Serum urate and the risk of Parkinson's disease: results from a meta-analysis

Can J Neurol Sci. 2013 Jan;40(1):73-9.

Shen C, Guo Y, Luo W, Lin C, Ding M.

Source

Department of Neurology, Second Affiliated Hospital.

Abstract

Objective: Serum urate may exert protective effects against Parkinson's disease (PD) through its antioxidant capacities. In this article, we examine the hypothesis that high serum urate levels are associated with lower risk of PD. Methods: We searched NCBI (PubMed), ISI Web of Science and EMBASE for studies that reported the risk of PD associated with serum urate. Fixed or random effects meta-analysis was used to pool results across studies, and further analysis was used to assess the effects by gender. Results: Six studies met the inclusion criteria involving a total of 33 185 participants. Overall, we found a 33% reduction in PD incidence among persons with high serum urate level (relative risk [RR]=0.67; 95% confidence interval [CI], 0.50-0.91). Subgroup analysis was performed with 20 641 men and 12 544 women included, indicating statistically significant protective effects of serum urate in men (RR=0.60; 95% CI, 0.40-0.90) but not in women. A dose-response trend of serum urate to reduce PD risk was also observed involving 11 795 participants (RR=0.77; 95% CI, 0.68-0.88). Additionally, high serum urate levels seemed to slow the clinical decline of PD patients (RR=0.56; 95% CI, 0.43-0.72). Conclusions: In light of these findings, our study confirms previous findings of a robust association between high serum urate level and PD risk, especially in men. It also suggests that long-term exposure to high serum urate may be linked to the delay of PD progression, however more well-designed investigations are needed.

Cohort Profile: A population-based cohort to study non-motor symptoms in parkinsonism (EPIPARK)

Int J Epidemiol. 2012 Dec 19. [Epub ahead of print]

Kasten M, Hagenah J, Graf J, Lorwin A, Vollstedt EJ, Peters E, Katalinic A, Raspe H, Klein C.

Source

Department of Psychiatry and Psychotherapy, University of Luebeck, Luebeck, Germany, Section of Clinical and Molecular Neurogenetics, Department of Neurology, University of Luebeck, Luebeck, Germany, Department of Neurology, Westkuestenklinikum Heide, Heide, Germany, Department of Clinical Epidemiology, University of Luebeck, Luebeck, Germany and Department of Public Health, University of Luebeck, Luebeck, Germany.

Abstract

Parkinson's disease is increasingly viewed as a complex disorder including a range of typical non-motor symptoms in addition to the cardinal motor signs. This cohort was set up in 2010 to investigate the specificity of non-motor symptoms for Parkinson's disease. For this, we included several control groups with decreasing contrast from Parkinson's disease patients. Group definitions ranged from healthy control subjects to those with suspected early motor signs of parkinsonism. Using a mailed questionnaire, we screened 5838 inhabitants of Lübeck, Germany, out of a target population of 10 000 citizens, enquiring about motor impairment, pain, quality of life, comorbidities, somatization and demographics. Based on this information, participants were assigned to screening groups, and selected participants were invited for in-person examination (n = 623). The examination included cognitive examinations, transcranial ultrasound, a brief psychiatric interview and a standardized motor examination that was used to assign examination groups. In addition, all participants answered questionnaires addressing depression, anxiety, sleep and quality of life. The first-year follow-up examination was performed either in person using the same protocol or via mailed questionnaires. This study is ongoing and publications are in preparation, but you may contact the first author (meike.kasten@neuro.uni-luebeck.de) with suggestions for collaboration or data requests.

Impulse control disorders in Parkinson's disease: Crossroads between neurology, psychiatry and neuroscience

Behav Neurol. 2012 Dec 14. [Epub ahead of print]

Bugalho P, Oliveira-Maia AJ.

Source

Department of Neurology, Hospital de Egas Moniz, Centro Hospitalar de Lisboa Ocidental, Lisboa, Portugal Department of Neurology and CEDOC, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisboa, Portugal.

Abstract

Non-motor symptoms contribute significantly to Parkinson's disease (PD) related disability. Impulse control disorders (ICDs) have been recently added to the behavioural spectrum of PD-related non-motor symptoms. Such behaviours are characterized by an inappropriate drive to conduct repetitive behaviours that are usually socially inadequate or result in harmful consequences. Parkinson disease impulse control disorders (PD-ICDs) have raised significant interest in the scientific and medical community, not only because of their incapacitating nature, but also because they may represent a valid model of ICDs beyond PD and a means to study the physiology of drive, impulse control and compulsive actions in the normal brain. In this review, we discuss some unresolved issues regarding PD-ICDs, including the association with psychiatric co-morbidities such as obsessive-compulsive disorder and with dopamine related side effects, such as hallucinations and dyskinesias; the relationship with executive cognitive dysfunction; and the neural underpinnings of ICDs in PD. We also discuss the contribution of neuroscience studies based on animal-models towards a mechanistic explanation of the development of PD-ICDs, specifically regarding corticostriatal control of goal directed and habitual actions.

New concepts in the early and preclinical detection of Parkinson's disease: therapeutic implications

Expert Rev Neurother. 2012 Dec;12(12):1429-38. doi: 10.1586/ern.12.144.

Akhtar RS, Stern MB.

Source

Parkinson's Disease and Movement Disorders Center, Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Abstract

Parkinson's disease is a chronic neurodegenerative disorder leading to progressive motor impairment for which there is no cure. Currently, the diagnosis is made by the presence of cardinal motor features and several associated non-motor symptoms. However, at this point, the underlying neuropathological changes are already underway, and efforts in basic and clinical research have converged to suggest that Parkinson's disease actually begins well before symptom onset. As a result, the identification and development of disease-modifying therapies is difficult. In this review, we begin by summarizing what is known of disease pathogenesis in the context of early symptomatology. We then discuss the Parkinson's at-risk syndrome and highlight how this conceptual framework can be a useful for studies of early disease biomarkers and putative disease-modifying neurotherapeutics. With this framework, we discuss several clinical assessments, radiological studies and molecular assays that may be useful in early disease detection.

Neuropathological findings in benign tremulous Parkinsonism

Mov Disord. 2012 Dec 12. doi: 10.1002/mds.25220. [Epub ahead of print]

Selikhova M, Kempster PA, Revesz T, Holton JL, Lees AJ.

Source

Queen Square Brain Bank for Neurological Disorders and Institute of Neurology, University College London, London, United Kingdom; Department of Neurology, Russian State Medical University, Moscow, Russia.

Abstract

Benign tremulous parkinsonism, a tremor dominant syndrome with a relatively slow rate of deterioration, is recognized by clinicians although its pathological basis is not well understood. A systematic review of Queen Square Brain Bank donors was carried out to determine the natural history and pathology of individuals who had tremor dominant parkinsonism with mild non-tremor components and minimal gait disability for at least 8 years. We identified 16 cases of pathologically proved benign tremulous Parkinson's disease (PD); another 5 individuals conformed to the definition but did not have the pathology of PD. Patients with verified benign tremulous PD had less severe neuronal loss in the substantia nigra than controls (χ(2) : P = .003). Twelve of these had been correctly diagnosed with PD at their first neurological evaluation, whereas the other 4 were originally thought to have another tremor disorder. The only consistent distinguishing feature of the 5 pathologically disproved cases, who may have had either essential tremor with associated rest tremor or dystonic tremor, was a failure to develop unequivocal bradykinesia within a decade of onset of tremor at rest. Our findings support the existence of a distinct subgroup of benign tremulous PD. The slower rate of clinical progression correlates with less severe nigral cell loss at postmortem, although many of these patients transgress the benign tremulous parkinsonism definition by the final third of their disease course and develop the common features of advanced PD. © 2012 Movement Disorder Society.

Unimpaired postprandial pancreatic polypeptide secretion in Parkinson's disease and REM sleep behavior disorder

Mov Disord. 2012 Dec 12. doi: 10.1002/mds.25246. [Epub ahead of print]

Unger MM, Ekman R, Björklund AK, Karlsson G, Andersson C, Mankel K, Bohne K, Tebbe JJ, Stiasny-Kolster K, Möller JC, Mayer G, Kann PH, Oertel WH.

Source

Philipps-University Marburg, Department of Neurology, Marburg, Germany; Saarland University, Department of Neurology, Homburg, Germany. 

Abstract

BACKGROUND:

Pancreatic polypeptide is released immediately after food ingestion. The release is operated by vagal-abdominal projections and has therefore been suggested as a test for vagal nerve integrity. Pathoanatomical and clinical studies indicate vagal dysfunction in early Parkinson's disease (PD).

METHODS:

We assessed the postprandial secretion of pancreatic polypeptide and motilin in healthy controls (n = 18) and patients with idiopathic rapid-eye-movement sleep behavior disorder (iRBD, n = 10), a potential premotor stage of PD, as well as in drug-naive (n = 19) and treated (n = 19) PD patients.

RESULTS:

The postprandial pancreatic polypeptide secretion showed a physiological pattern in all groups and even an enhanced response in drug-naive PD and iRBD. Motilin concentrations correlated with pancreatic polypeptide concentrations.

CONCLUSIONS:

Postprandial pancreatic polypeptide secretion is not a suitable test for vagal nerve integrity in PD. The unimpaired pancreatic polypeptide response in iRBD and PD might be explained by partially intact vagal-abdominal projections or compensatory mechanisms substituting a defective neuronal brain-gut axis. © 2012 Movement Disorder Society.

Patients with rest-tremor and scans with ipsilateral dopaminergic deficit

J Neurol. 2012 Nov 30. [Epub ahead of print]

Aguirregomozcorta M, Stamelou M, Antonini A, Schwingenschuh P, Prvulovich L, Edwards MJ, Dickson JC, Bhatia KP.

Source

Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, University College London, Queen Square, London, WC1N 3BG, UK.

Abstract

Dopamine transporter imaging is typically abnormal in Parkinson's disease and shows reduced striatal uptake, which is typically greater contralateral to the clinically more affected side. However, tremor-dominant Parkinson's disease patients may have significantly lower uptake in the striatum ipsilateral to the rest-tremor compared to akinetic-rigid PD patients, implying a possible role of an ipsilateral deficit in the generation of rest-tremor.We report here three patients with rest-tremor and the unexpected finding of an ipsilateral presynaptic dopaminergic deficit with normal uptake contralateral to the rest-tremor in dopamine transporter imaging. We divided them in two groups, with and without a corresponding structural lesion in brain imaging. These data may suggest a role of ipsilateral dopaminergic deficit in the generation of rest-tremor. An explanation of these findings could be damage of crossed dopaminergic fibres from the substantia nigra to thalamus, which can cause motor impairment ipsilateral to dopamine depletion experimentally. This is speculative but there is no doubt that these cases exist and we encourage others to report similar cases, as this may assist in the better understanding of the yet unknown pathophysiology of rest-tremor.

Switch from selegiline to rasagiline is beneficial in patients with Parkinson's disease

J Neural Transm. 2012 Nov 30. [Epub ahead of print]

Müller T, Hoffmann JA, Dimpfel W, Oehlwein C.

Source

Department of Neurology, St. Joseph-Hospital, Gartenstr. 1, 13088, Berlin, Germany.

Abstract

The objective of this study is to demonstrate that application of rasagiline instead of selegiline with concomitant determination of L-amphetamine and L-methamphetamine in plasma is safe and well tolerated and influences sleep, mood, and motor behavior in patients with Parkinson's disease on a stable drug therapy. 30 patients, who took 7.5 mg selegiline daily for at least 3 months, were switched to 1 mg rasagiline. Then they were followed over an interval of 4 months. The remaining drug therapy remained stable. This changeover was safe and well tolerated. L-Amphetamine and L-methamphetamine only appeared during selegiline treatment. Motor behavior, motor complications, mood and sleep improved during rasagiline administration. Amphetamine-like derivatives of selegiline could contribute to sleep disturbances, which may be involved in worsening of mood. Motor behavior and motor complications probably became better due to the additional glutamate receptor antagonizing properties of rasagiline in this open label study.

A randomized, controlled, delayed start trial of GM1 ganglioside in treated Parkinson's disease patients

J Neurol Sci. 2012 Nov 28. pii: S0022-510X(12)00581-3. doi: 10.1016/j.jns.2012.10.024. [Epub ahead of print]

Schneider JS, Gollomp SM, Sendek S, Colcher A, Cambi F, Du W.

Source

Dept. of Pathology, Anatomy and Cell Biology and Parkinson's Disease Research Unit, Thomas Jefferson University, Philadelphia, PA 19107, USA.

Abstract

The present single center, double-blind, delayed start study was conducted to examine possible symptomatic and disease-modifying effects of GM1 ganglioside in Parkinson's disease (PD). Seventy-seven subjects with PD were randomly assigned to receive GM1 for 120weeks (early-start group) or placebo for 24weeks followed by GM1 for 96weeks (delayed-start group). Washout evaluations occurred at 1 and 2years after the end of treatment. Seventeen additional subjects who received standard-of-care were followed for comparative information about disease progression. Primary outcome was change from baseline Unified Parkinson's Disease Rating Scale (UPDRS) motor scores. At week 24, the early-start group had significant improvement in UPDRS motor scores vs. a significant worsening of scores in the delayed-start group. The early-start group also showed a sustained benefit vs. the delayed-start group at week 72 and at week 120. Both groups had significant symptom worsening during washout. This study provides evidence that GM1 use for 24weeks was superior to placebo for improving motor symptoms and that extended GM1 use (up to 120weeks) resulted in a lower than expected rate of symptom progression. The data from this small study suggest that GM1 may have symptomatic and potentially disease modifying effects on PD.

Now to the North West to see participants...

Spending a week at my family home in order to see 15 or so participants in the area. Beautiful winter sun has given way to wet windiness now and I'm relieved to be off the motorbike and into a car! Pictures from yesterdays trip into the Welsh countryside to see a couple of participants.

A look back at the Welsh coast and Snowdonia from Anglesey. 

Finding my way around single track roads in North Wales.

Subthalamic nucleus versus globus pallidus bilateral deep brain stimulation for advanced Parkinson's disease (NSTAPS study): a randomised controlled trial

Lancet Neurol. 2012 Nov 15. pii: S1474-4422(12)70264-8. doi: 10.1016/S1474-4422(12)70264-8. [Epub ahead of print]

Odekerken VJ, van Laar T, Staal MJ, Mosch A, Hoffmann CF, Nijssen PC, Beute GN, van Vugt JP, Lenders MW, Contarino MF, Mink MS, Bour LJ, van den Munckhof P, Schmand BA, de Haan RJ, Schuurman PR, de Bie RM.

Source

Department of Neurology, Academic Medical Center, Amsterdam, Netherlands.

Abstract

BACKGROUND:

Patients with advanced Parkinson's disease often have rapid swings between mobility and immobility, and many respond unsatisfactorily to adjustments in pharmacological treatment. We assessed whether globus pallidus pars interna (GPi) deep brain stimulation (DBS) gives greater functional improvement than does subthalamic nucleus (STN) DBS.

METHODS:

We recruited patients from five centres in the Netherlands who were aged 18 years or older, had idiopathic Parkinson's disease, and had, despite optimum pharmacological treatment, at least one of the following symptoms: severe response fluctuations, dyskinesias, painful dystonias, or bradykinesia. By use of a computer-generated randomisation sequence, we randomly assigned patients to receive either GPi DBS or STN DBS (1:1), applying a minimisation procedure according to drug use (levodopa equivalent dose <1000 mg vs ≥1000 mg) and treatment centre. Patients and study assessors (but not those who assessed adverse events) were masked to treatment allocation. We had two primary outcomes: functional health as measured by the weighted Academic Medical Center Linear Disability Scale (ALDS; weighted by time spent in the off phase and on phase) and a composite score for cognitive, mood, and behavioural effects up to 1 year after surgery. Secondary outcomes were symptom scales, activities of daily living scales, a quality-of-life questionnaire, the occurrence of adverse events, and drug use. We used the intention-to-treat principle for all analyses. This trial is registered with www.controlled-trials.com, number ISRCTN85542074.

FINDINGS:

Between Feb 1, 2007, and March 29, 2011, we enrolled 128 patients, assigning 65 to GPi DBS and 63 to STN DBS. We found no statistically significant difference in either of our primary outcomes: mean change in weighted ALDS (3·0 [SD 14·5] in the GPi group vs 7·7 [23·2] in the STN group; p=0·28) and the number of patients with cognitive, mood, and behavioural side-effects (36 [58%] of 62 patients in the GPi group vs 35 [56%] of 63 patients in the STN group; p=0·94). Secondary outcomes showed larger improvements in off-drug phase in the STN group compared with the GPi group in the mean change in unified Parkinson's disease rating scale motor examination scores (20·3 [16·3] vs 11·4 [16·1]; p=0·03), the mean change in ALDS scores (20·3 [27·1] vs 11·8 [18·9]; p=0·04), and medication (mean levodopa equivalent drug reduction: 546 [SD 561] vs 208 [521]; p=0·01). We recorded no difference in the occurrence of adverse events between the two groups. Other secondary endpoints showed no difference between the groups.

INTERPRETATION:

Although there was no difference in our primary outcomes, our findings suggest that STN could be the preferred target for DBS in patients with advanced Parkinson's disease.

FUNDING:

Stichting Internationaal Parkinson Fonds, Prinses Beatrix Fonds, and Parkinson Vereniging.

Copyright © 2012 Elsevier Ltd. All rights reserved.

Effectiveness of Multidisciplinary Care for Parkinson's Disease: A Randomized, Controlled Trial

Mov Disord. 2012 Nov 19. doi: 10.1002/mds.25194. [Epub ahead of print]

van der Marck MA, Bloem BR, Borm GF, Overeem S, Munneke M, Guttman M.

Source

Radboud University Nijmegen Medical Centre; Nijmegen Centre for Evidence Based Practice, Department of Neurology, Nijmegen, The Netherlands.

Abstract

Multidisciplinary care is considered an optimal model to manage Parkinson's disease (PD), but supporting evidence is limited. We performed a randomized, controlled trial (RCT) to establish whether a multidisciplinary/specialist team offers better outcomes, compared to stand-alone care from a general neurologist. Patients with PD were randomly allocated to an intervention group (care from a movement disorders specialist, PD nurses, and social worker) or a control group (care from general neurologists). Both interventions lasted 8 months. Clinicians and researchers were blinded for group allocation. The primary outcome was the change in quality of life (Parkinson's Disease Questionnaire; PDQ-39) from baseline to 8 months. Other outcomes were the UPDRS, depression (Montgomery-Asberg Depression Scale; MADRS), psychosocial functioning (Scales for Outcomes in Parkinson's disease-Psychosocial; SCOPA-PS), and caregiver strain (Caregiver Strain Index; CSI). Group differences were analyzed using analysis of covariance adjusted for baseline values and presence of response fluctuations. A total of 122 patients were randomized and 100 completed the study (intervention, n = 51; control, n = 49). Compared to controls, the intervention group improved significantly on PDQ-39 (difference, 3.4; 95% confidence interval [CI]: 0.5-6.2) and UPDRS motor scores (4.1; 95% CI: 0.8-7.3). UPDRS total score (5.6; 95% CI: 0.9-10.3), MADRS (3.7; 95% CI: 1.4-5.9), and SCOPA-PS (2.1; 95% CI: 0.5-3.7) also improved significantly. This RCT gives credence to a multidisciplinary/specialist team approach. We interpret these positive findings cautiously because of the limitations in study design. Further research is required to assess teams involving additional disciplines and to evaluate cost-effectiveness of integrated approaches. © 2012 Movement Disorder Society.

A New Era of Clinical Dopamine Transporter Imaging Using 123I-FP-CIT

J Nucl Med Technol. 2012 Nov 16. [Epub ahead of print]

Park E.

Source

Department of Nuclear Medicine, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, New York.

Abstract

(123)I-labeled 2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)nortropane ((123)I-FP-CIT) was approved for clinical use in 2011 by the Food and Drug Administration. (123)I-FP-CIT is a radioligand for brain dopamine transporter (DAT) imaging that is useful for the differential diagnosis of Parkinson disease (PD) and other diseases that mimic PD. The sensitivity and specificity of (123)I-FP-CIT SPECT for PD diagnosis are more than 90% and equivalent to those of other DAT SPECT methods. In the near future, the clinical indications of DAT imaging are expected to be broadened; for example, including treatment response assessment, disease progression monitoring, and early diagnosis of premotor PD in each individual patient.

Pathological α-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice

Science. 2012 Nov 16;338(6109):949-53. doi: 10.1126/science.1227157.

Luk KC, Kehm V, Carroll J, Zhang B, O'Brien P, Trojanowski JQ, Lee VM.

Source

Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104-4283, USA.

Abstract

Parkinson's disease is characterized by abundant α-synuclein (α-Syn) neuronal inclusions, known as Lewy bodies and Lewy neurites, and the massive loss of midbrain dopamine neurons. However, a cause-and-effect relationship between Lewy inclusion formation and neurodegeneration remains unclear. Here, we found that in wild-type nontransgenic mice, a single intrastriatal inoculation of synthetic α-Syn fibrils led to the cell-to-cell transmission of pathologic α-Syn and Parkinson's-like Lewy pathology in anatomically interconnected regions. Lewy pathology accumulation resulted in progressive loss of dopamine neurons in the substantia nigra pars compacta, but not in the adjacent ventral tegmental area, and was accompanied by reduced dopamine levels culminating in motor deficits. This recapitulation of a neurodegenerative cascade thus establishes a mechanistic link between transmission of pathologic α-Syn and the cardinal features of Parkinson's disease.

Supportive evidence for 11 loci from genome-wide association studies in Parkinson's disease

Neurobiol Aging. 2012 Nov 12. pii: S0197-4580(12)00530-1. doi: 10.1016/j.neurobiolaging.2012.10.019. [Epub ahead of print]

Pihlstrøm L, Axelsson G, Bjørnarå KA, Dizdar N, Fardell C, Forsgren L, Holmberg B, Larsen JP, Linder J, Nissbrandt H, Tysnes OB, Ohman E, Dietrichs E, Toft M.

Source

Department of Neurology, Oslo University Hospital, Oslo, Norway.

Abstract

Genome-wide association studies have identified a number of susceptibility loci in sporadic Parkinson's disease (PD). Recent larger studies and meta-analyses have greatly expanded the list of proposed association signals. We performed a case-control replication study in a Scandinavian population, analyzing samples from 1345 unrelated PD patients and 1225 control subjects collected by collaborating centers in Norway and Sweden. Single-nucleotide polymorphisms representing 18 loci previously reported at genome-wide significance levels were genotyped, as well as 4 near-significant, suggestive, loci. We replicated 11 association signals at p < 0.05 (SNCA, STK39, MAPT, GPNMB, CCDC62/HIP1R, SYT11, GAK, STX1B, MCCC1/LAMP3, ACMSD, and FGF20). The more recently nominated susceptibility loci were well represented among our positive findings, including 3 which have not previously been validated in independent studies. Conversely, some of the more well-established loci failed to replicate. While future meta-analyses should corroborate disease associations further on the level of common markers, efforts to pinpoint functional variants and understand the biological implications of each risk locus in PD are also warranted.

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Serum Uric Acid in Patients with Parkinson's Disease and Vascular Parkinsonism: A Cross-Sectional Study

Neuroimmunomodulation. 2012 Nov 14;20(1):19-28. [Epub ahead of print]

Pan M, Gao H, Long L, Xu Y, Liu M, Zou J, Wu A, Wei X, Chen X, Tang B, Wang Q.

Source

Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, PR China.

Abstract

Background: Elevation of serum uric acid (UA) is correlated with a decreased risk of Parkinson's disease (PD); however, the association and clinical relevance of serum UA levels in patients with PD and vascular parkinsonism (VP) are unknown. Objective: We performed a cross-sectional study of 160 Chinese patients with PD and VP to determine whether UA levels in patients could predict the outcomes. Methods: Serum UA levels were divided into quartiles and the association between UA and the severity of PD or VP was investigated in each quartile. Results: The serum levels of UA in PD were significantly lower than those in normal subjects and VP. The serum UA levels in PD patients were significantly correlated with some clinical parameters. Strong correlations were observed in male PD patients, but significant correlations were observed only between UA and the non-motor symptoms (NMS) of burden of sleep/fatigue and mood in female PD patients. PD patients in the lowest quartile of serum UA levels had significant correlations between UA and the unified Parkinson's disease rating scale, the modified Hoehn and Yahr staging scale and NMS burden for attention/memory. Conclusion: Our findings support the hypothesis that subjects with low serum UA levels may be more prone to developing PD and indicate that the inverse relationship between UA and severity of PD was robust for men but weak for women. Our results strongly imply that either low serum UA level is a deteriorative predictor or that serum UA level serves as an indirect biomarker of prediction in PD but not in VP patients.

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Our systematic review and meta-analysis of risk factors for PD is Open Access

We recently published our comprehensive review of risk factors and early non-motor features for Parkinson's disease in the Annals of Neurology. Parkinson's UK have very kindly supported us to make this paper Open Access, which means that anyone is allowed to read it. You can find it at

http://onlinelibrary.wiley.com/doi/10.1002/ana.23687/abstract


Let me know what you think.

- Alastair Noyce

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Head injury and Parkinson's disease: A population-based study

Mov Disord. 2012 Nov 9. doi: 10.1002/mds.25143. [Epub ahead of print]

Fang F, Chen H, Feldman AL, Kamel F, Ye W, Wirdefeldt K.

Source

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Abstract

BACKGROUND:

The epidemiological evidence on head injury and the risk of Parkinson's disease (PD) has been inconsistent.

METHODS:

We examined the relation between previous hospitalization for head injury and PD using a population-based nested case-control design based on the Swedish National Patient Register from 2001 until 2007, including 18,648 PD cases and 93,240 controls, randomly selected from the general population. Exposure was defined as hospitalization for head injury between 1987 and index date.

RESULTS:

Overall, previous hospitalization resulting from head injury was associated with an increased risk of PD; this association appeared to be largely explained by head injuries experienced recently, especially within 1 year before PD ascertainment.

CONCLUSIONS:

Our results do not provide convincing evidence for a causal relationship between head injury later in life and PD. © 2012 Movement Disorder Society.

Ceruloplasmin and iron in Alzheimer's disease and Parkinson's disease: a synopsis of recent studies

Neuropsychiatr Dis Treat. 2012;8:515-21. doi: 10.2147/NDT.S34729. Epub 2012 Nov 2.

Kristinsson J, Snaedal J, Tórsdóttir G, Jóhannesson T.

Source

Department of Pharmacology and Toxicology, University of Iceland, Reykjavik, Iceland.

Abstract

Ceruloplasmin (Cp) concentration and oxidative activity in serum are lowered in Parkinson's disease (PD). In most PD patients, iron increases in the substantia nigra in the midbrain. In PD, the low Cp concentration and activity in serum and the high iron amounts in the substantia nigra appears to be correlated. An hereditary background is common in PD and variations in the Cp gene that have been found in PD are associated with high iron levels in the substantia nigra. Variations in Cp synthesis and in the incorporation of copper into the Cp molecule are essential features of PD. In Alzheimer's disease (AD), the Cp activity in serum is lowered but not the concentration, except in the advanced stages of the disease. Generally, iron is not increased in the AD brain. In the AD brain, iron accumulates in neuritic plaques and in neurofibrillary tangles. There is also increased risk of iron-mediated tissue damage, which may possibly be counteracted by Cp. At the same time, the AD brain is short in copper, which presumably results in the deficient activity of many copper enzymes in the brain, in addition to Cp. Lowered Cp activity in serum most likely stems from lessened incorporation of copper in the Cp molecule and similar incorporation defects might also apply to other copper enzymes in AD.

Symptoms and Quality of Life in Late Stage Parkinson Syndromes: A Longitudinal Community Study of Predictive Factors

PLoS One. 2012;7(11):e46327. Epub 2012 Nov 7.

Higginson IJ, Gao W, Saleem TZ, Chaudhuri KR, Burman R, McCrone P, Leigh PN.

Source

Cicely Saunders Institute, King's College London, London, United Kingdom.

Abstract

BACKGROUND:

Palliative care is increasingly offered earlier in the cancer trajectory but rarely in Idiopathic Parkinson's Disease(IPD), Progressive Supranuclear Palsy(PSP) or Multiple System Atrophy(MSA). There is little longitudinal data of people with late stage disease to understand levels of need. We aimed to determine how symptoms and quality of life of these patients change over time; and what demographic and clinical factors predicted changes.

METHODS:

We recruited 82 patients into a longitudinal study, consenting patients with a diagnosis of IPD, MSA or PSP, stages 3-5 Hoehn and Yahr(H&Y). At baseline and then on up to 3 occasions over one year, we collected self-reported demographic, clinical, symptom, palliative and quality of life data, using Parkinson's specific and generic validated scales, including the Palliative care Outcome Scale (POS). We tested for predictors using multivariable analysis, adjusting for confounders.

FINDINGS:

Over two thirds of patients had severe disability, over one third being wheelchair-bound/bedridden. Symptoms were highly prevalent in all conditions - mean (SD) of 10.6(4.0) symptoms. More than 50% of the MSA and PSP patients died over the year. Over the year, half of the patients showed either an upward (worsening, 24/60) or fluctuant (8/60) trajectory for POS and symptoms. The strongest predictors of higher levels of symptoms at the end of follow-up were initial scores on POS (AOR 1.30; 95%CI:1.05-1.60) and being male (AOR 5.18; 95% CI 1.17 to 22.92), both were more predictive than initial H&Y scores.

INTERPRETATION:

The findings point to profound and complex mix of non-motor and motor symptoms in patients with late stage IPD, MSA and PSP. Symptoms are not resolved and half of the patients deteriorate. Palliative problems are predictive of future symptoms, suggesting that an early palliative assessment might help screen for those in need of earlier intervention.

Clinical features, pathophysiology, and treatment of levodopa-induced dyskinesias in Parkinson's disease

Parkinsons Dis. 2012;2012:943159. doi: 10.1155/2012/943159. Epub 2012 Oct 17.

Guridi J, González-Redondo R, Obeso JA.

Source

Department of Neurosurgery and Neurology, Clinica Universidad de Navarra, 31008 Pamplona, Spain.

Abstract

Dyskinetic disorders are characterized by excess of motor activity that may interfere with normal movement control. In patients with Parkinson's disease, the chronic levodopa treatment induces dyskinetic movements known as levodopa-induced dyskinesias (LID). This paper analyzed the pathophysiology, clinical manifestations, pharmacological treatments, and surgical procedures to treat hyperkinetic disorders. Surgery is currently the only treatment available for Parkinson's disease that may improve both parkinsonian motor syndrome and LID. However, this paper shows the different mechanisms involved are not well understood.

Prevalence and Pharmacological Factors Associated With Impulse-Control Disorder Symptoms in Patients With Parkinson Disease

Clin Neuropharmacol. 2012 Nov 1. [Epub ahead of print]

Perez-Lloret S, Rey MV, Fabre N, Ory F, Spampinato U, Brefel-Courbon C, Montastruc JL, Rascol O.

Source

*Laboratoire de Pharmacologie Médicale et Clinique, Faculté de Médecine, Toulouse, France; †INSERM Centre d'Investigation Clinique CIC 9203, Toulouse, France; ‡Services de Neurologie, CHU Toulouse, France; §Department of Neurology, CHU Bordeaux, France; and ∥INSERM U 1027 Equipe de PharmacoEpidémiologie, Toulouse, France.

Abstract

BACKGROUND:

Impulse-control disorders (ICDs) occur in patients with Parkinson disease (PD), especially in younger patients on dopamine therapies.

OBJECTIVE:

To assess the prevalence of ICD symptoms and its pharmacological correlations in a sample of French patients with PD and without PD (poststroke).

METHODS:

Outpatients with PD and without PD (poststroke) were screened for compulsive behaviors related to hypersexuality, compulsive shopping, pathological gambling, or compulsive eating by means of the Questionnaire for Impulse-Control Disorders-short version. Full medical history and Unified Parkinson's Disease Rating Scale scores were also recorded. Dose of dopamine agonists were converted to defined daily doses (DDDs), according to the World Health Organization Anatomical Therapeutic Chemical classification system classification system.

RESULTS:

Two hundred three patients with PD and 52 patients without PD were recruited (mean ± SD age, 67 ± 1 vs 69 ± 2, P = 0.4; males: 62% vs 55% P = 0.2). Symptoms of ICDs were reported by 0% of poststroke patients and 25% of the patients with PD (P < 0.001). Hypersexuality was reported by 10% of the patients with PD, compulsive shopping by 6%, pathological gambling by 3%, and compulsive eating by 14%. A logistic regression analysis found that age younger than 68 years (odds ratio [OR], 3.3; 95% confidence interval, 1.6-6.6) and exposure to dopamine agonists (OR, 20.3; 95% confidence interval, 2.7-65.0) or monoaminooxidase-B inhibitor (OR, 3.7; 95% confidence interval, 1.1-12.6) were significant factors associated with increased ICD frequency. Patients with ICD symptoms were exposed to higher dopamine doses than those without them (1.6 ± 0.1 vs 1.0 ± 0.1 daily-defined doses; P < 0.001). A dose-response pharmacodynamic model disclosed a significant nonlinear dose-response relationship between dopamine agonists and frequency of ICD symptoms (P < 0.01).

CONCLUSIONS:

Impulse-control disorder symptoms were more frequent in the patients with PD than in the poststroke patients with PD. Impulse-control disorder symptoms were related to younger age and exposure to monoaminooxidase-B inhibitors, and showed a nonlinear dose-response relationship with dopamine agonists.

Cerebrospinal fluid amyloid-β and phenotypic heterogeneity in de novo Parkinson's disease

J Neurol Neurosurg Psychiatry. 2012 Oct 31. [Epub ahead of print]

Alves G, Pedersen KF, Bloem BR, Blennow K, Zetterberg H, Borm GF, Dalaker TO, Beyer MK, Aarsland D, Andreasson U, Lange J, Tysnes OB, Zivadinov R, Larsen JP.


Source

The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway.

Abstract

BACKGROUND:

In Parkinson's disease (PD), the motor presentation characterised by postural instability/gait difficulties (PIGD) heralds accelerated motor, functional and cognitive decline, as compared with the more benign tremor-dominant (TD) variant. This makes the PIGD complex an attractive target for the discovery of prognostic biomarkers in PD.

OBJECTIVE:

To explore in vivo whether variability in brain amyloid-β (Aβ) metabolism affects the initial motor presentation in PD.

METHODS:

We quantified cerebrospinal fluid (CSF) concentrations and ratios of Aβ42, Aβ40 and Aβ38 using a triplex immunoassay in 99 patients with de novo PD with the PIGD phenotype (n=39) or the TD phenotype (n=60). All patients underwent standardised assessments of motor and neuropsychological function and cerebral MRI. 46 age-matched normal controls served as external reference.

RESULTS:

Patients with PD with the PIGD phenotype had significantly reduced CSF Aβ42, Aβ38, Aβ42/40 and Aβ38/40 levels compared with patients with the TD phenotype and controls. CSF marker levels in patients with PD-TD did not differ from those in controls. Multivariate regression models demonstrated significant associations of CSF Aβ markers with severity of PIGD and lower limb bradykinesia in patients with PD, independently from age, MRI white matter hyperintensities and cognition. No associations were found between CSF markers and other motor features.

CONCLUSIONS:

Motor heterogeneity in de novo PD independently relates to CSF Aβ markers, with low levels found in patients with the PIGD presentation. This suggests that disturbed Aβ metabolism has an effect on PD beyond cognition and may contribute to the variable rate of motor and functional decline in PD.

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Parkinson's UK Conference

I'm taking a couple of days out from seeing study participants to attend the Parkinson's UK conference in York. It's a beautiful sunny but cold autumn day in the North of England - my favourite kind of day. There's lots of molecular biology on the menu so hopefully I can keep pace. I'm just looking forward to hearing about all the fantastic work that's being supported by Parkinson's UK and that's going on all round the country and beyond.

- Alastair Noyce

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Hippocampal perfusion predicts impending neurodegeneration in REM sleep behavior disorder

Neurology. 2012 Oct 31. [Epub ahead of print]

Dang-Vu TT, Gagnon JF, Vendette M, Soucy JP, Postuma RB, Montplaisir J.

Source

From the Center for Advanced Research in Sleep Medicine (T.T.D.-V., J.-F.G., M.V., R.B.P., J.M.), Hôpital du Sacré-Cœur de Montréal; Department of Exercise Science and Center for Studies in Behavioral Neurobiology (T.T.D.-V.), Concordia University, Montréal, Canada; Cyclotron Research Centre (T.T.D.-V.), University of Liege; Department of Neurology (T.T.D.-V.), Centre Hospitalier Universitaire de Liège, Belgium; Department of Psychology (J.-F.G.), Université du Québec à Montréal; Montreal Neurological Institute (P.S.), McGill University, Montréal; Department of Nuclear Medicine (J.P.-S.), Centre Hospitalier de l'Université de Montréal; Department of Neurology (R.B.P.), Montreal General Hospital; and Department of Psychiatry (J.M.), University of Montreal, Canada.

Abstract

OBJECTIVES:

Patients with idiopathic REM sleep behavior disorder (IRBD) are at risk for developing Parkinson disease (PD) and dementia with Lewy bodies (DLB). We aimed to identify functional brain imaging patterns predicting the emergence of PD and DLB in patients with IRBD, using SPECT with (99m)Tc-ethylene cysteinate dimer (ECD).

METHODS:

Twenty patients with IRBD were scanned at baseline during wakefulness using (99m)Tc-ECD SPECT. After a follow-up of 3 years on average, patients were divided into 2 groups according to whether or not they developed defined neurodegenerative disease (PD, DLB). SPECT data analysis comparing regional cerebral blood flow (rCBF) between groups assessed whether specific brain perfusion patterns were associated with subsequent clinical evolution. Regression analysis between rCBF and clinical markers of neurodegeneration (motor, color vision, olfaction) looked for neural structures involved in this process.

RESULTS:

Of the 20 patients with IRBD recruited for this study, 10 converted to PD or DLB during the follow-up. rCBF at baseline was increased in the hippocampus of patients who would later convert compared with those who would not (p < 0.05 corrected). Hippocampal perfusion was correlated with motor and color vision scores across all IRBD patients.

CONCLUSIONS:

(99m)Tc-ECD SPECT identifies patients with IRBD at risk for conversion to other neurodegenerative disorders such as PD or DLB; disease progression in IRBD is predicted by abnormal perfusion in the hippocampus at baseline. Perfusion within this structure is correlated with clinical markers of neurodegeneration, further suggesting its involvement in the development of presumed synucleinopathies.

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Sleep and Parkinson's disease: A review of case-control polysomnography studies

Mov Disord. 2012 Oct 31. doi: 10.1002/mds.25197. [Epub ahead of print]

Peeraully T, Yong MH, Chokroverty S, Tan EK.

Source


National Neuroscience Institute, Department of Neurology, Singapore General Hospital, Singapore, Singapore.

Abstract

The link between Parkinson's disease (PD) and certain primary sleep disorders has yet to be clarified. We performed a systematic review of case-control polysomnography studies to evaluate the relationship between PD and sleep disorders. A PubMed literature search and bibliography review yielded 15 case-control polysomnography studies in patients with PD. Studies differed by recruitment methods, duration of polysomnography monitoring, and sleep parameters measured. Subjective sleepiness was greater in patients than controls (50%-66% vs 2.9%-12%) despite lack of objective increase in daytime sleepiness by mean sleep latency testing. The 4 case-control polysomnography studies investigating rapid eye movement behavior disorder support a higher prevalence in PD (0%-47% vs 0%-1.8% in controls), although differences in diagnostic criteria hamper interpretation. The preponderance of evidence did not support an increased incidence of obstructive sleep apnea (27%-60% vs 13%-65%) or periodic leg movements of sleep in patients compared to controls. Adequately powered, prospective studies with uniform methodology and healthy controls are needed to further address the association and pathophysiological significance between PD and sleep problems. © 2012 Movement Disorder Society.

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Common variation in the LRRK2 gene is a risk factor for Parkinson's disease

Mov Disord. 2012 Oct 31. doi: 10.1002/mds.25226. [Epub ahead of print]

Mata IF, Checkoway H, Hutter CM, Samii A, Roberts JW, Kim HM, Agarwal P, Alvarez V, Ribacoba R, Pastor P, Lorenzo-Betancor O, Infante J, Sierra M, Gómez-Garre P, Mir P, Ritz B, Rhodes SL, Colcher A, Van Deerlin V, Chung KA, Quinn JF, Yearout D, Martinez E, Farin FM, Wan JY, Edwards KL, Zabetian CP.

Source

Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA; Department of Neurology, University of Washington School of Medicine, Seattle, Washington, USA.

Abstract

BACKGROUND:

Common variants in the LRRK2 gene influence the risk of Parkinson's disease (PD) in Asians, but whether the same is true in European-derived populations is less clear.

METHODS:

We genotyped 66 LRRK2 tagging single-nucleotide polymorphisms (SNPs) in 575 PD patients and 689 controls from the northwestern United States (tier 1). PD-associated SNPs (P < .05) were then genotyped in an independent sample of 3617 cases and 2512 controls from the United States and Spain (tier 2). Logistic regression was used to model additive SNP genotype effects adjusted for age and sex among white individuals.

RESULTS:

Two regions showed independent association with PD in tier 1, and SNPs in both regions were successfully replicated in tier 2 (rs10878226, combined odds ratio [OR], 1.20; 95% confidence interval [CI], 1.08-1.33; P = 6.3 × 10(-4) ; rs11176013, OR, 0.89; CI, 0.83-0.95; P = 4.6 × 10(-4) ).

CONCLUSIONS:

Our data suggest that common variation within LRRK2 conveys susceptibility for PD in individuals of European ancestry. © 2012 Movement Disorder Society.

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Long-term course of substantia nigra hyperechogenicity in Parkinson's disease

Mov Disord. 2012 Oct 31. doi: 10.1002/mds.25193. [Epub ahead of print]

Behnke S, Runkel A, Kassar HA, Ortmann M, Guidez D, Dillmann U, Fassbender K, Spiegel J.

Source

Department of Neurology, Saarland University, Homburg/Saar, Germany.

Abstract

A hyperechogenicity of the (SN+) in transcranial sonography corroborates the diagnosis of idiopathic Parkinson's disease (iPD). Although it is thought to represent a biomarker of the disease that is independent of disease severity and progression, differing results have been reported describing a positive correlation of the size and advancing clinical stage. In 50 parkinsonian patients, transcranial ultrasound and clinical examination was performed twice with a mean time interval of 6.4 years. SN+ did not change in size significantly between the first and second examination, whereas clinical parkinsonian symptoms-as determined by the motor part of the UPDRS-significantly worsened (P < 0.001). We found a highly significant intraindividual correlation in SN+ sizes between both examinations (P < 0.001). The size of SN+ did not correlate with the UPDRS part III at the time of first or second ultrasound examination. Progression of motor symptoms between the first and second investigation did not correlate with the size of SN+ at baseline. Furthermore, even in the subgroup of patients with an interval of ≥8 years between examinations, there was no significant change in SN+ size. SN+ represents a largely stable biomarker in iPD and does not reflect disease progression. The size of SN+ does not predict the further course of the disease. © 2012 Movement Disorder Society.

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Enlarged hyperechogenic substantia nigra as a risk marker for Parkinson's disease

Mov Disord. 2012 Oct 31. doi: 10.1002/mds.25192. [Epub ahead of print]

Berg D, Behnke S, Seppi K, Godau J, Lerche S, Mahlknecht P, Liepelt-Scarfone I, Pausch C, Schneider N, Gaenslen A, Brockmann K, Srulijes K, Huber H, Wurster I, Stockner H, Kiechl S, Willeit J, Gasperi A, Fassbender K, Gasser T, Poewe W.

Source

Center of Neurology, Department of Neurodegeneration and Hertie Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany; German Center for Neurodegenerative Diseases, University of Tuebingen, Tuebingen, Germany.

Abstract

BACKGROUND:

SN hyperechogenicity (SN+), determined by transcranial sonography, has been proposed as a risk factor for Parkinson's disease (PD). Recently, we reported a 17.4-fold increased risk for PD in individuals with SN+ older than 50 years within 3 years.

METHODS:

This is the second follow-up of a prospective, longitudinal, three-center observational study after 5 years. Of the initial 1,847 at baseline PD-free participants 50 years or older, 1,271 underwent the 5-year reassessment.

RESULTS:

Within 5 years, 21 individuals developed incident PD. Participants with SN+ at baseline had a more than 20.6 times increased risk to develop PD in this time span than those without this echo feature.

CONCLUSION:

We thus confirm our finding of the 3-year follow-up examination in a longer observation time and higher number of individuals with incident PD and suggest SN+ as an important risk marker for PD. © 2012 Movement Disorder Society.

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Sonographic abnormality of the substantia nigra in melanoma patients

Mov Disord. 2012 Oct 31. doi: 10.1002/mds.25233. [Epub ahead of print]

Rumpf JJ, Weise D, Fricke C, Wetzig T, Simon JC, Classen J.


Source

Department of Neurology, University of Leipzig, Leipzig, Germany.

Abstract

BACKGROUND:

Evidence derived from large epidemiological studies suggests an association between Parkinson's disease (PD) and malignant melanoma. Transcranial sonography of the midbrain reveals an extended echogenic substantia nigra (SN) area in a high proportion of patients with PD. This characteristic, in the context of PD, may signal degeneration of dopaminergic nigrostriatal projection neurons. Demonstration of an increased prevalence of abnormal echogenic SN in melanoma patients could add weight to the hypothesis of an underlying common pathogenic pathway of both diseases.

METHODS:

This was a cross-sectional observational study. Transcranial sonography of the SN region was performed on 31 patients suffering from malignant melanoma and 29 healthy participants. In addition, patients and controls were screened for motor and non-motor symptoms of PD.

RESULTS:

The echogenic SN area was abnormally extended in 42% of melanoma patients versus 7% of control subjects (χ(2) = 9.811, P = .002). Mean echogenic SN area (SN[R, L]) was significantly larger in melanoma patients than in controls (patients, 0.21 ± 0.07 cm(2) ; controls, 0.15 ± 0.04 cm(2) [mean ± SD]; unpaired t test, P < .001).

CONCLUSIONS:

These findings provide additional evidence in favor of a common pathogenic pathway of PD and malignant melanoma and raise the possibility that their association is closer than previously assumed. © 2012 Movement Disorder Society.

Copyright © 2012 Movement Disorder Society.

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Fatigue in Parkinson's disease: Motor or non-motor symptom?

Parkinsonism Relat Disord. 2012 Oct 26. pii: S1353-8020(12)00385-9. doi: 10.1016/j.parkreldis.2012.10.009. [Epub ahead of print]

Fabbrini G, Latorre A, Suppa A, Bloise M, Frontoni M, Berardelli A.

Source

Department of Neurology and Psychiatry, "Sapienza" University of Rome, Viale dell'Università 30, 00185 Rome, Italy; Neuromed Institute (IRCSS), Pozzilli (IS), Italy.

Abstract

Fatigue is one of the most disabling symptoms in patients with Parkinson's disease (PD), with a significant impact on patients' quality of life. Clinical studies using ad hoc questionnaires showed that in PD fatigue is associated with non-motor as well motor symptoms. Neurophysiological observations suggest that motor mechanisms play a role in the pathophysiology of fatigue but there is no clear correlation between fatigue measured with clinical instruments and fatigue assessed with neurophysiological tests. Neuroimaging studies show that fatigue is associated with an involvement of non-dopaminergic or extrastriatal dopaminergic pathways. It is conceivable that both motor and non-motor mechanisms underlie the pathophysiology of fatigue.

Over 700 now...

It's great to see that over 700 of our participants have continued in the study so far and I think this number will be close to 1000 when we finish the re-survey period. 

I had a fruitful trip to South East London last week, and I am seeing participants in South West London today (and yesterday) and North London tomorrow. November will see me travelling around the UK seeing as many participants as possible. 

It's wonderful to meet people and hear about their motivations for joining the study.

- Alastair Noyce

Essential tremor is not a neurodegenerative disease

Neurodegener Dis Manag. 2012 Jun;2(3):259-268.

Rajput AH, Adler CH, Shill HA, Rajput A.

Source

Movement Disorders Program, Neurology Division, University of Saskatchewan/Saskatoon Health Region, 103 Hospital Drive, Saskatoon, SK, S7N 0W8, Canada.

Abstract

The pathophysiology of essential tremor (ET) remains unknown. Standard neuropathological studies have reported no consistent changes but a detailed study found neurodegeneration in all ET cases - 24% demonstrated lower brainstem Lewy body (LB) inclusions and 76% experienced a loss of cerebellar Purkinje cells (PCs) and its sequelae. We review the evidence on neurodegeneration in ET. The prevalence of LB inclusions in ET brains is similar to that in the asymptomatic general population. These incidental LB disease cases have evidence for reduced striatal tyrosine hydroxylase levels, as found in Parkinson's disease, but there is no evidence for reduced tyrosine hydroxylase levels in ET patients. Reduced mean PC counts in ET cases compared with the controls reported by some studies could not be replicated by others. Most ET cases have the same number of PCs as controls of a comparable age. Neither the lower brainstem LB inclusions nor the cerebellar PC loss represent the neurodegenerative basis of ET. Further studies are needed to determine the pathophysiology of ET.

Parkinson's disease: Evidence for environmental risk factors

Mov Disord. 2012 Oct 24. doi: 10.1002/mds.25150. [Epub ahead of print]

Kieburtz K, Wunderle KB.

Source

Center for Human Experimental Therapeutics, University of Rochester Medical Center, Rochester, New York, USA.

Abstract

Parkinson's disease (PD) has no known cause. Although recent research has focused particularly on genetic causes of PD, environmental causes also play a role in developing the disease. This article reviews environmental factors that may increase the risk of PD, as well as the evidence behind those factors. Enough evidence exists to suggest that age has a causal relationship to PD. Significant evidence exists that gender, tobacco use, and caffeine consumption are also associated with the development of PD. Other environmental factors (pesticide exposure, occupation, blood urate levels, NSAID use, brain injury, and exercise) have limited or conflicting evidence of a relationship to PD. Future research must not neglect the impact of these environmental factors on the development of PD, especially with respect to potential gene-environment interactions. 

PREDICT PD on tour!

Today PREDICT PD starts the home visits phase of the project. A proportion of our participants will be visited at home for some additional tests. Over the next three months I will be travelling around the UK by bike, car, rail, and some cases planes and boats. I can't wait to get started on this phase and I'll post updates along the way. Off to South East London today...

- Alastair Noyce

Clinical features of Parkinson disease when onset of diabetes came first: A case-control study

Neurology [2012, 78(19):1507-1511]

Cereda E, Barichella M, Cassani E, Caccialanza R, Pezzoli G

Nutrition and Dietetics Service, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. 

Abstract

OBJECTIVE: Recent literature suggests that diabetes is a risk factor for Parkinson disease (PD). We investigated the clinical features of patients with idiopathic PD (IPD) in whom the onset of diabetes came first. METHODS: We designed a case-control study. From the cohort of all new patients with IPD free of vascular disease (n = 783) admitted and evaluated at our institute over a 3-year period (2007-2010), we included all the patients with a diagnosis of diabetes prior to PD onset (n = 89) and a control group (n = 89) matched (1:1) for gender, body mass index (± 1 kg/m(2)), and duration of PD (± 1 year). The Unified Parkinson's Disease Rating Scale (UPDRS) motor score was the primary endpoint. RESULTS: At study entry, patients with diabetes were similar to controls in terms of most demographic, lifestyle, and general medical features with exception of statins (18% vs 3.4%; p = 0.003). However, diabetes was associated with higher UPDRS motor (22.3 ± 9.0 vs 19.3 ± 7.9; p = 0.019) and activities of daily living (9.7 ± 5.1 vs 8.3 ± 4.3; p = 0.049) scores, more severe Hoehn & Yahr staging (p = 0.009), and higher treatment doses of levodopa (mg/day, 448 ± 265 vs 300 ± 213; p < 0.0001; mg/kg/day, 5.8 ± 4.0 vs 3.8 ± 2.9; p < 0.0001). CONCLUSIONS: Onset of diabetes before the onset of PD appears to be a risk factor for more severe PD symptoms. These findings support the hypothesis that diabetes has a role in the etiopathogenesis of PD. Neurologists should be aware of the potential impact of diabetes on overall PD management.

The PREDICT-PD Website went down for 24 hours but is now fully operational again

600 and counting...

600 of our participants have now completed the year 1 follow up of PREDICT-PD.

- Alastair Noyce

Istradefylline, an adenosine A(2A) receptor antagonist, for patients with Parkinson's Disease: A meta-analysis

J Neurol Sci. 2012 Oct 18. pii: S0022-510X(12)00482-0. doi: 10.1016/j.jns.2012.08.030. [Epub ahead of print]

Chen W, Wang H, Wei H, Gu S, Wei H.

Source

Department of Neurology, The Second People's Hospital of Gansu Province, Lanzhou, Gansu, China.

Abstract

OBJECTIVES:

To assess the efficacy and safety of istradefylline as an adjunct to levodopa in patients with Parkinson's Disease (PD).

METHODS:

In this study, we searched the Cochrane Library, MEDLINE, Embase, China Academic Journal Full-text Database (CNKI), China Biomedical Literature Database (CBM), Chinese Scientific Journals Database (VIP), and Wanfang Database. The quality of included studies was strictly evaluated. Data analyses were performed by the Cochrane Collaboration's RevMan5.0 software.

RESULTS:

Five randomized controlled trials (RCTs) were included. The result showed a significant reduction of the awake time per day spent in the OFF state and improvement of the Unified Parkinson's Disease Rating Scale (UPDRS) Part III in the ON state when receiving istradefylline compared with patients receiving placebo. There was no significant difference between the istradefylline 20mg and the istradefylline 40mg groups in the UPDRS Part III in the ON state (WMD=1.27, 95% CI [-0.40, 2.95]). The results showed significant differences in dyskinesia (RR=1.63, 95% CI [1.16, 2.29]) compared to istradefylline 40mg with placebo. There was no significant statistical difference with regard to other adverse events.

CONCLUSIONS:

The present study showed that istradefylline is safe and effective as an adjunct to levodopa in patients with PD. Future large-scale, higher-quality, long-treatment, and placebo-controlled trials are needed.

Over 400 now...

Thank you to everyone that has come back to us so far!

- Alastair Noyce

Transcranial sonography and functional imaging in glucocerebrosidase mutation Parkinson disease

Parkinsonism Relat Disord. 2012 Oct 9. pii: S1353-8020(12)00348-3. doi: 10.1016/j.parkreldis.2012.09.007. [Epub ahead of print]

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; The LRRK2 Ashkenazi Jewish Consortium.

Source

Department of Neurology, Beth Israel Medical Center, NY 10003, USA.

Abstract

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. [(18)F]-fluorodeoxyglucose or [(18)F]-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/homozygotes 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. [(18)F]-fluorodeoxyglucose (n = 3) and [(18)F]-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.

Dysfunction of the locus coeruleus-norepinephrine system and related circuitry in Parkinson's disease-related dementia

J Neurol Neurosurg Psychiatry. 2012 Oct 13. [Epub ahead of print]

Del Tredici K, Braak H.

Source

Clinical Neuroanatomy, Center for Biomedical Research, Department of Neurology, University of Ulm, Ulm, Germany.

Abstract

Although resting tremor, cogwheel rigidity, hypokinesia/bradykinesia and postural instability usually dominate the clinical picture of sporadic Parkinson's disease (PD), both clinical and epidemiological data reveal that a wide variety of additional symptoms impair patients' quality of life considerably, parallel to the chronic progressive neurodegenerative movement disorder. Autopsy based retrospective studies have shown that α-synuclein immunoreactive Lewy pathology (LP) develops in the locus coeruleus (LC) of patients with neuropathologically confirmed sporadic PD, as well as in individuals with incidental (prodromal or premotor) Lewy body disease but not in age and gender matched controls. Using five case studies, this review discusses the possible role of LP (axonopathy, cellular dysfunction and nerve cell loss) in the LC, catecholaminergic tract and related circuitry in the development of PD-related dementia. The contribution of noradrenergic deficit to cognitive dysfunction in PD has been underappreciated. Noradrenergic therapeutic interventions might not only alleviate depressive symptoms and anxiety but also delay the onset of cognitive decline.

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

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

ANN NEUROL 2012 (E-pub ahead of print)

Objective: To evaluate the association between diagnosis of Parkinson disease (PD) and risk factors or early symptoms amenable to population-based screening.

Methods: A systematic review and meta-analysis of risk factors for PD.

Results: The strongest associations with later diagnosis of PD were found for having a first-degree or any relative with PD (odds ratio [OR], 3.23; 95% confidence interval [CI], 2.65–3.93 and OR, 4.45; 95% CI, 3.39–5.83) or any relative with tremor (OR, 2.74; 95% CI, 2.10–3.57), constipation (relative risk [RR], 2.34; 95% CI, 1.55–3.53), or lack of smoking history (current vs never: RR, 0.44; 95% CI, 0.39–0.50), each at least doubling the risk of PD. Further positive significant associations were found for history of anxiety or depression, pesticide exposure, head injury, rural living, beta-blockers, farming occupation, and well-water drinking, and negative significant associations were found for coffee drinking, hypertension, nonsteroidal anti-inflammatory drugs, calcium channel blockers, and alcohol, but not for diabetes mellitus, cancer, oral contraceptive pill use, surgical menopause, hormone replacement therapy, statins, acetaminophen/paracetamol, aspirin, tea drinking, history of general anesthesia, or gastric ulcers. In the systematic review, additional associations included negative associations with raised serum urate, and single studies or studies with conflicting results.

Interpretation: The strongest risk factors associated with later PD diagnosis are having a family history of PD or tremor, a history of constipation, and lack of smoking history. Further factors also but less strongly contribute to risk of PD diagnosis or, as some premotor symptoms, require further standardized studies to demonstrate the magnitude of risk associated with them.

Here is the abstract for our comprehensive exploration of risk factors and early non-motor features for PD. This piece of work took 18-24 months to complete but is a strong foundation upon which the PREDICT-PD project is built. We are arranging for this to be made Open Access so that as many people as possible can see it.

- Alastair Noyce

300 complete the year 1 follow up

After sending out requests to undertake the year 1 survey and tapping test, I'm pleased to say that already 300 of our participants have done this. We will send further reminders after a few days.

- Alastair Noyce

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RBD as a biomarker for neurodegeneration: The past 10 years

Sleep Med. 2012 Oct 8. pii: S1389-9457(12)00329-2. doi: 10.1016/j.sleep.2012.09.001. [Epub ahead of print]

Postuma RB, Gagnon JF, Montplaisir J.


Source

Department of Neurology, McGill University, Montreal General Hospital, Montreal, Quebec, Canada; Centre d'Études Avancées en Médecine du Sommeil, Hôpital du Sacré-Coeur, Montreal, Canada.

Abstract

Since its original description, idiopathic RBD has become a well-established risk factor for neurodegenerative disease. Studies from sleep centers have found that at least 40-65% of patients with idiopathic RBD will develop a defined neurodegenerative phenotype over 10years. This elevated risk of neurodegeneration has been recently confirmed in a population-based study of probable RBD. When a defined syndrome develops, it is almost always a 'synucleinopathy' (Parkinson's disease, Dementia with Lewy Bodies or multiple system atrophy). Often, manifestations of parkinsonism and cognitive impairment overlap. The ability of RBD to predict disease has major implications for development of neuroprotective therapy. First, RBD is a prodromal marker with a disease risk sufficiently high for design of neuroprotective trials. Second, study of idiopathic RBD allows prospective testing of other predictive markers of neurodegeneration. Third, it allows an unprecedented direct examination of the evolution of prodromal disease into defined neurodegenerative syndromes. This review summarizes what is known about the risk of neurodegeneration in idiopathic RBD, the utility of prodromal/predictive markers in synuclein-mediated neurodegeneration, and the evolution of motor and non-motor markers in prodromal stages.

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Feedback from PREDICT-PD - Length of survey

We asked our participants what they though about the length of our survey. This is what they told us...

Year 1 Follow Up Launched

Whatever way you look at it, the PREDICT-PD project has been a great success so far: exceeding recruitment expectations, exciting early results, and now, on the morning of the launch of year 1 follow up, another great response from our participants!

Over the next few months I will share the feedback we get from PREDICT-PD, explain more about our research and post abstracts from other studies that are relevant to the overall goal of identifying Parkinson's at the earliest possible stages. 

I hope to drive more comments on this blog because your opinions count. At a recent patients' meeting with the Cure Parkinson's Trust I heard again how patients are too often not regarded as the experts they are in their own disease. I would like to hear more from the experts and their friends and relatives.

- Alastair Noyce

The impact of autonomic dysfunction on survival in patients with dementia with lewy bodies and Parkinson's disease with dementia

PLoS One. 2012;7(10):e45451. doi: 10.1371/journal.pone.0045451. Epub 2012 Oct 1.

Stubendorff K, Aarsland D, Minthon L, Londos E.

Source

Clinical Memory Research Unit, Department of Clinical Sciences, Malmö, Lund University, Sweden.

Abstract

INTRODUCTION:

Autonomic dysfunction is a well-known feature in neurodegenerative dementias, especially common in α-synucleinopathies like dementia with Lewy bodies and Parkinson's disease with dementia. The most common symptoms are orthostatic hypotension, incontinence and constipation, but its relevance in clinical practice is poorly understood. There are no earlier studies addressing the influence of autonomic dysfunction on clinical course and survival. The aim of this study was to investigate the frequency of the three most common features of autonomic dysfunction and analyze how it affects survival.

METHODS:

Thirty patients with dementia with Lewy bodies and Parkinson's disease with dementia were included in this prospective, longitudinal follow-up study. Presence of incontinence and constipation was recorded at baseline. Blood pressure was measured at baseline, after 3 months and after 6 months according to standardized procedures, with 5 measurements during 10 minutes after rising. Orthostatic hypotension was defined using consensus definitions and persistent orthostatic hypotension was defined as 5 or more measurements with orthostatic hypotension. Difference in survival was analyzed 36 months after baseline.

RESULTS:

There was a high frequency of persistent orthostatic blood pressure (50%), constipation (30%) and incontinence (30%). Patients with persistent orthostatic hypotension had a significantly shorter survival compared to those with no or non-persistent orthostatic hypotension (Log rank x(2) = 4.47, p = 0.034). Patients with constipation and/or urinary incontinence, in addition to persistent orthostatic hypotension, had a poorer prognosis compared to those with isolated persistent orthostatic hypotension or no orthostatic hypotension (Log rank x(2) = 6.370, p = 0.041).

DISCUSSION:

According to our findings, the identification of autonomic dysfunction seems to be of great importance in clinical practice, not only to avoid falls and other complications, but also as a possible predictor of survival.