Function In Parkinson's Disease Patients Research Articles

Comorbid states in Parkinson's disease: an effect of MAO-B inhibitors

The comorbidity in Parkinson's disease (PD), which is closely related to the tolerability of antiparkinsonian drugs, is-'analyzed. The authors present the results of the studies that have confirmed the greater safety of rasagiline compared to dopamine receptor agonists in elderly patients. The effects of rasagiline, including combinations of this drug with antidepressants, on-depression in PD and the low risk,of the serotonin -syndrome caused by these combinations are considered. The studies demonstrated the effect of rasagiline on fatigue and cognitive functions in PD patients are described. Single cases of the development of impulsive compulsive disorders:in patients treated with- rasagiline are presented.

Cortical physiology as a therapeutic target in Parkinson′s disease related dementia and cognitive dysfunction: study protocol for a randomized controlled trial

Background: Dementia is the leading cause of nursing home placement in Parkinson's disease (PD), yet little is known about the causes of cognitive dysfunction in PD and there are no effective treatments. Our preliminary data and other published studies suggest that abnormalities in brain activity involving networks important for normal thinking and memory may contribute to cognitive dysfunction in PD and may represent a target for treatment. Methods/Design: A randomized control trial will be conducted to assess the therapeutic potential of bifrontal repetitive transcranial magnetic stimulation (rTMS) in modulating cortical activity related to cognitive dysfunction in PD. This study will be performed at the University of Colorado Denver, Anschutz Campus, in Aurora, Colorado. Fifty-five PD patients (> 40 years of age) with mild cognitive impairment or mild dementia will be included and randomized in a 1:1 ratio to sham or real rTMS groups. Primary outcome measurement is the total score of the Mattis Dementia Rating Scale. Secondary outcome measurements are domain specific ratings of executive function, memory, language, attention, and visuospatial abilities. Discussion: If bifrontal rTMS results in positive changes to cognitive function in PD patients with mild cognitive impairment, this may represent a new and effective treatment for PD-related cognitive dysfunction. Secondly, evaluation of any bifrontal rTMS-induced changes to cognitive function will improve the current understanding of the mechanisms behind the causes of cognitive dysfunction in PD. Trial registration: Clinical Trials.gov identifier: NCT02346708; registered on 9 January 2015. Ethics: This study protocol was approved by the Colorado Multiple Institutional Review Board (COMIRB) (approval No. 13-2474) and will be performed in accordance with the Declaration of Helsinki. Informed consent: Signed informed consent will be obtained from the patients or their guardians.

Autonomic dysfunction in Parkinson's disease associated with common glucocerebrosidase gene mutations

Objectives: Non-motor symptoms have been described in Parkinson's disease (PD) associated with the glucocerebrosidase (GBA) gene mutations (1, 2). We aimed to evaluate whether autonomic function is altered in PD patients carriers of two common GBA mutations. We also assessed autonomic function in PD patients carrying GBA mutations and in non-carriers.

Brain-derived neurotrophic factor serum levels correlate with cognitive performance in Parkinson's disease patients with mild cognitive impairment.

Brain-derived neurotrophic factor (BDNF) is a trophic factor regulating cell survival and synaptic plasticity. Recent findings indicate that BDNF could be a potential regulatory factor for cognitive functioning in normal and/or neuropathological conditions. With regard to neurological disorders, recent data suggest that individuals with Parkinson’s disease (PD) may be affected by cognitive deficits and that they have altered BDNF production. Therefore, the hypothesis can be advanced that BDNF levels are associated with the cognitive state of these patients. With this in mind, the present study was aimed at exploring the relationship between BDNF serum levels and cognitive functioning in PD patients with mild cognitive impairment (MCI). Thirteen PD patients with MCI were included in the study. They were administered an extensive neuropsychological test battery that investigated executive, episodic memory, attention, visual-spatial and language domains. A single score was obtained for each cognitive domain by averaging z-scores on tests belonging to that specific domain. BDNF serum levels were measured by enzyme-linked immunoassay (ELISA). Pearson’s correlation analyses were performed between BDNF serum levels and cognitive performance. Results showed a significant positive correlation between BDNF serum levels and both attention (p < 0.05) and executive (p < 0.05) domains. Moreover, in the executive domain we found a significant correlation between BDNF levels and scores on tests assessing working memory and self-monitoring/inhibition. These preliminary data suggest that BDNF serum levels are associated with cognitive state in PD patients with MCI. Given the role of BDNF in regulating synaptic plasticity, the present findings give further support to the hypothesis that this trophic factor may be a potential biomarker for evaluating cognitive changes in PD and other neurological syndromes associated with cognitive decline.

Differential optimal dopamine levels for set-shifting and working memory in Parkinson's disease

Parkinson's disease (PD) is an important model for the role of dopamine in supporting human cognition. However, despite the uniformity of midbrain dopamine depletion only some patients experience cognitive impairment. The neurocognitive mechanisms of this heterogeneity remain unclear. A genetic polymorphism in the catechol O-methyltransferase (COMT) enzyme, predominantly thought to exert its cognitive effect through acting on prefrontal cortex (PFC) dopamine transmission, provides us with an experimental window onto dopamine’s role in cognitive performance in PD. In a large cohort of PD patients (n=372), we examined the association between COMT genotype and two tasks known to implicate prefrontal dopamine (spatial working memory and attentional set-shifting) and on a task less sensitive to prefrontal dopamine (paired associates learning). Consistent with the known neuroanatomical locus of its effects, differences between the COMT genotype groups were observed on dopamine-dependant tasks, but not the paired associates learning task. However, COMT genotype had differential effects on the two prefrontal dopamine tasks. Putative prefrontal dopamine levels influenced spatial working memory in an ‘Inverted-U’-shaped fashion, whereas a linear, dose-dependant pattern was observed for attentional set-shifting. Cumulatively, these results revise our understanding of when COMT genotype modulates cognitive functioning in PD patients by showing that the behavioural consequences of genetic variation vary according to task demands, presumably because set-shifting and working memory have different optimal dopamine levels.

Central cholinergic dysfunction could be associated with oropharyngeal dysphagia in early Parkinson's disease.

Dysphagia is an important issue in the prognosis of Parkinson's disease (PD). Although several studies have reported that oropharyngeal dysphagia may be associated with cognitive dysfunction, the exact relationship between cortical function and swallowing function in PD patients is unclear. Therefore, we investigated the association between an electrophysiological marker of central cholinergic function, which reflected cognitive function, and swallowing function, as measured by videofluoroscopic studies (VFSS). We enrolled 29 early PD patients. Using the Swallowing Disturbance Questionnaire (SDQ), we divided the enrolled patients into two groups: PD with dysphagia and PD without dysphagia. The videofluoroscopic dysphagia scale (VDS) was applied to explore the nature of the dysphagia. To assess central cholinergic dysfunction, short latency afferent inhibition (SAI) was evaluated. We analyzed the relationship between central cholinergic dysfunction and oropharyngeal dysphagia and investigated the characteristics of the dysphagia. The SAI values were significantly different between the two groups. The comparison of each VFSS component between the PD with dysphagia group and the PD without dysphagia group showed statistical significance for most of the oral phase components and for a single pharyngeal phase component. The total score on the VDS was higher in the PD with dysphagia group than in the PD without dysphagia group. The Mini-Mental State Examination and SAI values showed significant correlations with the total score of the oral phase components. According to binary logistic regression analysis, SAI value independently contributed to the presence of dysphagia in PD patients. Our findings suggest that cholinergic dysfunction is associated with dysphagia in early PD and that an abnormal SAI value is a good biomarker for predicting the risk of dysphagia in PD patients.

The motor-semantic meanings of verbs generated by Parkinson's disease patients on/off dopamine medication in a verbal fluency task

Abstract The human motor cortex is involved in the planning and execution of movements as well as in the processing of action language, and it is impaired in Parkinson's disease (PD) as a consequence of dopamine degeneration. The aim of this study is to understand the role of dopamine in the processing of action words by looking at PD patients with and without medication. A group of 23 healthy controls and 34 non-demented PD patients participated in an action verbal fluency task on and off dopamine medication. A repeated measures 2 × 2 ANOVA was conducted with dopamine (on/off) and type of verb (high and low specificity motor verbs) as independent variables and the number of words generated as a dependent variable. Our results showed that patients on dopamine medication produced a significantly greater number of high specificity motor verbs than low ones. In contrast, patients off dopamine medication generated a similar number of verbs with high and low motor specificity. MANOVA analyses showed a significantly lower production of verbs with high motor specificity on PD patients off medication compared to healthy controls. However, performance of PD patients in the on condition was similar to that found in healthy controls. In conclusion, the dopamine network from basal ganglia to brain motor areas might play a role in retrieving action verbs with specific semantic representations.

Betting on DBS: Effects of subthalamic nucleus deep brain stimulation on risk taking and decision making in patients with Parkinson's disease.

Concerns persist that deep brain stimulation (DBS) for Parkinson's disease (PD) increases impulsivity or induces excessive reward seeking. We report here the performance of PD patients with implanted subthalamic nucleus electrodes, with stimulation on and off, on 3 laboratory tasks of risk taking and decision making. They are compared with PD patients maintained on medication and healthy participants. In the Game of Dice Task, a test of "risky" decision making, PD patients with or without DBS made highest risk bets more often and ended up with less money than did healthy participants. There was a trend for DBS stimulation to ameliorate this effect. Deal or No-Deal is an "ambiguous" decision-making task that assessed preference for risk (holding on to one's briefcase) over a "sure thing" (accepting the banker's offer). Here, DBS patients were more conservative with stimulation on than with it off. They accepted smaller offers from the banker and won less money in the DBS-on condition. Overall, the 2 PD groups won less money than did healthy participants. The Framing Paradigm assessed willingness to gamble on a fixed (unambiguous) prize depending on whether the reward was "framed" as a loss or a gain. Nonsurgical PD patients tended to be more risk-averse than were healthy participants, whereas DBS patients were more willing to gamble for gains as well as losses both on and off stimulation. On risky decision-making tasks, DBS patients took more risks than did healthy participants, but stimulation may temper this tendency. In contrast, in an ambiguous-risk situation, DBS patients were more risk-averse (conservative) than were healthy participants, and this tendency was greatest with stimulation.

Combined auditory and visual cueing provided by eyeglasses influence gait performance in Parkinson Disease patients submitted to deep brain stimulation: a pilot study

Background: Auditory-visual cueing using portable cueing devices has been effective for gait training in rehabilitation programs with Parkinson patients. However, it is possible that some gait problems arise due to interference from chronic high frequency stimulation with the gait and balance neural networks in patients with Parkinson Disease. Thus, it should be useful to test whether advanced Parkinson Disease patients experiencing gait problems (despite the treatment with medication and high frequency deep brain stimulation) would benefit from therapy using cueing. Methods: Eyeglasses combining auditory-visual cueing were used with 18 patients with advanced Parkinson Disease and treated with medication and deep brain stimulation. Patients were assessed using the Dynamic Gait Index, Timed Up and Go and Six-Minute Walking Test and performance was measured with and without the cueing (with and without eyeglasses on). Results: One way ANOVA on the performance measures indicated that Dynamic Gait Index and Six-Minute Walking Test significantly improved in the cued condition. Since cueing was task specific, and Timed Up and Go includes subtasks such sitting and standing, the combined auditory-visual cueing did not improve performance on such tasks. Conversely, the combined cueing may have worked as distractors during these subtasks. Conclusion: Combined auditory-visual cueing provided by this wearable technology may have practical applicability in rehabilitation therapy. It provided additional benefits on gait in patients with advanced Parkinson Disease with deep brain stimulation in the subthalamic nucleus.

Cerebrospinal fluid biochemical studies in patients with Parkinson's disease: toward a potential search for biomarkers for this disease.

The blood-brain barrier supplies brain tissues with nutrients and filters certain compounds from the brain back to the bloodstream. In several neurodegenerative diseases, including Parkinson's disease (PD), there are disruptions of the blood-brain barrier. Cerebrospinal fluid (CSF) has been widely investigated in PD and in other parkinsonian syndromes with the aim of establishing useful biomarkers for an accurate differential diagnosis among these syndromes. This review article summarizes the studies reported on CSF levels of many potential biomarkers of PD. The most consistent findings are: (a) the possible role of CSF urate on the progression of the disease; (b) the possible relations of CSF total tau and phosphotau protein with the progression of PD and with the preservation of cognitive function in PD patients; (c) the possible value of CSF beta-amyloid 1-42 as a useful marker of further cognitive decline in PD patients, and (d) the potential usefulness of CSF neurofilament (NFL) protein levels in the differential diagnosis between PD and other parkinsonian syndromes. Future multicentric, longitudinal, prospective studies with long-term follow-up and neuropathological confirmation would be useful in establishing appropriate biomarkers for PD.

Effects of tDCS on executive function in Parkinson's disease

Non-motor symptoms in patients with Parkinson's disease (PD) are often poorly recognized, significantly impair quality of life and cause severe disability. Currently, there is limited evidence to guide treatment of associated psychiatric and cognitive problems. Non-invasive brain stimulation techniques have emerged as non-pharmacological alternatives to target cognitive symptoms without worsening motor function. In this context, we conducted a multicenter, sham controlled, double-blinded study to assess the immediate and long-term effects of ten consecutive sessions of transcranial direct current stimulation (tDCS) over the anode on the right dorsolateral prefrontal cortex (DLPFC) (n=5), left DLPFC (n=6) or sham (n=7). We assessed cognitive functions, depressive symptoms and motor functions in 18 PD patients at baseline, at the end of the 2-week stimulation sessions and at 1-month follow-up. Our results showed that active stimulation of both left and right DLPFC resulted in prolonged improvements in Trail Making Test B, an established test to measure executive function, compared to sham tDCS at the 1-month follow-up. These results suggest the existence of a beneficial long-term effect on executive functions in PD patients following active tDCS over the DLPFC. Thus, our findings encourage further investigation exploring tDCS as an adjuvant therapy for cognitive and behavioral treatment in PD.

A-27 * Differences in Cognitive Abilities among Fallers and Non-Fallers in Parkinson's Disease

Objective: Patients with Parkinson Disease (PD) are at increased risk of falls and those with cognitive impairment may be at even higher risk. This study examined cognitive performance in PD patients with and without a recent history of falls to better understand the relationship of cognition and falls in this population. Method: 131 patients (mean age = 61.94, SD = 9.99; mean education = 14.68, SD = 3.1; 85% Caucasian; 76% male) with advanced PD underwent neuropsychological evaluation as part of pre-surgical work up for deep brain stimulation surgery. According to chart review, subjects were grouped into categories (yes-no) based on their report of falls in the previous 6 months and compared on tasks of mental flexibility, processing speed, memory, language, attention, and visuospatial abilities. Results: 75 (57%) patients reported recent falls while 56 (43%) did not. Demographic variables did not differ between groups. Performances on cognitive measures ranged from low average to average for each group. The Recent Fall group performed significantly lower than the No Fall group on measures of visuospatial ability [Block Design: t(110) = 3.08, p = .003; Rey-Osterrieth Copy: t(114) = 2.05, p = .04], attention [Digit Span: t(125) = 2.55, p = .012], and mental flexibility [Trail Making Test B: t(123.63) = −2.37, p = .019]. Measures of simple processing speed, memory, and language did not significantly differ between groups. Conclusion(s): PD patients who reported recent falls had greater cognitive impairment than those without falls, particularly on measures of visuospatial abilities, attention, and mental flexibility. Examination of cognitive profiles in PD may help identify those at increased risk for falls.

Effects of combined MAO-B inhibitors and levodopa vs. monotherapy in Parkinson's disease.

Background: Prior studies report that monoamine oxidases inhibitors (MAO-I) when used as an adjunct to levodopa ameliorate motor symptoms in Parkinson’s disease (PD), but this was not tested in relation to cognitive or psychiatric measures.Objective: Here, we tested the effects of MAO-I as an adjunct to levodopa, in comparison to levodopa or dopamine (DA) agonists alone, on various cognitive, affective and quality of life measures.Methods: We studied three groups of subjects: healthy controls, PD patients on combined levodopa and MAO-I, and PD patients on levodopa or DA agonists only.Results: We found that compared to monotherapy, combined MAO-I and levodopa seemed to improve cognition, including probabilistic learning, working memory and executive functions. There were no differences between the different medication regimes on deterministic learning, attention or memory recall. It was also found that MAO-I as an adjunct to levodopa improves affective measures such as depression, apathy, anxiety and quality of life. Interestingly, this enhancing effect of combined levodopa and MAO-I was more pronounced in PD patients with severe akinesia, compared to patients with severe tremor.Conclusion: Our data are in agreement with (a) the Continuous Dopaminergic Stimulation (CDS) theory which states that continuous stimulation of the basal ganglia enhances motor, psychiatric and cognitive functions in PD patients; and/or (b) findings that MAO-I increase the bioavailability of monoamines that have beneficial effects on motor and behavioral dysfunction in PD.

A 2-year follow-up study on cognitive function of patients with Parkinson's disease

Objective To investigate the change and its related risk factors of cognitive function of patients with Parkinson's disease(PD). Methods The cognitive function of 70 idiopathic PD patients were assessed with Montreal cognitive assessment scale (MoCA), and other PD related neuropsychological test batteries were used to evaluate their movement symptoms and non-movement symptoms such as depression and anxiety.Patients’ personal information were collected at the same time. They were reassessed after 2 years. Results As the disease progressed, the MoCA score of the PD patients significantly reduced from (24.79±4.07) points to (21.69±5.22) points (P<0.01). Seven subdomains of MoCA were attenuated, and 5 of them reached statistical significance. Motor subtype was a main predictor of the outcome of the cognitive impairment in PD. Scores of MoCA total score, naming, language, abstract and directional domains reduced more notably in patients with postural instability gait difficulty(PIGD) than those in the tremor dominant(TD) patients. Conclusion Cognitive function of PD patients decreases obviously after 2 years. The patients' cognitive impairment should be identified and intervened as soon as possible, especially the patients with PIGD. Key words: Parkinson's disease; Cognitive impairment; Follow-up; MoCA

Large-scale resting state network correlates of cognitive impairment in Parkinson's disease and related dopaminergic deficits.

Cognitive impairment is a common non-motor feature of Parkinson's disease (PD). Understanding the neural mechanisms of this deficit is crucial for the development of efficient methods for treatment monitoring and augmentation of cognitive functions in PD patients. The current study aimed to investigate resting state fMRI correlates of cognitive impairment in PD from a large-scale network perspective, and to assess the impact of dopamine deficiency on these networks. Thirty PD patients with resting state fMRI were included from the Parkinson's Progression Marker Initiative (PPMI) database. Eighteen patients from this sample were also scanned with 123I-FP-CIT SPECT. A standardized neuropsychological battery was administered, evaluating verbal memory, visuospatial, and executive cognitive domains. Image preprocessing was performed using an SPM8-based workflow, obtaining time-series from 90 regions-of-interest (ROIs) defined from the AAL brain atlas. The Brain Connectivity Toolbox (BCT) was used to extract nodal strength from all ROIs, and modularity of the cognitive circuitry determined using the meta-analytical software Neurosynth. Brain-behavior covariance patterns between cognitive functions and nodal strength were estimated using Partial Least Squares. Extracted latent variable (LV) scores were matched with the performances in the three cognitive domains (memory, visuospatial, and executive) and striatal dopamine transporter binding ratios (SBR) using linear modeling. Finally, influence of nigrostriatal dopaminergic deficiency on the modularity of the “cognitive network” was analyzed. For the range of deficits studied, better executive performance was associated with increased dorsal fronto-parietal cortical processing and inhibited subcortical and primary sensory involvement. This profile was also characterized by a relative preservation of nigrostriatal dopaminergic function. The profile associated with better memory performance correlated with increased prefronto-limbic processing, and was not associated with presynaptic striatal dopamine uptake. SBR ratios were negatively correlated with modularity of the “cognitive network,” suggesting integrative effects of the preserved nigrostriatal dopamine system on this circuitry.

Subthalamic deep brain stimulation effects on odor identification in Parkinson's disease

Olfactory dysfunction is common in Parkinson's disease (PD) and it is one of the earliest non-motor symptoms. A few studies have suggested that deep brain stimulation of the subthalamic nucleus (STN-DBS) could improve olfactory function. Our aim was to evaluate the acute effect of bilateral STN-DBS on a commonly used smell test in PD patients. Fifteen PD patients who underwent bilateral STN-DBS and 15 controls were recruited. Patients and controls were tested for odor identification. No statistical differences were documented between ON and OFF STN-DBS acute stimulation concerning olfaction. Controls presented a better performance for olfactory identification than patients. Our exploratory study did not support that bilateral STN-DBS could have an acute effect on olfactory function in PD patients.

Cognitive functions in Parkinson's disease: Relation to disease severity and hallucination

ObjectiveWe wished to relate severity of Parkinson's disease (PD) with cognitive function in relation to cerebral blood flow (CBF). MethodsEighty-one consecutive PD patients were enrolled in this study. We used Mini-Mental State Examination (MMSE) and Wechsler Adult Intelligence Scale-Third edition (WAIS-III) to evaluate cognitive functions, and three-dimensional stereotactic ROI template (3DSRT) and Statistical Parametric Mapping (SPM) 8 to evaluate single photon emission CT (SPECT) recordings of regional CBF. ResultsThe mean MMSE score of PD patients was 27.4 ± 2.4. The scores of most patients were higher than 23/30. On the other hand, the mean Full-scale IQ of PD patients was 88.4 ± 17.3 in WAIS-III, which was lower than that of normal controls. In particular, visuospatial function score of most patients was lower. There was significant correlation between cognitive scores and Hoehn & Yahr stage and hallucinatory episodes. PD Patients with stage III and IV showed significant deterioration in cognitive functions compared to stage II patients. Analysis of CBF revealed relative reductions in perfusion in the cerebral cortex relative to that in normal control. SPM 8 showed that cognitive functions in PD patients were positively correlated with rCBF in the thalamus and cingulate gyrus. ConclusionsThis is the study to demonstrate the cognitive impairments in PD patients using WAIS-III. Visuospatial dysfunction might be caused by decrease in rCBF in the parietal and occipital lobes and dorsolateral prefrontal cortex. The severity of cognitive impairments in PD patients was correlated with disease severity and hallucinatory episodes.

Saccadic eye movements in Parkinson's disease.

This review focuses on saccadic eye movement research in Parkinson's disease (PD) patients. Results from various studies related to Parkinson disease and saccades have been discussed in terms of various saccadic parameters like latency, amplitude, velocity and gain. Neural circuitry of saccadic eye movements and cognitive processes and it's relation with altered saccadic performance in Parkinson disease has been discussed here. This article also covers various research paradigms commonly used to study saccades. Effects of medication on saccadic parameters in PD patients have also been discussed along with the effects of deep brain stimulation of subthalamic nucleus on saccadic performance in PD patients. Literature review was done using online Pubmed search engine and National Medical Library.

Plasma levels of soluble tumor necrosis factor receptors are associated with cognitive performance in Parkinson's disease

Inflammatory mechanisms have been implicated in a series of neuropsychiatric conditions, including behavioral disturbances, cognitive dysfunction, and affective disorders. Accumulating evidence also strongly suggests their involvement in the pathophysiology of Parkinson's disease (PD). This study aimed to evaluate plasma levels of inflammatory biomarkers, and their association with cognitive performance and other non-motor symptoms of PD. PD patients and control individuals were subjected to various psychometric tests, including the Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB), and Beck's Depression Inventory (BDI). Biomarker plasma levels were measured by enzyme-linked immunosorbent assay (ELISA). PD patients exhibited worse performance on MMSE and the programming task of FAB, and presented higher soluble tumor necrosis factor receptor (sTNFR) plasma levels than control individuals. Among PD patients, increased sTNFR1 and sTNFR2 concentrations were associated with poorer cognitive test scores. After multiple linear regression, sTNFR1 and education remained a significant predictor for FAB scores. Our data suggest that PD is associated with a proinflammatory profile, and sTNFRs are putative biomarkers of cognitive performance, with elevated sTNFR1 levels predicting poorer executive functioning in PD patients.

Magnetic resonance imaging and proton spectroscopy in the Huntington disease

Magnetic resonance imaging and proton spectroscopy in the Huntington disease