PD Subjects Research Articles

Central and systemic C-type Natriuretic Peptide are both reduced in Parkinson's Disease

IntroductionC-type Natriuretic Peptide is a neuropeptide widely expressed in the central nervous system including dopaminergic neurons projecting to basal ganglia. Previous work shows that concentrations of the peptide in cerebrospinal fluid are depressed in drug naïve PD subjects, decline over time and can be restored by doses of monoamine oxidase inhibitors that delay the need for levodopa. Whether plasma levels are similarly depressed in drug naïve subjects, or affected by dopaminergic drugs, is unknown. Our objectives were to determine whether (i) peptide products in plasma differ from normal in PD, and (ii) levels are affected by dopaminergic treatment. MethodsPlasma C-type Natriuretic Peptide and amino-terminal proCNP were measured in two groups – 27 drug naïve subjects with PD, and 30 subjects stabilized on dopaminergic drugs for at least 3 years. Values were compared with standard deviation scores from a population reference group without neurological disorder. Independent associations with predetermined variables known to affect plasma concentrations were assessed by multivariate analysis. ResultsIn both PD groups, plasma amino-terminal proCNP was significantly depressed compared to the reference range. Concentrations did not differ between the two groups. No correlation with disease duration or phenotype was found. Across all subjects, in a model initially comprising 7 factors, serum creatinine, PD and age were independent significant associations with amino-terminal proCNP. ConclusionsPlasma concentrations of amino-terminal proCNP are depressed in PD, are likely to result from diminished reabsorption from central sources, and may be useful in monitoring onset and effects of therapeutic interventions in PD.

Premotor symptoms and the risk of Parkinson’s disease: A case-control study in Mexican population

ObjectivesTo assess the prevalence of pre-motor symptoms and estimate the risk for developing Parkinson’s disease in Mexican population. Patients and MethodsA case-control study was carried out with consecutive subjects with Parkinson’s disease from two different referral centers in Mexico. Gender- and age-matched controls were randomly selected from the participating hospitals. All subjects were assessed using a structured questionnaire for the assessment of pre-motor symptoms (hyposmia, depression, anxiety, constipation, and sleep disorders). Odds ratios (OR) were calculated using logistic regression analysis. ResultsA total of 430 subjects with PD and 430 healthy subjects were included. Premotor symptoms prevalence was 77.7% (n=334) for the PD group, compared to 41.3% (n=178) in the control group (p<0.001). After logistic multivariate analysis, previous history of hyposmia (OR 2.02 [95% CI 1.33–3.06]), depression (OR 2.52 [95% CI 1.67–3.84]), anxiety (OR 4.37 [95% CI 2.73–6.98]) and sleep disorders (OR 2.03 [95% CI 1.41–2.93]) were independently associated with Parkinson’s disease. Overall prediction success of the model was 81.2% for controls and 61.2% for subjects with PD. ConclusionAll five premotor symptoms assessed were more commonly reported in PD subjects than healthy controls. The presence of non-motor symptoms yield a prediction success of 71.2% to discriminate between PD subjects and healthy controls.

Influence of diabetes mellitus on longitudinal atrophy and cognition in Parkinson's disease

ObjectiveTo investigate the impact of diabetes mellitus (DM) on cognitive performance and longitudinal volumetric brain changes in a cohort of cognitively normal mild PD patients. MethodsProspective study of idiopathic PD subjects who underwent baseline and follow-up MRI imaging and neuropsychological assessments at 6month intervals for 3years. Subjects were classified based on the presence (PD-DM) or absence of DM (PD-No DM) at baseline. Volumetric analysis was performed using FreeSurfer 5.3 image analysis suite. Brain volume and cognition were compared and analyzed cross-sectionally and longitudinally. Analyses were corrected for intracranial volume. ResultsThere were 65 PD-no DM and 12 PD-DM subjects at baseline with comparable global cognition at baseline. PD-DM subjects had lower cortical grey matter (GM), amygdala, frontal white matter and temporal white matter volumes and higher total white matter hyperintensity and periventricular hyperintensities. After mean follow-up of 29.08months, there were 51 PD-no DM and 11 PD-DM subjects. PD-DM subjects demonstrated greater decline in MMSE and MOCA scores compared to PD-No DM. PD-DM subjects had a higher rate of atrophy in the cortical WM, particularly in the parietal and occipital white matter. ConclusionMild PD patients with DM have lower GM and WM volumes at baseline and higher WMH volumes, despite comparable cognitive scores. Longitudinally, DM in PD results in greater rate of cognitive decline, associated with higher WM atrophy.

Misinterpretation of the Borg’s Rating of Perceived Exertion Scale by patients with panic disorder during ergospirometry challenge

IntroductionThe most widely used instrument to measure perceived exertion or exercise intensity is the Borg’s Rating of Perceived Exertion (RPE) Scale. Panic attacks are aversive experiences that may be triggered...

Olfactory dysfunction in early Parkinson's disease is associated with short latency afferent inhibition reflecting central cholinergic dysfunction.

Our study aimed to determine whether the short latency afferent inhibition (SAI) response could be associated with the severity of olfactory dysfunction in PD patients. A total of 71 PD patients and 20 controls were enrolled. All PD patients were classified into 3 groups by the severity of the olfactory deficit. Single-pulse transmagnetic stimulation (TMS) parameters and SAI were assessed. The integrated SAI in the PD with anosmia and PD with hyposomia groups was significantly less inhibited than that in the PD with normosmia and control groups [64.79 {Interquartile range (IQR): 59.96, 71.33}, 84.79 {IQR: 75.03, 90.63} versus 36.72 {IQR: 32.28, 48.33}, 42.15 {IQR: 34.60, 44.96}, respectively]. In PD subjects, the severity of olfactory dysfunction also showed a significant negative correlation with the SAI response (r=-0.829, p<0.001). Considering that the SAI response partly reflects central cholinergic dysfunction and that our study shows a relationship between the SAI response and the severity of olfactory dysfunction in PD, our findings indicate that cholinergic dysfunction could possibly contribute to the pathogenesis of olfactory dysfunction in early PD. SAI could be a useful marker to detect severe olfactory dysfunction in PD.

Identification of candidate cerebrospinal fluid biomarkers in parkinsonism using quantitative proteomics

IntroductionNeurodegenerative parkinsonian syndromes have significant clinical and pathological overlap, making early diagnosis difficult. Cerebrospinal fluid (CSF) biomarkers may aid the differentiation of these disorders, but other than α-synuclein and neurofilament light chain protein, which have limited diagnostic power, specific protein biomarkers remain elusive. ObjectivesTo study disease mechanisms and identify possible CSF diagnostic biomarkers through discovery proteomics, which discriminate parkinsonian syndromes from healthy controls. MethodsCSF was collected consecutively from 134 participants; Parkinson's disease (n = 26), atypical parkinsonian syndromes (n = 78, including progressive supranuclear palsy (n = 36), multiple system atrophy (n = 28), corticobasal syndrome (n = 14)), and elderly healthy controls (n = 30). Participants were divided into a discovery and a validation set for analysis. The samples were subjected to tryptic digestion, followed by liquid chromatography-mass spectrometry analysis for identification and relative quantification by isobaric labelling. Candidate protein biomarkers were identified based on the relative abundances of the identified tryptic peptides. Their predictive performance was evaluated by analysis of the validation set. Results79 tryptic peptides, derived from 26 proteins were found to differ significantly between atypical parkinsonism patients and controls. They included acute phase/inflammatory markers and neuronal/synaptic markers, which were respectively increased or decreased in atypical parkinsonism, while their levels in PD subjects were intermediate between controls and atypical parkinsonism. ConclusionUsing an unbiased proteomic approach, proteins were identified that were able to differentiate atypical parkinsonian syndrome patients from healthy controls. Our study indicates that markers that may reflect neuronal function and/or plasticity, such as the amyloid precursor protein, and inflammatory markers may hold future promise as candidate biomarkers in parkinsonism.

Epigenome-wide association study of DNA methylation in panic disorder

BackgroundPanic disorder (PD) is considered to be a multifactorial disorder emerging from interactions among multiple genetic and environmental factors. To date, although genetic studies reported several susceptibility genes with PD, few of them were replicated and the pathogenesis of PD remains to be clarified. Epigenetics is considered to play an important role in etiology of complex traits and diseases, and DNA methylation is one of the major forms of epigenetic modifications. In this study, we performed an epigenome-wide association study of PD using DNA methylation arrays so as to investigate the possibility that different levels of DNA methylation might be associated with PD.MethodsThe DNA methylation levels of CpG sites across the genome were examined with genomic DNA samples (PD, N = 48, control, N = 48) extracted from peripheral blood. Methylation arrays were used for the analysis. β values, which represent the levels of DNA methylation, were normalized via an appropriate pipeline. Then, β values were converted to M values via the logit transformation for epigenome-wide association study. The relationship between each DNA methylation site and PD was assessed by linear regression analysis with adjustments for the effects of leukocyte subsets.ResultsForty CpG sites showed significant association with PD at 5% FDR correction, though the differences of the DNA methylation levels were relatively small. Most of the significant CpG sites (37/40 CpG sites) were located in or around CpG islands. Many of the significant CpG sites (27/40 CpG sites) were located upstream of genes, and all such CpG sites with the exception of two were hypomethylated in PD subjects. A pathway analysis on the genes annotated to the significant CpG sites identified several pathways, including “positive regulation of lymphocyte activation.”ConclusionsAlthough future studies with larger number of samples are necessary to confirm the small DNA methylation abnormalities associated with PD, there is a possibility that several CpG sites might be associated, together as a group, with PD.

Structural Brain Sex Differences in Parkinson’s Disease: A Voxel-Based Morphometry Study

The aim of this study was to identify the brain’s structural differences between males and females and how they relate to clinical manifestations of PD. Voxel-based morphometry (VBM) was used to detect the differences between both sexes in PD and in healthy controls (HC). Also, a Pearson correlation coefficient was used to correlate depression values to grey matter (GM) for PD and HC subjects and for males and females within each group. The VBM analysis results have shown large loss of cortical and subcortical regions in males compared to females in the PD and HC group. Moreover, multiple positive and negative correlations were found between depression and GM, and considered significant at P<0.05. In addition, in PD group, depression scores were correlated positively to the right amygdala in females and positively in males. These results can provide insights for clinicians and researchers who are investigating PD structural differences in males and females and how they might influence PD clinical appearance, changes in motor and non-motor areas might explain the clinical manifestations.

Sixty-hertz stimulation improves bradykinesia and amplifies subthalamic low-frequency oscillations.

The objective of this study was to investigate the hypothesis that attenuation of subthalamic nucleus (STN) alpha-/beta-band oscillations is causal to improvement in bradykinesia. STN local field potentials from a sensing neurostimulator (Activa® PC+S; Medtronic, Inc.) and kinematics from wearable sensors were recorded simultaneously during 60- and 140-Hz deep brain stimulation (DBS) in 9 freely moving PD subjects (15 STNs) performing repetitive wrist flexion-extension. Kinematics were recorded during 20-Hz DBS in a subgroup. Both 60- and 140-Hz DBS improved the angular velocity and frequency of movement (P=0.002 and P=0.029, respectively, for 60 Hz; P<0.001 and P<0.001, respectively, for 140 Hz), but 60-Hz DBS did not attenuate beta-band power (13-30 Hz). In fact, 60-Hz DBS amplified alpha/low-beta (11-15 Hz, P=0.007) and attenuated high-beta power (19-27 Hz, P<0.001), whereas 140-Hz DBS broadly attenuated beta power (15-30 Hz, P<0.001). Only 60-Hz DBS improved the regularity of angular range (P=0.046) and 20-Hz DBS did not worsen bradykinesia. There was no correlation between beta-power modulation and bradykinesia. These novel results obtained from freely moving PD subjects demonstrated that both 140- and 60-Hz DBS improved bradykinesia and attenuated high beta oscillations; however, 60-Hz DBS amplified a subband of alpha/low-beta oscillations, and DBS at a beta-band frequency did not worsen bradykinesia. Based on recent literature, we suggest that both 140- and 60-Hz DBS decouple the cortico-STN hyperdirect pathway, whereas 60-Hz DBS increases coupling within striato-STN circuitry. These results inform future algorithms for closed-loop DBS in PD. © 2016 International Parkinson and Movement Disorder Society.

The Diagnostic Accuracy of Parkinson's Disease Mild Cognitive Impairment Battery Using the Movement Disorder Society Task Force Criteria.

The aim of the present study was to provide empirical evidence regarding the classification accuracy of the International Parkinson and Movement Disorder Society (MDS) neuropsychological battery (NB) in the determination of Parkinson's disease mild cognitive impairment (PD-MCI). The present cross-sectional study included 106 PD patients subjected to PD-MCI classification at Level I and 120 healthy controls (HCs). All HC and PD subjects were then assessed with MDS-NB at Level II and matched according to age and education using different thresholds (1.5 and 2.0 standard deviations [SDs] below average). We found that Level I and II resulted in different classifications of PD-MCI status. Detection thresholds of -1.5 SD and -2.0 SDs at Level II had also a significant impact on the discriminative validity of all measures in the MDS neuropsychological battery, based on area under the curve analyses. Overall, semantic fluency showed the highest potential in all comparisons not only between PD-MCI and HC, but also between PD-MCI and PD with no deficit (PD-ND). Our results show that the battery at Level II is applicable and that some measures, such as semantic fluency, have high discriminative validity in the detection of PD-MCI versus PD-ND and HCs.

Blood biomarker for Parkinson disease: peptoids

Parkinson disease (PD) is the second most common neurodegenerative disease. Because dopaminergic neuronal loss begins years before motor symptoms appear, a biomarker for the early identification of the disease is critical for the study of putative neuroprotective therapies. Brain imaging of the nigrostriatal dopamine system has been used as a biomarker for early disease along with cerebrospinal fluid analysis of α-synuclein, but a less costly and relatively non-invasive biomarker would be optimal. We sought to identify an antibody biomarker in the blood of PD patients using a combinatorial peptoid library approach. We examined serum samples from 75 PD patients, 25 de novo PD patients, and 104 normal control subjects in the NINDS Parkinson’s Disease Biomarker Program. We identified a peptoid, PD2, which binds significantly higher levels of IgG3 antibody in PD versus control subjects (P<0.0001) and is 68% accurate in identifying PD. The PD2 peptoid is 84% accurate in identifying de novo PD. Also, IgG3 levels are significantly higher in PD versus control serum (P<0.001). Finally, PD2 levels are positively correlated with the United Parkinson’s Disease Rating Scale score (r=0.457, P<0001), a marker of disease severity. The PD2 peptoid may be useful for the early-stage identification of PD, and serve as an indicator of disease severity. Additional studies are needed to validate this PD biomarker.

Neuropsychiatric symptoms in Serbian patients with Parkinson's disease

BackgroundParkinson's disease [PD] is associated with wide variety of neuropsychiatric symptoms, although it is primarily considered as a movement disorder. ObjectiveTo examine whether PD patients can be meaningfully classified into subgroups according to their neuropsychiatric symptoms, reported by their caregivers. MethodsThree hundred and sixty PD patients [mean age=63.5, SD=10.3] from the academic clinical setting were assessed with the 12-subscale Neuropsychiatric Inventory Questionnaire [NPI]. A two-stage cluster analysis was used to identify the subgroups groups of patients with specific neuropsychiatric profile. ResultsThree hundred and twenty-one PD patients [89%] showed at least one psychiatric symptom. The most common symptoms were anxiety [73.1%], depression [64.7%], and apathy [51.7%], and nighttime disturbance [51.3%], whereas the least common were euphoria [0.3%], and delusions [1.7%]. The mean [SD] total NPI composite score was 16.9 [17.4]. Two hundred eight PD subjects [58%] of the total sample had at least one symptom with a score ≥4. Three clusters were identified: a] Cluster 1, with no or few NPI symptoms [n=200; 55.6%]; b] Cluster 2, with mild to moderate symptoms on depression, anxiety and apathy scales [n=140; 38.9%]; and c] Cluster 3 with high agitation, disinhibition and irritability scores [n=20 patients; 5.6%]. PD subjects with clinically significant neuropsychiatric symptoms were older with more severe motor and cognitive impairment. ConclusionsThis study emphasizes the high prevalence and importance of neuropsychiatric symptoms in PD patients; therefore clinicians should also focus on treating in parallel with motor symptoms.

Effects of subthalamic nucleus deep brain stimulation on objective sleep outcomes in Parkinson's disease.

Sleep dysfunction is a common and disabling non-motor symptom in Parkinson's disease. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor symptoms and subjective sleep in PD, but alternative stimulation parameters to optimize sleep have not been explored. We hypothesized that low frequency STN DBS would improve objective sleep more than conventional settings. Twenty PD subjects with STN DBS (18 unilateral, 2 bilateral) underwent 3 non-consecutive nights of polysomnography: DBS off; DBS high frequency (≥130 Hz); and DBS low frequency (60 Hz). Motor symptom tolerability was assessed 30 minutes after resumption of baseline settings the morning following polysomnography. The primary outcome was change in sleep efficiency between high and low frequency nights measured with repeated measures ANOVA. There was no difference in sleep efficiency between nights at high frequency (82.1% (72.6-90.1)) (median (IQR)), low frequency (81.2% (56.2-88.8)), or DBS off (82.8% (75.7-87.4)), p=0.241. Additionally, there was no difference in sleep stage percent, arousals, limb movements, subjective sleep quality, or objective vigilance measures. These outcomes did not change after adjusting for age, sex, disease duration, or side of surgery. No residual adverse motor effects were noted. Although well tolerated, low frequency STN DBS did not improve objective sleep in PD. Remarkably, objective measures of sleep were not worse with DBS off. These observations point to the potential for adaptive stimulation approaches, through which DBS settings could be optimized during sleep to meet individual needs. Additionally, these changes could preserve battery life without compromising patient outcomes.

Cortical phosphorylated α-Synuclein levels correlate with brain wave spectra in Parkinson's disease.

Quantitative EEG features have been identified as surrogates and predictors of cognitive decline/dementia, a common feature of progressive PD. The biochemical correlates for altered quantitative EEG features are unknown. Our primary objective was to test the hypothesis that quantitative EEG measures correlate with cortical levels of phosphorylated α-synuclein, a modified form of the synaptic protein α-synuclein, in PD cases, in contrast to other pathology-associated proteins. A secondary objective was to explore the same correlations among cellular fractions of these proteins. We used posterior cingulate cortex autopsy tissue from 44 PD subjects with various degrees of cognitive decline, who had undergone EEG. In this brain region, which is a major hub of the default mode network, biochemical measurements for levels of phosphorylated α-synuclein, unmodified α-synuclein, amyloid beta peptide, phosphorylated tau, and key synaptic proteins were analyzed and data correlated with spectral EEG measures. Findings revealed significant correlations between background rhythm peak frequency and all bandpower values (highest in delta bandpower) with total phosphorylated α-synuclein, but not any correlation with total α-synuclein, phosphorylated tau protein, amyloid beta peptide, or synaptic proteins. Certain fractions of synaptosomal-associated protein 25 showed correlation with some quantitative EEG measures. These data show an association between increased phosphorylation of α-synuclein and the abnormal EEG signatures of cognitive decline. Results suggest that quantitative EEG may provide an in vivo approximation of phosphorylated α-synuclein in PD cortex. This adds to previous evidence that quantitative EEG measures can be considered valid biomarkers of PD cognitive decline. © 2016 International Parkinson and Movement Disorder Society.

High-Accuracy Classification of Parkinson's Disease Through Shape Analysis and Surface Fitting in 123I-Ioflupane SPECT Imaging.

Early and accurate identification of Parkinsonian syndromes (PS) involving presynaptic degeneration from nondegenerative variants such as scans without evidence of dopaminergic deficit (SWEDD) and tremor disorders is important for effective patient management as the course, therapy, and prognosis differ substantially between the two groups. In this study, we use single photon emission computed tomography (SPECT) images from healthy normal, early PD, and SWEDD subjects, as obtained from the Parkinson's Progression Markers Initiative (PPMI) database, and process them to compute shape- and surface-fitting-based features. We use these features to develop and compare various classification models that can discriminate between scans showing dopaminergic deficit, as in PD, from scans without the deficit, as in healthy normal or SWEDD. Along with it, we also compare these features with striatal binding ratio (SBR)-based features, which are well established and clinically used, by computing a feature-importance score using random forests technique. We observe that the support vector machine (SVM) classifier gives the best performance with an accuracy of 97.29%. These features also show higher importance than the SBR-based features. We infer from the study that shape analysis and surface fitting are useful and promising methods for extracting discriminatory features that can be used to develop diagnostic models that might have the potential to help clinicians in the diagnostic process.

Peripheral Synucleinopathy in Early Parkinson's Disease: Submandibular Gland Needle Biopsy Findings.

Finding a peripheral tissue biopsy site to diagnose early PD would be of value for clinical care, biomarker validation, and as research enrollment criteria. Whereas autopsy and advanced PD studies suggest that the submandibular gland is an important biopsy site, there are no studies in early PD. The aim of this study was to determine whether needle biopsy of the submandibular gland reveals Lewy type alpha-synucleinopathy in early PD. Twenty-five early PD (duration < 5 years) and 10 controls underwent transcutaneous needle core biopsies of the submandibular gland. Tissue was stained for phosphorylated alpha-synuclein, reviewed blind to clinical diagnosis, and only nerve element staining was considered positive. Mean (standard deviation) age was 69.5 (8.3) for the PD group, 64.8 (8.0) years for controls, and disease duration 2.6 (1.1) years. Six PD and 1 control subject had inadequate glandular tissue. Positive staining was found in 14 of 19 (74%) PD and 2 of 9 (22%) control subjects. PD-positive and -negative cases did not differ clinically. Adverse events (mainly swelling and bruising) were common (77% of cases), but were minor and transient. Submandibular gland needle biopsies identified phosphorylated alpha-synuclein staining in 74% of early PD subjects. False positives may be true false positives or may represent prodromal PD. If confirmed in larger studies with eventual autopsy confirmation, the potential value of submandibular gland biopsies for early PD may be to aid in clinical trial inclusion/exclusion and eventually serve as a gold standard for biomarker studies short of autopsy confirmation.

Neuroimaging and clinical predictors of fatigue in Parkinson disease

BackgroundFatigue is disabling in Parkinson disease. It is often associated with other non-motor symptoms, but little is known about its underlying pathophysiology. ObjectiveTo investigate neuroimaging (using dopaminergic and cholinergic PET) and clinical factors associated with fatigue severity in PD. Methods133 PD subjects (96M/37F) completed the Fatigue Severity Scale, Movement Disorders Society-Sponsored Revision of the Unified PD Rating Scale (MDS-UPDRS), Hoehn-Yahr staging, validated scales for depression, anxiety, apathy, sleep, and cognition, and underwent [11C]methyl-4-piperidinyl propionate (PMP) acetylcholinesterase (AChE) and [11C]dihydrotetrabenazine (DTBZ) monoaminergic PET imaging. We explored contributions to PD fatigue using separate regression models based either on neuroimaging parameters or clinicometric scales. ResultsIn a neuroimaging regression model, neither striatal DTBZ uptake nor AChE PMP uptake were predictors of fatigue in PD. In a post-hoc neuroimaging regression model, stratifying the total cohort into mild vs. moderate-to-severe PD, striatal DTBZ uptake was a significant predictor of fatigue in mild but not moderate-to-severe PD. In a clinicometric regression model, higher Beck Depression Inventory-somatic subscore, higher levodopa dose equivalents and younger age were all significant predictors of fatigue in PD, but the MDS-UPDRS non-motor experiences of daily living score was the best predictor overall. ConclusionsCholinergic uptake was not a predictor of fatigue in PD, but nigrostriatal dopaminergic denervation predicted fatigue in mild disease. Total non-motor symptom burden, somatic affective symptoms, levodopa dose equivalents, and younger age were independent clinical predictors of fatigue.

Temporal fluctuations of tremor signals from inertial sensor: a preliminary study in differentiating Parkinson's disease from essential tremor.

BackgroundParkinson’s disease (PD) and essential tremor (ET) are the two most common movement disorders but the rate of misdiagnosis rate in these disorders is high due to similar characteristics of tremor. The purpose of the study is to present: (a) a solution to identify PD and ET patients by using the novel measurement of tremor signal variations while performing the resting task, (b) the improvement of the differentiation of PD from ET patients can be obtained by using the ratio of the novel measurement while performing two specific tasks.Methods35 PD and 22 ET patients were asked to participate in the study. They were asked to wear a 6-axis inertial sensor on his/her index finger of the tremor dominant hand and perform three tasks including kinetic, postural and resting tasks. Each task required 10 s to complete. The angular rate signal measured during the performance of these tasks was band-pass filtered and transformed into a two-dimensional representation. The ratio of the ellipse area covering 95 % of this two-dimensional representation of different tasks was investigated and the two best tasks were selected for the purpose of differentiation.ResultsThe ellipse area of two-dimensional representation of the resting task of PD and ET subjects are statistically significantly different (p < 0.05). Furthermore, the fluctuation ratio, defined as a ratio of the ellipse area of two-dimensional representation of resting to kinetic tremor, of PD subjects were statistically significantly higher than ET subjects in all axes (p = 0.0014, 0.0011 and 0.0001 for x, y and z-axis, respectively). The validation shows that the proposed method provides 100 % sensitivity, specificity and accuracy of the discrimination in the 5 subjects in the validation group. While the method would have to be validated with a larger number of subjects, these preliminary results show the feasibility of the approach.ConclusionsThis study provides the novel measurement of tremor variation in time domain termed ‘temporal fluctuation’. The temporal fluctuation of the resting task can be used to discriminate PD from ET subjects. The ratio of the temporal fluctuation of the resting task to the kinetic task improves the reliability of the discrimination. While the method is powerful, it is also simple so it could be applied on low resource platforms such as smart phones and watches which are commonly equipped with inertial sensors.

Rasagiline for the symptomatic treatment of fatigue in Parkinson's disease.

Fatigue affects 40% to 50% of all PD patients and is a leading cause of disability, with no clearly established or efficacious established treatments. In this double-blinded, placebo-controlled, pilot trial, we investigated whether rasagiline improved fatigue among PD patients. Subjects were randomized to 1 mg daily of rasagiline or placebo for 12 weeks. The primary endpoint was a change in the Modified Fatigue Impact Scale from baseline to week 12. Thirty PD subjects (16 men), with Modified Fatigue Impact Scale baseline score of 67 ± 15, were randomized (16 to rasagiline vs. 14 to placebo). Significant improvement was noted in the mean Modified Fatigue Impact Scale score of the rasagiline group (12 points) as compared to placebo (8.5 points) from baseline to week 12 (P = 0.003). In this pilot study, rasagiline at a dose of 1 mg per day improved fatigue. Larger randomized studies are needed to confirm this finding.

Abnormal lipopolysaccharide binding protein as marker of gastrointestinal inflammation in Parkinson disease.

Objective: An inflammation-driven model of PD has been proposed based on the endotoxin lipopolysaccaride (LPS), a potential source of inflammation in the gastrointestinal system linked to neurotoxicity. Systemic exposure to bacterial endotoxin (LPS) can be determined by measuring plasma LPS binding protein (LBP). We aimed to evaluate whether lipopolysaccharide binding protein (LBP) can be used to distinguish PD subjects from control subjects and to assess whether LBP levels correlate with PD disease severity.Methods: We measured plasma LBP (ng/ml) using an ELISA kit in 94 PD subjects of various stages and 97 control subjects. Disease severity was assessed using the UPDRS and Hoehn and Yahr staging. The LBP level between the PD and control groups was compared using analysis of covariance. Spearman correlation was used to explore the relationship between LBP level and disease severity.Results: The mean LBP level in PD subjects (n = 94) was significantly different from control subjects (n = 95, p = 0.018). In PD subjects, we did not find a correlation between mean LBP level and disease severity.Conclusions: Our data suggests that LBP is one GI biomarker related to LPS induced neurotoxicity. However, there was significant variability in LBP levels within the PD and control groups, limiting its utility as a stand-alone biomarker. This study supports the role of LPS induced neurotoxicity in PD and further exploration of this pathway may be useful in developing sensitive and specific biomarkers for PD.