GIGYF2 mutations are not a frequent cause of familial Parkinson`s disease

Mutations in the Grb10-interacting GYF protein 2 (GIGYF2) gene, within the PARK11 locus, have been nominated as a cause of Parkinson`s disease in Italian and French populations. By sequencing the whole GIGYF2 coding region in forty-six probands (thirty-seven Italians) with familial Parkinson`s disease compatible with an autosomal dominant inheritance, we identified no mutations. Our data add to a growing body of evidence suggesting that GIGYF2 mutations are not a frequent cause of PD. (C) 2009 Elsevier Ltd. All rights reserved.

The Use of Smell Identification Tests in the Diagnosis of Parkinson`s Disease in Brazil

Smell identification tests may be of routine clinical value in the differential diagnosis of PD but are subject to cultural variation and have not been systematically evaluated in the Brazilian population. We have applied culturally adapted translations of the University of Pennsylvania 40-item smell identification test (UPSIT-40) and the 16-item identification test from Sniffin` Sticks (SS-16) to nondemented Brazilian PD patients and controls. Pearson`s correlation coefficient between the test scores was 0.76 (95% CI 0.70-0.81, n = 204, P < 0.001). To calculate reliability measures for each test we used the diagnosis (either PD or control) as outcome variable for separate logistic regression analyses using the score in the UPSIT-40 or the SS-16 as a covariate. The SS-16 specificity was 89.0% with a sensitivity of 81.1% (106 PD and 118 controls). The UPSIT-40 specificity was 83.5% and its sensitivity 82.1% (95 PD and 109 controls). Regression curves were used to associate an individual`s smell test score with the probability of belonging to the PD, as opposed to the control group. Our data provide support for the use of the UPSIT-40 and SS-16 to help distinguish early PD from controls. (c) 2008 Movement Disorder Society

Association between Parkinson`s disease and glucocerebrosidase mutations in Brazil

Objective: To evaluate the association between parkinsonism and mutations in the glucocerebrosidase gene (GBA) in Brazilian patients. Methods: We searched for three GBA common mutations (N370S, L444P and G377S) in 65 Brazilian patients affected by PD with disease onset before the age of 55 and compared the results to 267 age- and sex-matched controls. Results: GBA mutations were detected at a significantly higher frequency among Parkinson`s disease patients (2/65 = 3%), when compared to the control group (0/267): P = 0.0379. Conclusion: These results provide further evidence for GBA mutations being a possible hereditary risk factor for PD. (C) 2007 Elsevier Ltd. All rights reserved.

Voiding Dysfunction in Patients With Parkinson`s Disease: Impact of Neurological Impairment and Clinical Parameters

Aims: We assessed the lower urinary tract symptoms (LUTS) of patients with Parkinson`s disease (PD) and their association with different clinical parameters. Methods: We prospectively evaluated 110 patients (84 men), with a mean age of 61.8 +/- 9.6 years. Mean duration of the disease was 12.3 +/- 7.2 years. Neurological impairment was assessed by the Hoehn-Yahr and the Unified Parkinson Disease Rating scales. LUTS were assessed by the International Continence Society questionnaire. We evaluated the impact of age, PD duration, neurological impairment, gender, and use of anti-Parkinsonian drugs on the voiding function. Results: On multivariate analysis, voiding dysfunction increased with the neurological impairment, but not with patient`s age or disease duration. Quality of life (QOL) was affected by the severity of LUTS, and the symptoms with the worst impact were frequency and nocturia. Sixty-three (57.2%) patients were symptomatic. They did not differ with the asymptomatic as to age and disease duration, but had more severe neurological impairment. No impact on LUTS was associated with the use of levodopa, anticholinergics, and dopamine receptor agonists. Men and women were similarly affected by urinary symptoms. Conclusions: The severity of the neurological disease is the only predictive factor for the occurrence of voiding dysfunction, which affects men and women alike. Neztrourol. Urodynam. 28.510-515, 2009. (C) 2009 Wiley-Liss, Inc.

rTMS treatment for depression in Parkinson`s disease increases BOLD responses in the left prefrontal cortex

The mechanisms underlying the effects of antidepressant treatment in patients with Parkinson`s disease (PD) are unclear. The neural changes after successful therapy investigated by neuroimaging methods can give insights into the mechanisms of action related to a specific treatment choice. To study the mechanisms of neural modulation of repetitive transcranial magnetic Stimulation (rTMS) and fluoxetine, 21 PD depressed patients were randomized into only two active treatment groups for 4 wk: active rTMS over left dorsolateral prefrontal cortex (DLPFC) (5 Hz rTMS; 120% motor threshold) with placebo pill and sham rTMS with fluoxetine 20mg/d. Event-related functional magnetic resonance imaging (fMRI) with emotional stimuli was performed before and after treatment - in two sessions (test and re-test) at each time-point. The two groups of treatment had a significant, similar mood improvement. After rTMS treatment, there were brain activity decreases in left fusiform gyrus, cerebellum and right DLPFC and brain activity increases in left DLPFC and anterior cingulate gyrus compared to baseline. In contrast, after fluoxetine treatment, there were brain activity increases in right premotor and right medial prefrontal cortex. There was a significant interaction effect between groups vs. time in the left medial prefrontal cortex, suggesting that the activity in this area changed differently in the two treatment groups. Our findings show that antidepressant effects of rTMS and fluoxetine in PD are associated with changes in different areas of the depression-related neural network.

Abnormal Visual Activation in Parkinson`s Disease Patients

Among nonmotor symptoms observed in Parkinson`s disease (PD) dysfunction in the visual system, including hallucinations, has a significant impact in their quality of life. To further explore the visual system in PD patients we designed two fMRI experiments comparing 18 healthy volunteers with 16 PD patients without visual complaints in two visual fMRI paradigms: the flickering checkerboard task and a facial perception paradigm. PD patients displayed a decreased activity in the primary visual cortex (Broadmann area 17) bilaterally as compared to healthy volunteers during flickering checkerboard task and increased activity in fusiform gyms (Broadmann area 37) during facial perception paradigm. Our findings confirm the notion that PD patients show significant changes in the visual cortex system even before the visual symptoms are clinically evident. Further studies are necessary to evaluate the contribution of these abnormalities to the development visual symptoms in PD. (C) 2010 Movement Disorder Society

Depression in Parkinson`s disease: Convergence from voxel-based morphometry and functional magnetic resonance imaging in the limbic thalamus

Depression is the most frequent psychiatric disorder in Parkinson`s disease (PD). Although evidence Suggests that depression in PD is related to the degenerative process that underlies the disease, further studies are necessary to better understand the neural basis of depression in this population of patients. In order to investigate neuronal alterations underlying the depression in PD, we studied thirty-six patients with idiopathic PD. Twenty of these patients had the diagnosis of major depression disorder and sixteen did not. The two groups were matched for PD motor severity according to Unified Parkinson Disease Rating Scale (UPDRS). First we conducted a functional magnetic resonance imaging (fMRI) using an event-related parametric emotional perception paradigm with test retest design. Our results showed decreased activation in the left mediodorsal (MD) thalamus and in medial prefrontall cortex in PD patients with depression compared to those without depression. Based upon these results and the increased neuron count in MD thalamus found in previous studies, we conducted a region of interest (ROI) guided voxel-based morphometry (VBM) study comparing the thalamic volume. Our results showed an increased volume in mediodorsal thalamic nuclei bilaterally. Converging morphological changes and functional emotional processing in mediodorsal thalamus highlight the importance of limbic thalamus in PD depression. In addition this data supports the link between neurodegenerative alterations and mood regulation. (C) 2009 Elsevier Inc. All rights reserved.

Movement-related potentials in Parkinson's disease - Motor imagery and movement preparation

Movement-related potentials (MRPs) associated with voluntary movements reflect cortical activity associated with processes Of movement preparation and movement execution. Early-stage pre-movement activity is reduced in amplitude in Parkinson's disease. However it is unclear whether this neurophysiological deficit relates to preparatory or execution-related activity, since previous studies have not been able to separate different functional components of MRPs. Motor imagery is thought to involve mainly processes of movement preparation, with reduced involvement of end-stage movement execution-related processes. Therefore, MRP components relating to movement preparation and execution may be examined separately by comparing MRPs associated with imagined and actual movements. In this study, MRPs were recorded from 14 subjects with Parkinson's disease and 10 age-matched control subjects while they performed a sequential button-pressing task, and while they imagined performance of the same task. Early-stage pre-movement activity was present in both Parkinson's disease patients and control subjects when they imagined movement, but was reduced in amplitude compared with that for actual movement. Movement execution-related components, arising predominantly from the primary motor cortex, were relatively unaffected in Parkinson's disease subjects. However motor preparatory processes, probably involving the supplementary motor area, were reduced in amplitude overall and abnormally prolonged, Indicating impaired termination following the motor response. Further this impaired termination of preparatory-phase activity was observed only in patients with more severe parkinsonian symptoms, and not in early-stage Parkinson's disease.

Incidental Encoding Strategies Did Not Improve Contextual Memory in Parkinson`s Disease Patients

Background. This study investigated the performance of patients with idiopathic Parkinson`s disease (PD) without dementia for incidental recognition memory and the effect of encoding strategies on contextual memory. Methods. The authors studied 21 patients with PD (ages 60-85, 12 women; Hoehn and Yahr I-III, Activities of Daily Living 70%-100%) and 22 healthy controls (ages 60-84, 18 women). Participants completed the vocabulary subtest of the Wechsler Adult Intelligence Scale and the Wisconsin Card Sorting Test (WCST). To assess the incidental recognition memory for item (object) and context (location of the object), participants of each group were assigned to 1 of 2 encoding conditions: (a) an incidental associative instruction to bind the object to its location or (b) a nonassociative, nonspecific instruction. Results. PD patients showed performance comparable to the control group`s on the vocabulary subtest and WCST. In contrast to controls, PD patients were unable to take advantage of the associative encoding instruction, which also had a deleterious effect on item recognition. Conclusion. This sample of participants with PD showed diminished item and context recognition memory and an impaired ability to use incidental memory encoding strategy, suggesting a compromised cognitive reserve. The fact that these alterations occurred in early stages of PD, and prior to more general cognitive alterations such as executive dysfunction, should be considered in the management of patients by using specific cognitive rehabilitation interventions.

Validity of a Brazilian version of the Zung self-rating depression scale for screening of depression in patients with Parkinson`s disease

Introduction: Parkinson`s disease (PD) is a neurodegenerative disorder with prominent motor manifestations and many other non-motor symptoms that significantly decrease quality-of-life and are frequently under-recognized, for example depression. Objective: To study the validity of a Brazilian version of the Zung Self-rating Depression Scale (SDS) for the diagnosis of depression in patients with PD. Methods: We evaluated 78 consecutive non demented patients over the age of 40 with diagnosis of PD at a Movement Disorders Outpatient Clinic, who could read and understand questionnaires. They completed the SIDS and the Geriatric Depression Scale with 15 items (GDS-15). The diagnosis of depression was made after a structured clinical interview based on DSM-IV criteria for the diagnosis of major depression (SCID-CV). Results: The prevalence of major depression was 23.1%. Cronbach`s alpha was 0.73 and the area under the ROC curve was 0.93 for the SDS. The score index of 55 had a sensitivity of 88.9% and a specificity of 83.3% for the diagnosis of depression. The total scores of the SDS and GDS-15 were highly correlated (0.652, p < 0.0001) and correlated weakly with the scores of a motor scale. Discussion: The SIDS is a valid too] for screening depression in patients with PD since the specific SDS index of 55 is adopted. Two shortened versions could be used with good results. (C) 2009 Published by Elsevier Ltd.

Cannabidiol for the treatment of psychosis in Parkinson`s disease

The management of psychosis in Parkinson`s disease (PD) has been considered a great challenge for clinicians and there is a need for new pharmacological intervention. Previously an antipsychotic and neuroprotective effect of Cannabidiol (CBD) has been suggested. Therefore, the aim of the present study was to directly evaluate for the first time, the efficacy, tolerability and safety of CBD on PD patients with psychotic symptoms. This was an open-label pilot study. Six consecutive outpatients (four men and two women) with the diagnosis of PD and who had psychosis for at least 3 months were selected for the study. All patients received CBD in flexible dose (started with an oral dose of 150 mg/day) for 4 weeks, in addition to their usual therapy. The psychotic symptoms evaluated by the Brief Psychiatric Rating Scale and the Parkinson Psychosis Questionnaire showed a significant decrease under CBD treatment. CBD did not worsen the motor function and decreased the total scores of the Unified Parkinson`s Disease Rating Scale. No adverse effect was observed during the treatment. These preliminary data suggest that CBD may be effective, safe and well tolerated for the treatment of the psychosis in PD.

The neuroprotective effect of dental pulp cells in models of Alzheimer`s and Parkinson`s disease

Aim of the present study was to investigate the neuroprotective effect of dental pulp cells (DPCs) in in vitro models of Alzheimer and Parkinson disease. Primary cultures of hippocampal and ventral mesencephalic neurons were treated for 24 h with amyloid beta (A beta(1-42)) peptide 1-42 and 6-OHDA, respectively. DPCs isolated from adult rat incisors were previously cultured in tissue culture inserts and added to the neuron cultures 2 days prior to neurotoxin treatment. Cell viability was assessed by the MTT assay. The co-culture with DPCs significantly attenuated 6-OHDA and A beta(1-42)-induced toxicity in primary cultures of mesencephalic and hippocampal neurons, and lead to an increase in neuronal viability in untreated cultures, suggesting a neurotrophic effect in both models. Furthermore, human dental pulp cells expressed a neuronal phenotype and produced the neurotrophic factors NGF, GDNF, BDNF, and BMP2 shown by microarray screening and antibody staining for the representative proteins. DPCs protected primary neurons in in vitro models of Alzheimer`s and Parkinson`s disease and can be viewed as possible candidates for studies on cell-based therapy.

Evaluation of chronic omega-3 fatty acids supplementation on behavioral and neurochemical alterations in 6-hydroxydopamine-lesion model of Parkinson`s disease

Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) have been widely associated to beneficial effects over different neuropathologies, but only a few studies associate them to Parkinson`s disease (PD). Rats were submitted to chronic supplementation (21-90 days of life) with fish oil, rich in omega-3 PUFAs, and were uni- or bilaterally lesioned with 4 mu g of the neurotoxin 6-hydroxydopamine (6-OHDA) in the medial forebrain bundle Although lipid incorporation was evidenced in neuronal membranes, it was not sufficient to compensate motor deficits induced by 6-OHDA. In contrast, omega-3 PUFAs were capable of reducing rotational behavior induced by apomorphine, suggesting neuroprotection over dyskinesia The beneficial effects of omega-3 PUFAs were also evident in the maintenance of thiobarbituric acid reactive substances index from animals lesioned with 6-OHDA similar to levels from SHAM and intact animals. Although omega-3 PUFAs did not modify the tyrosine hydroxylase immunoreactivity in the substantia nigra pars compacta and in the ventral tegmental area, nor the depletion of dopamine (DA) and its metabolites in the striatum, DA turnover was increased after omega-3 PUFAs chronic supplementation Therefore, it is proposed that omega-3 PUFAs action characterizes the adaptation of remaining neurons activity. altering striatal DA turnover without modifying the estimated neuronal population. (C) 2009 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved

Single Intranasal Administration of 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine in C57BL/6 Mice Models Early Preclinical Phase of Parkinson`s Disease

Many studies have shown that deficits in olfactory and cognitive functions precede the classical motor symptoms seen in Parkinson`s disease (PD) and that olfactory testing may contribute to the early diagnosis of this disorder. Although the primary cause of PD is still unknown, epidemiological studies have revealed that its incidence is increased in consequence of exposure to certain environmental toxins. In this study, most of the impairments presented by C57BL/6 mice infused with a single intranasal (i.n.) administration of the proneurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (1 mg/nostril) were similar to those observed during the early phase of PD, when a moderate loss of nigral dopamine neurons results in olfactory and memory deficits with no major motor impairments. Such infusion decreased the levels of the enzyme tyrosine hydroxylase in the olfactory bulb, striatum, and substantia nigra by means of apoptotic mechanisms, reducing dopamine concentration in different brain structures such as olfactory bulb, striatum, and prefrontal cortex, but not in the hippocampus. These findings reinforce the notion that the olfactory system represents a particularly sensitive route for the transport of neurotoxins into the central nervous system that may be related to the etiology of PD. These results also provide new insights in experimental models of PD, indicating that the i.n. administration of MPTP represents a valuable mouse model for the study of the early stages of PD and for testing new therapeutic strategies to restore sensorial and cognitive processes in PD.

Mice with genetic deletion of the heparin-binding growth factor midkine exhibit early preclinical features of Parkinson`s disease

There is considerable evidence showing that the neurodegenerative processes that lead to sporadic Parkinson`s disease (PD) begin many years before the appearance of the characteristic motor symptoms and that impairments in olfactory, cognitive and motor functions are associated with time-dependent disruption of dopaminergic neurotransmission in different brain areas. Midkine is a 13-kDa retinoic acid-induced heparin-binding growth factor involved in many biological processes in the central nervous system such as cell migration, neurogenesis and tissue repair. The abnormal midkine expression may be associated with neurochemical dysfunction in the dopaminergic system and cognitive impairments in rodents. Here, we employed adult midkine knockout mice (Mdk(-/-)) to further investigate the relevance of midkine in dopaminergic neurotransmission and in olfactory, cognitive and motor functions. Mdk(/-) mice displayed pronounced impairments in their olfactory discrimination ability and short-term social recognition memory with no gross motor alterations. Moreover, the genetic deletion of midkine decreased the expression of the enzyme tyrosine hydroxylase in the substantia nigra reducing partially the levels of dopamine and its metabolites in the olfactory bulb and striatum of mice. These findings indicate that the genetic deletion of midkine causes a partial loss of dopaminergic neurons and depletion of dopamine, resulting in olfactory and memory deficits with no major motor impairments. Therefore, Mdk(-/-) mice may represent a promising animal model for the study of the early stages of PD and for testing new therapeutic strategies to restore sensorial and cognitive processes in PD.