Structural correlates of facial emotion recognition deficits in Parkinson's disease patients.

Neuropsychologia. 2012 May 25. [Epub ahead of print]

Baggio HC, Segura B, Ibarretxe-Bilbao N, Valldeoriola F, Marti MJ, Compta Y, Tolosa E, Junqué C.

Source

Department of Psychiatry and Clinical Psychobiology, University of Barcelona, Spain.

Abstract

The ability to recognize facial emotion expressions, especially negative ones, is described to be impaired in Parkinson's disease (PD) patients. Previous neuroimaging work evaluating the neural substrate of facial emotion recognition (FER) in healthy and pathological subjects has mostly focused on functional changes. This study was designed to evaluate gray matter (GM) and white matter (WM) correlates of FER in a large sample of PD. Thirty-nine PD patients and 23 healthy controls (HC) were tested with the Ekman 60 test for FER and with magnetic resonance imaging. Effects of associated depressive symptoms were taken into account. In accordance with previous studies, PD patients performed significantly worse in recognizing sadness, anger and disgust. In PD patients, voxel-based morphometry analysis revealed areas of positive correlation between individual emotion recognition and GM volume: in the right orbitofrontal cortex, amygdala and postcentral gyrus and sadness identification; in the right occipital fusiform gyrus, ventral striatum and subgenual cortex and anger identification, and in the anterior cingulate cortex (ACC) and disgust identification. WM analysis through diffusion tensor imaging revealed significant positive correlations between fractional anisotropy levels in the frontal portion of the right inferior fronto-occipital fasciculus and the performance in the identification of sadness. These findings shed light on the structural neural bases of the deficits presented by PD patients in this skill.

BBC - Ten-minute touch-pad test to predict dementia

http://www.bbc.co.uk/news/uk-england-cambridgeshire-18237056

A simple test to help predict people likely to develop dementia has been invented by a company in Cambridge.

The test, which is already being used in the NHS, involves memory tests that gradually get harder and asks question about how users live and feel.

Plasma levodopa peak delay and impaired gastric emptying in Parkinson's disease.

J Neurol Sci. 2012 May 24. [Epub ahead of print]

Doi H, Sakakibara R, Sato M, Masaka T, Kishi M, Tateno A, Tateno F, Tsuyusaki Y, Takahashi O.

Source

Pharmaceutical Unit, Sakura Medical Center, Toho University, Sakura, Japan.

Abstract

OBJECTIVES:

Whereas delayed gastric emptying is believed to be a causative factor for producing delayed-on and motor fluctuation in Parkinson's disease (PD), few studies have directly measured levodopa pharmacodynamics and gastric emptying together. In order to determine the relationship, we measured these two parameters in a single PD patients cohort.

METHODS:

Thirty-one patients with PD were enrolled in the study. They were 11 men and 20 women; age, 68.1±7.8years; disease duration, 4.2±3.8years; Unified Parkinson's Disease Rating Scale Part 3 Motor Score 18.37±8.60; bowel movement <3 times a week in 20; all taking 301mg±94mg/day levodopa/carbidopa. All patients underwent levodopa pharmacokinetic study and the gastric emptying study using (13)C-octanoic acid expiration breath test. Statistical analysis was performed by Student's t-test and Mann-Whitney's U test.

RESULTS:

Pharmacokinetic study showed that the plasma levodopa peak was at 2hours in 42% (13/31 patients) whereas at 1hour in 58% (18/31 patients), total of 50.7±16.4min (mean±standard deviation) in all 31 patients. The gastric emptying study showed that T(max) ((13)C)>60min was more common in patients with a plasma levodopa peak at 2hours (14/18, 69%) than in those with a plasma levodopa peak at 1hour (4/13, 22%) (p<0.05), total of 50.7±16.4min in all 31 patients.

CONCLUSION:

We found a significant relationship between levodopa pharmacokinetics and gastric emptying in PD patients, suggesting that delayed gastric emptying is a causative factor for producing delayed-on in PD. Therefore, studies of improved gastric emptying in order to ameliorate delayed-on in PD are warranted.

Direct Observation of the Interconversion of Normal and Toxic Forms of α-Synuclein.

Cell. 2012 May 25;149(5):1048-59.

Cremades N, Cohen SI, Deas E, Abramov AY, Chen AY, Orte A, Sandal M, Clarke RW, Dunne P, Aprile FA, Bertoncini CW, Wood NW, Knowles TP, Dobson CM, Klenerman D.

Source

Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.

Abstract

Here, we use single-molecule techniques to study the aggregation of α-synuclein, the protein whose misfolding and deposition is associated with Parkinson's disease. We identify a conformational change from the initially formed oligomers to stable, more compact proteinase-K-resistant oligomers as the key step that leads ultimately to fibril formation. The oligomers formed as a result of the structural conversion generate much higher levels of oxidative stress in rat primary neurons than do the oligomers formed initially, showing that they are more damaging to cells. The structural conversion is remarkably slow, indicating a high kinetic barrier for the conversion and suggesting that there is a significant period of time for the cellular protective machinery to operate and potentially for therapeutic intervention, prior to the onset of cellular damage. In the absence of added soluble protein, the assembly process is reversed and fibrils disaggregate to form stable oligomers, hence acting as a source of cytotoxic species.

Cognition in rapid eye movement sleep behavior disorder.

Front Neurol. 2012;3:82. Epub 2012 May 17.

Gagnon JF, Bertrand JA, Génier Marchand D.

Source

Center for Advanced Research in Sleep Medicine, Hôpital du Sacré-Coeur de Montréal Montréal, QC, Canada.

Abstract

Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by excessive muscle activity and undesirable motor events during REM sleep. RBD occurs in approximately 0.5% of the general population, with a higher prevalence in older men. RBD is a frequent feature of dementia with Lewy bodies (DLB), but is only rarely reported in Alzheimer's disease. RBD is also a risk factor for α-synuclein-related diseases, such as DLB, Parkinson's disease (PD), and multiple system atrophy. Therefore, RBD has major implications for the diagnosis and treatment of neurodegenerative disorders and for understanding specific neurodegeneration patterns. Several markers of neurodegeneration have been identified in RBD, including cognitive impairments such as deficits in attention, executive functions, learning capacities, and visuospatial abilities. Approximately 50% of RBD patients present mild cognitive impairment. Moreover, RBD is also associated with cognitive decline in PD.

Pesticide exposure and Parkinson's disease: Epidemiological evidence of association.

Neurotoxicology. 2012 May 21. [Epub ahead of print]

Freire C, Koifman S.

Source

National School of Public Health, Oswaldo Cruz Foundation, 21041-210 Rio de Janeiro, RJ, Brazil; Laboratory of Medical Investigations, San Cecilio University Hospital, University of Granada, 18071 Granada, Spain.

Abstract

It has been suggested that exposure to pesticides might be involved in the etiology of Parkinson's disease (PD). We conducted an updated systematic review of the epidemiologic literature over the past decade on the relationship between pesticide exposure and PD, using the MEDLINE database. Despite methodological differences, a significantly increased PD risk was observed in 13 out of 23 case-control studies that considered overall exposure to pesticides (risk estimates of 1.1-2.4) and in 10 out of 12 studies using other research designs (risk estimates of 2 or higher). Various studies found stronger associations in genetically susceptible individuals. Among a growing number of studies on the effects of exposure to specific pesticides (n=20), an increased PD risk has been associated with insecticides, especially chlorpyrifos and organochlorines, in six studies (odds ratios of 1.8-4.4), and with the herbicide paraquat, the fungicide maneb or the combination of both. Findings considerably strengthen the evidence that exposure to pesticides in well water may contribute to PD, whereas studies of farming and rural residence found inconsistent or little association with the disease. Taken together, this comprehensive set of results suggests that the hypothesis of an association between pesticide exposure and PD cannot be ruled out. However, inadequate data on consistent responses to exposure hinder the establishment of a causal relationship with PD. Given the extensive worldwide use of many pesticides, further studies are warranted in larger populations that include detailed quantitative data on exposure and determination of genetic polymorphisms.

Parkinson's choir sings at St Pancras station

http://www.bbc.co.uk/news/uk-england-london-18193522

A choir made up entirely of people with Parkinson's disease has been performing at St Pancras station.

Members of the Sing For Joy choir say the singing helps them cope with their condition.

α-Synuclein Genetic Variants Predict Faster Motor Symptom Progression in Idiopathic Parkinson Disease.

PLoS One. 2012;7(5):e36199. Epub 2012 May 15.

Ritz B, Rhodes SL, Bordelon Y, Bronstein J.

Source

Department of Epidemiology, University of California Los Angeles, Los Angeles, California, United States of America.

Abstract

Currently, there are no reported genetic predictors of motor symptom progression in Parkinson's disease (PD). In familial PD, disease severity is associated with higher α-synuclein (SNCA) expression levels, and in postmortem studies expression varies with SNCA genetic variants. Furthermore, SNCA is a well-known risk factor for PD occurrence. We recruited Parkinson's patients from the communities of three central California counties to investigate the influence of SNCA genetic variants on motor symptom progression in idiopathic PD. We repeatedly assessed this cohort of patients over an average of 5.1 years for motor symptom changes employing the Unified Parkinson's Disease Rating Scale (UPDRS). Of 363 population-based incident PD cases diagnosed less than 3 years from baseline assessment, 242 cases were successfully re-contacted and 233 were re-examined at least once. Of subjects lost to follow-up, 69% were due to death. Adjusting for covariates, risk of faster decline of motor function as measured by annual increase in motor UPDRS exam score was increased 4-fold in carriers of the REP1 263bp promoter variant (OR 4.03, 95%CI:1.57-10.4). Our data also suggest a contribution to increased risk by the G-allele for rs356165 (OR 1.66; 95%CI:0.96-2.88), and we observed a strong trend across categories when both genetic variants were considered (p for trend  = 0.002). Our population-based study has demonstrated that SNCA variants are strong predictors of faster motor decline in idiopathic PD. SNCA may be a promising target for therapies and may help identify patients who will benefit most from early interventions. This is the first study to link SNCA to motor symptom decline in a longitudinal progression study.

Gene therapy for Parkinson's disease.

Parkinsons Dis. 2012;2012:757305. Epub 2012 Mar 25.

Denyer R, Douglas MR.

Abstract

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

How does parkinsonism start? Prodromal parkinsonism motor changes in idiopathic REM sleep behaviour disorder.

Brain. 2012 May 4. [Epub ahead of print]

Postuma RB, Lang AE, Gagnon JF, Pelletier A, Montplaisir JY.

Source

1 Department of Neurology, McGill University, Montreal General Hospital, Montreal, QC H3G 1A4, Canada.

Abstract

Parkinsonism, as a gradually progressive disorder, has a prodromal interval during which neurodegeneration has begun but cardinal manifestations have not fully developed. A systematic direct assessment of this interval has never been performed. Since patients with idiopathic REM sleep behaviour disorder are at very high risk of parkinsonism, they provide a unique opportunity to observe directly the development of parkinsonism. Patients with idiopathic REM sleep behaviour disorder in an ongoing cohort study were evaluated annually with several quantitative motor measures, including the Unified Parkinson's Disease Rating Scale, Purdue Pegboard, alternate-tap test and timed up-and-go. Patients who developed parkinsonism were identified from this cohort and matched according to age to normal controls. Their results on motor testing from the preceding years were plotted, and then assessed with regression analysis, to determine when markers first deviated from normal values. Sensitivity and specificity of quantitative motor markers for diagnosing prodromal parkinsonism were assessed. Of 78 patients, 20 developed parkinsonism. On regression analysis, the Unified Parkinson's Disease Rating Scale first intersected normal values at an estimated 4.5 years before diagnosis. Voice and face akinesia intersected earliest (estimated prodromal interval = 9.8 years), followed by rigidity (4.4 years), gait abnormalities (4.4 years) and limb bradykinesia (4.2 years). Quantitative motor tests intersected normal values at longer prodromal intervals than subjective examination (Purdue Pegboard = 8.6 years, alternate-tap = 8.2, timed up-and-go = 6.3). Using Purdue Pegboard and the alternate-tap test, parkinsonism could be detected with 71-82% sensitivity and specificity 3 years before diagnosis, whereas a Unified Parkinson's Disease Rating Scale score >4 identified prodromal parkinsonism with 88% sensitivity and 94% specificity 2 years before diagnosis. Removal of action tremor scores improved sensitivity to 94% and specificity to 97% at 2 years before diagnosis (cut-off >3). Although distinction between conditions was often difficult, prodromal dementia with Lewy bodies appeared to have a slower progression than Parkinson's disease (prodromal interval = 6.0 versus 3.8 years). Using a cut-off of Unified Parkinson's Disease Rating Scale >3 (excluding action tremor), 25% of patients with 'still-idiopathic' REM sleep behaviour disorder demonstrated evidence of possible prodromal parkinsonism. Therefore, using direct assessment of motor examination before parkinsonism in a REM sleep behaviour disorder, we have estimated a prodromal interval of ∼4.5 years on the Unified Parkinson's Disease Rating Scale; other quantitative markers may detect parkinsonism earlier. Simple quantitative motor measures may be capable of reliably detecting parkinsonism, even before a clinical diagnosis can be made by experienced movement disorders neurologists.

Controlled Study of 50-Hz Repetitive Transcranial Magnetic Stimulation for the Treatment of Parkinson Disease.

Neurorehabil Neural Repair. 2012 May 15. [Epub ahead of print]

Benninger DH, Iseki K, Kranick S, Luckenbaugh DA, Houdayer E, Hallett M.

Abstract

OBJECTIVE:

To investigate the safety and efficacy of 50-Hz repetitive transcranial magnetic stimulation (rTMS) in the treatment of motor symptoms in Parkinson disease (PD).

BACKGROUND:

Progression of PD is characterized by the emergence of motor deficits that gradually respond less to dopaminergic therapy. rTMS has shown promising results in improving gait, a major cause of disability, and may provide a therapeutic alternative. Prior controlled studies suggest that an increase in stimulation frequency might enhance therapeutic efficacy.

METHODS:

In this randomized, double blind, sham-controlled study, the authors investigated the safety and efficacy of 50-Hz rTMS of the motor cortices in 8 sessions over 2 weeks. Assessment of safety and clinical efficacy over a 1-month period included timed tests of gait and bradykinesia, Unified Parkinson's Disease Rating Scale (UPDRS), and additional clinical, neurophysiological, and neuropsychological parameters. In addition, the safety of 50-Hz rTMS was tested with electromyography-electroencephalogram (EMG-EEG) monitoring during and after stimulation.

RESULTS:

The authors investigated 26 patients with mild to moderate PD: 13 received 50-Hz rTMS and 13 sham stimulation. The 50-Hz rTMS did not improve gait, bradykinesia, and global and motor UPDRS, but there appeared a short-lived "on"-state improvement in activities of daily living (UPDRS II). The 50-Hz rTMS lengthened the cortical silent period, but other neurophysiological and neuropsychological measures remained unchanged. EMG/EEG recorded no pathological increase of cortical excitability or epileptic activity. There were no adverse effects.

CONCLUSION:

It appears that 50-Hz rTMS of the motor cortices is safe, but it fails to improve motor performance and functional status in PD. Prolonged stimulation or other techniques with rTMS might be more efficacious but need to be established in future research.

The use of next-generation sequencing in movement disorders.

Front Genet. 2012;3:75. Epub 2012 May 14.

Krebs CE, Paisán-Ruiz C.

Source

Department of Neurology, Mount Sinai School of Medicine New York, NY, USA.

Abstract

New advances in genomic technology are being introduced at a greater speed and are revolutionizing the field of genetics for both complex and Mendelian diseases. For instance, during the past few years, genome-wide association studies (GWAS) have identified a large number of significant associations between genomic loci and movement disorders such as Parkinson's disease and progressive supranuclear palsy. GWAS are carried out through the use of high-throughput SNP genotyping arrays, which are also used to perform linkage analyses in families previously considered statistically underpowered for genetic analyses. In inherited movement disorders, using this latter technology, it has repeatedly been shown that mutations in a single gene can lead to different phenotypes, while the same clinical entity can be caused by mutations in different genes. This is being highlighted with the use of next-generation sequencing technologies and leads to the search for genes or genetic modifiers that contribute to the phenotypic expression of movement disorders. Establishing an accurate genome-epigenome-phenotype relationship is becoming a major challenge in the post-genomic research that should be facilitated through the implementation of both functional and cellular analyses.

Parkinson's disease and immune system: is the culprit LRRKing in the periphery?

J Neuroinflammation. 2012 May 17;9(1):94. [Epub ahead of print]

Greggio E, Civiero L, Bisaglia M, Bubacco L.

Abstract

ABSTRACT: Leucine-rich repeat kinase 2 (LRRK2) is a large multidomain kinase/GTPase that has been recently linked to three pathological conditions: Parkinson's disease; Crohn's disease; and leprosy. Although LRRK2 physiological function is poorly understood, a potential role in inflammatory response is suggested by its high expression in immune cells and tissues, its up-regulation by interferon gamma, and its function as negative regulator of the immune response transcription factor NFAT1. In this review we discuss the most recent findings regarding how LRRK2 could be a player in the inflammatory response and we propose a scenario where the detrimental effects mediated by Parkinson's disease LRRK2 mutations may initiate in the periphery and extend to the central nervous system as a consequence of increased levels of pro-inflammatory factors permeable to the blood brain barrier.

The MAPT p.A152T variant is a risk factor associated with tauopathies with atypical clinical and neuropathological features.

Neurobiol Aging. 2012 May 15. [Epub ahead of print]

Kara E, Ling H, Pittman AM, Shaw K, de Silva R, Simone R, Holton JL, Warren JD, Rohrer JD, Xiromerisiou G, Lees A, Hardy J, Houlden H, Revesz T.

Source

Reta Lila Weston Laboratories and Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK.

Abstract

Microtubule-associated protein tau (MAPT) mutations have been shown to underlie frontotemporal dementia and a variety of additional sporadic tauopathies. We identified a rare p.A152T variant in MAPT exon 7 in two (of eight) patients with clinical presentation of parkinsonism and postmortem finding of neurofibrillary tangle pathology. Two siblings of one patient also carried the p.A152T variant, and both have progressive cognitive impairment. Further screening identified the variant in two other cases: one with pathologically confirmed corticobasal degeneration and another with the diagnosis of Parkinson's disease with dementia. The balance of evidence suggests this variant is associated with disease, but the very varied phenotype of the cases with the mutation is not consistent with it being a fully penetrant pathogenic mutation. Interestingly, this variation results in the creation of a new phosphorylation site that could cause reduced microtubule binding. We suggest that the A152T variant is a risk factor associated with the development of atypical neurodegenerative conditions with abnormal tau accumulation.

Low serum uric acid concentration in Parkinson's disease in southern Spain.

Eur J Neurol. 2012 May 12. doi: 10.1111/j.1468-1331.2012.03745.x. [Epub ahead of print]

Jesús S, Pérez I, Cáceres-Redondo MT, Carrillo F, Carballo M, Gómez-Garre P, Mir P.

Abstract

BACKGROUND:

Uric acid (UA) is thought to have an antioxidant effect on the central nervous system and may also prevent cerebral damage induced by oxidative stress. Our study aimed to investigate whether patients with Parkinson's disease had lower serum UA concentrations than controls and whether UA concentration was related to clinical parameters of the disease.

METHODS:

We included 161 patients with Parkinson's disease and 178 controls from southern Spain. UA concentration was compared between these two groups. Clinical parameters including severity of the disease were related to serum uric acid.

RESULTS:

Patients with Parkinson's disease showed statistically significant lower serum UA concentrations than controls. Serum UA concentration was lower in patients with Parkinson's disease in severe stages (4 and 5) than in those in moderate stage (2) according to the modified Hoehn and Yahr scale. Other clinical parameters were not related to serum UA concentration, except for levodopa equivalent daily dose that was associated with lower serum UA concentration in men.

CONCLUSIONS:

Our study produced consistent findings that UA might have a protective effect against Parkinson's disease and could influence its clinical progression.

Urate in Parkinson's Disease: More Than a Biomarker?

Curr Neurol Neurosci Rep. 2012 May 12. [Epub ahead of print]

Chen X, Wu G, Schwarzschild MA.

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disease with characteristic motor manifestations. Although appreciation of PD as a multisystem disorder has grown, loss of dopaminergic neurons in the substantia nigra remains a pathological and neurochemical hallmark, accounting for the substantial symptomatic benefits of dopamine replacement therapies. However, currently no treatment has been shown to prevent or forestall the progression of the disease in spite of tremendous efforts. Among multiple environmental and genetic factors that have been implicated in the pathogenesis of PD, oxidative stress is proposed to play a critical role. A recent confluence of clinical, epidemiological, and laboratory evidence identified urate, an antioxidant and end product of purine metabolism, as not only a molecular predictor for both reduced risk and favorable progression of PD but also a potential neuroprotectant for the treatment of PD. This review summarizes recent findings on urate in PD and their clinical implications.

Impulse Control Disorders in Parkinson's Disease: A Psychosocial Perspective.

J Clin Psychol Med Settings. 2012 May 12. [Epub ahead of print]

Delaney M, Leroi I, Simpson J, Overton PG.

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disease primarily characterised by motor symptoms. However, another feature of PD which is receiving increasing attention is the phenomenon of impulse control disorders (ICDs), such as pathological gambling. To date, research into ICDs in PD has centred on a biomedical model of cause, related to the effects of dopamine replacement therapy. However, there are several areas of discrepancy in the current biomedical account of ICDs in PD. In addition, we argue that social and psychological factors also need to be considered to achieve a more complete understanding of the phenomenon. We present a novel conceptual model which combines biomedical and psychosocial factors in the genesis of ICDs in PD and use the model to identify a number of potential treatment intervention points and to highlight important outstanding questions concerning the inter-relationship between psychosocial and biomedical factors in the genesis of ICDs in PD.

Vitamin K2 Is a Mitochondrial Electron Carrier That Rescues Pink1 Deficiency.

Science. 2012 May 14. [Epub ahead of print]

Vos M, Esposito G, Edirisinghe JN, Vilain S, Haddad DM, Slabbaert JR, Van Meensel S, Schaap O, De Strooper B, Meganathan R, Morais VA, Verstreken P.

Abstract

Human UBIAD1 localizes to mitochondria and converts vitamin K(1) to vitamin K(2). Vitamin K(2) is best known as a cofactor in blood coagulation, but in bacteria it is a membrane-bound electron carrier. Whether vitamin K(2) exerts a similar carrier function in eukaryotic cells is unknown. We identified Drosophila UBIAD1/Heix as a modifier of pink1, a gene mutated in Parkinson's disease that affects mitochondrial function. Here, we found that vitamin K(2) was necessary and sufficient to transfer electrons in Drosophila mitochondria. Heix mutants showed severe mitochondrial defects that were rescued by vitamin K(2), and, similar to ubiquinone, vitamin K(2) transferred electrons in Drosophila mitochondria, resulting in more efficient adenosine triphosphate (ATP) production. Thus, mitochondrial dysfunction was rescued by vitamin K(2) that serves as a mitochondrial electron carrier, helping to maintain normal ATP production.

Is alpha-synuclein in the colon a biomarker for premotor Parkinson's Disease? Evidence from 3 cases.

Mov Disord. 2012 May 1. doi: 10.1002/mds.25020. [Epub ahead of print]

Shannon KM, Keshavarzian A, Dodiya HB, Jakate S, Kordower JH.

Abstract

Background: Despite clinicopathological evidence that Parkinson's disease (PD) may begin in peripheral tissues, identification of premotor Parkinson's disease is not yet possible. Alpha-synuclein aggregation underlies Parkinson's disease pathology, and its presence in peripheral tissues may be a reliable disease biomarker. Objective: We sought evidence of alpha-synuclein pathology in colonic tissues before the development of characteristic Parkinson's disease motor symptoms. Methods: Old colon biopsy samples were available for three subjects with PD. Biopsies were obtained 2-5 years before PD onset. We performed immunohistochemistry studies for the presence of alpha-synuclein and Substance P in these samples. Results: All subjects showed immunostaining for alpha-synuclein (two, five and two years before first motor Parkinson's disease symptom). No similar alpha-synuclein immunostaining was seen in 23 healthy controls. Staining of samples for substance P suggested colocalization of alpha-synuclein and substance P in perikarya and neurites. Conclusions: This is the first demonstration of alpha-synuclein in colon tissue prior to onset of PD. Additional study is required to determine whether colonic mucosal biopsy may be a biomarker of premotor PD.

Tricyclic antidepressants delay the need for dopaminergic therapy in early Parkinson's disease.

Mov Disord. 2012 May 3. doi: 10.1002/mds.24978. [Epub ahead of print]

Paumier KL, Siderowf AD, Auinger P, Oakes D, Madhavan L, Espay AJ, Revilla FJ, Collier TJ; for the Parkinson Study Group Genetics Epidemiology Working Group.

Abstract

This study examined whether antidepressants delay the need for dopaminergic therapy or change the degree of motor impairment and disability in a population of early Parkinson's disease (PD) patients. Preclinical studies have indicated that antidepressants modulate signaling pathways involved in cell survival and plasticity, suggesting they may serve to both treat PD-associated depression and slow disease progression. A patient-level meta-analysis included 2064 patients from the treatment and placebo arms of the following trials: FS1, FS-TOO, ELLDOPA, QE2, TEMPO, and PRECEPT. Depression severity was determined at baseline, and antidepressant use was reported in a medication log each visit. Kaplan-Meier curves and time-dependent Cox proportional hazards models determined associations between depression severity and antidepressant use with the primary outcome, time to initiation of dopaminergic therapy. ANCOVAs determined associations with the secondary outcome, degree of motor impairment and disability, reported as annualized change in UPDRS scores from baseline to final visit. When controlling for baseline depression, the initiation of dopaminergic therapy was delayed for subjects taking tricyclic antidepressants compared with those not taking antidepressants. No significant differences were found in UPDRS scores for subjects taking antidepressants compared with those not taking antidepressants. Tricyclic antidepressants are associated with a delay in reaching the end point of need to start dopaminergic therapy. The lack of change in overall UPDRS scores suggests the delay was not attributable to symptomatic effects.