Investigating the aspect of asymmetry in brain-first versus body-first Parkinson's disease.

Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons in the substantia nigra. Recent literature has proposed two subgroups of PD. The "body-first subtype" is associated with a prodrome of isolated REM-sleep Behavior Disorder (iRBD) and a relatively symmetric brain degeneration. The "brain-first subtype" is suggested to have a more asymmetric degeneration and a prodromal stage without RBD. This study aims to investigate the proposed difference in symmetry of the degeneration pattern in the presumed body and brain-first PD subtypes. We analyzed 123I-FP-CIT (DAT SPECT) and 18F-FDG PET brain imaging in three groups of patients (iRBD, n = 20, de novo PD with prodromal RBD, n = 22, and de novo PD without RBD, n = 16) and evaluated dopaminergic and glucose metabolic symmetry. The RBD status of all patients was confirmed with video-polysomnography. The PD groups did not differ from each other with regard to the relative or absolute asymmetry of DAT uptake in the putamen (p = 1.0 and p = 0.4, respectively). The patient groups also did not differ from each other with regard to the symmetry of expression of the PD-related metabolic pattern (PDRP) in each hemisphere. The PD groups had no difference in symmetry considering mean FDG uptake in left and right regions of interest and generally had the same degree of symmetry as controls, while the iRBD patients had nine regions with abnormal left-right differences (p < 0.001). Our findings do not support the asymmetry aspect of the "body-first" versus "brain-first" hypothesis.

Hippocampus activation related to 'real-time' processing of visuospatial change.

The delay associated with cerebral processing time implies a lack of real-time representation of changes in the observed environment. To bridge this gap for motor actions in a dynamical environment, the brain uses predictions of the most plausible future reality based on previously provided information. To optimise these predictions, adjustments to actual experiences are necessary. This requires a perceptual memory buffer. In our study we gained more insight how the brain treats (real-time) information by comparing cerebral activations related to judging past-, present- and future locations of a moving ball, respectively. Eighteen healthy subjects made these estimations while fMRI data was obtained. All three conditions evoked bilateral dorsal-parietal and premotor activations, while judgment of the location of the ball at the moment of judgment showed increased bilateral posterior hippocampus activation relative to making both future and past judgments at the one-second time-sale. Since the condition of such 'real-time' judgments implied undistracted observation of the ball's actual movements, the associated hippocampal activation is consistent with the concept that the hippocampus participates in a top-down exerted sensory gating mechanism. In this way, it may play a role in novelty (saliency) detection.

How typical are 'typical' tremor characteristics? Sensitivity and specificity of five tremor phenomena.

INTRODUCTION: Distinguishing between different tremor disorders can be challenging. Some tremor disorders are thought to have typical tremor characteristics: the current study aims to provide sensitivity and specificity for five 'typical' tremor phenomena. METHODS: Retrospectively, we examined 210 tremor patients referred for electrophysiological recordings between January 2008 and January 2014. The final clinical diagnosis was used as the gold standard. The first step was to determine whether patients met neurophysiological criteria for their type of tremor. Once established, we focused on 'typical' characteristics: tremor frequency decrease upon loading (enhanced physiological tremor (EPT)), amplitude increase upon loading, distractibility and entrainment (functional tremor (FT)), and intention tremor (essential tremor (ET)). The prevalence of these phenomena in the 'typical' group was compared to the whole group. RESULTS: Most patients (87%) concurred with all core clinical neurophysiological criteria for their tremor type. We found a frequency decrease upon loading to be a specific (95%), but not a sensitive (42%) test for EPT. Distractibility and entrainment both scored high on sensitivity (92%, 91%) and specificity (94%, 91%) in FT, whereas a tremor amplitude increase was specific (92%), but not sensitive (22%). Intention tremor was a specific finding in ET (85%), but not a sensitive test (45%). Combination of characteristics improved sensitivity. CONCLUSION: In this study, we retrospectively determined sensitivity and specificity for five 'typical' tremor characteristics. Characteristics proved specific, but few were sensitive. These data on tremor phenomenology will help practicing neurologists to improve distinction between different tremor disorders.

Muscle co-activity tuning in Parkinsonian hand movement: disease-specific changes at behavioral and cerebral level.

We investigated simple directional hand movements based on different degrees of muscle co-activity, at behavioral and cerebral level in healthy subjects and Parkinson's disease (PD) patients. We compared "singular" movements, dominated by the activity of one agonist muscle, to "composite" movements, requiring conjoint activity of multiple muscles, in a center-out (right hand) step-tracking task. Behavioral parameters were obtained by EMG and kinematic recordings. fMRI was used to investigate differences in underlying brain activations between PD patients (N = 12) and healthy (age-matched) subjects (N = 18). In healthy subjects, composite movements recruited the striatum and cortical areas comprising bilaterally the supplementary motor area and premotor cortex, contralateral medial prefrontal cortex, primary motor cortex, primary visual cortex, and ipsilateral superior parietal cortex. Contrarily, the ipsilateral cerebellum was more involved in singular movements. This striking dichotomy between striatal and cortical recruitment vs. cerebellar involvement was considered to reflect the complementary roles of these areas in motor control, in which the basal ganglia are involved in movement selection and the cerebellum in movement optimization. Compared to healthy subjects, PD patients showed decreased activation of the striatum and cortical areas in composite movement, while performing worse at behavioral level. This implies that PD patients are especially impaired on tasks requiring highly tuned muscle co-activity. Singular movement, on the other hand, was characterized by a combination of increased activation of the ipsilateral parietal cortex and left cerebellum. As singular movement performance was only slightly compromised, we interpret this as a reflection of increased visuospatial processing, possibly as a compensational mechanism.

Classification of Parkinsonian syndromes from FDG-PET brain data using decision trees with SSM/PCA features.

Medical imaging techniques like fluorodeoxyglucose positron emission tomography (FDG-PET) have been used to aid in the differential diagnosis of neurodegenerative brain diseases. In this study, the objective is to classify FDG-PET brain scans of subjects with Parkinsonian syndromes (Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy) compared to healthy controls. The scaled subprofile model/principal component analysis (SSM/PCA) method was applied to FDG-PET brain image data to obtain covariance patterns and corresponding subject scores. The latter were used as features for supervised classification by the C4.5 decision tree method. Leave-one-out cross validation was applied to determine classifier performance. We carried out a comparison with other types of classifiers. The big advantage of decision tree classification is that the results are easy to understand by humans. A visual representation of decision trees strongly supports the interpretation process, which is very important in the context of medical diagnosis. Further improvements are suggested based on enlarging the number of the training data, enhancing the decision tree method by bagging, and adding additional features based on (f)MRI data.

Can repetitive transcranial magnetic stimulation increase muscle strength in functional neurological paresis? A proof-of-principle study.

BACKGROUND AND PURPOSE: Therapeutic options are limited in functional neurological paresis disorder. Earlier intervention studies did not control for a placebo effect, hampering assessment of effectivity. A proof-of-principle investigation was conducted into the therapeutic potential of repetitive transcranial magnetic stimulation (rTMS), using a single-blind two-period placebo-controlled cross-over design. METHODS: Eleven patients received active 15 Hz rTMS over the contralateral motor cortex (hand area), in two periods of 5 days, for 30 min once a day at 80% of resting motor threshold, with a train length of 2 s and an intertrain interval of 4 s. Eight of these eleven patients were also included in the placebo treatment condition. Primary outcome measure was change in muscle strength as measured by dynamometry after treatment. Secondary outcome measure was the subjective change in muscle strength after treatment. RESULTS: In patients who received both treatments, active rTMS induced a significantly larger median increase in objectively measured muscle strength (24%) compared to placebo rTMS (6%; P < 0.04). Subjective ratings showed no difference due to treatment, i.e. patients did not perceive these objectively measured motor improvements (P = 0.40). CONCLUSIONS: Our findings suggest that rTMS by itself can potentially improve muscle weakness in functional neurological paresis disorder. Whereas patients' muscle strength increased as measured with dynamometry, patients did not report increased functioning of the affected hand, subjectively. The results may indicate that decreased muscle strength is not the core symptom and that rTMS should be added to behavioral approaches in functional neurological paresis.

Adenosine A(2A) receptor antagonists as Positron Emission Tomography (PET) tracers.

The adenosine A(2A) receptor (A(2A)R) is highly concentrated in the striatum, and a therapeutic target for Parkinson's disorder (PD) and Huntington's disease. High affinity and selective radiolabeled A(2A)R antagonists can be important research and diagnostic tools for PD. Positron Emission Tomography (PET) can play an important role by measuring radiolabeled A(2A) antagonists non-invasively in the brain. However, till date no complete review on A(2A)R PET ligands is available. The present article has been therefore focused on available PET tracers for A(2A)R and their detailed biological evaluation in rodents, nonhuman primates and humans. Drug design and development by molecular modeling including new lead structures that are potential candidates for radiolabeling and mapping of cerebral A(2A)Rs is discussed in the present article. A brief overview of functions of adenosine in health and disease, including the relevance of A(2A)R for PD has also been presented.

Motor behavior correlates with striatal [¹8F]-DOPA uptake in MPTP-lesioned primates.

The MPTP-lesioned monkey is considered as the best animal model for Parkinson's disease (PD). It has damage to dopaminergic cell groups and motor dysfunction similar to that seen in PD. Correlations between these two parameters have been described but there is a lack of formal statistical analyses on dopaminergic function as assessed by [(18)F]-F-DOPA PET and objectively rated motor behavior in longitudinal experiments. Eight rhesus monkeys received two MPTP infusions: first in one carotid artery, and after eight weeks in the other. Motor behavior and [(18)F]-F-DOPA uptake were measured at three stages: baseline, unilateral and bilateral. We correlated movement with radiotracer uptake across these three stages. MPTP caused the expected parkinsonian motor signs which were accompanied by lower radioactivity concentrations in the striatum. There were significant correlations between dopaminergic function and behavior. In conclusion, striatal [(18)F]-F-DOPA uptake correlates inversely with the severity of motor impairment in MPTP-lesioned non-human primates. Both behavioral scoring and [(18)F]-F-DOPA PET scans are useful and sensitive methods to monitor dopaminergic degeneration within subjects.

11C-verapamil to assess P-gp function in human brain during aging, depression and neurodegenerative disease.

P-glycoprotein (P-gp) at the blood-brain barrier (BBB) functions as an active efflux pump by extruding a wide range of substrates from the brain. This is important for maintaining loco-regional homeostasis and for protecting the brain against blood-borne toxic substances. Altered P-gp function seems to be involved in the pathophysiology of neurodegenerative disease and various neurological and psychiatric disorders. Positron emission tomography (PET) with the radiotracer (11)C-verapamil (VPM-PET) is a validated technique allowing measurement of P-gp function at the human BBB. In this review, we highlight changes of P-gp function, as measured with VPM-PET, in aging and in the pathogenesis and progression of neurodegenerative disease, as well as their role in depressive disorders.

Dystonia in neurodegeneration with brain iron accumulation: outcome of bilateral pallidal stimulation.

Neurodegeneration with brain iron accumulation encompasses a heterogeneous group of rare neurodegenerative disorders that are characterized by iron accumulation in the brain. Severe generalized dystonia is frequently a prominent symptom and can be very disabling, causing gait impairment, difficulty with speech and swallowing, pain and respiratory distress. Several case reports and one case series have been published concerning therapeutic outcome of pallidal deep brain stimulation in dystonia caused by neurodegeneration with brain iron degeneration, reporting mostly favourable outcomes. However, with case studies, there may be a reporting bias towards favourable outcome. Thus, we undertook this multi-centre retrospective study to gather worldwide experiences with bilateral pallidal deep brain stimulation in patients with neurodegeneration with brain iron accumulation. A total of 16 centres contributed 23 patients with confirmed neurodegeneration with brain iron accumulation and bilateral pallidal deep brain stimulation. Patient details including gender, age at onset, age at operation, genetic status, magnetic resonance imaging status, history and clinical findings were requested. Data on severity of dystonia (Burke Fahn Marsden Dystonia Rating Scale-Motor Scale, Barry Albright Dystonia Scale), disability (Burke Fahn Marsden Dystonia Rating Scale-Disability Scale), quality of life (subjective global rating from 1 to 10 obtained retrospectively from patient and caregiver) as well as data on supportive therapy, concurrent pharmacotherapy, stimulation settings, adverse events and side effects were collected. Data were collected once preoperatively and at 2-6 and 9-15 months postoperatively. The primary outcome measure was change in severity of dystonia. The mean improvement in severity of dystonia was 28.5% at 2-6 months and 25.7% at 9-15 months. At 9-15 months postoperatively, 66.7% of patients showed an improvement of 20% or more in severity of dystonia, and 31.3% showed an improvement of 20% or more in disability. Global quality of life ratings showed a median improvement of 83.3% at 9-15 months. Severity of dystonia preoperatively and disease duration predicted improvement in severity of dystonia at 2-6 months; this failed to reach significance at 9-15 months. The study confirms that dystonia in neurodegeneration with brain iron accumulation improves with bilateral pallidal deep brain stimulation, although this improvement is not as great as the benefit reported in patients with primary generalized dystonias or some other secondary dystonias. The patients with more severe dystonia seem to benefit more. A well-controlled, multi-centre prospective study is necessary to enable evidence-based therapeutic decisions and better predict therapeutic outcomes.

Increased activation in cingulate cortex in conversion disorder: what does it mean?

Conversion disorder is one of the terms used to describe various psychosomatic neurological symptoms that are thought to originate from a psychological conflict. Psychological stressors can usually be identified but appear to be almost similar to the severity of psychological stress in non-psychosomatic neurological disorders. Recent neuroimaging research provides one rather robust finding of increased activation in the anterior cingulate gyrus. This activation has been explained as a reflection of 'active inhibition' or 'self-monitoring' but its meaning in conversion disorder still remains mysterious. In this paper, current theories are re-examined from a neuroanatomical point of view.

[11C]-PK11195 PET: quantification of neuroinflammation and a monitor of anti-inflammatory treatment in Parkinson's disease?

UNLABELLED: [(11)C]-PK11195 PET has been used for in vivo brain imaging of microglia activation in Parkinson's disease (PD) patients. COX-2 inhibition has been shown to reduce neuroinflammation and neurodegeneration in animal models of PD. This pilot study assessed the use of [(11)C]-PK11195 PET to quantify neuroinflammation and evaluate the ability of COX-2 inhibition to reduce neuroinflammation in PD patients. METHODS: Fourteen PD patients and eight healthy, age matched controls underwent a [(11)C]-PK11195 PET and MRI scan. Five PD patients were scanned before and after one month of celecoxib treatment 200 mg/day. Arterial plasma sampling and metabolite analysis were performed to create plasma input curves. A 2-compartment model and Logan analysis were applied and parametric DV images were compared using t-test in SPM2. In addition a simplified reference region model (SRTM) was applied, with both the cerebellum and a reference region derived from cluster analysis. RESULTS: Using the cluster analysis, PD patients showed higher contralateral putamen BP and midbrain BP compared to controls, although considerable overlap was seen and differences were not statistically significant. Unexpectedly, BP and DV after celecoxib were slightly higher. Cerebellum as reference region resulted in lower BP values and k(3)/k(4) gave 10-fold higher BP values. Linearization of the data did not show differences between PD patients and controls. CONCLUSIONS: In current practice, [(11)C]-PK11195 seems an unsuitable tracer for accurate or reliable quantification of neuroinflammation. Refinement of [(11)C]-PK11195 uptake analysis and, more importantly, further development of better tracers is necessary to enable accurate measurement of neuroinflammation and effects of anti-inflammatory treatment in patients.

Psychological assessment of malingering in psychogenic neurological disorders and non-psychogenic neurological disorders: relationship to psychopathology levels.

BACKGROUND AND PURPOSE: It remains unknown whether psychological distress causes malingering in patients with psychogenic symptoms. METHODS: We studied 26 patients with psychogenic neurological disorders on psychopathology and malingering in comparison with 26 patients with various neurological conditions and 18 matched healthy controls (HC). RESULTS: Psychogenic patients showed the highest levels of psychological complaints and malingering, but non-psychogenic neurological patients also showed significantly more psychological distress and malingering compared with HC. Psychological distress was related to the degree of malingering, in both patient groups. CONCLUSION: This data does not formally support a causal relationship between psychological distress and psychogenic neurological disorders, but suggests that a part of the psychological complaints is a general result of having an illness. The clinical implication of this study is that psychological distress is not sufficient for diagnosing functional complaints. Also, if a patient scores normal on a test for malingering, this does not mean that he or she is not suffering from psychogenic symptoms.

128-channel somatosensory evoked potentials in the differential diagnosis of parkinsonian disorders.

PURPOSE: The differential diagnosis of parkinsonian disorders can be very difficult, especially at an early stage. In this study, we investigated whether SEP amplitude recorded by 128-channel EEG is useful for diagnosis of parkinsonian disorders, and in particular whether SEP asymmetry can differentiate corticobasal degeneration (CBGD) from other parkinsonian disorders. METHODS: We recorded median nerve SEPs in 47 patients suspected of CBGD, supranuclear palsy or definite Parkinson's disease at an early stage. We compared SEP asymmetry and parietal peak amplitudes of the patients after grouping them based on their clinical diagnosis after 1-5 years of follow-up. In nine subjects the diagnosis remained unclear. RESULTS: Three of 13 patients with a clinical diagnosis of CBGD had an abnormal SEP asymmetry. Furthermore, we found extremely high N20 amplitudes in three other patients with CBGD. However, similar asymmetry abnormalities were found in patients with other Parkinsonian disorders. CONCLUSION: Despite the use of 128-channel SEP recordings and analysis techniques, which are more accurate than conventional techniques, sensitivity and specificity of cortical median nerve SEP asymmetry and parietal amplitude for differentiating CBGD from other parkinsonian disorders were low at an early stage of the disease. A possible reason for this may be that the hand area of the primary somatosensory cortex was not yet affected in most CBGD patients.

Changes in striatal dopamine D2 receptor binding in pre-clinical Huntington's disease.

BACKGROUND: Carriers of the Huntington disease (HD) mutation develop a progressive neurodegenerative disorder after a pre-clinical phase. We examined the value of (11)C-raclopride PET (RAC) as a biomarker for pre-clinical HD pathophysiology. METHODS: In a prospective cohort study with clinical and neuropsychological assessment we collected complete RAC data in 18 pre-clinical mutation carriers (HD-PMC) and 11 controls. Follow-up was 2 years. We calculated striatal RAC binding potential (BP) to measure dopamine D2 receptor availability. RESULTS: No HD-PMC had overt neuropsychological dysfunction. RAC-BP in putamen was abnormal in up to 44% of HD-PMC. The rate of RAC-BP decline (2.6% per year) was not significantly higher than in controls. Follow-up putaminal BP correlated weakly with predicted distance to onset of clinical HD (P = 0.034), but the rate of decline did not. Three HD-PMC developed motor abnormalities suspect for HD but did not show an increased rate of decline of putaminal BP. CONCLUSIONS: Many HD-PMC have striatal abnormalities but we found no clearly increased rate of D2 receptor changes around the onset of clinical HD. A longer follow-up of the present study cohort is needed to establish the value of RAC-BP in assessing the risk of clinical conversion from striatal D2 binding data.

Direct comparison of FP-CIT SPECT and F-DOPA PET in patients with Parkinson's disease and healthy controls.

PURPOSE: Diagnosing Parkinson's disease (PD) on clinical grounds may be difficult, especially in the early stages of the disease. F-DOPA PET and FP-CIT SPECT scans are able to determine presynaptic dopaminergic activity in different ways. The aim of this study was to determine and compare the sensitivity and specificity of the two methods in the detection of striatal dopaminergic deficits in the same cohort of PD patients and healthy controls. METHODS: Movement disorder specialists recruited 11 patients with early-stage PD and 17 patients with advanced PD. The patients underwent both an FP-CIT SPECT scan and an F-DOPA PET scan. In addition, 10 FP-CIT SPECT scans or 10 F-DOPA PET scans were performed in 20 healthy controls. A template with regions of interest was used to sample tracer activity of the caudate, putamen and a reference region in the brain. The outcome parameter was the striatooccipital ratio (SOR). Normal SOR values were determined in the controls. The sensitivity and specificity of both scanning methods were calculated. RESULTS: FP-CIT SPECT and F-DOPA PET scans were both able to discriminate PD patients from healthy controls. For the early phases of the disease, sensitivity and specificity of the contralateral striatal and putaminal uptake of FP-CIT and F-DOPA was 100%. When only caudate uptake was considered, the specificities were 100% and 90% for FP-CIT and F-DOPA, respectively, while the sensitivity was 91% for both scanning techniques. CONCLUSION: FP-CIT SPECT and F-DOPA PET scans are both able to diagnose presynaptic dopaminergic deficits in early phases of PD with excellent sensitivity and specificity.

Cerebral representations of space and time.

A link between perception of time and spatial change is particularly revealed in dynamic conditions. By fMRI, we identified regional segregation as well as overlap in activations related to spatial and temporal processing. Using spatial and temporal anticipation concerning movements of a ball provided a balanced paradigm for contrasting spatial and temporal conditions. In addition, momentary judgments were assessed. Subjects watched a monitor-display with a moving ball that repeatedly disappeared. Ordered in 4 conditions, they indicated either where or when the ball would hit the screen bottom, where it actually disappeared or what its speed was. Analysis with SPM showed posterior parietal activations related to both spatial- and temporal predictions. After directly contrasting these two conditions, parietal activations remained robust in spatial prediction but virtually disappeared in temporal prediction, while additional left cerebellar-right prefrontal and pre-SMA activations in temporal prediction remained unchanged. Speed contrasted to the location of disappearance showed similar parietal decrease with maintained cerebellar-prefrontal activations, but also increased caudate activation. From these results we inferred that parietal-based spatial information was a prerequisite for temporal processing, while prefrontal-cerebellar activations subsequently reflected working memory and feedforward processing for the assessment of differences between past and future spatial states. We propose that a temporal component was extracted from speed, i.e. approximated momentary time, which demarcated minimal intervals of spatial change (defined by neuronal processing time). The caudate association with such interval demarcation provided an argument to integrate concepts of space-referenced time processing and a clock-like processing model.

Multichannel recording of tibial-nerve somatosensory evoked potentials.

STUDY AIMS: The topography of the peaks of tibial-nerve somatosensory evoked potential (SEP) varies among healthy subjects, most likely because of differences in position and orientation of their cortical generator(s). Therefore, amplitude estimation with a standard one- or two-channel derivation is likely to be inaccurate and might partly cause the low sensitivity of SEP amplitude to pathological changes. In this study, we investigate whether 128-channel tibial-nerve SEP recordings can improve amplitude estimation and reduce the coefficient of variation. METHODS: We recorded tibial-nerve SEPs using a 128-channel EEG system in 48 healthy subjects aged 20 to 70 years (47 provided analyzable data). We compared P39, N50, and P60 amplitudes obtained with a 128-channel analysis method (based on butterfly plots and spatial topographies) with those obtained using a one-channel conventional configuration and analysis. Scalp and earlobe references were compared. RESULTS: Tibial-nerve SEP amplitudes obtained with the 128-channel method were significantly higher as compared to the one-channel conventional method. Consequently, the coefficient of variation was lower for the 128-channel method. In addition, in both methods, the N50-peak amplitude was sometimes hard to identify, because of its low amplitude. Besides, in some subjects, the N50 peak, as obtained with the conventional method, rather seemed to be a period between two positivities rather than an activation peak on itself. CONCLUSIONS: The 128-channel method can measure tibial-nerve SEP amplitude more accurately and might therefore be more sensitive to pathological changes. Our results indicate that the N50 component is less useful for clinical practice.

The assessment of depression in Parkinson's disease.

BACKGROUND: Motor symptoms form the hallmark of Parkinson's Disease (PD), although features like depression are often present. Depression rating scales [e.g. Montgomery-Asberg Depression Rating Scale (MADRS)] used in PD measure affective, cognitive and somatic symptoms. An important clinical question is which items of the MADRS are likely to be influenced by PD symptoms. METHODS: Depression was assessed in 43 PD patients who scored below the cut-off of the MADRS and who differed widely in motor severity. RESULTS: Parkinson's Disease patients scored relatively highest on Concentration difficulties, Reduced sleep and Inner tension. Reduced sleep, Lassitude and Suicidal thoughts were associated with motor severity and specifically with Bradykinesia, Rigidity and Axial impairment, however not with Tremor. To avoid a possible influence on our results of coincidentally included PD patients with a depression, all associations between somatic MADRS items and motor severity were corrected for the influence of affective symptoms of depression. All associations remained significant. DISCUSSION: In conclusion, the items Reduced sleep and Lassitude of the MADRS are likely to be influenced by motor symptoms. The high score on Concentration difficulties is suggested to be a reflection of cognitive dysfunction in PD. Thus, when assessing depression in PD, using a depression rating scale like the MADRS, adjusted cut-off scores are required.

Blood-brain barrier P-glycoprotein function is not impaired in early Parkinson's disease.

The cause of Parkinson's disease (PD) is unknown. Genetic susceptibility and exposure to environmental toxins contribute to specific neuronal loss in PD. Decreased blood-brain barrier (BBB) P-glycoprotein (P-gp) efflux function has been proposed as a possible causative link between toxin exposure and PD neurodegeneration. In the present study BBB P-gp function was investigated in vivo in 10 early stage PD patients and 8 healthy control subjects using (R)-[(11)C]-verapamil and PET. Cerebral volume of distribution (V(d)) of verapamil was used as measure of P-gp function. Both region of interest (ROI) analysis and voxel analysis using statistical parametric mapping (SPM) were performed to assess regional brain P-gp function. In addition, MDR1 genetic polymorphism was assessed. In the present study, a larger variation in V(d) of (R)-[(11)C]-verapamil was seen in the PD group as compared to the control group. However, decreased BBB P-gp function in early stage PD patients could not be confirmed.