Effects In Parkinson's Disease Research Articles

Curcumin neuroprotective effects in Parkinson disease during pregnancy

BackgroundYoung onset Parkinson disease (YOPD) accounts for about 10% of PD patients, with the onset of symptoms between the ages of 21 and 40. At this age, the probability of pregnancy is high and there is a concern that the disease affects the fetuses. Therefore, in the present study, the effects of rotenone-induced PD on female mice as well as their fetuses and curcumin supplementation on the cerebral tissue of both female mice and their resulted fetuses were studied. MethodsThe rotenone was injected subcutaneously to induce PD model of female mice. The different concentrations of curcumin were administrated every day i.p. for 3 weeks and the rotarod test was done on day 1 and 19. Cell viability was measured by MTT test and apoptosis and necrosis of cells were evaluate using flow cytometry technique. After primer design, the expressions of bax, bcl-2, miR-211 and circRNA 0001518 genes were measured using RT-PCR technique. ResultsCurcumin administration were improved cerebral cell viability of both female PD mice and resulted fetuses by preventing cell apoptosis and necrosis. bax, miR-211 and circRNA 0001518 were downregulated and bcl-2 overexpressed in cerebral neurons of PD mice and their fetuses. ConclusionPD induction in mice affects their fetal brain, and curcumin can partially reduce the negative effects of PD on fetal brain cells by overexpressing bcl-2 and decreasing bax expression genes.

Co-Administration of Vitamins B12 and D During Pregnancy Have Strong Neuroprotective Effects in Parkinson Disease.

Parkinson's disease (PD) is a common disease whose pathophysiological mechanism is not well understood. Recent research studies have shown that PD patients have low serum levels of vitamins B12 and D. Therefore, in this study, the effects of supplementation with vitamins B12 and D on PD female mice as well as their fetuses were studied. After preparation of female mice and induction of Parkinson's by rotenone administration for 19days, rotarod test was used to confirm PD induction. During this time, supplementations with vitamins B12 and D were performed. On day 19, after confirmation of PD induction, half of the mice were killed and the other half were allowed to mate with males. Viability was measured by the MTT method, and apoptosis and necrosis of cerebellar neurons were measured by flow cytometry. The RT-PCR technique was used to evaluate the relative expressions of the bax, bcl-2, miR-211, and circRNA 0,001,518 genes. Data analysis was performed by the GraphPad Prism V.8 software. Co-administration of vitamins B12 and D resulted in highest viability percentage and greatest reduction in apoptosis and necrosis of cerebellar neurons in the female mice as well as their fetuses compared to the PD females. A decrease in the relative expression of the bax and miR-211 genes and an increase in bcl-2 expression were observed in the cerebellar tissue of PD mice receiving both vitamins. Vitamins B12 and D have neuroprotective effects on PD conditions. Therefore, co-administration of these two vitamins is recommended in PD patients during pregnancy.

Management of Hypertension and Blood Pressure Dysregulation in Patients with Parkinson's Disease-a Systematic Review.

The aim of this review article was to summarize the cardiovascular and blood pressure profile regarding Parkinson disease patients and to provide an update on the recent advancements in the field of the diagnosis and management of blood pressure abnormalities in these patients. Our goal was to guide physicians to avoid pitfalls in current practice while treating patients with Parkinson disease and blood pressure abnormalities. For this purpose, we searched bibliographic databases (PubMed, Google Scholar) for all publications published on blood pressure effects in Parkinson disease until May 2020. Furthermore, we highlight some thoughts and potential perspectives for the next possible steps in the field. Blood pressure dysregulation in patients with Parkinson's disease has several implications in clinical practice and presents an ongoing concern. Compared with chronic essential hypertension, the syndrome of combined neurogenic orthostatic hypotension and supine hypertension in Parkinson's disease has received little attention. If left untreated, hypertension may lead to cardiovascular disease whereas hypotension may lead to fall-related complications, with tremendous impact on the quality of life of affected individuals. The effect of blood Epressure control and the risk of death from cardiovascular disease in Parkinson disease are largely unexplored. Blood pressure abnormalities in Parkinson disease present bidirectional relationship and the rationale for treating and controlling hypertension in persons with Parkinson disease and concurrent neurogenic orthostatic hypotension and/or supine hypertension is compelling. Further research is warranted in order to clarify the mechanisms, clinical implications, and potential reversibility of compromised cardiovascular function, in persons with Parkinson disease.

Parkinson's disease effect on autonomic modulation: an analysis using geometric indices.

Parkinson's disease (PD) produces autonomic changes, indicating lower parasympathetic modulation and global variability, but these changes need further studying regarding geometric methods. To investigate the autonomic modulation in individuals with PD using heart rate variability (HRV) indices obtained through geometric methods. This is a cross-sectional study that assessed 50 individuals, split into two groups: PD group (PDG; n=26; 75.36±5.21 years) and control group (CG; n=24; 75.36±5.21 years). We evaluated the autonomic modulation by measuring the heart rate beat-to-beat for 30 min with the individual in supine rest using a heart rate monitor and assessed geometric indices (RRtri, TINN, SD1, SD2, SD1/SD2 ratio, and qualitative analysis of the Poincaré plot). Significant reductions were found in RRtri, TINN, SD1, and SD2 indices among PDG compared to CG. Regarding the SD1/SD2 ratio, no significant changes were detected between the groups. The Poincaré plot demonstrated that individuals with PD had lower beat-to-beat dispersion in RR intervals, in addition to greater long-term dispersion of RR intervals compared to CG. The results suggest a reduction in the parasympathetic autonomic modulation and global variability in individuals with PD compared to controls, regardless of sex, age, and body mass index.

Changes in Step Characteristics Over a Known Outdoor Surface Transition: The Effect of Parkinson Disease.

The factors that contribute to the difficulties persons with Parkinson Disease (PwPD) have when negotiating transitions in walking surfaces are not completely known. The authors investigated if PwPD adjusted their step characteristics when negotiating a familiar outdoor surface transition between synthetic concrete and synthetic turf. Force plate and motion capture data were collected for 10 participants with mild to moderate Parkinson disease and 5 healthy older control participants ambulating bidirectionally across the transition between synthetic concrete and synthetic turf. Between groups, PwPD had a significantly higher minimum toe clearance (P = .007) for both directions of travel compared with the healthy control group. Within groups, PwPD significantly increased their hip (P < .001) and ankle (P = .016) range of motion walking from concrete to turf, while the healthy control participants significantly increased their minimum toe clearance (P = .013), margin of stability (P = .019), hip (P < .001) and ankle (P = .038) range of motion, and step length (P < .001). Walking from turf to concrete, both the Parkinson disease group (P = .014) and the healthy control group (P < .001) increased their knee range of motion. Both groups adjusted their step characteristics when negotiating known surface transitions, indicating that surface transitions result in step changes regardless of health status. However, PwPD exhibited overcompensations, particularly in their minimum toe clearance.

Cognitive health care system and its application in pill‐rolling assessment

AbstractDirectional antennas have been extensively used in wireless sensor networks (WSNs) for various applications. This work presents the application of a four‐beam patch antenna as a sensor node to assess the pill‐rolling effect in Parkinson disease. The four‐beam patch is small in size, highly directive, and can suppress the multipath fading encountered in indoor settings that adversely affects the measurements. The pill‐rolling effect refers to tremors in the hands, particularly in the forefinger and the thumb, which the patient involuntary rubs together. The core idea is to develop a low‐cost framework that effectively evaluates the particular movement disorder to assist doctors or clinicians in carrying out an objective assessment using the S‐band sensing technique leveraging small wireless devices operating at 2.4 GHz. The proposed framework uses the perturbations in amplitude and phase information to efficiently identify tremors and nontremors experienced in the fingers. The unique imprint induced by each body motion is used to determine the particular body motion disorder. The performance of the framework is evaluated using the support vector machine algorithm. The results indicate that the framework provides high classification accuracy (higher than 90%).

Emergent Functional Network Effects in Parkinson Disease.

Emergent Functional Network Effects in Parkinson Disease.

ESM-CT: a precise method for localization of DBS electrodes in CT images

BackgroundDeep brain stimulation (DBS) of the subthalamic nucleus produces variable effects in Parkinson disease. Variation may result from different electrode positions relative to target. Thus, precise electrode localization is crucial when investigating DBS effects. New methodWe developed a semi-automated method, Electrode Shaft Modeling in CT images (ESM-CT) to reconstruct DBS lead trajectories and contact locations. We evaluated methodological sensitivity to operator-dependent steps, robustness to image resampling, and test-retest replicability. ESM-CT was applied in 56 patients to study electrode position change (and relation to time between scans, postoperative subdural air volume, and head tilt during acquisition) between images acquired immediately post-implantation (DBS-CT) and months later (DEL-CT). ResultsElectrode tip localization was robust to image resampling and replicable to within ∼ 0.2 mm on test-retest comparisons. Systematic electrode displacement occurred rostral-ventral-lateral between DBS-CT and DEL-CT scans. Head angle was a major explanatory factor (p < 0.001,Pearson’s r = 0.46, both sides) and volume of subdural air weakly predicted electrode displacement (p = 0.02,r = 0.29:p = 0.1,r = 0.25 for left:right). Modeled shaft curvature was slightly greater in DEL-CT. Magnitude of displacement and degree of curvature were independent of elapsed time between scans. Comparison with Existing MethodsComparison of ESM-CT against two existing methods revealed systematic differences in one coordinate (1 ± 0.3 mm,p < 0.001) for one method and in three coordinates for another method (x:0.1 ± 0.1 mm, y:0.4 ± 0.2 mm, z:0.4 ± 0.2 mm, p < 10−10). Within-method coordinate variability across participants is similar. ConclusionWe describe a robust and precise method for CT DBS contact localization. Application revealed that acquisition head angle significantly impacts electrode position. DBS localization schemes should account for head angle.

O 076 - Electromyography for determination of muscle response: Effects of Parkinson disease

Nowadays muscle response constitutes one of the important topic in the field of medicine and rehabilitation. For rehabilitation purposes muscle response time can be analyzed by using electromyography. With the development of ADAS system, muscle response time can be determined as a part of driver reaction time for purposes of traffic analyzes and assessments. The aim of this work is to analyze muscle response within two investigated groups of drivers, i.e drivers suffering by Parkinson disease (PD drivers) and drivers without Parkinson disease (NON-PD drivers). Muscle response was found out for both drivers’ groups and it was studied how it affects the overall reaction time of driver.

Emergent Functional Network Effects in Parkinson Disease.

The hallmark pathology underlying Parkinson disease (PD) is progressive synucleinopathy, beginning in caudal brainstem that later spreads rostrally. However, the primarily subcortical pathology fails to account for the wide spectrum of clinical manifestations in PD. To reconcile these observations, resting-state functional connectivity (FC) can be used to examine dysfunction across distributed brain networks. We measured FC in a large, single-site study of nondemented PD (N = 107; OFF medications) and healthy controls (N = 46) incorporating rigorous quality control measures and comprehensive sampling of cortical, subcortical and cerebellar regions. We employed novel statistical approaches to determine group differences across the entire connectome, at the network-level, and for select brain regions. Group differences respected well-characterized network delineations producing a striking "block-wise" pattern of network-to-network effects. Surprisingly, these results demonstrate that the greatest FC differences involve sensorimotor, thalamic, and cerebellar networks, with notably smaller striatal effects. Split-half replication demonstrates the robustness of these results. Finally, block-wise FC correlations with behavior suggest that FC disruptions may contribute to clinical manifestations in PD. Overall, these results indicate a concerted breakdown of functional network interactions, remote from primary pathophysiology, and suggest that FC deficits in PD are related to emergent network-level phenomena rather than focal pathology.

Effects of Parkinson disease and antiparkinson medication on central adaptations to repetitive grasping

Cortical activity during motor task performance is attenuated in individuals with Parkinson disease (PD) relative to age-matched adults without PD, and this activity is enhanced with antiparkinson medication. It remains unclear, however, whether the relative change in cortical activity over the duration of the task, i.e., central adaptation, is affected individuals with PD, and if so, whether medication corrects for any unique behaviors. Movement-related cortical potentials (MRCPs) were recorded from scalp electrode sites Cz and C1 during 150 repetitive handgrip contractions at 70% of maximal voluntary contraction, in individuals with PD (n = 10) both ON and OFF of their PD medication, and neurologically normal age- and sex-matched controls (n = 10). Repetitions were divided into two Blocks (Block 1 and 2: repetitions 1–60 and 91–150, respectively), and the composite MRCP slopes were calculated during periods representing movement initiation (−2 s to movement onset) and execution (movement onset to 1 s). No significant interactions were noted for either comparison (PD OFF vs. control; PD OFF vs. PD ON), irrespective of electrode site (Cz or C1) or movement period (initiation or execution). Despite similar MRCP slopes and task performance, PD OFF endorsed greater perceived exertion during task performance than controls. In the present study, we observed attenuated task-related cortical activity among individuals with PD OFF relative to controls, but a similar relative adaptive response to a fatiguing task. Additionally, although antiparkinson medication enhanced cortical activity (PD OFF vs. PD ON), central adaptation was similar.

Speech Motor Sequence Learning: Effect of Parkinson Disease and Normal Aging on Dual-Task Performance.

Everyday communication is carried out concurrently with other tasks. Therefore, determining how dual tasks interfere with newly learned speech motor skills can offer insight into the cognitive mechanisms underlying speech motor learning in Parkinson disease (PD). The current investigation examines a recently learned speech motor sequence under dual-task conditions. A previously learned sequence of 6 monosyllabic nonwords was examined using a dual-task paradigm. Participants repeated the sequence while concurrently performing a visuomotor task, and performance on both tasks was measured in single- and dual-task conditions. The younger adult group exhibited little to no dual-task interference on the accuracy and duration of the sequence. The older adult group exhibited variability in dual-task costs, with the group as a whole exhibiting an intermediate, though significant, amount of dual-task interference. The PD group exhibited the largest degree of bidirectional dual-task interference among all the groups. These data suggest that PD affects the later stages of speech motor learning, as the dual-task condition interfered with production of the recently learned sequence beyond the effect of normal aging. Because the basal ganglia is critical for the later stages of motor sequence learning, the observed deficits may result from the underlying neural dysfunction associated with PD.

Informed Consent for Deep Brain Stimulation: Increasing Transparency for Psychiatric Neurosurgery Patients

What should a patient know before he or she allows a physician to control a part of the patient's brain? While this sounds like a philosophical thought experiment designed to twist the intuition, it is meant to address the ramifications of a widely used clinical therapy called deep brain stimulation (DBS). Deep brain stimulation is a therapy, approved by the Food and Drug Administration (FDA), to relieve the symptoms of movement disorders, specifically dystonia [1], essential tremor [2], and the effects of Parkinson disease [3], and is currently being studied for a wide variety of psychiatric illnesses [4]. DBS is complicated to employ, requiring the coordinated effort of a team of health care professionals, chiefly a neurosurgeon, a neurologist, and a neuropsychologist.

The effect of Parkinson disease on voice onset time: Temporal differences in voicing contrast

Parkinson disease (PD) affects the basal ganglia, which is involved with the selection, sequencing, and implementation of movement. Investigations suggest an extension of deficits to the speech motor and linguistic systems. Previous studies examining voice onset time (VOT) suggest that VOTs are neither systematically delayed nor systematically advanced in PD as compared to controls. The VOTs for voiced and voiceless stops are expected to differ for both individuals with PD and controls. However, inefficiencies in the sequencing and implementation of the voicing gesture may result in a smaller difference between VOT values of voiced and voiceless cognates. The current study examined VOT in individuals with PD and controls. Participants produced a corpus of stimuli to evaluate VOT using the carrier phrase “CVp again.” The four corner vowels and all stop consonants were used. Speech was recorded and VOT values were manually measured for every utterance. Overall VOTs were significantly shorter for voiceless stops across all speakers. However, the average difference between the voice and voiceless cognates produced by the PD group was significantly smaller than the control group. These data suggest that the PD group exhibited less temporal distinction between voiced and voiceless stops.

Effects of subthalamic deep brain stimulation on blink abnormalities of 6-OHDA lesioned rats.

Parkinson's disease (PD) patients and the 6-hydroxydopamine (6-OHDA) lesioned rat model share blink abnormalities. In view of the evolutionarily conserved organization of blinking, characterization of blink reflex circuits in rodents may elucidate the neural mechanisms of PD reflex abnormalities. We examine the extent of this shared pattern of blink abnormalities by measuring blink reflex excitability, blink reflex plasticity, and spontaneous blinking in 6-OHDA lesioned rats. We also investigate whether 130-Hz subthalamic nucleus deep brain stimulation (STN DBS) affects blink abnormalities, as it does in PD patients. Like PD patients, 6-OHDA-lesioned rats exhibit reflex blink hyperexcitability, impaired blink plasticity, and a reduced spontaneous blink rate. At 130 Hz, but not 16 Hz, STN DBS eliminates reflex blink hyperexcitability and restores both short- and long-term blink plasticity. Replicating its lack of effect in PD patients, 130-Hz STN DBS does not reinstate a normal temporal pattern or rate to spontaneous blinking in 6-OHDA lesioned rats. These data show that the 6-OHDA lesioned rat is an ideal model system for investigating the neural bases of reflex abnormalities in PD and highlight the complexity of PD's effects on motor control, by showing that dopamine depletion does not affect all blink systems via the same neural mechanisms.

Diabetes mellitus is independently associated with more severe cognitive impairment in Parkinson disease.

There is increasing interest in interactions between metabolic syndromes and neurodegeneration. Diabetes mellitus (DM) contributes to cognitive impairment in the elderly but its effect in Parkinson disease (PD) is not well studied. To investigate effects of comorbid DM on cognition in PD independent from PD-specific primary neurodegenerations. Cross-sectional study. Patients with PD (n=148); age 65.6±7.4 years, Hoehn and Yahr stage 2.4±0.6, with (n=15) and without (n=133) comorbid type II DM, underwent [(11)C]methyl-4-piperidinyl propionate (PMP) acetylcholinesterase (AChE) PET imaging to assess cortical cholinergic denervation, [(11)C]dihydrotetrabenazine (DTBZ) PET imaging to assess nigrostriatal denervation, and neuropsychological assessments. A global cognitive Z-score was calculated based on normative data. Analysis of covariance was performed to determine cognitive differences between subjects with and without DM while controlling for nigrostriatal denervation, cortical cholinergic denervation, levodopa equivalent dose and education covariates. There were no significant differences in age, gender, Hoehn and Yahr stage or duration of disease between diabetic and non-diabetic PD subjects. There was a non-significant trend toward lower years of education in the diabetic PD subjects compared with non-diabetic PD subjects. PD diabetics had significantly lower mean (±SD) global cognitive Z-scores (-0.98±1.01) compared to the non-diabetics (-0.36±0.91; F=7.78, P=0.006) when controlling for covariate effects of education, striatal dopaminergic denervation, and cortical cholinergic denervation (total model F=8.39, P<0.0001). Diabetes mellitus is independently associated with more severe cognitive impairment in PD likely through mechanisms other than disease-specific neurodegenerations.

Advanced Parkinson's disease effect on goal-directed and habitual processes involved in visuomotor associative learning

The present behavioral study re-addresses the question of habit learning in Parkinson's disease (PD). Patients were early onset, non-demented, dopa-responsive, candidates for surgical treatment, similar to those we found earlier as suffering greater dopamine depletion in the putamen than in the caudate nucleus. The task was the same conditional associative learning task as that used previously in monkeys and healthy humans to unveil the striatum involvement in habit learning. Sixteen patients and 20 age- and education-matched healthy control subjects learned sets of 3 visuo-motor associations between complex patterns and joystick displacements during two testing sessions separated by a few hours. We distinguished errors preceding vs. following the first correct response to compare patients' performance during the earliest phase of learning dominated by goal-directed actions with that observed later on, when responses start to become habitual. The disease significantly retarded both learning phases, especially in patients under 60 years of age. However, only the late phase deficit was disease severity-dependent and persisted on the second testing session. These findings provide the first corroboration in Parkinson patients of two ideas well-established in the animal literature. The first is the idea that associating visual stimuli to motor acts is a form of habit learning that engages the striatum. It is confirmed here by the global impairment in visuo-motor learning induced by PD. The second idea is that goal-directed behaviors are predominantly caudate-dependent whereas habitual responses are primarily putamen-dependent. At the advanced PD stages tested here, dopamine depletion is greater in the putamen than in the caudate nucleus. Accordingly, the late phase of learning corresponding to the emergence of habitual responses was more vulnerable to the disease than the early phase dominated by goal-directed actions.

Parkinson Disease's Effect on Mortality Eclipses Heart Disease and Other Common Illnesses of the Elderly

Parkinson Disease's Effect on Mortality Eclipses Heart Disease and Other Common Illnesses of the Elderly

SNCA and MAPT genes: Independent and joint effects in Parkinson disease in the Italian population

BackgroundSignificant efforts have been focused on investigating the contribution of common variants to Parkinson disease (PD) risk. Several independent GWAS and metanalysis studies have shown a genome-wide significant association of single nucleotide polymorphisms (SNPs) in the α-synuclein (SNCA) and microtubule-associated protein tau (MAPT) regions. Here we investigated the role of SNCA and MAPT as PD susceptibility genes in a large Italian population of 904 patients and 891 controls. An evaluation of gene–gene and gene-environment interactions in association with PD was also attempted. MethodsThe SNCA Rep1 microsatellite was genotyped by a fluorescent PCR assay, whereas the SNPlex genotyping system was used to genotype 12 additional markers across the SNCA gene, and 2 SNPs tagging the risk MAPT H1 haplotype. ResultsSingle-marker analysis demonstrated nominal evidence of association for: i) the 261-bp-long allele of Rep1; ii) 7 SNPs in the SNCA region (top SNP: rs356186, P = 3.08 × 10−04, intron 4); iii) both SNPs identifying the MAPT H1 haplotype (P = 4.63 × 10−04 and P = 4.23 × 10−04 for rs1800547 and rs9468, respectively). Moreover, we found a highly significant protective haplotype spanning ∼83 kb from intron 4 to the 3′ end of SNCA (P = 1.29 × 10−05). ConclusionsOur findings strongly confirm SNCA and MAPT as major PD susceptibility genes for idiopathic PD in the Italian population. Interaction analyses did not evidence either epistatic effects between the two loci or gene-environment interactions.

Does vigorous exercise have a neuroprotective effect in Parkinson disease?

Parkinson disease (PD) is progressive, with dementia and medication-refractory motor problems common reasons for late-stage nursing-home placement. Increasing evidence suggests that ongoing vigorous exercise/physical fitness may favorably influence this progression. Parkinsonian animal models reveal exercise-related protection from dopaminergic neurotoxins, apparently mediated by brain neurotrophic factors and neuroplasticity (predicted from in vitro studies). Similarly, exercise consistently improves cognition in animals, also linked to enhanced neuroplasticity and increased neurotrophic factor expression. In these animal models, immobilization has the opposite effect. Brain-derived neurotrophic factor (BDNF) may mediate at least some of this exercise benefit. In humans, exercise increases serum BDNF, and this is known to cross the blood-brain barrier. PD risk in humans is significantly reduced by midlife exercise, documented in large prospective studies. No studies have addressed whether exercise influences dementia risk in PD, but exercised patients with PD improve cognitive scores. Among seniors in general, exercise or physical fitness has not only been associated with better cognitive scores, but midlife exercise significantly reduces the later risk of both dementia and mild cognitive impairment. Finally, numerous studies in seniors with and without dementia have reported increased cerebral gray matter volumes associated with physical fitness or exercise. These findings have several implications for PD clinicians. (1) Ongoing vigorous exercise and physical fitness should be highly encouraged. (2) PD physical therapy programs should include structured, graduated fitness instruction and guidance for deconditioned patients with PD. (3) Levodopa and other forms of dopamine replenishment therapy should be utilized to achieve the maximum capability and motivation for patients to maintain fitness.