments related to apathy, depression and anxiety. They also put forward D2/D3 receptors as potential targets for the treatment of such neuropsychiatric symptoms in PD. PMID:26954980

  6. Association Analysis of Proteasome Subunits and Transporter Associated with Antigen Processing on Chinese Patients with Parkinson's Disease

    PubMed Central

    Mo, Ming-Shu; Huang, Wei; Sun, Cong-Cong; Zhang, Li-Min; Cen, Luan; Xiao, You-Sheng; Li, Guo-Fei; Yang, Xin-Ling; Qu, Shao-Gang; Xu, Ping-Yi

    2016-01-01

    Background: Proteasome subunits (PSMB) and transporter associated with antigen processing (TAP) loci are located in the human leukocyte antigen (HLA) Class II region play important roles in immune response and protein degradation in neurodegenerative diseases. This study aimed to explore the association between single nucleotide polymorphisms (SNPs) of PSMB and TAP and Parkinson's disease (PD). Methods: A case–control study was conducted by genotyping SNPs in PSMB8, PSMB9, TAP1, and TAP2 genes in the Chinese population. Subjects included 542 sporadic patients with PD and 674 healthy controls. Nine identified SNPs in PSMB8, PSMB9, TAP1, and TAP2 were genotyped through SNaPshot testing. Results: The stratified analysis of rs17587 was specially performed on gender. Data revealed that female patients carry a higher frequency of rs17587-G/G versus (A/A + G/A) compared with controls. But there was no significant difference with respect to the genotypic frequencies of the SNPs in PSMB8, TAP1, and TAP2 loci in PD patients. Conclusion: Chinese females carrying the rs17587-G/G genotype in PSMB9 may increase a higher risk for PD, but no linkage was found between other SNPs in HLA Class II region and PD. PMID:27098790

  7. Parkinson's Disease and Systemic Inflammation

    PubMed Central

    Ferrari, Carina C.; Tarelli, Rodolfo

    2011-01-01

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

  8. Parkinson's disease and systemic inflammation.

    PubMed

    Ferrari, Carina C; Tarelli, Rodolfo

    2011-01-01

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

  9. Parkinson's disease managing reversible neurodegeneration.

    PubMed

    Hinz, Marty; Stein, Alvin; Cole, Ted; McDougall, Beth; Westaway, Mark

    2016-01-01

    Traditionally, the Parkinson's disease (PD) symptom course has been classified as an irreversible progressive neurodegenerative disease. This paper documents 29 PD and treatment-induced systemic depletion etiologies which cause and/or exacerbate the seven novel primary relative nutritional deficiencies associated with PD. These reversible relative nutritional deficiencies (RNDs) may facilitate and accelerate irreversible progressive neurodegeneration, while other reversible RNDs may induce previously undocumented reversible pseudo-neurodegeneration that is hiding in plain sight since the symptoms are identical to the symptoms being experienced by the PD patient. Documented herein is a novel nutritional approach for reversible processes management which may slow or halt irreversible progressive neurodegenerative disease and correct reversible RNDs whose symptoms are identical to the patient's PD symptoms. PMID:27103805

  10. Association of Polymorphism of Neuronal Nitric Oxide Synthase Gene with Risk to Parkinson's Disease.

    PubMed

    Gupta, Satya Prakash; Kamal, Ritul; Mishra, Sarad Kumar; Singh, Maneesh Kumar; Shukla, Rakesh; Singh, Mahendra Pratap

    2016-07-01

    Environmental factors are implicated in aging as well as genetic predisposition-induced Parkinson's disease (PD) pathogenesis. Wrongdoers increase oxidative stress and nitrosative burden, which eventually degenerate the nigrostriatal dopaminergic neurons. Inhibition of the expression of nitric oxide synthase (NOS), an enzyme responsible for nitric oxide (NO) biosynthesis, prevents the demise of the nigrostriatal dopaminergic neurons. Polymorphism of NOS is thus expected to alter PD susceptibility. The study therefore aimed to examine an association of neuronal NOS (nNOS) gene polymorphism with nitrite, an indicator of nitrosative load; lipid peroxidation, an index of oxidative stress and PD susceptibility. An age-matched case-control study was performed in the north Indian residents enrolled at the Neurology Department of the King George's Medical University, Lucknow, India. While nNOS exon 29 TT variant genotype [odds ratio (OR) = 2.20, 95 % CI = 1.08-5.34, P = 0.040], combined TT and CT variants [OR = 1.68, 95 % CI = 1.05-2.69, P = 0.031] and T allele [OR = 1.58, 95 % CI = 1.10-2.28, P = 0.014] were found to be significantly associated with PD susceptibility, no association between nNOS exon 18 [OR for TT carriers = 1.97, 95 % CI = 0.89-4.20, P = 0.09 and OR for T allele = 1.35, 95 % CI = 0.94-1.93, P = 0.098] and PD risk was observed. Lipid peroxidation was augmented in all patients irrespective of their genotype. While genotype independent increase in nitrite content was observed in PD patients of exon 29 polymorphic groups, only heterozygous variant genotype of exon 18 was associated with augmentation in nitrite level as compared with respective control. The results obtained thus demonstrate that selected nNOS polymorphisms do not significantly contribute to PD risk in north Indian population. PMID:26081147

  11. Nutraceuticals in Parkinson's Disease.

    PubMed

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

    2016-09-01

    Current pharmacological strategies for Parkinson's disease (PD), the most common neurological movement disorder worldwide, are predominantly symptom relieving and are often plagued with undesirable side effects after prolonged treatment. Despite this, they remain as the mainstay treatment for PD due to the lack of better alternatives. Nutraceuticals are compounds derived from natural food sources that have certain therapeutic value and the advent of which has opened doors to the use of alternative strategies to tackle neurodegenerative diseases such as PD. Notably, nutraceuticals are able to position themselves as a "safer" strategy due to the fact that they are naturally derived compounds, therefore possibly having less side effects. Significant efforts have been put into better comprehending the role of nutraceuticals in PD, and we will look at some of them in this review. Broadly speaking, these compounds execute their positive effects via modulating signalling pathways, inhibiting oxidative stress, inflammation and apoptosis, as well as regulating mitochondrial homoeostasis. Importantly, we will highlight how a component of green tea, epigallocatechin-3-gallate (EGCG), confers neuroprotection in PD via its ability to activate AMP kinase and articulate how its beneficial effects in PD are possibly due to enhancing mitochondrial quality control. PMID:27147525

  12. Copper and Copper Proteins in Parkinson's Disease

    PubMed Central

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

    2014-01-01

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

  13. Prevalence and associated features of self-reported freezing of gait in Parkinson disease: The DEEP FOG study.

    PubMed

    Amboni, M; Stocchi, F; Abbruzzese, G; Morgante, L; Onofrj, M; Ruggieri, S; Tinazzi, M; Zappia, M; Attar, M; Colombo, D; Simoni, L; Ori, A; Barone, P; Antonini, A

    2015-06-01

    Freezing of Gait (FOG) is a common and disabling symptom in patients with Parkinson disease (PD). The relationship between FOG and dopaminergic medication is complex. The aim of the present study was to estimate the prevalence of self-reported FOG, its associated clinical features, and its relationship with wearing-off in a wide PD population. This is an observational multicenter study of 634 consecutive non-demented PD patients. Patients were identified either as freezers or non-freezers based on item-3 of the Freezing of Gait-Questionnaire. FOG was then classified as on, off and onoff freezing based on its relationship with wearing-off. Patients were assessed with Unified Parkinson's Disease Rating Scale, Hoehn and Yahr scale, 8-item Parkinson's disease Questionnaire, Mini-Mental State Examination. Data from 593 patients were analyzed, 325 (54.3%) were freezers of whom 200 (61.6%) experienced FOG only during off state (off-freezers), 6 (1.8%) only during on state and 119 (36.6%) either in on and off states or independently of dopaminergic response-related symptoms (onoff-freezers). Overall, freezers vs non-freezers had longer disease duration, more advanced disease and greater disability. Moreover, freezers more frequently reported wearing-off and experienced worse quality of life. Onoff-freezers vs off-freezers were older, more severely disabled, less likely to experience wearing-off, treated with lower levodopa equivalent daily dose and with poorer cognitive performance. Self-reported FOG is mainly recognizable in advanced PD and is associated with more disability and worse quality of life. Onoff-FOG may represent the result of under-treatment or rather interpretable as a distinct clinical entity. PMID:25899545

  14. Parkinson disease and driving

    PubMed Central

    Classen, Sherrilene; Uc, Ergun Y.

    2012-01-01

    ABSTRACT The growing literature on driving in Parkinson disease (PD) has shown that driving is impaired in PD compared to healthy comparison drivers. PD is a complex neurodegenerative disorder leading to motor, cognitive, and visual impairments, all of which can affect fitness to drive. In this review, we examined studies of driving performance (on-road tests and simulators) in PD for outcome measures and their predictors. We searched through various databases and found 25 (of 99) primary studies, all published in English. Using the American Academy of Neurology criteria, a study class of evidence was assigned (I–IV, I indicating the highest level of evidence) and recommendations were made (Level A: predictive or not; B: probably predictive or not; C: possibly predictive or not; U: no recommendations). From available Class II and III studies, we identified various cognitive, visual, and motor measures that met different levels of evidence (usually Level B or C) with respect to predicting on-road and simulated driving performance. Class I studies reporting Level A recommendations for definitive predictors of driving performance in drivers with PD are needed by policy makers and clinicians to develop evidence-based guidelines. PMID:23150533

  15. Association between fatigue and other motor and non-motor symptoms in Parkinson's disease patients.

    PubMed

    Solla, Paolo; Cannas, Antonino; Mulas, Cesare Salvatore; Perra, Silvia; Corona, Andrea; Bassareo, Pier Paolo; Marrosu, Francesco

    2014-02-01

    Although fatigue is a common non-motor symptom in patients affected by Parkinson's disease (PD), its association with motor and other non-motor symptoms is still largely unclear. We assessed fatigue in PD patients studying the possible association with motor and non-motor symptoms. Eighty-one PD patients were included in the study. The PD Fatigue Scale (PFS) and the Fatigue Severity Scale (FSS) scale were used to measure fatigue. Non-motor symptoms were assessed with the Non-Motor Symptoms Scale (NMSS). Motor impairment was assessed using the modified Hoehn and Yahr (HY) staging and the Unified PD Rating Scale (UPDRS) part-III and IV. Bivariate tests comparing all independent variables between patients with our without fatigue were used. Significant predictors of presence and severity of fatigue were determined with different models of logistic regression analyses. Fatigue severity was significantly higher in female patients. Bivariate test showed significant higher NMSS score in fatigued patients according to PFS (p < 0.00001) and FFS (p < 0.001), while HY was higher only in fatigued patients according to FSS (p < 0.022). Significant correlations between severity of fatigue and HY stage (p < 0.002) and UPDRS-III score (p < 0.001) were found, while, among specific non-motor symptoms, anhedonia presented with the most significant correlation (p < 0.003). Binary logistic regression confirmed NMSS as the main variable predicting presence of fatigue, while HY was significant as predicting variable only in the FSS model. Strongest non-motor symptoms predictors of severity were those included in Domain 3 (mood/anxiety) and Domain 2 (sleep disorders) of the NMSS. A significant increase in severity of fatigue related to the burden of non-motor symptoms (mainly affective and sleep disorders) was observed. Our findings indicate a moderate discrepancy in the ratings of the two fatigue scales, with PFS principally directed towards the burden of non-motor symptoms

  16. Nuclear microscopy in Parkinson's disease

    NASA Astrophysics Data System (ADS)

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

    1995-09-01

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

  17. Web-Based Genome-Wide Association Study Identifies Two Novel Loci and a Substantial Genetic Component for Parkinson's Disease

    PubMed Central

    Do, Chuong B.; Tung, Joyce Y.; Dorfman, Elizabeth; Kiefer, Amy K.; Drabant, Emily M.; Francke, Uta; Mountain, Joanna L.; Goldman, Samuel M.; Tanner, Caroline M.; Langston, J. William; Wojcicki, Anne; Eriksson, Nicholas

    2011-01-01

    Although the causes of Parkinson's disease (PD) are thought to be primarily environmental, recent studies suggest that a number of genes influence susceptibility. Using targeted case recruitment and online survey instruments, we conducted the largest case-control genome-wide association study (GWAS) of PD based on a single collection of individuals to date (3,426 cases and 29,624 controls). We discovered two novel, genome-wide significant associations with PD–rs6812193 near SCARB2 (, ) and rs11868035 near SREBF1/RAI1 (, )—both replicated in an independent cohort. We also replicated 20 previously discovered genetic associations (including LRRK2, GBA, SNCA, MAPT, GAK, and the HLA region), providing support for our novel study design. Relying on a recently proposed method based on genome-wide sharing estimates between distantly related individuals, we estimated the heritability of PD to be at least 0.27. Finally, using sparse regression techniques, we constructed predictive models that account for 6%–7% of the total variance in liability and that suggest the presence of true associations just beyond genome-wide significance, as confirmed through both internal and external cross-validation. These results indicate a substantial, but by no means total, contribution of genetics underlying susceptibility to both early-onset and late-onset PD, suggesting that, despite the novel associations discovered here and elsewhere, the majority of the genetic component for Parkinson's disease remains to be discovered. PMID:21738487

  18. Vaccination strategies for Parkinson disease

    PubMed Central

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

    2014-01-01

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

  19. Nonmotor manifestations of Parkinson's disease.

    PubMed

    Simuni, Tanya; Sethi, Kapil

    2008-12-01

    Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease. Traditionally, attention has focused on the motor symptomatology of PD, but it is now appreciated that the nonmotor symptoms affecting neuropsychiatric, sleep, autonomic, and sensory domains occur in up to 88% of PD patients and can be an important source of disability. Nonmotor manifestations of PD play a significant role in the impairment of disease-related quality of life. The cause of nonmotor manifestations of PD is multifactorial, but to a large extent, these manifestations are related to the nature of the neurodegenerative process and the widespread nondopaminergic neuropathological changes associated with the disease. Recognition of nonmotor disability is essential not only for ascertaining the functional status of patients but also for better appreciating the nature of the neurodegenerative process in PD. In addition, a number of nonmotor manifestations can precede the onset of motor symptoms in PD and can be used as screening tools allowing for early disease identification and for trials of possible disease-modifying interventions. This article reviews depression, sleep, and autonomic dysfunction in PD. PMID:19127582

  20. Imaging prodromal Parkinson disease

    PubMed Central

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

    2014-01-01

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

  1. Freezing of gait in Parkinson's disease is associated with functional decoupling between the cognitive control network and the basal ganglia.

    PubMed

    Shine, James M; Matar, Elie; Ward, Philip B; Frank, Michael J; Moustafa, Ahmed A; Pearson, Mark; Naismith, Sharon L; Lewis, Simon J G

    2013-12-01

    Recent neuroimaging evidence has led to the proposal that freezing of gait in Parkinson's disease is due to dysfunctional interactions between frontoparietal cortical regions and subcortical structures, such as the striatum. However, to date, no study has employed task-based functional connectivity analyses to explore this hypothesis. In this study, we used a data-driven multivariate approach to explore the impaired communication between distributed neuronal networks in 10 patients with Parkinson's disease and freezing of gait, and 10 matched patients with no clinical history of freezing behaviour. Patients performed a virtual reality gait task on two separate occasions (once ON and once OFF their regular dopaminergic medication) while functional magnetic resonance imaging data were collected. Group-level independent component analysis was used to extract the subject-specific time courses associated with five well-known neuronal networks: the motor network, the right- and left cognitive control networks, the ventral attention network and the basal ganglia network. We subsequently analysed both the activation and connectivity of these neuronal networks between the two groups with respect to dopaminergic state and cognitive load while performing the virtual reality gait task. During task performance, all patients used the left cognitive control network and the ventral attention network and in addition, showed increased connectivity between the bilateral cognitive control networks. However, patients with freezing demonstrated functional decoupling between the basal ganglia network and the cognitive control network in each hemisphere. This decoupling was also associated with paroxysmal motor arrests. These results support the hypothesis that freezing behaviour in Parkinson's disease is because of impaired communication between complimentary yet competing neural networks. PMID:24142148

  2. Auditory musical hallucinations associated with extended-release pramipexole in an elderly patient with Parkinson's disease.

    PubMed

    Kataoka, Hiroshi; Ueno, Satoshi

    2014-12-01

    Auditory musical hallucinations (AMHs) are rare complex auditory hallucinations in Parkinson's disease (PD) that have been limited previously. The characteristics of AMHs in PD remain uncertain. We describe a 72-year-old woman with PD who presented with AMHs. The AMHs occurred after immediate-release pramipexole was switched to extended-release pramipexole. The AMHs were a quiet piano or often songs on a loud radio or background music over other sounds. The music was unpleasant, but not objectionable, threatening, or ego-syntonic, and it did not interrupt her daily activities. AMHs in PD were non-threatening, and dopaminergic treatment may predispose patients to AMHs or be a unique possible cause of AMHs. The hallucinations can occur after immediate-release pramipexole was switched to extended-release pramipexole. PMID:25501095

  3. Auditory Musical Hallucinations Associated With Extended-Release Pramipexole in an Elderly Patient With Parkinson's Disease

    PubMed Central

    Kataoka, Hiroshi; Ueno, Satoshi

    2014-01-01

    Abstract Auditory musical hallucinations (AMHs) are rare complex auditory hallucinations in Parkinson's disease (PD) that have been limited previously. The characteristics of AMHs in PD remain uncertain. We describe a 72-year-old woman with PD who presented with AMHs. The AMHs occurred after immediate-release pramipexole was switched to extended-release pramipexole. The AMHs were a quiet piano or often songs on a loud radio or background music over other sounds. The music was unpleasant, but not objectionable, threatening, or ego-syntonic, and it did not interrupt her daily activities. AMHs in PD were non-threatening, and dopaminergic treatment may predispose patients to AMHs or be a unique possible cause of AMHs. The hallucinations can occur after immediate-release pramipexole was switched to extended-release pramipexole. PMID:25501095

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

    PubMed

    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). PMID:12548347

  5. Parkinson's disease. Diagnosis and treatment.

    PubMed Central

    Ng, D C

    1996-01-01

    Although Parkinson's disease is primarily a neurologic disorder, primary care physicians should be knowledgeable about the disease and its treatment because most patients will see their primary care physician first for their symptoms. Furthermore, in today's setting of managed care, primary care physicians will likely be called on even more to assume primary responsibility for the treatment of patients afflicted with Parkinson's disease; neurologists will likely play the role of consultants who see a patient only periodically and offer recommendations and advice for the primary care physicians to implement. PMID:8987437

  6. Functional Performance and Associations between Performance Tests and Neurological Assessment Differ in Men and Women with Parkinson's Disease

    PubMed Central

    Medijainen, Kadri; Pääsuke, Mati; Lukmann, Aet; Taba, Pille

    2015-01-01

    Background. Neurological assessment of a patient with Parkinson's disease (PD) is expected to reflect upon functional performance. As women are known to report more limitations even for same observed functional performance level, present study was designed to examine whether associations between neurological assessments and functional performance differ across genders. Methods. 14 men and 14 women with PD participated. Functional performance was assessed by measuring walking speeds on 10-meter walk test (10MWT) and by performing timed-up-and-go-test (TUG). Neurological assessment included Hoehn and Yahr Scale (HY), Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Schwab and England Activities of Daily Living Scale (S-E), and Mini Mental State Examination (MMSE). Results. In women with PD, Kendall's tau-b correlation analyses revealed significant correlations between functional performance tests and neurological assessment measures, with the exception in MMSE. No corresponding associations were found for men, although they demonstrated better functional performance, as expected. Conclusion. Men in similar clinical stage of the PD perform better on functional tests than women. Disease severity reflects upon functional performance differently in men and women with PD. Results indicate that when interpreting the assessment results of both functional performance and neurological assessment tests, the gender of the patient should be taken into consideration. PMID:26586928

  7. Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease.

    PubMed

    Nalls, Mike A; Pankratz, Nathan; Lill, Christina M; Do, Chuong B; Hernandez, Dena G; Saad, Mohamad; DeStefano, Anita L; Kara, Eleanna; Bras, Jose; Sharma, Manu; Schulte, Claudia; Keller, Margaux F; Arepalli, Sampath; Letson, Christopher; Edsall, Connor; Stefansson, Hreinn; Liu, Xinmin; Pliner, Hannah; Lee, Joseph H; Cheng, Rong; Ikram, M Arfan; Ioannidis, John P A; Hadjigeorgiou, Georgios M; Bis, Joshua C; Martinez, Maria; Perlmutter, Joel S; Goate, Alison; Marder, Karen; Fiske, Brian; Sutherland, Margaret; Xiromerisiou, Georgia; Myers, Richard H; Clark, Lorraine N; Stefansson, Kari; Hardy, John A; Heutink, Peter; Chen, Honglei; Wood, Nicholas W; Houlden, Henry; Payami, Haydeh; Brice, Alexis; Scott, William K; Gasser, Thomas; Bertram, Lars; Eriksson, Nicholas; Foroud, Tatiana; Singleton, Andrew B

    2014-09-01

    We conducted a meta-analysis of Parkinson's disease genome-wide association studies using a common set of 7,893,274 variants across 13,708 cases and 95,282 controls. Twenty-six loci were identified as having genome-wide significant association; these and 6 additional previously reported loci were then tested in an independent set of 5,353 cases and 5,551 controls. Of the 32 tested SNPs, 24 replicated, including 6 newly identified loci. Conditional analyses within loci showed that four loci, including GBA, GAK-DGKQ, SNCA and the HLA region, contain a secondary independent risk variant. In total, we identified and replicated 28 independent risk variants for Parkinson's disease across 24 loci. Although the effect of each individual locus was small, risk profile analysis showed substantial cumulative risk in a comparison of the highest and lowest quintiles of genetic risk (odds ratio (OR) = 3.31, 95% confidence interval (CI) = 2.55-4.30; P = 2 × 10(-16)). We also show six risk loci associated with proximal gene expression or DNA methylation. PMID:25064009

  8. Behavioral dysfunction in Parkinson's disease.

    PubMed

    Friedman, J H

    1998-01-01

    Behavioral manifestations of Parkinson's disease (PD) are often more debilitating than the motor manifestations. These occur both as primary manifestations of the disease and as drug-induced complications. While dementia and abulia are common problems that are not currently treatable, depression and psychosis often respond extremely well to medication. Phenomenology, pathology, and general approaches to treatment will be discussed. PMID:10785833

  9. Idiopathic Parkinson's disease: epidemiology, diagnosis and management.

    PubMed Central

    Ben-Shlomo, Y; Sieradzan, K

    1995-01-01

    Since the introduction of levodopa therapy for idiopathic Parkinson's disease over 20 years ago, there has been an awakening of research interest in this chronic neuro-degenerative disorder. This paper describes current understanding of the role of genetic and environmental factors in the aetiology of idiopathic Parkinson's disease and problems associated with both diagnosis and management. It briefly outlines both pharmacological and non-pharmacological options for treatment. Despite an increasing armoury of available treatments, the optimum management for this condition remains controversial. PMID:7619574

  10. Cholinergic dysfunction in Parkinson's disease.

    PubMed

    Müller, Martijn L T M; Bohnen, Nicolaas I

    2013-09-01

    There is increasing interest in the clinical effects of cholinergic basal forebrain and tegmental pedunculopontine complex (PPN) projection degeneration in Parkinson's disease (PD). Recent evidence supports an expanded role beyond cognitive impairment, including effects on olfaction, mood, REM sleep behavior disorder, and motor functions. Cholinergic denervation is variable in PD without dementia and may contribute to clinical symptom heterogeneity. Early in vivo imaging evidence that impaired cholinergic integrity of the PPN associates with frequent falling in PD is now confirmed by human post-mortem evidence. Brainstem cholinergic lesioning studies in primates confirm the role of the PPN in mobility impairment. Degeneration of basal forebrain cholinergic projections correlates with decreased walking speed. Cumulatively, these findings provide evidence for a new paradigm to explain dopamine-resistant features of mobility impairments in PD. Recognition of the increased clinical role of cholinergic system degeneration may motivate new research to expand indications for cholinergic therapy in PD. PMID:23943367

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

    PubMed

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

    2016-06-01

    Glycation is a spontaneous age-dependent posttranslational modification that can impact the structure and function of several proteins. Interestingly, glycation can be detected at the periphery of Lewy bodies in the brain in Parkinson's disease. Moreover, α-synuclein can be glycated, at least under experimental conditions. In Alzheimer's disease, glycation of amyloid β peptide exacerbates its toxicity and contributes to neurodegeneration. Recent studies establish diabetes mellitus as a risk factor for several neurodegenerative disorders, including Parkinson's and Alzheimer's diseases. However, the mechanisms underlying this connection remain unclear. We hypothesize that hyperglycemia might play an important role in the development of these disorders, possibly by also inducing protein glycation and thereby dysfunction, aggregation, and deposition. Here, we explore protein glycation as a common player in Parkinson's and Alzheimer's diseases and propose it may constitute a novel target for the development of strategies for neuroprotective therapeutic interventions. © 2016 International Parkinson and Movement Disorder Society. PMID:26946341

  12. Lewy body pathology is associated with mitochondrial DNA damage in Parkinson's disease.

    PubMed

    Müller, Sarina K; Bender, Andreas; Laub, Christoph; Högen, Tobias; Schlaudraff, Falk; Liss, Birgit; Klopstock, Thomas; Elstner, Matthias

    2013-09-01

    Mitochondrial dysfunction has been strongly implicated in the pathogenesis of Parkinson's disease (PD) and Alzheimer's disease (AD), but its relation to protein aggregation is unclear. PD is characterized by synuclein aggregation (i.e., Lewy body [LB] formation). In AD, the abnormal accumulation of tau protein forms neurofibrillary tangles. In this study, we laser-dissected LB-positive and -negative neurons from the substantia nigra of postmortem PD brains, and tau-positive and -negative hippocampal neurons from AD brains. We quantified mitochondrial DNA deletions in relation to the cellular phenotype and in comparison with age-matched controls. Deletion levels were highest in LB-positive neurons of PD brains (40.5 ± 16.8%), followed by LB-negative neurons of PD cases (31.8 ± 14.4%) and control subjects (25.6 ± 17.5%; analysis of variance p < 0.005). In hippocampal neurons, deletion levels were 25%-30%, independent of disease status and neurofibrillary tangles. The presented findings imply increased mitochondrial DNA damage in LB-positive midbrain neurons, but do not support a direct causative link of respiratory chain dysfunction and protein aggregation. PMID:23566333

  13. Environmental risk factors for Parkinson's disease and parkinsonism: the Geoparkinson study

    PubMed Central

    Dick, F D; De Palma, G; Ahmadi, A; Scott, N W; Prescott, G J; Bennett, J; Semple, S; Dick, S; Counsell, C; Mozzoni, P; Haites, N; Wettinger, S Bezzina; Mutti, A; Otelea, M; Seaton, A; Söderkvist, P; Felice, A

    2007-01-01

    Objective To investigate the associations between Parkinson's disease and other degenerative parkinsonian syndromes and environmental factors in five European countries. Methods A case–control study of 959 prevalent cases of parkinsonism (767 with Parkinson's disease) and 1989 controls in Scotland, Italy, Sweden, Romania and Malta was carried out. Cases were defined using the United Kingdom Parkinson's Disease Society Brain Bank criteria, and those with drug‐induced or vascular parkinsonism or dementia were excluded. Subjects completed an interviewer‐administered questionnaire about lifetime occupational and hobby exposure to solvents, pesticides, iron, copper and manganese. Lifetime and average annual exposures were estimated blind to disease status using a job‐exposure matrix modified by subjective exposure modelling. Results were analysed using multiple logistic regression, adjusting for age, sex, country, tobacco use, ever knocked unconscious and family history of Parkinson's disease. Results Adjusted logistic regression analyses showed significantly increased odds ratios for Parkinson's disease/parkinsonism with an exposure–response relationship for pesticides (low vs no exposure, odds ratio (OR) = 1.13, 95% CI 0.82 to 1.57, high vs no exposure, OR = 1.41, 95% CI 1.06 to 1.88) and ever knocked unconscious (once vs never, OR = 1.35, 95% CI 1.09 to 1.68, more than once vs never, OR = 2.53, 95% CI 1.78 to 3.59). Hypnotic, anxiolytic or antidepressant drug use for more than 1 year and a family history of Parkinson's disease showed significantly increased odds ratios. Tobacco use was protective (OR = 0.50, 95% CI 0.42 to 0.60). Analyses confined to subjects with Parkinson's disease gave similar results. Conclusions The association of pesticide exposure with Parkinson's disease suggests a causative role. Repeated traumatic loss of consciousness is associated with increased risk. PMID:17332139

  14. Early diagnosis of Parkinson's disease.

    PubMed

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

    2002-10-01

    In idiopathic Parkinson's disease (IPD) approximately 60 % of the nigrostriatal neurons of the substantia nigra (SN) are degenerated before neurologists can establish the diagnosis according to the widely accepted clinical diagnostic criteria. It is conceivable that neuroprotective therapy starting at such an 'advanced stage' of the disease will fail to stop the degenerative process. Therefore, the identification of patients at risk and at earlier stages of the disease appears to be essential for any successful neuroprotection. The discovery of several genetic mutations associated with IPD raises the possibility that these, or other biomarkers, of the disease may help to identify persons at risk of IPD. Transcranial ultrasound have shown susceptibility factors for IPD related to an increased iron load of the substantia nigra. In the early clinical phase, a number of motor and particularly non-motor signs emerge, which can be identified by the patients and physicians years before the diagnosis is made, notably olfactory dysfunction, depression, or 'soft' motor signs such as changes in handwriting, speech or reduced ambulatory arm motion. These signs of the early, prediagnostic phase of IPD can be detected by inexpensive and easy-to-administer tests. As one single instrument will not be sensitive enough, a battery of tests has to be composed measuring independent parameters of the incipient disease. Subjects with abnormal findings in this test battery should than be submitted to nuclear medicine examinations to quantify the extent of dopaminergic injury and to reach the goal of a reliable, early diagnosis. PMID:12522572

  15. Semantic profiles in mild cognitive impairment associated with Alzheimer's and Parkinson's diseases.

    PubMed

    Guidi, Marco; Paciaroni, Lucia; Paolini, Susy; Scarpino, Osvaldo; Burn, David J

    2015-01-01

    The temporal and the prefrontal cortices have different roles in semantic information processing: the temporal lobe is where knowledge is stored (Graham and Hodges, 1997), whereas the prefrontal cortex is more specifically involved in executive aspects of semantic processing. Relatively little is known about the semantic profiles of mild cognitive impairment (MCI) in Alzheimer's disease (AD) and Parkinson's disease (PD). This observational study investigated naming and semantic questionnaire performances in three groups of subjects: 10 patients with the amnestic-type MCI prodrome of AD (aMCI), 10 patients with early-stage executive-type MCI in PD (MCI-PD), and 10 normal subjects. The MCI-PD subjects demonstrated inferior performances on a semantic questionnaire, whereas the aMCI group displayed modest difficulties in a naming task. These differences may be explained by topographical differences in pathological involvement. Since the frontal areas are more functionally impaired in PD, we hypothesize that the semantic deficit may be a consequence of a deficiency in control of semantic processing. On the other hand, the semantic deficit in aMCI may be related to a lexical-semantic storage dysfunction resulting from pathological involvement of the temporal lobe. PMID:26415783

  16. The Parkinson's disease-associated genes ATP13A2 and SYT11 regulate autophagy via a common pathway.

    PubMed

    Bento, Carla F; Ashkenazi, Avraham; Jimenez-Sanchez, Maria; Rubinsztein, David C

    2016-01-01

    Forms of Parkinson's disease (PD) are associated with lysosomal and autophagic dysfunction. ATP13A2, which is mutated in some types of early-onset Parkinsonism, has been suggested as a regulator of the autophagy-lysosome pathway. However, little is known about the ATP13A2 effectors and how they regulate this pathway. Here we show that ATP13A2 depletion negatively regulates another PD-associated gene (SYT11) at both transcriptional and post-translational levels. Decreased SYT11 transcription is controlled by a mechanism dependent on MYCBP2-induced ubiquitination of TSC2, which leads to mTORC1 activation and decreased TFEB-mediated transcription of SYT11, while increased protein turnover is regulated by SYT11 ubiquitination and degradation. Both mechanisms account for a decrease in the levels of SYT11, which, in turn, induces lysosomal dysfunction and impaired degradation of autophagosomes. Thus, we propose that ATP13A2 and SYT11 form a new functional network in the regulation of the autophagy-lysosome pathway, which is likely to contribute to forms of PD-associated neurodegeneration. PMID:27278822

  17. The Parkinson's disease-associated genes ATP13A2 and SYT11 regulate autophagy via a common pathway

    PubMed Central

    Bento, Carla F.; Ashkenazi, Avraham; Jimenez-Sanchez, Maria; Rubinsztein, David C.

    2016-01-01

    Forms of Parkinson's disease (PD) are associated with lysosomal and autophagic dysfunction. ATP13A2, which is mutated in some types of early-onset Parkinsonism, has been suggested as a regulator of the autophagy–lysosome pathway. However, little is known about the ATP13A2 effectors and how they regulate this pathway. Here we show that ATP13A2 depletion negatively regulates another PD-associated gene (SYT11) at both transcriptional and post-translational levels. Decreased SYT11 transcription is controlled by a mechanism dependent on MYCBP2-induced ubiquitination of TSC2, which leads to mTORC1 activation and decreased TFEB-mediated transcription of SYT11, while increased protein turnover is regulated by SYT11 ubiquitination and degradation. Both mechanisms account for a decrease in the levels of SYT11, which, in turn, induces lysosomal dysfunction and impaired degradation of autophagosomes. Thus, we propose that ATP13A2 and SYT11 form a new functional network in the regulation of the autophagy–lysosome pathway, which is likely to contribute to forms of PD-associated neurodegeneration. PMID:27278822

  18. Multiple Modes of Impulsivity in Parkinson's Disease

    PubMed Central

    Nombela, Cristina; Rittman, Timothy; Robbins, Trevor W.; Rowe, James B.

    2014-01-01

    Cognitive problems are a major factor determining quality of life of patients with Parkinson's disease. These include deficits in inhibitory control, ranging from subclinical alterations in decision-making to severe impulse control disorders. Based on preclinical studies, we proposed that Parkinson's disease does not cause a unified disorder of inhibitory control, but rather a set of impulsivity factors with distinct psychological profiles, anatomy and pharmacology. We assessed a broad set of measures of the cognitive, behavioural and temperamental/trait aspects of impulsivity. Sixty adults, including 30 idiopathic Parkinson's disease patients (Hoehn and Yahr stage I–III) and 30 healthy controls, completed a neuropsychological battery, objective behavioural measures and self-report questionnaires. Univariate analyses of variance confirmed group differences in nine out of eleven metrics. We then used factor analysis (principal components method) to identify the structure of impulsivity in Parkinson's disease. Four principal factors were identified, consistent with four different mechanisms of impulsivity, explaining 60% of variance. The factors were related to (1) tests of response conflict, interference and self assessment of impulsive behaviours on the Barrett Impulsivity Scale, (2) tests of motor inhibitory control, and the self-report behavioural approach system, (3) time estimation and delay aversion, and (4) reflection in hypothetical scenarios including temporal discounting. The different test profiles of these four factors were consistent with human and comparative studies of the pharmacology and functional anatomy of impulsivity. Relationships between each factor and clinical and demographic features were examined by regression against factor loadings. Levodopa dose equivalent was associated only with factors (2) and (3). The results confirm that impulsivity is common in Parkinson's disease, even in the absence of impulse control disorders, and that it is

  19. Aberrant structures of Parkinson's disease-associated ubiquitin C-terminal hydrolase L1 predicted by molecular dynamics

    NASA Astrophysics Data System (ADS)

    Koseki, Yuji; Kinjo, Tomohiro; Kuroki, Masato; Aoki, Shunsuke

    2012-05-01

    Ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) is a neuron-specific deubiquitinating enzyme. Single amino acid changes (S18Y and I93M) within UCH-L1 are associated with decreased and increased risk of Parkinson's disease (PD), respectively. However, the molecular mechanism of pathogenesis in UCH-L1-associated PD remains to be elucidated. In this study, we performed molecular dynamics simulations of UCH-L1 variants. The simulation results show that I93M UCH-L1 is less stable than S18Y UCH-L1. In particular, the H7 and H8 α-helices in I93M UCH-L1 are partially denatured. Information regarding the aberrant UCH-L1 structures provides new insight into UCH-L1-associated PD.

  20. Lack of evidence for a genetic association between FGF20 and Parkinson's disease in Finnish and Greek patients

    PubMed Central

    Clarimon, Jordi; Xiromerisiou, Georgia; Eerola, Johanna; Gourbali, Vanesa; Hellström, Olli; Dardiotis, Euthimios; Peuralinna, Terhi; Papadimitriou, Alexandros; Hadjigeorgiou, George M; Tienari, Pentti J; Singleton, Andrew B

    2005-01-01

    Background Fibroblast growth factor 20 (FGF20) is a neurotrophic factor preferentially expressed in the substantia nigra of rat brain and could be involved in dopaminergic neurons survival. Recently, a strong genetic association has been found between FGF20 gene and the risk of suffering from Parkinson's disease (PD). Our aim was to replicate this association in two independent populations. Methods Allelic, genotypic, and haplotype frequencies of four biallelic polymorphisms were assessed in 151 sporadic PD cases and 186 controls from Greece, and 144 sporadic PD patients and 135 controls from Finland. Results No association was found in any of the populations studied. Conclusion Taken together, these findings suggest that common genetic variants in FGF20 are not a risk factor for PD in, at least, some European populations. PMID:15967032

  1. Milestones in Parkinson's disease therapeutics.

    PubMed

    Rascol, Olivier; Lozano, Andres; Stern, Matthew; Poewe, Werner

    2011-05-01

    In the mid-1980s, the treatment of Parkinson's disease was quite exclusively centered on dopatherapy and was focusing on dopamine systems and motor symptoms. A few dopamine agonists and a monoamine oxidase B inhibitor (selegiline) were used as adjuncts in advanced Parkinson's disease. In the early 2010s, levodopa remains the gold standard. New insights into the organization of the basal ganglia paved the way for deep brain stimulation, especially of the subthalamic nucleus, providing spectacular improvement of drug-refractory levodopa-induced motor complications. Novel dopamine agonists (pramipexole, ropinirole, rotigotine), catecholmethyltransferase inhibitors (entacapone), and monoamine oxidase B inhibitors (rasagiline) have also been developed to provide more continuous oral delivery of dopaminergic stimulation in order to improve motor outcomes. Using dopamine agonists early, before levodopa, proved to delay the onset of dyskinesia, although this is achieved at the price of potentially disabling daytime somnolence or impulse control disorders. The demonstration of an antidyskinetic effect of the glutamate antagonist amantadine opened the door for novel nondopaminergic approaches of Parkinson's disease therapy. More recently, nonmotor symptoms (depression, dementia, and psychosis) have been the focus of the first randomized controlled trials in this field. Despite therapeutic advances, Parkinson's disease continues to be a relentlessly progressive disorder leading to severe disability. Neuroprotective interventions able to modify the progression of Parkinson's disease have stood out as a failed therapeutic goal over the last 2 decades, despite potentially encouraging results with compounds like rasagiline. Newer molecular targets, new animal models, novel clinical trial designs, and biomarkers to assess disease modification have created hope for future therapeutic interventions. PMID:21626552

  2. Impulse control disorders and compulsive behaviors associated with dopaminergic therapies in Parkinson disease

    PubMed Central

    Marsh, Laura

    2012-01-01

    Summary Impulse control disorders (ICD) (most commonly pathologic gambling, hypersexuality, and uncontrollable spending) and compulsive behaviors can be triggered by dopaminergic therapies in Parkinson disease (PD). ICD are especially prevalent in patients receiving a dopamine agonist as part of their treatment regimen for PD, and have also been reported when dopamine agonists are used for other indications (e.g., restless legs syndrome). Although these iatrogenic disorders are common, affecting 1 in 7 patients with PD on dopamine agonists, they often elude detection by the treating physician. ICD lead to serious consequences, causing significant financial loss and psychosocial morbidity for many patients and families. ICD can appear at any time during treatment with dopamine agonists, sometimes within the first few months, but most often after years of treatment, particularly when patients receive dopamine agonists and levodopa together. In most cases ICD resolve if the dopamine agonist is withdrawn, and PD motor symptoms are managed with levodopa monotherapy. Familiarity with the clinical aspects, risk factors, pathophysiology, and management of ICD is essential for physicians using dopaminergic therapies to treat PD and other disorders. PMID:23634371

  3. [Impulse control disorders in Parkinson's disease].

    PubMed

    Joutsa, Juho; Kaasinen, Valtteri

    2013-01-01

    Of the patients having Parkinson's disease, up to third encounters some degree of impulse control problems and one out of seven suffers from true impulse control disorders such as pathological gambling, hypersexuality, compulsive shopping and binge eating. Dopaminergic drugs used in anti-Parkinson therapy, especially dopamine agonists, increase the risk of these disorders. Impulse control disorders are associated with a relatively more active dopamine-mediated neurotransmission of the mesolimbic and mesocortical system. Discontinuation of dopamine agonist medication can thus be considered as the first line treatment of these disorders. PMID:24397147

  4. Stimulus Timing by People with Parkinson's Disease

    ERIC Educational Resources Information Center

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

    2008-01-01

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

  5. Environmental Exposures and Parkinson's Disease.

    PubMed

    Nandipati, Sirisha; Litvan, Irene

    2016-01-01

    Parkinson's disease (PD) affects millions around the world. The Braak hypothesis proposes that in PD a pathologic agent may penetrate the nervous system via the olfactory bulb, gut, or both and spreads throughout the nervous system. The agent is unknown, but several environmental exposures have been associated with PD. Here, we summarize and examine the evidence for such environmental exposures. We completed a comprehensive review of human epidemiologic studies of pesticides, selected industrial compounds, and metals and their association with PD in PubMed and Google Scholar until April 2016. Most studies show that rotenone and paraquat are linked to increased PD risk and PD-like neuropathology. Organochlorines have also been linked to PD in human and laboratory studies. Organophosphates and pyrethroids have limited but suggestive human and animal data linked to PD. Iron has been found to be elevated in PD brain tissue but the pathophysiological link is unclear. PD due to manganese has not been demonstrated, though a parkinsonian syndrome associated with manganese is well-documented. Overall, the evidence linking paraquat, rotenone, and organochlorines with PD appears strong; however, organophosphates, pyrethroids, and polychlorinated biphenyls require further study. The studies related to metals do not support an association with PD. PMID:27598189

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

    ERIC Educational Resources Information Center

    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…

  7. Parkinson's disease in the limelight.

    PubMed

    Graul, A I; Kamerkar, S

    2014-09-01

    The 2014 Lasker-DeBakey Clinical Medical Research Award -one of three prestigious awards granted by the Lasker Foundation in recognition of scientists, clinicians and public servants who have made major advances in the understanding, diagnosis, treatment, cure or prevention of human disease- has been granted to two pioneers in the field of Parkinson's disease therapy. In spite of the availability of more than two dozen drugs and fixed-dose combination products to treat the symptoms of Parkinson's disease -most notably the gold standard levodopa, a dopamine precursor- as well as nonpharmacological treatments like deep brain stimulation, many patients do not respond to available drugs or experience breakthrough symptoms, and the disease is ultimately uncurable. This article reviews currently available therapies as well as biomarkers and novel diagnostics. PMID:25313370

  8. Transcranial sonography and functional imaging in glucocerebrosidase mutation Parkinson disease

    PubMed Central

    Barrett, MJ; Hagenah, J; Dhawan, V; Peng, S; Stanley, K; Raymond, D; Deik, A; Gross, SJ; Schreiber-Agus, N; Mirelman, A; Marder, K; Ozelius, LJ; Eidelberg, D; Bressman, SB; Saunders-Pullman, R

    2012-01-01

    Background Heterozygous glucocerebrosidase (GBA) mutations are the leading genetic risk factor for Parkinson disease, yet imaging correlates, particularly transcranial sonography, have not been extensively described. Methods To determine whether GBA mutation heterozygotes with Parkinson disease demonstrate hyperechogenicity of the substantia nigra, transcranial sonography was performed in Ashkenazi Jewish Parkinson disease subjects, tested for the eight most common Gaucher disease mutations and the LRRK2 G2019S mutation, and in controls. [18F]-fluorodeoxyglucose or [18F]-fluorodopa positron emission tomography is also reported from a subset of Parkinson disease subjects with heterozygous GBA mutations. Results Parkinson disease subjects with heterozygous GBA mutations (n=23) had a greater median maximal area of substantia nigral echogenicity compared to controls (n=34, aSNmax=0.30 vs. 0.18, p=0.007). There was no difference in median maximal area of nigral echogenicity between Parkinson disease groups defined by GBA and LRRK2 genotype: GBA heterozygotes; GBA homozygotes/compound heterozygotes (n=4, aSNmax=0.27); subjects without LRRK2 or GBA mutations (n=32, aSNmax=0.27); LRRK2 heterozygotes/homozyogotes without GBA mutations (n=27, aSNmax=0.28); and GBA heterozygotes/LRRK2 heterozygotes (n=4, aSNmax=0.32, overall p=0.63). In secondary analyses among Parkinson disease subjects with GBA mutations, maximal area of nigral echogenicity did not differ based on GBA mutation severity or mutation number. [18F]-fluorodeoxyglucose (n=3) and [18F]-fluorodopa (n=2) positron emission tomography in Parkinson disease subjects with heterozygous GBA mutations was consistent with findings in idiopathic Parkinson disease. Conclusions Both transcranial sonography and positron emission tomography are abnormal in GBA mutation associated Parkinson disease, similar to other Parkinson disease subjects. PMID:23062841

  9. [Cognitive dysfunction in Parkinson's disease].

    PubMed

    Maruyama, T

    2000-10-01

    The neuropsychological impairments associated with Parkinson's disease(PD) have been often documented. However, the pathological mechanisms underlying cognitive dysfunction are hardly solved, as compared with motor dysfunction. Moreover, the precise relationships between the two dysfunctions have remained aloof. This paper attempts to clarify three specific domains of isolated cognitive impairments: dysexecutive syndrome, memory disturbance, and bradyphrenia, which are specifically observed in PD. It especially discusses the neuropsychological relationships between these impairments and the stages of illness. Several neuropsychological experiments to examine these three domains of cognitive impairments were conducted. Significant results were obtained in the following: set-shifting and divergent thinking were significantly impaired in both the early group and the advanced group; while set-maintaining, procedural learning, and cognitive speed, were only significantly disturbed in the advanced group. The failure to acquire procedural skills and the slowing of cognitive speed, were correlated with decreased attention of working memory in the advanced group. These results indicate that the shifting of cognitive sets maybe disturbed in the embryonic stage of the disease. The results also indicated that other cognitive dysfunctions might manifest themselves during the advanced stages due to attentional deficits. In conclusion, it is possible that other neurotransmitters maybe involved in the progressive degeneration of other systems in addition to the dopaminergic system. For example: serotoninergic, noradrenergic and cholinergic systems. Therefore, further research is required to establish which neurotransmitters are involved in their corresponding cognitive impairments in PD. PMID:11068439

  10. Disease-modifying strategies for Parkinson's disease.

    PubMed

    Kalia, Lorraine V; Kalia, Suneil K; Lang, Anthony E

    2015-09-15

    Parkinson's disease (PD) is an increasingly prevalent and progressively disabling neurodegenerative disease. The impact of PD on patients and their families as well as its burden on health care systems could be substantially reduced by disease-modifying therapies that slow the rate of neurodegeneration or stop the disease process. Multiple agents have been studied in clinical trials designed to assess disease modification in PD, but all have failed. Over the last 3 years, clinical trials investigating the potential of adeno-associated virus serotype 2 (AAV)-neuturin, coenzyme Q10, creatine, pramipexole, and pioglitazone reported negative findings or futility. Despite these disappointments, progress has been made by expanding our understanding of molecular pathways involved in PD to reveal new targets, and by developing novel animal models of PD for preclinical studies. Currently, at least eight ongoing clinical trials are testing the promise of isradipine, caffeine, nicotine, glutathione, AAV2-glial cell-line derived neurotrophic factor (GDNF), as well as active and passive immunization against α-synuclein (α-Syn). In this review, we summarize the clinical trials of disease-modifying therapies for PD that were published since 2013 as well as clinical trials currently in progress. We also discuss promising approaches and ongoing challenges in this area of PD research. PMID:26208210

  11. [Molecular genetics of Parkinson's disease].

    PubMed

    Toda, Tatsushi

    2007-08-01

    Parkinson's disease (PD) is the second most common neurodegenerative disorder in the world. The occurrence of PD is largely sporadic, while several families with Mendelian segregation of PD have been reported. PD is thought to be caused by mitochondrial dysfunction, oxidative stress and inflammation based on multiple genetic and environmental factors, resulting in the apoptosis of dopaminergic cells. Six causal genes for Mendelian inherited PD have been identified to date, which indicate the importance of the ubiquitin-proteasome pathway in the molecular pathogenesis of dopaminergic cell death. Recent studies have also indicated the involvement of genetic factors in the pathogenesis of sporadic PD. Many association studies on candidate genes have examined the relationship between PD and polymorphisms; We identified a-synuclein as a definite susceptibility gene for sporadic PD. Since 2001, significant linkage to several loci have been reported in samples of affected sibling pairs. With the recent advances in human genome analyses, genome-wide association studies by SNP chip are being performed to identify susceptibility genes and to establish tailor-made medicine for PD. PMID:17713117

  12. Lower plasma apolipoprotein A1 levels are found in Parkinson's disease and associate with apolipoprotein A1 genotype.

    PubMed

    Swanson, Christine R; Li, Katherine; Unger, Travis L; Gallagher, Michael D; Van Deerlin, Vivianna M; Agarwal, Pinky; Leverenz, James; Roberts, John; Samii, Ali; Gross, Rachel Goldmann; Hurtig, Howard; Rick, Jacqueline; Weintraub, Daniel; Trojanowski, John Q; Zabetian, Cyrus; Chen-Plotkin, Alice S

    2015-05-01

    The discovery of novel plasma-based biomarkers could lead to new approaches in the treatment of Parkinson's disease (PD). Here, we explore the role of plasma apolipoprotein A1 (ApoA1) as a risk marker for PD and evaluate the influence of APOA1 promoter variation on plasma ApoA1 levels. Plasma ApoA1 and the single-nucleotide polymorphism, rs670, were assayed in a discovery cohort (cohort 1) of 301 PD patients, 80 normal controls (NCs), and 165 subjects with other neurodegenerative diseases, as well as a cohort (cohort 2) of 158 PD patients from a second clinical site. Additionally, rs670 was genotyped in a third cohort of 1,494 PD and 925 NC subjects from both clinical sites. Compared to both normal and disease controls, PD patients have lower plasma ApoA1 (P < 0.001 for both comparisons). Moreover, in PD patients, plasma ApoA1 levels are correlated with genotype at the APOA1 promoter polymorphism, rs670. Specifically, lower plasma ApoA1 levels were found in rs670 major allele (G) homozygotes in both cohort 1 (P = 0.009) and in a replication cohort (cohort 2; n = 158 PD patients; P = 0.024). Finally, evaluating rs670 genotype frequencies in 1,930 PD cases versus 997 NCs, the rs670 GG genotype shows a trend toward association (odds ratio: 1.1; P = 0.10) with PD. Our results are compatible with a model whereby circulating ApoA1 levels may be useful in risk-stratifying subjects for the development of PD, with higher ApoA1 levels suggesting relative protection. Future studies evaluating modulation of ApoA1 as a novel therapeutic strategy in PD are warranted. © 2014 International Parkinson and Movement Disorder Society. PMID:25227208

  13. Reduced risk of Parkinson's disease associated with lower body mass index and heavy leisure-time physical activity.

    PubMed

    Sääksjärvi, Katri; Knekt, Paul; Männistö, Satu; Lyytinen, Jukka; Jääskeläinen, Tuija; Kanerva, Noora; Heliövaara, Markku

    2014-04-01

    The risk factors for Parkinson's disease (PD) are not well established. We therefore examined the prediction of various lifestyle factors on the incidence of PD in a cohort drawn from the Finnish Mobile Clinic Health Examination Survey, conducted in 1973-1976. The study population comprised 6,715 men and women aged 50-79 years and free of PD at the baseline. All of the subjects completed a baseline health examination (including height and weight measurements) and a questionnaire providing information on leisure-time physical activity, smoking, and alcohol consumption. During a 22-year follow-up, 101 incident cases of PD occurred. The statistical analyses were based on Cox's model including age, sex, education, community density, occupation, coffee consumption, body mass index (BMI), leisure-time physical activity, smoking and alcohol consumption as independent variables. At first, BMI was not associated with PD risk, but after exclusion of the first 15 years of follow-up, an elevated risk appeared at higher BMI levels (P for trend 0.02). Furthermore, subjects with heavy leisure-time physical activity had a lower PD risk than those with no activity [relative risk (RR) 0.27, 95 % confidence interval (CI) 0.08-0.90]. In variance with findings for other chronic diseases, current smokers had a lower PD risk than those who had never smoked (RR 0.23, 95 % CI 0.08-0.67), and individuals with moderate alcohol intake (at the level of <5 g/day) had an elevated PD risk compared to non-drinkers. The results support the hypothesis that lifestyle factors predict the occurrence of Parkinson's disease, but more research is needed. PMID:24633681

  14. Autonomic disorders predicting Parkinson disease

    PubMed Central

    Palma, Jose-Alberto; Kaufmann, Horacio

    2014-01-01

    It is now well recognized that there is a premotor phase of Parkinson disease with hyposmia and REM sleep behavior disorder caused by degeneration of specific CNS neurons. Most patients with PD describe autonomic symptoms at the time of diagnosis suggesting that these features may have potential sensitivity as clinical biomarkers of the premotor phase. The recognition that damage to peripheral autonomic neurons is present in the early stages of Parkinson disease has led to a search for specific abnormalities in autonomic function that could serve as predictive biomarkers. There is evidence that constipation, urinary and sexual dysfunction and more recently decreased cardiac chronotropic response during exercise, are part of the premotor parkinsonian phenotype. The sensitivity and specificity of these features has yet to be accurately assessed. We briefly review the evidence for autonomic dysfunction as biomarkers of premotor PD. PMID:24262198

  15. Virtual visits for Parkinson disease

    PubMed Central

    Venkataraman, Vinayak; Donohue, Sean J.; Biglan, Kevin M.; Wicks, Paul

    2014-01-01

    Summary We sought to characterize recommendations and feedback of patients with Parkinson disease, each offered a free telemedicine consultation with a specialist. Visits consisted of history, neurologic examination, and recommendations. Midway through the program, patients were asked to complete an online satisfaction survey. From August 2012 to May 2013, 55 patients in 5 states (mean age 67.8 years) participated, with 80% of visits conducted from their home. Patients with Parkinson disease were recommended to exercise (86%), change current medication (63%), and add new medication (53%). Thirty-three of 35 consecutive patients completed a survey. Patient satisfaction exceeded 90% for virtually all aspects of the visit measured. Providing care to patients in their homes via telemedicine is feasible, results in changes to care, and is well-received. PMID:24790799

  16. Associative learning in degenerative neostriatal disorders: contrasts in explicit and implicit remembering between Parkinson's and Huntington's diseases.

    PubMed

    Sprengelmeyer, R; Canavan, A G; Lange, H W; Hömberg, V

    1995-01-01

    The performances of 12 patients with Parkinson's disease (PD), 16 with Huntington's disease (HD), and young and old healthy controls were assessed on a number of tests of verbal and nonverbal declarative memory, on a test of nonmotor conditional associative learning (words and colors), and on a number of reaction time (RT) tasks. The RT tasks consisted of cued simple and choice reactions. The relationship between the precue and the imperative stimulus in the S1-S2 paradigm was nonarbitrary in the first series and arbitrary in the second series. The series with arbitrary S1-S2 associations was repeated across two successive blocks of trials. The rationale of the study was to investigate the function of the basal ganglia "complex loop," and it was postulated that HD patients would show greater deficits because of greater involvement of the caudate nucleus. The patients with HD had the slowest RTs. Across the two blocks with arbitrary S1-S2 associations, the patients with HD but not PD nevertheless showed evidence of learning in their precued RTs. In contrast, the patients with PD were better able to remember the associations in free recall than were the HD patients. It is concluded that patients with PD have relatively greater deficits in procedural learning, whereas those with HD have relatively more impairments in declarative memory, and the greater level of cognitive impairment in HD overall is interpreted as being due to more serious damage to the caudate loop. PMID:7885356

  17. The analysis of association between SNCA, HUSEYO and CSMD1 gene variants and Parkinson's disease in Iranian population.

    PubMed

    Shahmohammadibeni, Neda; Rahimi-Aliabadi, Simin; Jamshidi, Javad; Emamalizadeh, Babak; Shahmohammadibeni, Hossein Ali; Zare Bidoki, Alireza; Akhavan-Niaki, Haleh; Eftekhari, Hajar; Abdollahi, Shokoufeh; Shekari Khaniani, Mahmoud; Shahmohammadibeni, Mahnaz; Fazeli, Atena; Motallebi, Marzieh; Taghavi, Shaghayegh; Ahmadifard, Azadeh; Shafiei Zarneh, Amir Ehtesham; Andarva, Monavvar; Dadkhah, Tahereh; Khademi, Ehteram; Alehabib, Elham; Rahimi, Mahnoosh; Tafakhori, Abbas; Atakhorrami, Minoo; Darvish, Hossein

    2016-05-01

    Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder. Both genetic and environmental factors are involved in the etiology of the disease. Many studies have revealed the susceptibility genes and variations for PD which need further confirmation. Here we evaluated the association of variations in SNCA, HUSEYO and CSMD1 genes with PD. A case-control study was conducted with 489 PD patients and 489 healthy controls. DNA was extracted from peripheral blood of all subjects and rs356220 and rs11931074 in SNCA, rs2338971 in HUSEYO and rs12681349 in CSMD1 were genotyped using PCR-RFLP method. The genotypes and allele frequencies were significantly different between case and control groups for rs356220, rs11931074 and rs2338971 but not for rs12681349. We provided further evidence that rs356220 is associated with increased risk of PD supporting previous studies in Caucasian-based and Japanese populations. The association of rs11931074 with decreased risk of PD was also significant. This study revealed the first evidence of the association of rs2338971 with increased risk of PD in the Iranian population. Nevertheless, these findings need further validation via more replication studies. PMID:26732583

  18. Cognitive impairment in Parkinson's disease.

    PubMed

    Cosgrove, Jeremy; Alty, Jane Elizabeth; Jamieson, Stuart

    2015-04-01

    Cognitive impairment is a significant non-motor symptom of Parkinson's disease (PD). Longitudinal cohort studies have demonstrated that approximately 50% of those with PD develop dementia after 10 years, increasing to over 80% after 20 years. Deficits in cognition can be identified at the time of PD diagnosis in some patients and this mild cognitive impairment (PD-MCI) has been studied extensively over the last decade. Although PD-MCI is a risk factor for developing Parkinson's disease dementia there is evidence to suggest that PD-MCI might consist of distinct subtypes with different pathophysiologies and prognoses. The major pathological correlate of Parkinson's disease dementia is Lewy body deposition in the limbic system and neocortex although Alzheimer's related pathology is also an important contributor. Pathological damage causes alteration to neurotransmitter systems within the brain, producing behavioural change. Management of cognitive impairment in PD requires a multidisciplinary approach and accurate communication with patients and relatives is essential. PMID:25814509

  19. Targeting delivery in Parkinson's disease.

    PubMed

    Newland, Ben; Dunnett, Stephen B; Dowd, Eilís

    2016-08-01

    Disease-modifying therapies for Parkinson's disease (PD), with the potential to halt the neurodegenerative process and to stimulate the protection, repair, and regeneration of dopaminergic neurons, remain a vital but unmet clinical need. Targeting the delivery of current and new therapeutics directly to the diseased brain region (in particular the nigrostriatal pathway) could result in greater improvements in the motor functions that characterise PD. Here, we highlight some of the opportunities and challenges facing the development of the next generation of therapies for patients with PD. PMID:27312875

  20. Parkinson's Disease: Assay of Phosphorylated α-Synuclein in Skin Biopsy for Early Diagnosis and Association with Melanoma.

    PubMed

    Surguchov, Andrei

    2016-01-01

    Parkinson's disease (PD) is a degenerative disorder of the central nervous system, in which a small naturally unfolded protein α-synuclein plays an essential role. α-Synuclein belongs to a synuclein family comprising three members: α, β, and γ-synucleins associated with neurodegenerative and neoplastic diseases and involved in development. Several studies revealed that α-synuclein is present not only in the brain, but also in the skin and other peripheral tissues. This finding open a new approach to PD diagnosis based on the assay of α-synuclein from a biological sample of a living patient. Furthermore, PD is associated with an increased risk of skin melanoma. An important posttranslational modification of α-synuclein is phosphorylation at serine-129, which may convert the protein into pathological species both in PD and melanoma. Thus, analysis of phosphorylated α-synuclein might be an important diagnostic test for both diseases providing additional information about the mechanism of pathology. PMID:27240409

  1. Associations between Vitamin D Status, Supplementation, Outdoor Work and Risk of Parkinson's Disease: A Meta-Analysis Assessment.

    PubMed

    Shen, Liang; Ji, Hong-Fang

    2015-06-01

    The present study aimed to quantitatively assess the associations between vitamin D and Parkinson's Disease (PD) risks, which include: (i) risk of PD in subjects with deficient and insufficient vitamin D levels; (ii) association between vitamin D supplementation and risk of PD; and (iii) association between outdoor work and PD risk, through meta-analyzing available data. An electronic literature search supplemented by hand searching up to March 2015 identified seven eligible studies comprising 5690 PD patients and 21251 matched controls. Odds ratio (OR) and 95% confidence interval (CI) of PD risk were assessed through pooling the collected data from eligible studies using Stata software. Pooled data showed that subjects with deficient and insufficient vitamin D levels had increased PD risks compared with matched-controls according to the corresponding OR: 2.08, 95% CI: 1.63 to 2.65, and 1.29, 95% CI: 1.10 to 1.51. Vitamin D supplementation was associated with significantly reduced risk of PD (OR: 0.62, 95% CI: 0.35 to 0.90). Outdoor work was also related to reduced risk of PD (OR: 0.72, 95% CI: 0.63 to 0.81). The findings may stimulate larger, well-designed studies to further verify the associations between vitamin D and PD risk. PMID:26083115

  2. Familial Parkinson Disease-associated Mutations Alter the Site-specific Microenvironment and Dynamics of α-Synuclein*

    PubMed Central

    Sahay, Shruti; Ghosh, Dhiman; Dwivedi, Saumya; Anoop, Arunagiri; Mohite, Ganesh Maruti; Kombrabail, Mamata; Krishnamoorthy, Guruswamy; Maji, Samir K.

    2015-01-01

    Human α-synuclein (α-Syn) is a natively unstructured protein whose aggregation into amyloid fibrils is associated with Parkinson disease (PD) pathogenesis. Mutations of α-Syn, E46K, A53T, and A30P, have been linked to the familial form of PD. In vitro aggregation studies suggest that increased propensity to form non-fibrillar oligomers is the shared property of these familial PD-associated mutants. However, the structural basis of the altered aggregation propensities of these PD-associated mutants is not yet clear. To understand this, we studied the site-specific structural dynamics of wild type (WT) α-Syn and its three PD mutants (A53T, E46K, and A30P). Tryptophan (Trp) was substituted at the N terminus, central hydrophobic region, and C terminus of all α-Syns. Using various biophysical techniques including time-resolved fluorescence studies, we show that irrespective of similar secondary structure and early oligomerization propensities, familial PD-associated mutations alter the site-specific microenvironment, solvent exposure, and conformational flexibility of the protein. Our results further show that the common structural feature of the three PD-associated mutants is more compact and rigid sites at their N and C termini compared with WT α-Syn that may facilitate the formation of a partially folded intermediate that eventually leads to their increased oligomerization propensities. PMID:25635052

  3. Orthostatic and Supine Blood Pressures Are Associated with White Matter Hyperintensities in Parkinson Disease

    PubMed Central

    Oh, Yoon-Sang; Kim, Joong-Seok; Lee, Kwang-Soo

    2013-01-01

    Background and Purpose: Several reports on the elderly population have suggested that orthostatic hypotension is associated with white matter hyperintensities (WMH); however, little information is available on patients with Parkinson’s disease (PD). Methods: We analyzed the association blood pressure profiles during tilt table testing with WMH scores in 117 patients with PD. WMH were rated using the semiquantitative visual rating system proposed by Scheltens et al. Results: The presence of orthostatic hypotension was associated with increasing tendency of WMH score and the blood pressure changes during tilting and supine blood pressure were positively correlated with increasing WMH score. Conclusions: This finding indicates that hemodynamic changes associated with orthostatic hypotension may be associated with white matter changes in patients with PD. PMID:24868422

  4. Exercise therapy for Parkinson's disease.

    PubMed

    Palmer, S S; Mortimer, J A; Webster, D D; Bistevins, R; Dickinson, G L

    1986-10-01

    The outcomes of two different 12-week exercise programs were assessed by machine measurements of motor signs, tests of grip strength, motor coordination and speed, and neurophysiologic determinations of long-latency stretch responses in two groups of Parkinson patients matched for age, sex and stage of disease. The programs tested included an exercise program developed by the United Parkinson Foundation and a program of upper body karate training. Outcomes of these programs were similar. The majority of patients in both groups showed improvements in gait, tremor, grip strength and motor coordination on tasks requiring fine control. In one task involving whole body coordination there was a decline in function, while muscle rigidity was unchanged. The findings suggest that exercise is a useful adjunct to pharmacologic therapy. PMID:3767624

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

    PubMed

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

    2015-10-01

    Post-mortem and neuroimaging studies suggest that the serotonergic system, which originates from the brainstem raphe nuclei, is disrupted in Parkinson's disease. This could contribute to the occurrence of non-motor symptoms and tremor, which are only partially explained by dopamine loss. However, the level of involvement of the serotonergic raphe nuclei in early Parkinson's disease is still debated. (123)I-FP-CIT single photon emission computed tomography is a marker of dopamine and serotonin transporter availability. While (123)I-FP-CIT binds primarily to dopamine transporters in the striatum, its binding in the brainstem raphe nuclei reflects serotonin transporter availability. We interrogated baseline single photon emission computed tomography scans of subjects recruited by the Parkinson's Progression Markers Initiative to determine: (i) the integrity of the brainstem raphe nuclei in early Parkinson's disease; and (ii) whether raphe serotonin transporter levels correlate with severity of tremor and symptoms of fatigue, depression, and sleep disturbance. Three hundred and forty-five patients with early drug-naïve Parkinson's disease, 185 healthy controls, and 56 subjects with possible Parkinson's disease without evidence of dopaminergic deficit were included. In the Parkinson's disease cohort, 37 patients had a tremulous, 106 patients had a pure akinetic-rigid, and 202 had a mixed phenotype. Patients with Parkinson's disease had significantly lower serotonin transporter availability in the brainstem raphe nuclei compared to controls (P < 0.01) and subjects without evidence of dopaminergic deficit (P < 0.05). However, only 13% of patients with Parkinson's disease individually had reduced signals. Raphe serotonin transporter availability over the entire Parkinson's disease cohort were associated with rest tremor amplitude (β = -0.106, P < 0.05), rest tremor constancy (β = -0.109, P < 0.05), and index of rest tremor severity (β = -0.104, P < 0.05). The tremulous

  6. Clinical and Epidemiological Factors Associated with Mortality in Parkinson's Disease in a Brazilian Cohort

    PubMed Central

    Fernandes, Gustavo Costa; Socal, Mariana Peixoto; Schuh, Artur Francisco Schumacher; Rieder, Carlos R. M.

    2015-01-01

    Background. Prognosis of PD is variable. Most studies show higher mortality rates in PD patients compared to the general population. Clinical and epidemiologic factors predicting mortality are poorly understood. Methods. Clinical and epidemiologic features including patient history and physical, functional, and cognitive scores were collected from a hospital-based cohort of PD patients using standardized protocols and clinical scales. Data on comorbidities and mortality were collected on follow-up. Results. During a mean follow-up of 4.71 years (range 1–10), 43 (20.9%) of the 206 patients died. Those who died had higher mean age at disease onset than those still alive at the last follow-up (67.7 years versus 56.3 years; p < 0.01). In the univariate analysis, age at baseline was associated with decreased survival. In the adjusted Cox proportional hazards model, age at disease onset and race/ethnicity were predictors of mortality. Conclusions. Late age at disease onset and advanced chronological age are associated with decreased survival. Comorbidities and PD characteristics were not associated with decreased survival in our sample. Race/ethnicity was found in our study to be associated with increased hazard of mortality. Our findings indicate the importance of studying survival among different populations of PD patients. PMID:26819798

  7. Clinical and Epidemiological Factors Associated with Mortality in Parkinson's Disease in a Brazilian Cohort.

    PubMed

    Fernandes, Gustavo Costa; Socal, Mariana Peixoto; Schuh, Artur Francisco Schumacher; Rieder, Carlos R M

    2015-01-01

    Background. Prognosis of PD is variable. Most studies show higher mortality rates in PD patients compared to the general population. Clinical and epidemiologic factors predicting mortality are poorly understood. Methods. Clinical and epidemiologic features including patient history and physical, functional, and cognitive scores were collected from a hospital-based cohort of PD patients using standardized protocols and clinical scales. Data on comorbidities and mortality were collected on follow-up. Results. During a mean follow-up of 4.71 years (range 1-10), 43 (20.9%) of the 206 patients died. Those who died had higher mean age at disease onset than those still alive at the last follow-up (67.7 years versus 56.3 years; p < 0.01). In the univariate analysis, age at baseline was associated with decreased survival. In the adjusted Cox proportional hazards model, age at disease onset and race/ethnicity were predictors of mortality. Conclusions. Late age at disease onset and advanced chronological age are associated with decreased survival. Comorbidities and PD characteristics were not associated with decreased survival in our sample. Race/ethnicity was found in our study to be associated with increased hazard of mortality. Our findings indicate the importance of studying survival among different populations of PD patients. PMID:26819798

  8. [Music therapy on Parkinson disease].

    PubMed

    Côrte, Beltrina; Lodovici Neto, Pedro

    2009-01-01

    This study is a result of a qualitative research, in the Gerontology and Music therapy scenario. It was analyzed the importance of alternative practices like playing an instrument (piano, violin, etc.), singing, or practicing a guided musical exercise as a therapy activity for elder people with Parkinson Disease. The analysis, systematization and interpretation of the data pointed: music therapy is an excellent way to improve the life of the patient that becomes more sociable, decreasing physical and psychological symptoms ('symptomatology') and the subject change for a singular and own position in the relation with your disease and the people around. PMID:20069199

  9. O-GlcNAc modification blocks the aggregation and toxicity of the protein α-synuclein associated with Parkinson's disease

    NASA Astrophysics Data System (ADS)

    Marotta, Nicholas P.; Lin, Yu Hsuan; Lewis, Yuka E.; Ambroso, Mark R.; Zaro, Balyn W.; Roth, Maxwell T.; Arnold, Don B.; Langen, Ralf; Pratt, Matthew R.

    2015-11-01

    Several aggregation-prone proteins associated with neurodegenerative diseases can be modified by O-linked N-acetyl-glucosamine (O-GlcNAc) in vivo. One of these proteins, α-synuclein, is a toxic aggregating protein associated with synucleinopathies, including Parkinson's disease. However, the effect of O-GlcNAcylation on α-synuclein is not clear. Here, we use synthetic protein chemistry to generate both unmodified α-synuclein and α-synuclein bearing a site-specific O-GlcNAc modification at the physiologically relevant threonine residue 72. We show that this single modification has a notable and substoichiometric inhibitory effect on α-synuclein aggregation, while not affecting the membrane binding or bending properties of α-synuclein. O-GlcNAcylation is also shown to affect the phosphorylation of α-synuclein in vitro and block the toxicity of α-synuclein that was exogenously added to cells in culture. These results suggest that increasing O-GlcNAcylation may slow the progression of synucleinopathies and further support a general function for O-GlcNAc in preventing protein aggregation.

  10. Parkinson's Disease Dementia

    MedlinePlus

    ... Is Dementia Types of Dementia Chronic Traumatic Encephalopathy (CTE) Creutzfeldt-Jakob Disease Dementia with Lewy Bodies Down ... Research Traumatic Brain Injury and Chronic Traumatic Encephalopathy (CTE) Awardees Year Researcher Study Name 2015 Jesse Mez ...

  11. Parkinson's Disease Glossary

    MedlinePlus

    ... by stereotactic methods. They are connected to the operating room computer and used to measure the electrical ... categorized as movement disorders include essential tremor , multiple system atrophy , progressive supranuclear palsy , Huntington's disease, Tourette's syndrome ...

  12. Psychiatric aspects of Parkinson's disease

    PubMed Central

    Grover, Sandeep; Somaiya, Mansi; Kumar, Santhosh; Avasthi, Ajit

    2015-01-01

    Parkinson's disease (PD) is essentially characterized by the motor symptoms in the form of resting tremor, rigidity and bradykinesia. However, over the years it has been recognized that motor symptoms are just the “tip of the iceberg” of clinical manifestations of PD. Besides motor symptoms, PD characterized by many non-motor symptoms, which include cognitive decline, psychiatric disturbances (depression, psychosis and impulse control), sleep difficulties, autonomic failures (gastrointestinal, cardiovascular, urinary, thermoregulation) and pain syndrome. This review evaluates the various aspects of psychiatric disorders including cognitive decline and sleep disturbances in patients with PD. The prevalence rate of various psychiatric disorders is high in patients with PD. In terms of risk factors, various demographic, clinical and treatment-related variables have been shown to be associated with higher risk of development of psychiatric morbidity. Evidence also suggests that the presence of psychiatric morbidity is associated with poorer outcome. Randomized controlled trials, evaluating the various pharmacological and non-pharmacological treatments for management of psychiatric morbidity in patients with PD are meager. Available evidence suggests that tricyclic antidepressants like desipramine and nortriptyline are efficacious for management of depression. Among the antipsychotics, clozapine is considered to be the best choice for management of psychosis in patients with PD. Among the various cognitive enhancers, evidence suggest efficacy of rivastigmine in management of dementia in patients with PD. To conclude, this review suggests that psychiatric morbidity is highly prevalent in patients with PD. Hence, a multidisciplinary approach must be followed to improve the overall outcome of PD. Further studies are required to evaluate the efficacy of various other measures for management of psychiatric morbidity in patients with PD. PMID:25552854

  13. The neuropsychiatry of Parkinson's disease.

    PubMed

    Lauterbach, E C

    2005-06-01

    The neuropsychiatry of Parkinson's disease (PD) and its correlates are reviewed. Dementia occurs in up to 30% and can be treated with cholinesterase inhibitors. Cognitive impairments involve executive, visuospatial, attentional, and memory dysfunctions. Apathy may respond to dopamine agonists or cholines-terase inhibitors. Cognitive impairment, psychosis, and depression predict quality of life. Visual hallucinations and paranoia are common, and respond to low dose clozapine. Depression is common and predicts caregiver burden and depression. The best data suggest the efficacy of nortriptyline and the safety of SSRIs. Anxiety disorders occur in 40% of patients, especially off-period panic attacks and specific phobias. Bromazepam has proven useful for anxiety in PD, but buspirone has only diminished drug-induced dyskinesias to date. Sleep disorders occur in up to 94% of patients. Insomnia is common and is treated by dopaminergic agent dose reduction, nocturnal dosing, treatment of depression, or use of short half-lived hypnotics, depending on etiology. Parasomnias include REM behavior disorder and vivid dreams and nightmares. Excessive daytime somnolence occurs in at least 15% of patients. Sleep attacks are common and patients should be warned about driving when taking dopamine agonists. Sexual disorders occur in most patients. Paraphilias are associated with dopamine agonists, and clozapine may be useful in their treatment. Surgical therapies are associated with a wide variety of neuropsychiatric features, and vigilance for suicide attempts with subthalamic nucleus stimulation seems warranted. Neuropsychiatric disorders are important determinants of quality of life and caregiver burden in PD. More clinical research is needed to establish effective treatments. PMID:16175159

  14. Psychiatric aspects of Parkinson's disease.

    PubMed

    Grover, Sandeep; Somaiya, Mansi; Kumar, Santhosh; Avasthi, Ajit

    2015-01-01

    Parkinson's disease (PD) is essentially characterized by the motor symptoms in the form of resting tremor, rigidity and bradykinesia. However, over the years it has been recognized that motor symptoms are just the "tip of the iceberg" of clinical manifestations of PD. Besides motor symptoms, PD characterized by many non-motor symptoms, which include cognitive decline, psychiatric disturbances (depression, psychosis and impulse control), sleep difficulties, autonomic failures (gastrointestinal, cardiovascular, urinary, thermoregulation) and pain syndrome. This review evaluates the various aspects of psychiatric disorders including cognitive decline and sleep disturbances in patients with PD. The prevalence rate of various psychiatric disorders is high in patients with PD. In terms of risk factors, various demographic, clinical and treatment-related variables have been shown to be associated with higher risk of development of psychiatric morbidity. Evidence also suggests that the presence of psychiatric morbidity is associated with poorer outcome. Randomized controlled trials, evaluating the various pharmacological and non-pharmacological treatments for management of psychiatric morbidity in patients with PD are meager. Available evidence suggests that tricyclic antidepressants like desipramine and nortriptyline are efficacious for management of depression. Among the antipsychotics, clozapine is considered to be the best choice for management of psychosis in patients with PD. Among the various cognitive enhancers, evidence suggest efficacy of rivastigmine in management of dementia in patients with PD. To conclude, this review suggests that psychiatric morbidity is highly prevalent in patients with PD. Hence, a multidisciplinary approach must be followed to improve the overall outcome of PD. Further studies are required to evaluate the efficacy of various other measures for management of psychiatric morbidity in patients with PD. PMID:25552854

  15. Genetic Variants in MicroRNAs and Their Binding Sites Are Associated with the Risk of Parkinson Disease.

    PubMed

    Ghanbari, Mohsen; Darweesh, Sirwan K L; de Looper, Hans W J; van Luijn, Marvin M; Hofman, Albert; Ikram, M Arfan; Franco, Oscar H; Erkeland, Stefan J; Dehghan, Abbas

    2016-03-01

    MicroRNAs (miRNAs) are small noncoding RNAs that serve as key regulators of gene expression. They have been shown to be involved in a wide range of biological processes including neurodegenerative diseases. Genetic variants in miRNAs or miRNA-binding sites on their target genes could affect miRNA function and contribute to disease risk. Here, we investigated the association of miRNA-related genetic variants with Parkinson disease (PD) using data from the largest GWAS on PD. Of 243 miRNA variants, we identified rs897984:T>C in miR-4519 (P value = 1.3×10(-5) and OR = 0.93) and rs11651671:A>G in miR-548at-5p (P value = 1.1×10(-6) and OR = 1.09) to be associated with PD. We showed that the variant's mutant alleles change the secondary structure and decrease expression level of their related miRNAs. Subsequently, we highlighted target genes that might mediate the effects of miR-4519 and miR-548at-5p on PD. Among them, we experimentally showed that NSF is a direct target of miR-4519. Furthermore, among 48,844 miRNA-binding site variants, we found 32 variants (within 13 genes) that are associated with PD. Four of the host genes, CTSB, STX1B, IGSF9B, and HSD3B7, had not previously been reported to be associated with PD. We provide evidence supporting the potential impact of the identified miRNA-binding site variants on miRNA-mediated regulation of their host genes. PMID:26670097

  16. [Epigenetics in Parkinson's Disease].

    PubMed

    Wüllner, U

    2016-07-01

    The genetic information encoded in the DNA sequence provides a blueprint of the entire organism. The epigenetic modifications, in particular DNA methylation and histone modifications, determine how and when this information is made available and define the specific gene transcription pattern of a given cell. Epigenetic modifications determine the functional differences of genetically identical cells in multicellular organisms and are important factors in various processes from embryonic development to learning and memory consolidation. DNA methylation patterns are altered by environmental conditions and some alterations are preserved through mitosis and meiosis. Thus, DNA methylation can mediate environmental impact on health and disease, contributes to the severity of diseases and probably contributes to the effects and side effects of drugs. In addition to the classical monogenic epigenetic diseases such as Prader-Willi syndrome and Rett syndrome, recent data point to an epigenetic component also in sporadic neuro-psychiatric disorders. PMID:27299943

  17. Impulse control disorders in Parkinson's disease are associated with dysfunction in stimulus valuation but not action valuation.

    PubMed

    Piray, Payam; Zeighami, Yashar; Bahrami, Fariba; Eissa, Abeer M; Hewedi, Doaa H; Moustafa, Ahmed A

    2014-06-01

    A substantial subset of Parkinson's disease (PD) patients suffers from impulse control disorders (ICDs), which are side effects of dopaminergic medication. Dopamine plays a key role in reinforcement learning processes. One class of reinforcement learning models, known as the actor-critic model, suggests that two components are involved in these reinforcement learning processes: a critic, which estimates values of stimuli and calculates prediction errors, and an actor, which estimates values of potential actions. To understand the information processing mechanism underlying impulsive behavior, we investigated stimulus and action value learning from reward and punishment in four groups of participants: on-medication PD patients with ICD, on-medication PD patients without ICD, off-medication PD patients without ICD, and healthy controls. Analysis of responses suggested that participants used an actor-critic learning strategy and computed prediction errors based on stimulus values rather than action values. Quantitative model fits also revealed that an actor-critic model of the basal ganglia with different learning rates for positive and negative prediction errors best matched the choice data. Moreover, whereas ICDs were associated with model parameters related to stimulus valuation (critic), PD was associated with parameters related to action valuation (actor). Specifically, PD patients with ICD exhibited lower learning from negative prediction errors in the critic, resulting in an underestimation of adverse consequences associated with stimuli. These findings offer a specific neurocomputational account of the nature of compulsive behaviors induced by dopaminergic drugs. PMID:24899705

  18. Parkinson's Disease and Autophagy

    PubMed Central

    Sánchez-Pérez, Ana María; Claramonte-Clausell, Berta; Sánchez-Andrés, Juan Vicente; Herrero, María Trinidad

    2012-01-01

    It is generally accepted that a correlation between neurodegenerative disease and protein aggregation in the brain exists; however, a causal relationship has not been elucidated. In neurons, failure of autophagy may result in the accumulation of aggregate-prone proteins and subsequent neurodegeneration. Thus, pharmacological induction of autophagy to enhance the clearance of intracytoplasmic aggregate-prone proteins has been considered as a therapeutic strategy to ameliorate pathology in cell and animal models of neurodegenerative disorders. However, autophagy has also been found to be a factor in the onset of these diseases, which raises the question of whether autophagy induction is an effective therapeutic strategy, or, on the contrary, can result in cell death. In this paper, we will first describe the autophagic machinery, and we will consider the literature to discuss the neuroprotective effects of autophagy. PMID:23125941

  19. Association study of TREM2 polymorphism rs75932628 with leucoaraiosis or Parkinson's disease in the Han Chinese population

    PubMed Central

    Li, Zhiming; Zhong, Li; Gu, Long; Huang, Wenqing; Shi, Xinzhen; Zhang, Xilin; An, Xingkai; Lin, Qing; Tzeng, Chi-Meng

    2016-01-01

    Objectives The previously reported functional mutation rs75932628-T (p.R47H) in the triggering receptor expressed on myeloid cells 2 (TREM2) is a genetic risk factor for Alzheimer's disease, Parkinson's disease (PD) and frontotemporal dementia, in European populations. This study aims to assess the genetic association of the variant rs75932628-T with PD and leucoaraiosis (LA) in a Han Chinese population. Setting This population-based study was conducted in China by Xiamen University and its affiliated hospital. Participants 308 patients with LA, 342 patients with PD and 198 healthy blood donors were recruited from the First Affiliated Hospital of Xiamen University. Outcome measures Genotyping was performed by molecular beacon real-time PCR and Sanger sequencing. Results None of our participants carried the rs75932628-T mutation. Conclusions Our results corroborate and extend previous findings, concluding that the variant rs75932628-T (p.R47H) in TREM2 is not a risk factor for LA or PD in the Han Chinese population. PMID:26758262

  20. Parkinson disease and smoking revisited

    PubMed Central

    Lee, Pei-Chen; Lassen, Christina F.; Arah, Onyebuchi A.

    2014-01-01

    Objective: To assess whether being able to quit smoking is an early marker of Parkinson disease (PD) onset rather than tobacco being “neuroprotective,” we analyzed information about ease of quitting and nicotine substitute use. Methods: For this case-control study, we identified 1,808 patients with PD diagnosed between 1996 and 2009 from Danish registries, matched 1,876 population controls on sex and year of birth, and collected lifestyle information. We estimated odds ratios and 95% confidence intervals with logistic regression adjusting for matching factors and confounders. Results: Fewer 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 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 that patients with PD are able to quit smoking more easily than controls. These findings are compatible with a decreased responsiveness to nicotine during the prodromal phase of PD. We propose that ease of smoking cessation is an aspect of premanifest PD similar to olfactory dysfunction, REM sleep disorders, or constipation and suggests that the apparent “neuroprotective” effect of smoking observed in epidemiologic studies is due to reverse causation. PMID:25217056

  1. Plasma Ceramide and Glucosylceramide Metabolism Is Altered in Sporadic Parkinson's Disease and Associated with Cognitive Impairment: A Pilot Study

    PubMed Central

    Haughey, Norman J.; Bandaru, Veera V. R.; Savica, Rodolfo; Deuschle, Christian; Gasser, Thomas; Hauser, Ann-Kathrin; Gräber-Sultan, Susanne; Schleicher, Erwin; Berg, Daniela; Liepelt-Scarfone, Inga

    2013-01-01

    Background Mutations in the gene coding for glucocerebrosidase (GBA), which metabolizes glucosylceramide (a monohexosylceramide) into glucose and ceramide, is the most common genetic risk factor for sporadic Parkinson's disease (PD). GBA mutation carriers are more likely to have an earlier age of onset and to develop cognitive impairment and dementia. We hypothesized that plasma levels of lipids involved in ceramide metabolism would also be altered in PD non-GBA mutation carriers and associated with worse cognition. Methods Plasma ceramide, monohexosylceramide, and lactosylceramide levels in 26 cognitively normal PD patients, 26 PD patients with cognitive impairment or dementia, and 5 cognitively normal non-PD controls were determined by LC/ESI/MS/MS. Results Levels of all lipid species were higher in PD patients versus controls. Among PD patients, levels of ceramide C16:0, C18:0, C20:0, C22:0, and C24:1 and monohexosylceramide C16:0, C20:0 and C24:0 species were higher (all P<0.05) in those with versus without cognitive impairment. Conclusion These results suggest that plasma ceramide and monohexosylceramide metabolism is altered in PD non-GBA mutation carriers and that higher levels are associated with worse cognition. Additional studies with larger sample sizes, including cognitively normal controls, are needed to confirm these findings. PMID:24058461

  2. Increased risk of parkinsonism associated with welding exposure

    PubMed Central

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

    2013-01-01

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

  3. Body weight and food intake in Parkinson's disease. A review of the association to non-motor symptoms.

    PubMed

    Aiello, Marilena; Eleopra, Roberto; Rumiati, Raffella I

    2015-01-01

    Research on eating behaviours has extensively highlighted that cognitive systems interact with the metabolic system in driving food intake and in influencing body weight regulation. Parkinson's disease is a good model for studying these complex interactions since alterations in both body weight and cognitive domains have been frequently reported among these patients. Interestingly, even if different non-motor symptoms may characterize the course of the disease, their contribution to weight and food preference has been poorly investigated. This review describes body weight alterations and eating habits in patients with Parkinson's disease, including those who underwent deep brain stimulation surgery. In particular, the review considers the link between non-motor symptoms, affecting sensory perception, cognition, mood and motivation, and food intake and weight alterations. The take home message is twofold. First, we recommend a comprehensive approach in order to develop effective strategies in the management of patients' weight. Second, we also suggest that investigating this issue in patients with Parkinson's disease may provide some useful information about the mechanisms underlying food and weight regulation in healthy subjects. PMID:25453591

  4. Parkinsonism in FMR1 premutation carriers may be indistinguishable from Parkinson disease

    PubMed Central

    Hall, Deborah A.; Howard, Katherine; Hagerman, Randi; Leehey, Maureen A.

    2009-01-01

    Premutation carriers of repeat expansions in the fragile X mental retardation (FMR1) gene develop kinetic tremor and ataxia or the ‘fragile X associated tremor/ataxia syndrome’ (FXTAS). Affected FMR1 premutation carriers also have parkinsonism, but have not been reported to meet criteria for Parkinson disease. This case series illustrates that some patients who are FMR1 premutation carriers may appear by history and examination to have idiopathic Parkinson disease. Based on previous studies, it is likely that the genetic mutation and parkinsonism are associated. Although screening all PD patients is likely to be low yield, genetic testing of FMR1 in individuals with PD and a family history of fragile X syndrome, autism or developmental delay, or other related FMR1 phenotypes is warranted. PMID:18565783

  5. Meta-analysis supports association of a functional SNP (rs1801133) in the MTHFR gene with Parkinson's disease.

    PubMed

    Zhu, Zhi-Gang; Ai, Qing-Long; Wang, Wen-Min; Xiao, Zhi-Cheng

    2013-11-15

    The MTHFR is a candidate risk gene for Parkinson's disease (PD), and a functional SNP (rs1801133) in the coding region of this gene has been investigated for the associations with the illness extensively among worldwide populations, but overall the results were inconsistent. Here, to assess the relationship between rs1801133 and risk of PD in general populations, we conducted a systematic meta-analysis by combining all available case-control samples in European and Asian populations, with a total of 1820 PD cases and 7530 healthy controls, and the pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) for rs1801133 and PD were calculated using the Mantel-Haenszel method with a fixed-effect model. Overall, rs1801133 was significantly associated with the risk of PD (allelic model, pooled OR=1.212 for T allele, 95% CI=1.097-1.340, p-value=0.0002). When stratifying for ethnicity, significant association was also observed in European (allelic model, pooled OR=1.187 for T allele, 95% CI=1.058-1.332, p-value=0.004) and Asian samples (allelic model, pooled OR=1.293 for T allele, 95% CI=1.058-1.580, p-value=0.012) respectively. In addition, rs1801133 was also significantly associated with MTHFR mRNA expression in both CEU (European, p-value=0.0149) and CHB (Chinese, p-value=0.0178) HapMap populations. Collectively, our meta-analysis suggests that rs1801133 is significantly associated with susceptibility to PD in European and Asian populations, and MTHFR is likely an authentic risk gene for PD. PMID:23916622

  6. BDNF G196A (Val66Met) polymorphism associated with cognitive impairment in Parkinson's disease.

    PubMed

    Białecka, Monika; Kurzawski, Mateusz; Roszmann, Anna; Robowski, Piotr; Sitek, Emilia J; Honczarenko, Krystyna; Mak, Monika; Deptuła-Jarosz, Monika; Gołąb-Janowska, Monika; Droździk, Marek; Sławek, Jarosław

    2014-02-21

    Brain-derived neurotrophic factor (BDNF) is a neurotrophin widely expressed in the mammalian brain, regulating neuronal survival and known to influence dopaminergic neurons and cognitive processes. The present study investigated the BDNF Val66Met polymorphism associations with PD risk, and cognitive impairment in PD. A total of 486 study subjects (244 PD and 242 age and sex matched controls) were included in the study. UPDRS score, Hoehn-Yahr staging and the Schwab-England scale were used to assess motor abilities and activity during daily life. The patients were classified into groups with dementia (PDD, n=69) and without it (nPDD, n=166) on the basis of neuropsychological assessment. The most common functional polymorphism in BDNF Val66Met (rs6265, G196A) gene was determined using TaqMan real-time PCR assay. Frequencies of evaluated BDNF alleles and genotypes were similar in PD and the controls. The mean age of disease onset among BDNF Met/Met carriers was later (65.00±6.13) in comparison to Val/Val (57.45±10.68) and Val/Met (56.33±10.91) subjects (p=0.077). The studied BDNF polymorphism was not associated with cognitive status in PD patients. However, patients with Met/Met alleles demonstrated better delayed recall of information than patients with Val/Val alleles. The results of multivariate logistic regression analysis revealed age (p=0.0003) and the disease stage (p=0.002) as independent risk factors predisposing to PD dementia. PMID:24394906

  7. [Cognitive impairment in Parkinson's disease].

    PubMed

    Tachibana, Hisao

    2013-01-01

    Cognitive impairment is a common finding in Parkinson's disease (PD), even in the early stages. The concept of mild cognitive impairment (MCI) in PD was recently formalized with diagnosis being reached after impairments in neuropsychological tasks become significant in at least one domain. The brain profile of cognitive deficits involves executive functions (e. g., planning, set shifting, set maintenance, problem solving), attention and memory function. Memory deficits are characterized by impairments in delayed recall, temporal ordering and conditional associate learning. PD patients demonstrate relatively preserved recognition. Visuospatial dysfunctions have also been reported, while language is largely preserved. The existence of two distinct mild cognitive syndromes has also been suggested. One of these affects mainly the frontostriatal executive deficits that are modulated by dopaminergic medications and by a genetically determined level of prefrontal cortex dopamine release. The other affects the more-posterior cortical abilities, such as visuospatial and memory functions, and is suggested to be associated with an increased risk for conversion to dementia. Cross-sectional studies have commonly reported dementia in 20-30% of PD patients, although the 8-year cumulative incidence of dementia may be as high as 78%. Factors associated with dementia in PD are age at onset, age at the time of examination, akinetic-rigid form PD, depression, hallucination, rapid eye movement sleep behavioral disorder and severe olfactory deficits. Clinical features generally involve the same type of deficits as those found in MCI patients, which are more severe and more extensive. The phenomenology of the dementia syndrome is similar to that seen in dementia with Lewy bodies, and clinicopathological correlation studies have revealed varying results with regard to neurochemical deficits and the pathological substrate underlying cognitive impairment and dementia. Early cognitive

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

    PubMed Central

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

    2014-01-01

    Background Nonmotor symptoms are probably present prior to, early on, and following, a diagnosis of Parkinson's disease. Nonmotor symptoms may hold important information about the progression of Parkinson's disease. Objective To evaluated the total early and prediagnostic morbidities in the 3 years before a hospital contact leading to a diagnosis of Parkinson's disease. Methods Retrospective morbidity data from Danish National Patient Registry records (1997–2007) of 10,490 adult patients with a secondary care diagnosis of Parkinson's disease were compared with 42,505 control cases. Results Parkinson's disease was associated with significantly higher morbidity rates associated with conditions in the following categories: mental and psychiatric, nervous system, gastrointestinal, musculoskeletal system and connective tissue, genitourinary, abnormal clinical and laboratory findings, injury, poisoning and certain other external causes, and other factors influencing health status and contact with health services. It was negatively associated with neoplasm, cardiovascular, and respiratory diseases. Conclusions Patients with a diagnosis of Parkinson's disease present significant differences in morbidities early on, following, and prior to, their diagnosis, compared with healthy controls. PMID:24944873

  9. Atropinic (Anticholinergic) Burden in Parkinson's Disease.

    PubMed

    De Germay, Sibylle; Montastruc, Jean-Louis; Rousseau, Vanessa; Chebane, Leila; Bondon-Guitton, Emmanuelle; Moulis, Florence; Durrieu, Genevieve; Bagheri, Haleh; Rascol, Olivier; Pariente, Antoine; Bégaud, Bernard; Montastruc, François

    2016-05-01

    Use of atropinic drugs remains controversial in Parkinson's disease (PD) because there is insufficient evidence about their efficacy and they can induce serious adverse drug reactions. Atropinic risk scales were developed to help to identify atropinic drugs in prescription forms and to evaluate their burden in clinical practice. In the present review, we discuss the few studies investigating atropinic burden in PD and present the results of our study indicating that atropinic drugs are still widely prescribed in PD (almost 3 of 5 prescriptions) with a clinically significant atropinic burden in around 1 of 6 PD patients. Drugs mainly responsible for high values of atropinic burden were those used for nonmotor symptoms. Clinically significant atropinic burdens were mainly induced by associations of several "low-risk" drugs. Physicians must be aware that in addition to classical atropinic antiparkinsonian drugs, many others (psychotropics) can contribute to increased atropinic burden in PD patients. © 2016 International Parkinson and Movement Disorder Society. PMID:27028036

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

    PubMed

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

    2016-02-01

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

  11. Loss of enteric dopaminergic neurons and associated changes in colon motility in an MPTP mouse model of Parkinson's disease

    PubMed Central

    Anderson, Grant; Noorian, Ali Reza; Taylor, Georgia; Anitha, Mallappa; Bernhard, Doug; Srinivasan, Shanthi; Greene, James G.

    2007-01-01

    Gastrointestinal (GI) dysfunction is the most common non-motor symptom of Parkinson's disease (PD). Symptoms of GI dysmotility include early satiety and nausea from delayed gastric emptying, bloating from poor small bowel coordination, and constipation and defecatory dysfunction from impaired colonic transit. Understanding the pathophysiology and treatment of these symptoms in PD patients has been hampered by the lack of investigation into GI symptoms and pathology in PD animal models. We report that the prototypical parkinsonian neurotoxin, MPTP (1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine), is a selective dopamine neuron toxin in the enteric nervous system (ENS). When examined 10 days after treatment, there was a 40% reduction of dopamine neurons in the ENS of C57Bl/6 mice administered MPTP (60 mg/kg). There were no differences in the density of cholinergic or nitric oxide neurons. Electrophysiological recording of neural-mediated muscle contraction in isolated colon from MPTP-treated animals confirmed a relaxation defect associated with dopaminergic degeneration. Behaviorally, MPTP induced a transient increase in colon motility, but no changes in gastric emptying or small intestine transit. These results provide the first comprehensive assessment of gastrointestinal pathophysiology in an animal model of PD. They provide insight into the impact of dopaminergic dysfunction on gastrointestinal motility and a benchmark for assessment of other PD model systems. PMID:17586496

  12. How Is Parkinson's Disease Treated?

    MedlinePlus

    ... can help make life better for people with Parkinson's General Gift Tribute Gift Moving Day ® Team Hope ... can help make life better for people with Parkinson's General Gift Tribute Gift Moving Day ® Team Hope ...

  13. Dissection of the genetics of Parkinson's disease identifies an additional association 5′ of SNCA and multiple associated haplotypes at 17q21

    PubMed Central

    Spencer, Chris C.A.; Plagnol, Vincent; Strange, Amy; Gardner, Michelle; Paisan-Ruiz, Coro; Band, Gavin; Barker, Roger A.; Bellenguez, Celine; Bhatia, Kailash; Blackburn, Hannah; Blackwell, Jennie M.; Bramon, Elvira; Brown, Martin A.; Brown, Matthew A.; Burn, David; Casas, Juan-Pablo; Chinnery, Patrick F.; Clarke, Carl E.; Corvin, Aiden; Craddock, Nicholas; Deloukas, Panos; Edkins, Sarah; Evans, Jonathan; Freeman, Colin; Gray, Emma; Hardy, John; Hudson, Gavin; Hunt, Sarah; Jankowski, Janusz; Langford, Cordelia; Lees, Andrew J.; Markus, Hugh S.; Mathew, Christopher G.; McCarthy, Mark I.; Morrison, Karen E.; Palmer, Colin N.A.; Pearson, Justin P.; Peltonen, Leena; Pirinen, Matti; Plomin, Robert; Potter, Simon; Rautanen, Anna; Sawcer, Stephen J.; Su, Zhan; Trembath, Richard C.; Viswanathan, Ananth C.; Williams, Nigel W.; Morris, Huw R.; Donnelly, Peter; Wood, Nicholas W.

    2011-01-01

    We performed a genome-wide association study (GWAS) in 1705 Parkinson's disease (PD) UK patients and 5175 UK controls, the largest sample size so far for a PD GWAS. Replication was attempted in an additional cohort of 1039 French PD cases and 1984 controls for the 27 regions showing the strongest evidence of association (P< 10−4). We replicated published associations in the 4q22/SNCA and 17q21/MAPT chromosome regions (P< 10−10) and found evidence for an additional independent association in 4q22/SNCA. A detailed analysis of the haplotype structure at 17q21 showed that there are three separate risk groups within this region. We found weak but consistent evidence of association for common variants located in three previously published associated regions (4p15/BST1, 4p16/GAK and 1q32/PARK16). We found no support for the previously reported SNP association in 12q12/LRRK2. We also found an association of the two SNPs in 4q22/SNCA with the age of onset of the disease. PMID:21044948

  14. Therapeutic directions for Parkinson's disease.

    PubMed

    Shoulson, Ira

    2010-01-01

    The focus on disease-modifying treatments and cures for Parkinson's disease (PD) has raised expectations for quantum leaps and overshadowed incremental gains that have been slowly achieved. Large multi-center clinical trials such as DATATOP and PRECEPT keep on generating new knowledge that is relevant to clinical care as well as experimental therapeutics. The largely unforeseen relationship between circulating uric acid and the occurrence and progression of PD was developed and confirmed in these clinical trials. Systematic follow-up of clinical trial cohorts after conclusion of the interventional phase provides added value that continues to inform about natural history, state and trait biomarkers, and genotype-phenotype relationships. These efforts are enhanced by data mining, public reporting, and timely sharing of data and biological samples. PMID:20187232

  15. Association of DRD3 and GRIN2B with impulse control and related behaviors in Parkinson's disease.

    PubMed

    Lee, Jee-Young; Lee, Eun Kyung; Park, Sung Sup; Lim, Ji-Yeon; Kim, Hee Jin; Kim, Ji Sun; Jeon, Beom S

    2009-09-15

    We aimed to assess whether allelic variants of dopamine receptor, glutamate receptor, and serotonin transporter genes are associated with the appearance of impulse control and related behaviors (ICRB) in Parkinson's disease (PD) with dopamine replacement therapy (DRT). We surveyed ICRB in consecutive Korean patients with PD who were treated with stable DRT using modified Minnesota Impulsive Disorders Interview over a period of 4 months. In the 404 patients who completed the interview and the 559 Korean healthy normal controls, genotyping was performed for variants of the DRD3 p.S9G, DRD2 Taq1A, GRIN2B c.366C>G, c.2664C>T and c.-200T>G, and the promoter region of the serotonin transporter gene (5-HTTLPR). Behavioral abnormalities suggestive of ICRB including compulsive buying, gambling, sexual behavior and eating, and punding, were present in 14.4% of the patients. Variants of DRD2 and 5-HTTLPR were not associated with the risk of developing ICRB. However, the AA genotype of DRD3 p.S9G and the CC genotype of GRIN2B c.366C>G were more frequent in patients with ICRB than in nonaffected patients (odds ratio [OR] = 2.21, P = 0.0094; and 2.14, P = 0.0087, after adjusting for age and sex). After controlling for clinical variables in the multivariate analysis, carriage of either AA genotype of DRD3 or CC genotype of GRIN2B was identified as an independent risk factor for ICRB (adjusted OR: 2.57, P = 0.0087). Variants of DRD3 p.S9G and GRIN2B c.366C>G may be associated with the appearance of ICRB in PD. PMID:19562769

  16. Great shakes: famous people with Parkinson disease.

    PubMed

    Jones, Jeffrey M

    2004-12-01

    James Parkinson is credited with the first complete clinical description of the syndrome attributed to his name, Parkinson disease. It is recognized as the first syndrome defined after neurology became a specialty. Descriptions of Parkinson features are rare in antiquity, and famous people with this disorder have not been found before the 1800s. During the 20th century, more and more famous people appear to be afflicted with Parkinson, and this article reviews some of those who have withstood the "test of Time magazine," and examines some of the reasons why the syndrome is a relatively recent disorder. PMID:15646755

  17. Gaucher disease and comorbidities: B-cell malignancy and parkinsonism.

    PubMed

    Cox, Timothy M; Rosenbloom, Barry E; Barker, Roger A

    2015-07-01

    Data emerging from the International Collaborative Gaucher Group (ICGG) Gaucher Registry together with other contemporary clinical surveys have revealed a close association between Gaucher disease and non-Hodgkin's B-cell lymphoma and myeloma and Gaucher disease and Parkinson's disease. Several possible explanations for increased B-cell proliferation and neoplasia in Gaucher disease have been proposed, including the possible influence of sphingosine (derived from the extra lysosomal metabolism of glucosylceramide), gene modifiers, splenectomy and immune system deregulation induced by cytokines, chemokines, and hydrolases released from Gaucher cells. Parkinson's disease is frequently seen in the otherwise-healthy relatives of Gaucher disease patients leading to the finding that GBA mutations represent a genetic risk factor for Parkinson's disease. The mechanism of the association between GBA mutations and Parkinson's disease has yet to be elucidated but the pathogenesis appears distinct from that of Gaucher disease. Several pathogenic pathways have been proposed including lysosomal and/or mitochondrial dysfunction. The effect of Gaucher disease specific therapies on the incidence of cancer or Parkinson's disease are not clear and will likely be evaluated in future ICGG Gaucher Registry studies. PMID:26096744

  18. Parkinson's disease as a result of aging

    PubMed Central

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

    2015-01-01

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

  19. Recent developments in biomarkers in Parkinson disease

    PubMed Central

    Schapira, Anthony H.V.

    2013-01-01

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

  20. Asymmetrical Pedaling Patterns in Parkinson's Disease Patients

    PubMed Central

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

    2015-01-01

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

  1. Gene therapy for Parkinson's disease.

    PubMed

    Lawlor, Patricia A; During, Matthew J

    2004-03-01

    Parkinson's disease (PD) is a debilitating neurodegenerative disorder arising from loss of dopaminergic neurons in the substantia nigra pars compacta and subsequent depletion of striatal dopamine levels, which results in distressing motor symptoms. The current standard pharmacological treatment for PD is direct replacement of dopamine by treatment with its precursor, levodopa (L-dopa). However, this does not significantly alter disease progression and might contribute to the ongoing pathology. Several features of PD make this disease one of the most promising targets for clinical gene therapy of any neurological disease. The confinement of the major pathology to a compact, localised neuronal population and the anatomy of the basal ganglia circuitry mean that global gene transfer is not required and there are well-defined sites for gene transfer. The multifactorial aetiology of idiopathic PD means that it is unlikely any single gene will cure the disease, and as a result at least three separate gene-transfer strategies are currently being pursued: transfer of genes for enzymes involved in dopamine production; transfer of genes for growth factors involved in dopaminergic cell survival and regeneration; and transfer of genes to reset neuronal circuitry by switching cellular phenotype. The merits of these strategies are discussed here, along with remaining hurdles that might impede transfer of gene therapy technology to the clinic as a treatment for PD. PMID:15000692

  2. Psychosocial factors in Parkinson's disease.

    PubMed

    MacCarthy, B; Brown, R

    1989-02-01

    Self-report measures were administered to 136 patients with Parkinson's disease in order to explore the relationships between aspects of psychological adjustment (depression, positive affect and acceptance of illness) and physical illness (duration of the illness, stage of illness and functional disability). Many psychosocial variables which, it was hypothesized, might intervene in the relationship between physical and psychological status were also measured. These were coping style, social support, self-esteem, attributions about the onset and course of the illness, perceived control and previous psychiatric history. A variable pattern of relationships between the different indices of psychological adjustment and physical illness emerged. Self-esteem, coping style and practical support contributed significantly to the variance in psychological adjustment. It was concluded that well-being in Parkinsonian patients is not exclusively dependent on a simple relationship between disability and depression, and that other factors should be taken into account in the clinical management of the illness. PMID:2924026

  3. [Autonomic features in Parkinson disease].

    PubMed

    Yamamoto, Toshimasa; Tamura, Naotoshi

    2012-04-01

    Nonmotor symptoms such as autonomic and neuropsychiatric dysfunctions, are commonly seen in Parkinson disease (PD). Recent studies have shown that PD is accompanied by cardiac sympathetic denervation and constipation even in the early stage. Neuropathological studies confirmed changes in the cardiac sympathetic nerves and the gastrointestinal tract. These findings suggest that PD neuropathology may occur first in the peripheral autonomic pathways and extend to the central autonomic pathways, in agreement with the "Braak theory". This article will reviews the symptoms and pathophysiology of gastrointestinal dysfunction, urinary disturbance, sexual dysfunction, sweating dysfunction, pupillary autonomic dysfunction, and orthostatic and postprandial hypotension in PD patients, and discuss to organ selectiveness in autonomic dysfunction in PD. PMID:22481512

  4. [Parkinson's disease and nucleolar stress].

    PubMed

    Zhou, Qingqing; Chen, Yongping; Wei, Qianqian; Shang, Huifang

    2016-06-01

    Parkinson's disease (PD) is a common age-related neurodegenerative disorder characterized mainly by motor dysfunction resulting in bradykinesia, rigidity, tremor, gait impairment, and postural instability. The classic pathogenic feature of PD is preferential loss of dopaminergic neurons in the substantia nigra. Downregulation of rRNA transcription is one of major mechanisms to maintain cellular homeostasis under stress conditions. Nucleolar stress has emerged as a component of the degenerative process caused by impaired rRNA transcription and altered nucleolar integrity. Recent study has indicated that the response to stress conditions and quality control mechanisms are impaired in PD, and that metabolic stress may be a trigger mechanism for PD. This review aims to present evidence for a role of nucleolar stress in PD and has summarized mechanisms by which nucleolar stress may play a role in the progression of PD. PMID:27264829

  5. Balance Dysfunction in Parkinson's Disease

    PubMed Central

    Rinalduzzi, Steno; Missori, Paolo; Fattapposta, Francesco; Currà, Antonio

    2015-01-01

    Stability and mobility in functional motor activities depend on a precise regulation of phasic and tonic muscular activity that is carried out automatically, without conscious awareness. The sensorimotor control of posture involves a complex integration of multisensory inputs that results in a final motor adjustment process. All or some of the components of this system may be dysfunctional in Parkinsonian patients, rendering postural instability one of the most disabling features of Parkinson's disease (PD). Balance control is critical for moving safely in and adapting to the environment. PD induces a multilevel impairment of this function, therefore worsening the patients' physical and psychosocial disability. In this review, we describe the complex ways in which PD impairs posture and balance, collecting and reviewing the available experimental evidence. PMID:25654100

  6. Sleep disorders in Parkinson's disease.

    PubMed

    Thorpy, Michael J

    2004-01-01

    Depression, dementia, and physiologic changes contribute to the high prevalence of sleep disturbances in patients with Parkinson's disease (PD). Antiparkinsonian drugs also play a role in insomnia by increasing daytime sleepiness and affecting motor symptoms and depression. Common types of sleep disturbances in PD patients include nocturnal sleep disruption and excessive daytime sleepiness, restless legs syndrome, rapid eye movement sleep behavior disorder, sleep apnea, sleep walking and sleep talking, nightmares, sleep terrors, and panic attacks. A thorough assessment should include complete medical and psychiatric histories, sleep history, and a 1- to 2-week sleep diary or Epworth Sleepiness Scale evaluation. Polysomnography or actigraphy may also be indicated. Treatment should address underlying factors such as depression or anxiety. Hypnotic therapy for sleep disturbances in PD patients should be approached with care because of the risks of falling, agitation, drowsiness, and hypotension. Behavioral interventions may also be useful. PMID:15259535

  7. Genitourinary dysfunction in Parkinson's disease.

    PubMed

    Sakakibara, Ryuji; Uchiyama, Tomoyuki; Yamanishi, Tomonori; Kishi, Masahiko

    2010-01-15

    Bladder dysfunction (urinary urgency/frequency) and sexual dysfunction (erectile dysfunction) are common nonmotor disorders in Parkinson's disease (PD). In contrast to motor disorders, genitourinary autonomic dysfunctions are often nonresponsive to levodopa treatment. The brain pathology causing the bladder dysfunction (appearance of overactivity) involves an altered dopamine-basal ganglia circuit, which normally suppresses the micturition reflex. By contrast, hypothalamic dysfunction is mostly responsible for the sexual dysfunction (decrease in libido and erection) in PD, via altered dopamine-oxytocin pathways, which normally promote libido and erection. The pathophysiology of the genitourinary dysfunction in PD differs from that in multiple system atrophy; therefore, it might aid in differential diagnosis. Anticholinergic agents are used to treat bladder dysfunction in PD, although these drugs should be used with caution particularly in elderly patients who have cognitive decline. Phosphodiesterase inhibitors are used to treat sexual dysfunction in PD. These treatments might be beneficial in maximizing the patients' quality of life. PMID:20077468

  8. Ipsilateral coordination features for automatic classification of Parkinson's disease

    NASA Astrophysics Data System (ADS)

    Sarmiento, Fernanda; Atehortúa, Angélica; Martínez, Fabio; Romero, Eduardo

    2015-12-01

    A reliable diagnosis of the Parkinson Disease lies on the objective evaluation of different motor sub-systems. Discovering specific motor patterns associated to the disease is fundamental for the development of unbiased assessments that facilitate the disease characterization, independently of the particular examiner. This paper proposes a new objective screening of patients with Parkinson, an approach that optimally combines ipsilateral global descriptors. These ipsilateral gait features are simple upper-lower limb relationships in frequency and relative phase spaces. These low level characteristics feed a simple SVM classifier with a polynomial kernel function. The strategy was assessed in a binary classification task, normal against Parkinson, under a leave-one-out scheme in a population of 16 Parkinson patients and 7 healthy control subjects. Results showed an accuracy of 94;6% using relative phase spaces and 82;1% with simple frequency relations.

  9. Orthostatic Hypotension in Patients with Parkinson's Disease and Atypical Parkinsonism

    PubMed Central

    Lökk, Johan

    2014-01-01

    Orthostatic hypotension (OH) is one of the commonly occurring nonmotor symptoms in patients with idiopathic Parkinson's disease (IPD) and atypical parkinsonism (AP). We aimed to review current evidences on epidemiology, diagnosis, treatment, and prognosis of OH in patients with IPD and AP. Major electronic medical databases were assessed including PubMed/MEDLINE and Embase up to February 2013. English-written original or review articles with keywords such as “Parkinson's disease,” “atypical parkinsonism,” and “orthostatic hypotension” were searched for relevant evidences. We addressed different issues such as OH definition, epidemiologic characteristics, pathophysiology, testing and diagnosis, risk factors for symptomatic OH, OH as an early sign of IPD, prognosis, and treatment options of OH in parkinsonian syndromes. Symptomatic OH is present in up to 30% of IPD, 80% of multiple system atrophy (MSA), and 27% of other AP patients. OH may herald the onset of PD before cardinal motor symptoms and our review emphasises the importance of its timely diagnosis (even as one preclinical marker) and multifactorial treatment, starting with patient education and lifestyle approach. Advancing age, male sex, disease severity, and duration and subtype of motor symptoms are predisposing factors. OH increases the risk of falls, which affects the quality of life in PD patients. PMID:24634790

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

    PubMed

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

    2016-06-01

    Cognitive decline is one of the most frequent and disabling nonmotor features of Parkinson's disease. Around 30% of patients with Parkinson's disease experience mild cognitive impairment, a well-established risk factor for the development of dementia. However, mild cognitive impairment in patients with Parkinson's disease is a heterogeneous entity that involves different types and extents of cognitive deficits. Because it is not currently known which type of mild cognitive impairment confers a higher risk of progression to dementia, it would be useful to define biomarkers that could identify these patients to better study disease progression and possible interventions. In this sense, the identification among patients with Parkinson's disease and mild cognitive impairment of biomarkers associated with dementia would allow the early detection of this process. This review summarizes studies from the past 25 years that have assessed the potential biomarkers of dementia and mild cognitive impairment in Parkinson's disease patients. Despite the potential importance, no biomarker has as yet been validated. However, features such as low levels of epidermal and insulin-like growth factors or uric acid in plasma/serum and of Aß in CSF, reduction of cerebral cholinergic innervation and metabolism measured by PET mainly in posterior areas, and hippocampal atrophy in MRI might be indicative of distinct deficits with a distinct risk of dementia in subgroups of patients. Longitudinal studies combining the existing techniques and new approaches are needed to identify patients at higher risk of dementia. © 2016 International Parkinson and Movement Disorder Society. PMID:27193487

  11. Antidyskinetic Effect of 7-Nitroindazole and Sodium Nitroprusside Associated with Amantadine in a Rat Model of Parkinson's Disease.

    PubMed

    Bortolanza, Mariza; Bariotto-Dos-Santos, Keila D; Dos-Santos-Pereira, Maurício; da-Silva, Célia Aparecida; Del-Bel, Elaine

    2016-07-01

    Amantadine is the noncompetitive antagonist of N-methyl-D-aspartate, receptor activated by the excitatory neurotransmitter glutamate. It is the only effective medication used to alleviate dyskinesia induced by L-3,4-dihydroxyphenylalanine (L-DOPA) in Parkinson's disease patients. Unfortunately, adverse effects as abnormal involuntary movements (AIMs) known as L-DOPA-induced dyskinesia limit its clinical utility. Combined effective symptomatic treatment modalities may lessen the liability to undesirable events. Likewise drugs known to interfere with nitrergic system reduce AIMs in animal models of Parkinson's disease. We aimed to analyze an interaction between amantadine, neuronal nitric oxide synthase inhibitor (7-nitroindazole, 7NI), and nitric oxide donor (sodium nitroprusside, SNP) in 6-hydroxydopamine-(6-OHDA)-lesioned rats (microinjection in the medial forebrain bundle) presenting L-DOPA-induced dyskinesia (20 mg/kg, gavage, during 21 days). We confirm that 7NI-30 mg/kg, SNP-2/4 mg/kg and amantadine-40 mg/kg, individually reduced AIMs. Our results revealed that co-administration of sub-effective dose of amantadine (10 mg/kg) plus sub-effective dose of 7NI (20 mg/kg) potentiates the effect of reducing AIMs scores when compared to the effect of the drugs individually. No superior benefit on L-DOPA-induced AIMs was observed with the combination of amantadine and SNP. The results revealed that combination of ineffective doses of amantadine and 7NI represents a new strategy to increase antidyskinetic effect in L-DOPA-induced AIMs. It may provide additional therapeutic benefits to Parkinson's disease patients from these disabling complications at lower and thus safer and more tolerable doses than required when either drug is used alone. To close, we discuss the paradox of both nitric oxide synthase inhibitor and/or donor produced AIMs reduction by targeting nitric oxide synthase. PMID:27053252

  12. Synaptic dysfunction in Parkinson's disease.

    PubMed

    Picconi, Barbara; Piccoli, Giovanni; Calabresi, Paolo

    2012-01-01

    Activity-dependent modifications in synaptic efficacy, such as long-term depression (LTD) and long-term potentiation (LTP), represent key cellular substrates for adaptive motor control and procedural memory. The impairment of these two forms of synaptic plasticity in the nucleus striatum could account for the onset and the progression of motor and cognitive symptoms of Parkinson's disease (PD), characterized by the massive degeneration of dopaminergic neurons. In fact, both LTD and LTP are peculiarly controlled and modulated by dopaminergic transmission coming from nigrostriatal terminals. Changes in corticostriatal and nigrostriatal neuronal excitability may influence profoundly the threshold for the induction of synaptic plasticity, and changes in striatal synaptic transmission efficacy are supposed to play a role in the occurrence of PD symptoms. Understanding of these maladaptive forms of synaptic plasticity has mostly come from the analysis of experimental animal models of PD. A series of cellular and synaptic alterations occur in the striatum of experimental parkinsonism in response to the massive dopaminergic loss. In particular, dysfunctions in trafficking and subunit composition of glutamatergic NMDA receptors on striatal efferent neurons contribute to the clinical features of the experimental parkinsonism. Interestingly, it has become increasingly evident that in striatal spiny neurons, the correct assembly of NMDA receptor complex at the postsynaptic site is a major player in early phases of PD, and it is sensitive to distinct degrees of DA denervation. The molecular defects at the basis of PD progression may be not confined just at the postsynaptic neuron: accumulating evidences have recently shown that the genes linked to PD play a critical role at the presynaptic site. DA release into the synaptic cleft relies on a proper presynaptic vesicular transport; impairment of SV trafficking, modification of DA flow, and altered presynaptic plasticity have

  13. Cognitive dysfunction and dementia in Parkinson disease.

    PubMed

    Caballol, Nuria; Martí, Maria J; Tolosa, Eduardo

    2007-09-01

    Impairment in different cognitive domains such as executive functions, language, memory, and visuospatial skills occurs frequently in Parkinson disease (PD) even in the early stages of the disease. Although frank dementia (Parkinson disease dementia, PDD) is less frequent, risk for developing dementia is two to six times greater than the prevalence rate in general population and it increases in relation to disease duration. Clinically, dementia in PD is characterized by uninsidious onset and slowly progressive cognitive decline, with a predominant dysexecutive syndrome accompanied frequently by a variety of behavioral symptoms such as hallucinations, depression, anxiety, and excessive daytime sleepiness. Although the exact pathophysiology and neurobiological basis of PDD is not known, dementia in PD probably develops as a result of progressive involvement of subcortical and cortical structures by Lewy-type pathology and associated Alzheimer-like histological changes. Dysfunction of different monoamine transmitter has also been implicated in the cognitive deterioration of PD but reduced cholinergic activity in the cortex is thought to account for the strongest mechanism in the development of dementia. Recent evidence suggests that cholinesterase inhibitors are effective in the treatment of dementia and accompanying behavioral symptoms in PD. PMID:18175397

  14. Loss-of-function mutations in RAB39B are associated with typical early-onset Parkinson disease.

    PubMed

    Lesage, Suzanne; Bras, Jose; Cormier-Dequaire, Florence; Condroyer, Christel; Nicolas, Aude; Darwent, Lee; Guerreiro, Rita; Majounie, Elisa; Federoff, Monica; Heutink, Peter; Wood, Nicholas W; Gasser, Thomas; Hardy, John; Tison, François; Singleton, Andrew; Brice, Alexis

    2015-06-01

    Rab proteins are small molecular weight guanosine triphosphatases involved in the regulation of vesicular trafficking.(1) Three of 4 X-linked RAB genes are specific to the brain, including RAB39B. Recently, Wilson et al.(2) reported that mutations in RAB39B cause X-linked intellectual disability (ID) and pathologically confirmed Parkinson disease (PD). They identified a ∼45-kb deletion resulting in the complete loss of RAB39B in an Australian kindred and a missense mutation in a large Wisconsin kindred. Here, we report an additional affected man with typical PD and mild mental retardation harboring a new truncating mutation in RAB39B. PMID:27066548

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

    MedlinePlus

    ... are spent, browse our financial information. Learn More Gambling, Sex, and…Parkinson's Disease? By Laura Marsh, M. ... elevated, expansive, grandiose or irritable mood states. Pathological gambling Pathological gambling refers to recurrent, maladaptive gambling behaviors, ...

  16. [Problem of alternative medicine in Parkinson's disease].

    PubMed

    Fujimoto, Ken-Ichi

    2013-01-01

    I asked about the usage of alternative medicine to 300 outpatients with Parkinson's disease. 163 patients (54.3%) had experience with health appliance and 128 patients (42.7%) had experience with supplements. There is no health appliance or supplement whose efficacy for Parkinson's disease is approved publicly. Most of the patients understood it but some patients who purchased the goods believed to be effective in Parkinson's disease. In addition some patients feel affected because the purchase price is abnormally high. Continuous usage rate is generally high in supplements, relatively high in massage machine, but significantly low in equipment to move the body, such as muscle training equipment of various types or exercise bike. It seems important to inform this fact to Parkinson's disease patients. PMID:24291878

  17. Imaging Systemic Dysfunction in Parkinson's Disease.

    PubMed

    Borghammer, Per; Knudsen, Karoline; Brooks, David J

    2016-06-01

    Parkinson's disease is now widely recognized to be a multisystem disorder affecting the brain and peripheral autonomic nerves. Extensive pathology is present in both the sympathetic and parasympathetic nervous system and the intrinsic gastrointestinal plexuses in patients. Autonomic pathology and symptoms such as constipation can predate the clinical diagnosis by years or decades. Imaging studies have contributed greatly to our understanding of Parkinson's disease but focused primarily on imaging cerebral pathology. However, given the importance of understanding the nature, chronology, and functional consequences of peripheral pathology, there has been renewed interest in imaging peripheral organs in Parkinson's disease. Suitable imaging tools can be divided into two types: radiotracer studies that directly estimate loss of sympathetic or parasympathetic nerve terminals, and imaging modalities to quantitate dysphagia, gastric emptying, esophageal and intestinal transit times, and anorectal dyssynergia. In this review, we summarize current knowledge about peripheral imaging in Parkinson's disease. PMID:27072951

  18. Nutrition and Parkinson's Disease: What Matters Most?

    MedlinePlus

    ... information. Learn More Nutrition and Parkinson's Disease: What Matters Most? Note from PDF: Are you interested in ... calcium-fortified soy-based beverages, orange juice and dark leafy greens), calcium from non-dairy sources may ...

  19. Michael J. Fox and his Parkinson's disease.

    PubMed

    Kempster, Peter A

    2004-01-01

    Michael J. Fox was a popular and successful film and television comic actor who developed Parkinson's disease at the age of 29 years. His recently published book, Lucky Man, structured around the story of his Parkinson's disease, is an amusing, briskly paced yet introspective memoir that covers the first 40 years of his life. Although quite anecdotal, it contains interesting observations on the preclinical phase of the disorder, evolution of motor fluctuations, and tactics for pharmacological treatment. PMID:14743369

  20. Mutation analyses and association studies to assess the role of the presenilin-associated rhomboid-like gene in Parkinson's disease.

    PubMed

    Wüst, Richard; Maurer, Brigitte; Hauser, Kathrin; Woitalla, Dirk; Sharma, Manu; Krüger, Rejko

    2016-03-01

    Presenilin-associated rhomboid-like (PARL), a serine protease located in the inner mitochondrial membrane, has been shown to genetically interact and process PTEN-induced putative kinase a protein known for its critical role in mitochondrial homeostasis and early-onset forms of Parkinson's disease (PD). The identification of a PD-associated variant in the PARL gene (p.Ser77Asn) led us to assess the relevance of PARL for PD pathogenesis using a mutation screening of the coding sequences and adjacent intronic sequences. We investigated 3 single nucleotide polymorphisms (rs3792589, rs13091, and rs3732581), a synonymous base substitution (Leu79Leu) and the previously described p.Ser77Asn mutation, which were subsequently screened in more than 2000 patients and controls. Not detecting the p.Ser77Asn mutation in our cohort, nor a robust association between variations in the PARL gene and PD, the role of disease causing genetic variants in the PARL gene could not be further substantiated in our samples. Our findings indicate that PARL mutations are a rare cause of PD and genetic variants are neither strong nor common risk factors in PD. PMID:26778534

  1. Baseline and longitudinal grey matter changes in newly diagnosed Parkinson's disease: ICICLE-PD study.

    PubMed

    Mak, Elijah; Su, Li; Williams, Guy B; Firbank, Michael J; Lawson, Rachael A; Yarnall, Alison J; Duncan, Gordon W; Owen, Adrian M; Khoo, Tien K; Brooks, David J; Rowe, James B; Barker, Roger A; Burn, David J; O'Brien, John T

    2015-10-01

    Mild cognitive impairment in Parkinson's disease is associated with progression to dementia (Parkinson's disease dementia) in a majority of patients. Determining structural imaging biomarkers associated with prodromal Parkinson's disease dementia may allow for the earlier identification of those at risk, and allow for targeted disease modifying therapies. One hundred and five non-demented subjects with newly diagnosed idiopathic Parkinson's disease and 37 healthy matched controls had serial 3 T structural magnetic resonance imaging scans with clinical and neuropsychological assessments at baseline, which were repeated after 18 months. The Movement Disorder Society Task Force criteria were used to classify the Parkinson's disease subjects into Parkinson's disease with mild cognitive impairment (n = 39) and Parkinson's disease with no cognitive impairment (n = 66). Freesurfer image processing software was used to measure cortical thickness and subcortical volumes at baseline and follow-up. We compared regional percentage change of cortical thinning and subcortical atrophy over 18 months. At baseline, cases with Parkinson's disease with mild cognitive impairment demonstrated widespread cortical thinning relative to controls and atrophy of the nucleus accumbens compared to both controls and subjects with Parkinson's disease with no cognitive impairment. Regional cortical thickness at baseline was correlated with global cognition in the combined Parkinson's disease cohort. Over 18 months, patients with Parkinson's disease with mild cognitive impairment demonstrated more severe cortical thinning in frontal and temporo-parietal cortices, including hippocampal atrophy, relative to those with Parkinson's disease and no cognitive impairment and healthy controls, whereas subjects with Parkinson's disease and no cognitive impairment showed more severe frontal cortical thinning compared to healthy controls. At baseline, Parkinson's disease with no cognitive impairment

  2. Parkinson's Disease and Sleep/Wake Disturbances

    PubMed Central

    Swick, Todd J.

    2012-01-01

    Parkinson's disease (PD) has traditionally been characterized by its cardinal motor symptoms of bradykinesia, rigidity, resting tremor, and postural instability. However, PD is increasingly being recognized as a multidimensional disease associated with myriad nonmotor symptoms including autonomic dysfunction, mood disorders, cognitive impairment, pain, gastrointestinal disturbance, impaired olfaction, psychosis, and sleep disorders. Sleep disturbances, which include sleep fragmentation, daytime somnolence, sleep-disordered breathing, restless legs syndrome (RLS), nightmares, and rapid eye movement (REM) sleep behavior disorder (RBD), are estimated to occur in 60% to 98% of patients with PD. For years nonmotor symptoms received little attention from clinicians and researchers, but now these symptoms are known to be significant predictors of morbidity in determining quality of life, costs of disease, and rates of institutionalization. A discussion of the clinical aspects, pathophysiology, evaluation techniques, and treatment options for the sleep disorders that are encountered with PD is presented. PMID:23326757

  3. Diagnosis and management of Parkinson's disease dementia

    PubMed Central

    Poewe, W; Gauthier, S; Aarsland, D; Leverenz, J B; Barone, P; Weintraub, D; Tolosa, E; Dubois, B

    2008-01-01

    Parkinson's disease (PD) has long been considered predominantly a motor disorder. However, its frequent association with dementia, which contributes significantly to the morbidity and mortality of the condition, is gaining increasing recognition. PD dementia (PDD) has a unique clinical profile and neuropathology, distinct from Alzheimer's disease (AD). Cholinergic deficits, a feature of both AD and PDD, underlie the rationale for cholinesterase inhibitor therapy in both conditions. In clinical practice, it is important that PDD should be recognised and appropriately treated. This review aims to outline the recently proposed clinical diagnostic criteria for PDD and to summarise the guidelines/recommendations published since 2006 on the use of cholinesterase inhibitors in the management of PDD. Although the cholinesterase inhibitor rivastigmine has recently been approved for the management of PDD, there remains a need for the development of novel therapies that can affect key mechanisms of the disease or prevent/delay patients with PD and mild cognitive impairment from progressing to PDD. PMID:18822028

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

    PubMed

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

    2015-08-01

    Learning and motivation are intrinsically related, and both have been linked to dopamine. Parkinson's disease results from a progressive loss of dopaminergic inputs to the striatum and leads to impairments in motivation and learning from feedback. However, the link between motivation and learning in Parkinson's disease is not well understood. To address this gap, we leverage a well-established psychological theory of motivation, regulatory mode theory, which distinguishes between two functionally independent motivational concerns in regulating behavior: a concern with having an effect by initiating and maintaining movement (Locomotion) and a concern with establishing what is correct by critically evaluating goal pursuit means and outcomes (Assessment). We examined Locomotion and Assessment in patients with Parkinson's disease and age-matched controls. Parkinson's disease patients demonstrated a selective decrease in Assessment motivation but no change in Locomotion motivation, suggesting that Parkinson's disease leads to a reduced tendency to evaluate and monitor outcomes. Moreover, weaker Assessment motivation was correlated with poorer performance on a feedback-based learning task previously shown to depend on the striatum. Together, these findings link a questionnaire-based personality inventory with performance on a well-characterized experimental task, advancing our understanding of how Parkinson's disease affects motivation with implications for well-being and treatment outcomes. PMID:25552569

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

    SciTech Connect

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

    1995-04-24

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

  6. Resting-state functional connectivity associated with mild cognitive impairment in Parkinson's disease.

    PubMed

    Amboni, Marianna; Tessitore, Alessandro; Esposito, Fabrizio; Santangelo, Gabriella; Picillo, Marina; Vitale, Carmine; Giordano, Alfonso; Erro, Roberto; de Micco, Rosa; Corbo, Daniele; Tedeschi, Gioacchino; Barone, Paolo

    2015-02-01

    Cognitive impairment is common in PD, even in early stages. The construct of mild cognitive impairment has been used to identify clinically evident cognitive impairment without functional decline in PD patients (PD-MCI). The aim of the present study was to investigate brain connectivity associated with PD-MCI through RS-fMRI. RS-fMRI at 3T was collected in 42 PD patients and 20 matched healthy controls. Among PD patients, 21 were classified as having MCI (PD-MCI) and 21 as cognitively unimpaired (PD-nMCI) based on criteria for possible PD-MCI (level I category). Single-subject and group-level ICA was used to investigate the integrity of brain networks related to cognition in PD patients with and without MCI. Image data processing and statistical analysis were performed in BrainVoyager QX. In addition, we used VBM to test whether functional connectivity differences were related to structural abnormalities. PD-nMCI and PD-MCI patients compared with controls showed decreased DMN connectivity. PD-MCI patients, but not PD-nMCI, compared with controls, showed decreased functional connectivity of bilateral prefrontal cortex within the frontoparietal network. The decreased prefrontal cortex connectivity correlated with cognitive parameters but not with clinical variables. VBM analysis did not reveal any difference in local gray matter between patients and controls. Our findings suggest that an altered DMN connectivity characterizes PD patients, regardless of cognitive status, whereas a functional disconnection of the frontoparietal network could be associated with MCI in PD in the absence of detectable structural changes. PMID:25428532

  7. Initial treatment of Parkinson's disease.

    PubMed

    Tarsy, Daniel

    2006-05-01

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

  8. Sleepiness in Idiopathic REM Sleep Behavior Disorder and Parkinson Disease

    PubMed Central

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

    2015-01-01

    Objective: 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. Methods: 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. Results: 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 < 0.0001). They reached the levels of 114 patients with Parkinson disease (ESS: 8.7 ± 4.8), whether they had (n = 78) or did not have (n = 36) concomitant RBD. The severity of sleepiness in idiopathic RBD correlated with younger age, but not with 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). Conclusions: 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. Citation: Arnulf I, Neutel D, Herlin B, Golmard JL, Leu-Semenescu S, Cochen de Cock V, Vidailhet M. Sleepiness in idiopathic REM sleep behavior disorder and Parkinson disease. SLEEP 2015;38(10):1529–1535. PMID:26085299

  9. The Demise of Poskanzer and Schwab's Influenza Theory on the Pathogenesis of Parkinson's Disease

    PubMed Central

    Okun, Michael S.

    2013-01-01

    In 1961, David C. Poskanzer and Robert S. Schwab presented a paper, “Studies in the epidemiology of Parkinson's disease predicting its disappearance as a major clinical entity by 1980.” This paper introduced the hypothesis that Parkinson's disease was derived from a single aetiology, the influenza virus. We review the original Poskanzer and Schwab hypothesis that Parkinson's disease was based on the association between the 1918-19 influenza epidemic and the later observation of Parkinsonism in some influenza sufferers. We also further explore the prediction that Parkinson's disease would totally disappear as an entity once original influenza victims were all deceased. Current research has revealed that there are many potential causes and factors important in the occurrence of Parkinson's disease, postencephalitic Parkinsonism, and encephalitis lethargica. Poskanzer and Schwab presented a novel hypothesis; however, it was proven false by a combination of research and time. PMID:23853734

  10. [Health-related quality of life in Parkinson's disease].

    PubMed

    Cano-de la Cuerda, Roberto; Vela-Desojo, Lydia; Miangolarra-Page, Juan C; Macías-Macías, Yolanda; Muñoz-Hellin, Elena

    2010-01-01

    Parkinson's disease is a disabling and progressive neurological condition characterized by multiple motor and non motor symptoms that contribute to deterioration in quality of life. The diversity of symptoms associated with the disease and its management affect the patients on their physical, social and mental quality of life. The aim of this study was to identify key dimensions of health related quality of life (HRQOL) in a population affected with Parkinson's disease with a degree of mild-moderate impairment. Thirty six patients with Parkinson were recruited. The Hoehn and Yarh scale, the Unified Parkinson's Disease Rate Scale, the scale of activities of daily life and Schwab & England Get Up & Go Test were applied. HRQOL was assessed with the EuroQol-5D and the specific questionnaire Parkinson's Disease Questionnaire-39 items. The dimensions of the PDQ-39, except the PDQ-39 Pain domain and the EuroQol-5D correlated significantly with the severity of the disease. HRQOL was correlated with the functional status of patients. Only the PDQ-39 pain domain correlated with the risk of falls. Our results suggest that the HRQOL of patients with PD, in a state of mild-moderate impairment, is strongly influenced by disease severity and functional status. PMID:21163736