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1.
Gastrointestinal Dysfunction in Parkinson's Disease.
Safarpour, D, Sharzehi, K, Pfeiffer, RF
Drugs. 2022;(2):169-197
Abstract
There has been exponential growth in the awareness and understanding of gastrointestinal (GI) dysfunction in Parkinson's disease (PD) over the past 3 decades. The clinical features of GI dysfunction in PD have been clearly identified and innovative research has demonstrated the presence of pathology within the enteric nervous system (ENS) in individuals with PD, leading to suggestions that the GI system may be ground zero for the genesis and the portal of entry of PD pathology, which then ascends via the vagus nerve to the central nervous system (CNS). This theory, as well as the more recent recognition of the association of PD with dysbiosis within the gut microbiota, has been the object of intense study and scrutiny. Since most PD medications are absorbed through the GI system, the need for better understanding of changes within the GI tract that may potentially affect the pattern of response to medications has become evident. In this review, current knowledge of the pathophysiology of changes within the GI tract and the gut microbiome of individuals with PD, including changes that occur with progression of the disease, will be addressed. We focus on common clinical GI problems in PD that can arise from different segments of the GI tract. Relevant diagnostic evaluations and treatment options for each of these problems will be reviewed.
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2.
Minimum Alveolar Concentration-Awake of Sevoflurane is Decreased in Patients with Parkinson's Disease: An Up-and-Down Sequential Allocation Trial.
Yang, C, Kang, F, Meng, W, Dong, M, Huang, X, Wang, S, Zuo, Z, Li, J
Clinical interventions in aging. 2021;:129-137
Abstract
BACKGROUND An increasing number of patients with Parkinson's disease (PD) will have surgery under general anesthesia. A previous study demonstrated that propofol requirement for inducing unconsciousness in PD patients was lower than that in non-PD (NPD) patients. However, the requirement of inhaled anesthetics in PD patients has not been clarified. The aim of this study was to investigate the minimum alveolar concentration-awake (MACawake) of sevoflurane in patients with PD compared to NPD patients. PATIENTS AND METHODS The current study is an up-and-down sequential allocation trial. The initial end-tidal concentration of sevoflurane (CETsevo) was estimated by the response of the previous patient to verbal command using the Dixon's up-and-down method. The first patient in each group received CETsevo at 1%, and the step size between patients was 0.2%. RESULTS Forty-one patients including 20 PD patients and 21 NPD patients were enrolled. Patients' characteristics and arterial blood gas parameters (except blood sodium) were comparable between two groups. The MACawake of sevoflurane estimated by the Dixon's up-and-down method in PD patients (0.47% ± 0.08% [Mean ± S.D.]) was significantly lower than that in NDP patients (0.64% ± 0.10%) (P=0.003). The estimated difference in means was 0.17% (95% CI, 0.10-0.24%). Probit analysis showed that the MACawake of sevoflurane in PD and NPD patients was 0.49% (95% CI, 0.42-0.57%) and 0.67% (95% CI, 0.59-0.76%), respectively. The relative median potency was 0.73 (95% CI, 0.38-0.94). CONCLUSION Patients with PD exhibit a significantly lower MACawake of sevoflurane compared with NPD patients. Clinicians should avoid an overdose of sevoflurane in patients with PD. TRIAL REGISTRATION Registered at ChiCTR1900026956.
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3.
Imaging the Substantia Nigra in Parkinson Disease and Other Parkinsonian Syndromes.
Bae, YJ, Kim, JM, Sohn, CH, Choi, JH, Choi, BS, Song, YS, Nam, Y, Cho, SJ, Jeon, B, Kim, JH
Radiology. 2021;(2):260-278
Abstract
Parkinson disease is characterized by dopaminergic cell loss in the substantia nigra of the midbrain. There are various imaging markers for Parkinson disease. Recent advances in MRI have enabled elucidation of the underlying pathophysiologic changes in the nigral structure. This has contributed to accurate and early diagnosis and has improved disease progression monitoring. This article aims to review recent developments in nigral imaging for Parkinson disease and other parkinsonian syndromes, including nigrosome imaging, neuromelanin imaging, quantitative iron mapping, and diffusion-tensor imaging. In particular, this article examines nigrosome imaging using 7-T MRI and 3-T susceptibility-weighted imaging. Finally, this article discusses volumetry and its clinical importance related to symptom manifestation. This review will improve understanding of recent advancements in nigral imaging of Parkinson disease. Published under a CC BY 4.0 license.
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4.
Effect of dietary vitamins C and E on the risk of Parkinson's disease: A meta-analysis.
Chang, MC, Kwak, SG, Kwak, S
Clinical nutrition (Edinburgh, Scotland). 2021;(6):3922-3930
Abstract
BACKGROUND & AIMS A neuroprotective effect of dietary vitamins C and E on Parkinson's disease (PD) has been suggested, however, several human studies have reported controversial results. Therefore, we conducted a meta-analysis on the effect of vitamins C and E on the risk of Parkinson's disease. METHODS A comprehensive literature search was conducted using the PubMed, EMBASE, Cochrane Library, and SCOPUS databases for studies published up to January 23, 2021. We included studies that reported (1) intake of vitamins C and E using validated methods; (2) assessment of odds ratio (OR), relative risk (RR), or hazard ratio (HR); and (3) patients with PD identified by a neurologist, hospital records, or death certificates. The Comprehensive Meta-Analysis Software 2 program was used for statistical analyses of the pooled data. RESULTS A total of 12 studies (four prospective cohort and eight case-control studies) were included in our meta-analysis. No significant risk reduction was observed in the high vitamin C intake group compared to low intake group. On the other hand, the high vitamin E intake group showed a significantly lower risk of development of PD than the low intake group (pooled OR = 0.799. 95% CI = 0.721 to 0.885). CONCLUSIONS We conclude that vitamin E might have a protective effect against PD, while vitamin C does not seem to have such an effect. However, the exact mechanism of the transport and regulation of vitamin E in the CNS remains elusive, and further studies would be necessary in this field.
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5.
Role of luteolin in overcoming Parkinson's disease.
Siddique, YH
BioFactors (Oxford, England). 2021;(2):198-206
Abstract
Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting elderly people (>60 years old) worldwide. There is no permanent cure for the disease but the symptomatic relief can be obtained by using dopamine agonists besides L-dopa therapy. The longer use of the drugs is associated with several side effects. Hence, the researchers have made a considerable attention toward the development of neuroprotective agents from plants. A number of phytochemicals have been demonstrated for their protective effects in various in vitro, in vivo, and clinical studies. In this context, luteolin, a flavone which is present in fruits and vegetables has been attributed to a number of pharmacological properties including neuroprotective. The present review demonstrates the bioavailability, oral absorption, and mechanism of action against PD.
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6.
Diet Quality and Risk of Parkinson's Disease: A Prospective Study and Meta-Analysis.
Liu, YH, Jensen, GL, Na, M, Mitchell, DC, Wood, GC, Still, CD, Gao, X
Journal of Parkinson's disease. 2021;(1):337-347
Abstract
BACKGROUND Several dietary components have been shown to be neuroprotective against risk of neurodegeneration. However, limited observational studies have examined the role of overall diet quality on risk of Parkinson's disease. OBJECTIVES We examined the associations between diet quality and risk of Parkinson's disease in a prospective cohort study and meta-analysis. METHODS Included in the cohort study were 3,653 participants (1,519 men and 2,134 women; mean age: 81.5 years) in the Geisinger Rural Aging Study longitudinal cohort in Pennsylvania. Diet quality was assessed using a validated dietary screening tool containing 25 food- and behavior-specific questions in 2009. Potential Parkinson's cases were identified using electronic health records based on ICD9 (332.*), ICD10 (G20), and Parkinson-related treatments. Hazard ratios (HRs) and 95% confidence intervals (CIs) across diet quality tertiles were calculated using Cox proportional hazards models after adjusting for potential confounders. We further performed a meta-analysis by pooling our study with four published papers on this topic. Random-effects model was utilized to calculate the pooled risk ratios and 95% CIs. RESULTS During a mean of 6.94 years of follow-up, 47 incident Parkinson's cases were documented. Having high diet quality at baseline was associated with lower Parkinson's disease risk (adjusted HR for the highest vs the lowest diet quality tertile = 0.39; 95% CI: 0.17, 0.89; p-trend = 0.02). The meta-analysis including 140,617 individuals also showed that adherence to high diet quality or a healthy dietary pattern was associated with lower risk of Parkinson's disease (pooled risk ratio = 0.64; 95% CI: 0.49, 0.83). CONCLUSION Having high diet quality or a healthy dietary pattern was associated with lower future risk of Parkinson's disease.
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7.
Design of a virtual longitudinal observational study in Parkinson's disease (AT-HOME PD).
Schneider, RB, Omberg, L, Macklin, EA, Daeschler, M, Bataille, L, Anthwal, S, Myers, TL, Baloga, E, Duquette, S, Snyder, P, et al
Annals of clinical and translational neurology. 2021;(2):308-320
Abstract
OBJECTIVE The expanding power and accessibility of personal technology provide an opportunity to reduce burdens and costs of traditional clinical site-centric therapeutic trials in Parkinson's disease and generate novel insights. The value of this approach has never been more evident than during the current COVID-19 pandemic. We sought to (1) establish and implement the infrastructure for longitudinal, virtual follow-up of clinical trial participants, (2) compare changes in smartphone-based assessments, online patient-reported outcomes, and remote expert assessments, and (3) explore novel digital markers of Parkinson's disease disability and progression. METHODS Participants from two recently completed phase III clinical trials of inosine and isradipine enrolled in Assessing Tele-Health Outcomes in Multiyear Extensions of Parkinson's Disease trials (AT-HOME PD), a two-year virtual cohort study. After providing electronic informed consent, individuals complete annual video visits with a movement disorder specialist, smartphone-based assessments of motor function and socialization, and patient-reported outcomes online. RESULTS From the two clinical trials, 226 individuals from 42 states in the United States and Canada enrolled. Of these, 181 (80%) have successfully downloaded the study's smartphone application and 161 (71%) have completed patient-reported outcomes on the online platform. INTERPRETATION It is feasible to conduct a large-scale, international virtual observational study following the completion of participation in brick-and-mortar clinical trials in Parkinson's disease. This study, which brings research to participants, will compare established clinical endpoints with novel digital biomarkers and thereby inform the longitudinal follow-up of clinical trial participants and design of future clinical trials.
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8.
Adopting a multidisciplinary telemedicine intervention for fall prevention in Parkinson's disease. Protocol for a longitudinal, randomized clinical trial.
Cubo, E, Garcia-Bustillo, A, Arnaiz-Gonzalez, A, Ramirez-Sanz, JM, Garrido-Labrador, JL, Valiñas, F, Allende, M, Gonzalez-Bernal, JJ, Gonzalez-Santos, J, Diez-Pastor, JF, et al
PloS one. 2021;(12):e0260889
Abstract
BACKGROUND Approximately 40-70% of people with Parkinson's disease (PD) fall each year, causing decreased activity levels and quality of life. Current fall-prevention strategies include the use of pharmacological and non-pharmacological therapies. To increase the accessibility of this vulnerable population, we developed a multidisciplinary telemedicine program using an Information and Communication Technology (ICT) platform. We hypothesized that the risk for falling in PD would decrease among participants receiving a multidisciplinary telemedicine intervention program added to standard office-based neurological care. OBJECTIVE To determine the feasibility and cost-effectiveness of a multidisciplinary telemedicine intervention to decrease the incidence of falls in patients with PD. METHODS Ongoing, longitudinal, randomized, single-blinded, case-control, clinical trial. We will include 76 non-demented patients with idiopathic PD with a high risk of falling and limited access to multidisciplinary care. The intervention group (n = 38) will receive multidisciplinary remote care in addition to standard medical care, and the control group (n = 38) standard medical care only. Nutrition, sarcopenia and frailty status, motor, non-motor symptoms, health-related quality of life, caregiver burden, falls, balance and gait disturbances, direct and non-medical costs will be assessed using validated rating scales. RESULTS This study will provide a cost-effectiveness assessment of multidisciplinary telemedicine intervention for fall reduction in PD, in addition to standard neurological medical care. CONCLUSION In this challenging initiative, we will determine whether a multidisciplinary telemedicine intervention program can reduce falls, as an alternative intervention option for PD patients with restricted access to multidisciplinary care. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT04694443.
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9.
Ambroxol increases glucocerebrosidase (GCase) activity and restores GCase translocation in primary patient-derived macrophages in Gaucher disease and Parkinsonism.
Kopytova, AE, Rychkov, GN, Nikolaev, MA, Baydakova, GV, Cheblokov, AA, Senkevich, KA, Bogdanova, DA, Bolshakova, OI, Miliukhina, IV, Bezrukikh, VA, et al
Parkinsonism & related disorders. 2021;:112-121
Abstract
Mutations in the glucocerebrosidase gene (GBA) encoding the lysosomal enzyme glucocerebrosidase (GCase) cause Gaucher disease (GD) and are the most commonly known genetic risk factor for Parkinson disease (PD). Ambroxol is one of the most effective pharmacological chaperones of GCase. Fourteen GD patients, six PD patients with mutations in the GBA gene (GBA-PD), and thirty controls were enrolled. GCase activity and hexosylsphingosine (HexSph) concentration were measured in dried blood and macrophage spots using liquid chromatography coupled with tandem mass spectrometry. The effect of ambroxol on GCase translocation to lysosomes was assessed using confocal microscopy. The results showed that ambroxol treatment significantly increased GCase activity in cultured macrophages derived from patient blood monocytic cell (PBMC) of GD (by 3.3-fold) and GBA-PD patients (by 3.5-fold) compared to untreated cells (p < 0.0001 and p < 0.0001, respectively) four days after cultivation. Ambroxol treatment significantly reduced HexSph concentration in GD (by 2.1-fold) and GBA-PD patients (by 1.6-fold) (p < 0.0001 and p < 0.0001, respectively). GD macrophage treatment resulted in increased GCase level and increased enzyme colocalization with the lysosomal marker LAMP2. The possible binding modes of ambroxol to mutant GCase carrying N370S amino acid substitution at pH 4.7 were examined using molecular docking and molecular dynamics simulations. The ambroxol position characterized by minimal binding free energy was observed in close vicinity to the residue, at position 370. Taken together, these data showed that PBMC-derived macrophages could be used for assessing ambroxol therapy response for GD patients and also for GBA-PD patients.
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10.
Assessment of real life eating difficulties in Parkinson's disease patients by measuring plate to mouth movement elongation with inertial sensors.
Kyritsis, K, Fagerberg, P, Ioakimidis, I, Chaudhuri, KR, Reichmann, H, Klingelhoefer, L, Delopoulos, A
Scientific reports. 2021;(1):1632
Abstract
Parkinson's disease (PD) is a neurodegenerative disorder with both motor and non-motor symptoms. Despite the progressive nature of PD, early diagnosis, tracking the disease's natural history and measuring the drug response are factors that play a major role in determining the quality of life of the affected individual. Apart from the common motor symptoms, i.e., tremor at rest, rigidity and bradykinesia, studies suggest that PD is associated with disturbances in eating behavior and energy intake. Specifically, PD is associated with drug-induced impulsive eating disorders such as binge eating, appetite-related non-motor issues such as weight loss and/or gain as well as dysphagia-factors that correlate with difficulties in completing day-to-day eating-related tasks. In this work we introduce Plate-to-Mouth (PtM), an indicator that relates with the time spent for the hand operating the utensil to transfer a quantity of food from the plate into the mouth during the course of a meal. We propose a two-step approach towards the objective calculation of PtM. Initially, we use the 3D acceleration and orientation velocity signals from an off-the-shelf smartwatch to detect the bite moments and upwards wrist micromovements that occur during a meal session. Afterwards, we process the upwards hand micromovements that appear prior to every detected bite during the meal in order to estimate the bite's PtM duration. Finally, we use a density-based scheme to estimate the PtM durations distribution and form the in-meal eating behavior profile of the subject. In the results section, we provide validation for every step of the process independently, as well as showcase our findings using a total of three datasets, one collected in a controlled clinical setting using standardized meals (with a total of 28 meal sessions from 7 Healthy Controls (HC) and 21 PD patients) and two collected in-the-wild under free living conditions (37 meals from 4 HC/10 PD patients and 629 meals from 3 HC/3 PD patients, respectively). Experimental results reveal an Area Under the Curve (AUC) of 0.748 for the clinical dataset and 0.775/1.000 for the in-the-wild datasets towards the classification of in-meal eating behavior profiles to the PD or HC group. This is the first work that attempts to use wearable Inertial Measurement Unit (IMU) sensor data, collected both in clinical and in-the-wild settings, towards the extraction of an objective eating behavior indicator for PD.