Parkinson's Disease Medication Research Articles

The Microbiome-Gut-Brain Axis, Nutrition and Parkinson’s Disease

Parkinson’s disease (PD) is a chronic progressive neurodegenerative disorder characterised by both motor and non-motor symptoms. While most PD medications currently available can improve motor symptoms, there is currently no treatment available to halt or slow down the progression of the disease. Recently, there has been increasing focus on environmental factors in the pathophysiology of PD and their possible neuroprotective effects. According to Braak’s hypothesis, an unknown pathogen in the gastrointestinal tract may initiate the production of pathogenic α synuclein, which would subsequently spread to the central nervous system. The microbiome-gut-brain axis may be implicated in this process, whereas nutrition can be one of the modifiable regulatory variables. A variety of foods and nutrients have been suggested as either risk or protective factors based on biological theories. Although epidemiological and experimental studies in animal models have shown their neuroprotective properties, their effectiveness was not confirmed in clinical trials. However, daily food intake comprises many nutrients that can interact and produce either a synergistic or antagonistic effect on the human body. Therefore, dietary patterns that include a certain set of nutrients have recently gained increased interest as potential modifiers of disease progression and alleviators of symptoms. This article reviews the current literature on the role of different nutritional factors and diets in the pathogenesis of PD and their possible neuroprotective and symptomatic effects.

Disease progression strikingly differs in research and real-world Parkinson’s populations

Characterization of Parkinson’s disease (PD) progression using real-world evidence could guide clinical trial design and identify subpopulations. Efforts to curate research populations, the increasing availability of real-world data, and advances in natural language processing, particularly large language models, allow for a more granular comparison of populations than previously possible. This study includes two research populations and two real-world data-derived (RWD) populations. The research populations are the Harvard Biomarkers Study (HBS, N = 935), a longitudinal biomarkers cohort study with in-person structured study visits; and Fox Insights (N = 36,660), an online self-survey-based research study of the Michael J. Fox Foundation. Real-world cohorts are the Optum Integrated Claims-electronic health records (N = 157,475), representing wide-scale linked medical and claims data and de-identified data from Mass General Brigham (MGB, N = 22,949), an academic hospital system. Structured, de-identified electronic health records data at MGB are supplemented using a manually validated natural language processing with a large language model to extract measurements of PD progression. Motor and cognitive progression scores change more rapidly in MGB than HBS (median survival until H&Y 3: 5.6 years vs. >10, p < 0.001; mini-mental state exam median decline 0.28 vs. 0.11, p < 0.001; and clinically recognized cognitive decline, p = 0.001). In real-world populations, patients are diagnosed more than eleven years later (RWD mean of 72.2 vs. research mean of 60.4, p < 0.001). After diagnosis, in real-world cohorts, treatment with PD medications has initiated an average of 2.3 years later (95% CI: [2.1–2.4]; p < 0.001). This study provides a detailed characterization of Parkinson’s progression in diverse populations. It delineates systemic divergences in the patient populations enrolled in research settings vs. patients in the real-world. These divergences are likely due to a combination of selection bias and real population differences, but exact attribution of the causes is challenging. This study emphasizes a need to utilize multiple data sources and to diligently consider potential biases when planning, choosing data sources, and performing downstream tasks and analyses.

Impact of Acute Dopamine Replacement on Cognitive Function in Parkinson's Disease.

PD causes striatal dopaminergic denervation in a posterior/dorsal to anterior/ventral gradient, leaving motor and associative cortico-striato-pallido-thalamic loops differentially susceptible to hyperdopaminergic effects with treatment. As the choice and titration of symptomatic PD medications are guided primarily by motor symptoms, it is important to understand their cognitive implications. To investigate the effects of acute dopaminergic medication administration on executive function in Parkinson's disease (PD). Participants with idiopathic PD were administered the oral Symbol Digit Modalities Test (SDMT; n = 181) and the Stroop test (n = 172) in the off-medication and "best on" medication states. ANCOVA was used to test for differences between off-medication and on-medication scores corrected for age and years of education. After administration of symptomatic medications, scores worsened on the SDMT (F = 11.70, P < 0.001, d = -0.13), improved on the Stroop color (F = 26.89, P < 0.001, d = 0.184), word (F = 6.25, P = 0.013, d = 0.09), and color-word (F = 13.22, P < 0.001, d = 0.16) test components, and the Stroop difference and ratio-based interference scores did not significantly change. Longer disease duration correlated with lower scores on the SDMT, Stroop color, word, and color-word scores; however, longer disease duration and higher levodopa-equivalents correlated with higher Stroop difference-based interference scores. Symptomatic medication differentially affects performance on two cognitive tests in PD. After acute treatment, core Stroop measures improved, Stroop interference was unchanged, and SDMT performance worsened, likely reflecting complex changes in processing speed and executive function related to acute treatment. When considering motor symptom therapies in PD, an individual's cognitive demands and expectations, especially regarding executive function, should be considered.

The Interplay of Mitochondrial Bioenergetics and Dopamine Agonists as an Effective Disease-Modifying Therapy for Parkinson's Disease.

Parkinson's disease (PD) is a progressive neurological ailment with a slower rate of advancement that is more common in older adults. The biggest risk factor for PD is getting older, and those over 60 have an exponentially higher incidence of this condition. The failure of the mitochondrial electron chain, changes in the dynamics of the mitochondria, and abnormalities in calcium and ion homeostasis are all symptoms of Parkinson's disease (PD). Increased mitochondrial reactive oxygen species (mROS) and an energy deficit are linked to these alterations. Levodopa (L-DOPA) is a medication that is typically used to treat most PD patients, but because of its negative effects, additional medications have been created utilizing L-DOPA as the parent molecule. Ergot and non-ergot derivatives make up most PD medications. PD is successfully managed with the use of dopamine agonists (DA). To get around the motor issues produced by L-DOPA, these dopamine derivatives can directly excite DA receptors in the postsynaptic membrane. In the past 10years, two non-ergoline DA with strong binding properties for the dopamine D2 receptor (D2R) and a preference for the dopamine D3 receptor (D3R) subtype, ropinirole, and pramipexole (PPx) have been developed for the treatment of PD. This review covers the most recent research on the efficacy and safety of non-ergot drugs like ropinirole and PPx as supplementary therapy to DOPA for the treatment of PD.

Oscillatory and non-oscillatory features of the magnetoencephalic sensorimotor rhythm in Parkinson’s disease

Parkinson’s disease (PD) is associated with changes in neural activity in the sensorimotor alpha and beta bands. Using magnetoencephalography (MEG), we investigated the role of spontaneous neuronal activity within the somatosensory cortex in a large cohort of early- to mid-stage PD patients (N = 78) on Parkinsonian medication and age- and sex-matched healthy controls (N = 60) using source reconstructed resting-state MEG. We quantified features of the time series data in terms of oscillatory alpha power and central alpha frequency, beta power and central beta frequency, and 1/f broadband characteristics using power spectral density. Furthermore, we characterised transient oscillatory burst events in the mu-beta band time-domain signals. We examined the relationship between these signal features and the patients’ disease state, symptom severity, age, sex, and cortical thickness. PD patients and healthy controls differed on PSD broadband characteristics, with PD patients showing a steeper 1/f exponential slope and higher 1/f offset. PD patients further showed a steeper age-related decrease in the burst rate. Out of all the signal features of the sensorimotor activity, the burst rate was associated with increased severity of bradykinesia, whereas the burst duration was associated with axial symptoms. Our study shows that general non-oscillatory features (broadband 1/f exponent and offset) of the sensorimotor signals are related to disease state and oscillatory burst rate scales with symptom severity in PD.

Prescribing medications for Parkinson's disease

Around 10 million people worldwide have Parkinson's disease and in the UK the estimated figure is 153000. The condition is characterised by motor symptoms including tremors, stiffness, slowness, balance problems and/or gait disorders, but sufferers can develop a wide range of associated psychological and physical problems. Treatment includes a combination of pharmacological and supportive physical therapies, supplied by a multidisciplinary team. As the condition progresses, medication regimens expand to include a combination of drug therapies. For those who do not benefit from pharmacological therapy deep brain stimulation surgery can be considered. Some people find that alternative therapies such as homeopathy, music and massage are useful additions to standard medical treatments. This article will give an overview of Parkinson's disease, including symptoms and diagnosis, and explore issues for consideration when prescribing common first-line Parkinson's medications.

Protocol for a randomized, placebo-controlled, double-blind phase IIa study of the safety, tolerability, and symptomatic efficacy of the ROCK-inhibitor Fasudil in patients with Parkinson's disease (ROCK-PD).

The Rho-kinase (ROCK) inhibitor Fasudil has shown symptomatic and disease-modifying effects in Parkinson's disease (PD) models in vitro and in vivo. In Japan, Fasudil has been approved for the treatment of subarachnoid haemorrhage since 1995 and shows a favourable safety profile. To investigate the safety, tolerability, and symptomatic efficacy of ROCK-inhibitor Fasudil in comparison to placebo in a randomized, national, multicenter, double-blind phase IIa study in patients with PD. We plan to include 75 patients with at least 'probable' PD (MDS criteria), Hoehn and Yahr stages 1-3, and age 30-80 years in 13 German study sites. Patients must be non-fluctuating and their response to PD medication must have been stable for 6 weeks. Patients will be randomly allocated to treatment with the oral investigational medicinal product (IMP) containing either Fasudil in two dosages, or placebo, for a total of 22 days. As primary analysis, non-inferiority of low/high dose of Fasudil on the combined endpoint consisting of occurrence of intolerance and/or treatment-related serious adverse events (SAEs) over 22 days will be assessed in a sequential order, starting with the lower dose. Secondary endpoints will include tolerability alone over 22 days and occurrence of treatment-related SAEs (SARs) over 22 and 50 days and will be compared on group level. Additional secondary endpoints include efficacy on motor and non-motor symptoms, measured on established scales, and will be assessed at several timepoints. Biomaterial will be collected to determine pharmacokinetics of Fasudil and its active metabolite, and to evaluate biomarkers of neurodegeneration. After positive evaluation by the competent authority and the ethics committee, patient recruitment started in the 3rd quarter of 2023. ROCK-PD is registered with Eudra-CT (2021-003879-34) and clinicaltrials.gov (NCT05931575). Results of this trial can pave way for conducting extended-duration studies assessing both symptomatic efficacy and disease-modifying properties of Fasudil.

Buspirone and Zolmitriptan Combination for Dyskinesia: A Randomized, Controlled, Crossover Study.

Preclinical evidence suggests that co-administration of the 5-HT1A agonist buspirone and the 5-HT1B/1D agonist zolmitriptan act synergistically to reduce dyskinesia to a greater extent than that achieved by either drug alone. Assess the therapeutic potential of a fixed-dose buspirone and zolmitriptan combination in Parkinson's disease (PD) patients with levodopa-induced dyskinesia. Single-center, randomized, placebo-controlled, two-way crossover study (NCT02439203) of a fixed-dose buspirone/zolmitriptan regimen (10/1.25 mg three times a day) in 30 patients with PD experiencing at least moderately disabling peak-effect dyskinesia. Seven days of treatment with buspirone/zolmitriptan added to levodopa significantly reduced dyskinesia as assessed by Abnormal Involuntary Movement Scale scores versus placebo (mean treatment effect vs. placebo: -4.2 [-6.1, -2.3]) without significantly worsening Unified Parkinson's Disease Rating Scale (UPDRS) Part III (ON) scores (mean treatment effect vs. placebo: 0.6 [-0.1, 1.3]). No serious adverse events were reported. In this proof-of-concept study, addition of buspirone/zolmitriptan to the patients' PD medication regimen significantly reduced dyskinesia severity without worsening motor function. © 2024 International Parkinson and Movement Disorder Society.

Management of Impulse Control and Related Disorders in Parkinson's Disease: An Expert Consensus.

Impulse-control and related behavioral disorders (ICBDs) significantly impact the lives of Parkinson's disease (PD) patients and caregivers, with lasting consequences if undiagnosed and untreated. While ICBD pathophysiology and risk factors are well-studied, a standardized severity definition and treatment evidence remain elusive. This work aimed to establish international expert consensus on ICBD treatment strategies. To comprehensively address diverse treatment availabilities, experts from various continents were included. From 2021 to 2023, global movement disorders specialists engaged in a Delphi process. A core expert group initiated surveys, involving a larger panel in three iterations, leading to refined severity definitions and treatment pathways. Experts achieved consensus on defining ICBD severity, emphasizing regular PD patient screenings for early detection. General treatment recommendations focused on continuous monitoring, collaboration with significant others, and seeking specialist advice for legal or financial challenges. For mild to severe ICBDs, gradual reduction in dopamine agonists was endorsed, followed by reductions in other PD medications. Second-line treatment strategies included diverse approaches like reversing the last medication change, cognitive behavior therapy, subthalamic nucleus deep brain stimulation, and specific medications like quetiapine, clozapine, and antidepressants. The panel reached consensus on distinct treatment pathways for punding and dopamine dysregulation syndrome, formulating therapy recommendations. Comprehensive discussions addressed management strategies for the exacerbation of either motor or non-motor symptoms following the proposed treatments. The consensus offers in-depth insights into ICBD management, presenting clear severity criteria and expert consensus treatment recommendations. The study highlights the critical need for further research to enhance ICBD management. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Parkinson’s disease medications in hospital: A retrospective audit of prescribing and administration errors

Background: Managing Parkinson’s disease (PD) medications in the acute hospital setting is complex. Mismanagement of PD medications such as inaccurate medication administration time and prescribing errors is common which can lead to the worsening of PD symptoms. Aim and Objectives: The aim of the study was to identify the extent of PD medication prescribing and administration errors in adult inpatients and pharmacists’ impact across a Victorian metropolitan hospital. Materials and Methods: A retrospective review analyzed a sample of 30 patients admitted between January and April 2022. PD medication orders (PDMO) and medication administration records (MAR) were reviewed; charting errors were identified based on reconciliation of PDMO with the pharmacist-led best-possible medication history (p-BPMH). Administration errors were identified through a review of MAR and PDMO charted time or p-BPMH documented administration time for each PD medication. Results: A total of 60 PDMO and 469 administration instances were reviewed. About 83.3% (50) of PDMOs had at least one instance of delay or omission in administration. 45.0% (27) of PDMO charting errors led to delays or omissions in administration. The timing of administration was the most common charting error accounting for 18.3% (11) of PDMOs. Documentation of p-BPMH within 24 h of admission led to a reduction of charting errors (52.9% vs. 76.9%, respectively). PD medications that were administered on time compared to p-BPMH documented time and PDMO charted time were 48.6% (228/469) and 53.7% (252/469), respectively. Conclusion: This study identified a high degree of PDMO charting and administration errors for patients with PD. Strategies to improve PD medication management are warranted.

A Qualitative Study on Perspectives of Parkinson's Disease Medications: Insights from Patient Focus Groups.

Medication is an important component of the management of Parkinson's disease (PD), yet few studies investigate factors that inform medication decision-making from the perspective of those who use these therapies. This qualitative study aimed to better understand the medication experiences and perspectives of people with PD (PwPD). Thirty-two PwPD recruited from five large movement disorder clinics from five US states participated in 1-hour on-line focus groups in 2022. Thematic analysis was used to analyze the data. Four primary themes (subthemes in parentheses) emerged concerning PD medications: (1) medication effectiveness (uncertainty, inconsistent effects, adjusting expectations); (2) medication burden (morning doses, timing challenges, constant reminder); (3) side effects (toleration, treatment, confusion with disease symptoms); and (4) preferences/requests (important attributes, therapy advancement). This study identified four core dimensions associated with PD medications from the perspective of PwPD. Results indicate the need for enhanced communication between providers and patients regarding PD medication to reduce the uncertainties and burden associated with PD medication regimens and promote better health outcomes for PwPD.

Enhanced Parkinson's gait, reduced fall risk, and improved cognitive function through multimodal rehabilitation combined with rivastigmine treatment.

This study aimed to examine the effects of combined rehabilitation and rivastigmine treatment on patients with Parkinson's disease (PD). Gait parameters were assessed using the Gibbon Gait Analyzer in fifteen patients. Baseline gait data and cognitive assessments were collected. Each patient underwent external counterpulsation therapy, transcranial magnetic stimulation therapy, and exercise therapy for one hour per day, five days a week for three weeks. Post-intervention, gait and cognitive data were re-evaluated. Alongside their standard PD medications, all participants were administered rivastigmine throughout the study period. The intervention significantly enhanced motor function in the single-task test, evidenced by marked improvements in gait metrics such as stride width and walking speed, and a substantial reduction in fall risk. Cognitive function, assessed by mini-mental state examination and Montreal cognitive assessment, showed an improvement trend after the three-week intervention. Improvements in dual-task walking function were observed, although these changes did not reach statistical significance. Multimodal exercise training combined with rivastigmine treatment significantly improves certain gait parameters in the single-task test, enhances balance, and reduces the risk of falling in patients with PD. Cognitive function also demonstrated improvement.

Druggable targets for Parkinson’s disease: An overview

One of the most crippling conditions affecting the brain and its progression causes neurodegeneration is Parkinson's disease (PD). The disease is characterized by accumulation of α-synuclein having Lewy bodies and further loss of dopaminergic neuron in substantia nigra, ultimately causing reduced ability of voluntary movements. The main symptoms of PD include tremor, bradykinesia and rigidity. Though, various symptomatic treatment options are available targeting both motor and non-motor signs but none of them claim to improve quality of life of PD patients. Recent studies indicated the identification of targets for PD such as glutamate receptors, α-Syn, c-Abl, molecular chaperones, GPR109Aand metals have been and some drugs targeting these targets are already there in market. The effectiveness of these pharmacological targets in treating PD has to be confirmed by a larger-scale trial. Effective PD therapy may also target pathways mediated by autophagy. Gene therapy and gene editing all have strong therapeutic effects and provide fresh PD medication targets. Additionally, the therapy of PD is more effective when a multi-target response is used. Further, research should be conducted to validate and explore new targets for treatment ofPD.

Custom order entry for Parkinson's medications in the hospital improves timely administration: an analysis of over 31,000 medication doses.

Patients with Parkinson's disease (PD) are at increased risk for hospital acquired complications. Deviations from home medication schedules and delays in administration are major contributing factors. We had previously developed a protocol to ensure adherence to home medication schedules using "custom" ordering. In this study we are assessing the impact this order type may have on reducing delays in PD medication administration in the hospital. We reviewed 31,404 orders placed for PD medications from January 2, 2016 to April 30 2021. We evaluated the orders to determine if they were placed in a Custom format or using a default non-custom order entry. We further evaluated all orders to determine if there was a relationship with the order type and timely administration of medications. We compared medications that were administered within 1 min, 15 min, 30 min and 60 min of due times across custom orders vs. non-custom default orders. We also evaluated the relationship between ordering providers and type of orders placed as well as hospital unit and type of orders placed. 14,204 (45.23%) orders were placed using a custom schedule and 17,200 (54.77%) orders were placed using non-custom defaults. The custom group showed a significantly lower median delay of 3.06 minutes compared to the non-custom group (p<.001). Custom orders had a significantly more recent median date than non-custom default orders (2019-10-07 vs. 2018-01-06, p<0.001). In additional analyses, medication administration delays were significantly improved for custom orders compared to non-custom orders, with likelihoods 1.64 times higher within 1 minute, 1.40 times higher within 15 minutes, and 1.33 times higher within 30 minutes of the due time (p<0.001 for all comparisons). This is the largest study to date examining the effects of order entry type on timely administration of PD medications in the hospital. Orders placed using a custom schedule may help reduce delays in administration of PD medications.

Risk of Parkinson's disease-related death in cancer survivors: A population-based study in Japan

BackgroundThe risk of Parkinson's disease (PD)-related death in patients with cancer largely unexplored. MethodsWe analyzed data from the Neoplasms ANd other causes of DEath (NANDE) study, which investigates the causes of death in patients with cancer in Japan. Standardized mortality ratios (SMRs) were calculated to compare the risk of PD-related deaths in patients with cancer to that of the general population. Poisson regression models were employed to estimate the relative risk of PD-related death in the subgroups. ResultsThe cohort included 548,485 patients with cancer, yielding 2,047,398 person-years at risk from 1995 to 2013. During the study period, 242,250 patients died and 145 deaths were attributable to PD. The SMR for PD-related death was 2.34 (95% confidence interval [CI]: 1.99–2.75). Patients who were diagnosed with cancer before 70 years of age had a high SMR (>5) for PD-related deaths. The SMR of patients with mouth-to-stomach cancers (lip, oral cavity, pharynx, esophagus, and stomach cancers) was 3.72 (95% CI: 2.84–4.86), while that of those with other cancers was 1.93 (95% CI: 1.57–2.37). The multivariate Poisson regression model revealed that patients with mouth-to-stomach cancers were more likely to die of PD than those without (relative risk 2.07, 95 % CI; 1.46–2.93). ConclusionsPatients with cancer are at a high risk of PD-related death; particularly, mouth-to-stomach cancers and potentially obstructing medication for PD are attributable to a high mortality risk. Careful management, including adequate PD treatment, would benefit cancer survivors with PD and reduce the risk of PD-related death.

Association between dietary intake and risk of Parkinson's disease: cross-sectional analysis of survey data from NHANES 2007-2016.

While dietary factors have shown an association with Parkinson's disease (PD), the available data remains a subject of ongoing debate and controversy. We sought to evaluate potential relationships between dietary consumption of nutrients and micronutrients and risk of PD in a large sample. Cross-sectional data were retrospectively analyzed for 10,651 adults aged 40-80 years that had been collected in the US between 2007 and 2016 as a component of the nationwide National Health and Nutrition Examination Survey. Aspects of dietary intake were compared between those who reported having specific PD medication regimens or not when they completed the survey, and potential associations between diet and risk of PD were explored using binomial logistic regression. We employed Propensity Score Matching (PSM) to minimize the impact of potential confounding factors, thus enhancing the reliability of the results. Additionally, subgroup analysis based on gender and age was conducted to investigate these relationships. Higher dietary intake of iron was linked to greater PD risk [odds ratio (OR) 1.065, 95% confidence interval (CI) 1.019-1.114, p = 0.006], whereas risk decreased with higher intake of vitamin K (OR 0.999, 95% CI 0.998-1.000, p = 0.024) or vitamin C (OR 0.998, 95% CI 0.996-0.999, p = 0.039). Even after applying PSM, the connection between dietary iron intake and dietary vitamin C intake with PD risk remained substantial. Subgroup analysis results revealed a significant positive association between dietary intake of iron from food and the PD risk, which was evident among individuals under 60 years of age and among males. The intake of micronutrients can influence risk of PD, which should be verified and explored further in prospective samples with other dietary habits and ethnic backgrounds.

Changes in Anticholinergic Burden in Parkinson’s Disease After Deep Brain Stimulation

ObjectiveThis study aimed to evaluate the effect of deep brain stimulation (DBS) on anticholinergic burden in Parkinson’s disease (PD) and the association of anticholinergic burden with cognition. Materials and MethodsA retrospective chart review in patients with PD who underwent bilateral subthalamic nucleus (STN) or globus pallidus internus (GPi) DBS from 2010 to 2020 reviewed medications with anticholinergic burden at baseline, six months, and one year (N = 216) after surgery. The cumulative anticholinergic burden at each visit was calculated using the Anticholinergic Risk Scale (ARS). ResultsARS scores were significantly lower for patients six months and one year after surgery than at baseline (z = 6.58, p < 0.0001; z = 6.99, p < 0.0001). Change in ARS scores at both six months and one year were driven by down-titration of PD medications (z = 9.35, p < 0.0001; z = 8.61, p < 0.0001), rather than changes in pain, psychiatric, or urinary medications with anticholinergic effects. There was no significant difference in change in ARS scores at one year between targets (t = 0.41, p = 0.68). In addition, there was no significant association between anticholinergic burden and cognitive performance. ConclusionGPi and STN DBS are associated with decreased anticholinergic burden due to PD medications in the first year after surgery.

Microbiota-mediated effects of Parkinson's disease medications on Parkinsonian non-motor symptoms in male transgenic mice.

Parkinson's disease (PD) is characterized by motor symptoms and a loss of dopaminergic neurons, as well as a variety of non-motor symptoms, including constipation, depression, and anxiety. Recently, evidence has also accumulated for a link between gut microbiota and PD. Most PD patients are on dopamine replacement therapy, primarily a combination of L-DOPA and carbidopa; however, the effect of these medications on the microbiota and non-motor symptoms in PD is still unclear. In this study, we explored the effects of chronic oral treatment with L-DOPA plus carbidopa (LDCD) on the gut microbiota and non-motor symptoms in males of a transgenic mouse model of PD (dbl-PAC-Tg(SNCAA53T);Snca-/-). To further test whether the effects of these PD medications were mediated by the gut microbiota, oral antibiotic treatment (Abx; vancomycin and neomycin) was included both with and without concurrent LDCD treatment. Post-treatment, the gastrointestinal, motor, and behavioral phenotypes were profiled, and fecal, ileal, and jejunal samples were analyzed for gut microbiota composition by 16S sequencing. LDCD treatment was found to improve symptoms of constipation and depression in this model, concurrent with increases in Turicibacter abundance in the ileum. Abx treatment worsened the symptoms of constipation, possibly through decreased levels of short-chain fatty acids and disrupted gut barrier function. LDCD + Abx treatment showed an interaction effect on behavioral symptoms that was also associated with ileal Turicibacter levels. This study demonstrates that, in a mouse model, PD medications and antibiotics affect PD-related non-motor symptoms potentially via the gut microbiota.IMPORTANCEThe motor symptoms of Parkinson's disease (PD) are caused by a loss of dopamine-producing neurons and are commonly treated with dopamine replacement therapy (L-DOPA plus carbidopa). PD has also been associated with altered gut microbiota composition. However, the effects of these PD medications on PD-related non-motor symptoms and the gut microbiota have not been well characterized. This study uses a transgenic mouse model of PD to help resolve medication-induced microbiota alterations from those that are potentially disease relevant within a PD context, and explores how long-term treatment may interact with the gut microbiota to impact non-motor symptoms.

Improving Parkinson's Medicine Administration in Hospitals: The Impact of an Out-of-Hours Drug Box.

Background Parkinson'sdisease (PD) is a progressive neurodegenerative condition characterised by the loss of dopaminergic neurons and the presence of Lewy bodies. PD medications, notably Levodopa, are critical in controlling patients' symptoms and improving their quality of life. These medications are time-critical, and a delay in administration can have a negative impact on a patient's mobility, quality of life and symptoms. Objective The objective of this quality improvement project (QIP) was to (1) determine the occurrence and underlying factors contributing to delays in PD medication administration at Huddersfield Royal Infirmary and (2) evaluate the impact of subsequent interventions in improving the administration of time-critical PD medications. Methods A total of 20 patients were recruited from Ward 5, a care of the elderly ward, at Huddersfield Royal Infirmary for the entire duration of this QIP; 10 in the pre-intervention phase and 10 for the post-intervention phase one month following the implementation of three interventions: 'Parkinson's Drug Box', ward-based teaching and a hospital-wide screensaver reminder. Datawascollected from the electronic patient record (EPR) to determine and compare the following measures before and after the interventions: the percentage of PD medications administered within the 30-minuterecommendedwindow, the admission-to-medication reconciliation time, scheduled-to-actual dose administration time, and factors causing delays. Results Following the implementation of three interventions, the percentage of patients receiving PD medications within the recommended 30-minute window doubled, increasing from 10% to 20%. Moreover, the average delay in patients receiving their initial PD medication dose decreased from 7.8 hours to 3.7 hours. The percentage of patients experiencing medication delays due to stock shortages also dropped from 50% to 10%. Conclusions Earlier medicines reconciliation and the availability of time-critical drugs out of hours are both key factors in helping to ensure PD medication is administered on time in hospitals. Staff education and a 'Parkinson's Drug Box' are two relatively simple measures that have resulted in improved outcomes for Parkinson's inpatients.

Safety comparisons among monoamine oxidase inhibitors against Parkinson’s disease using FDA adverse event reporting system

Monoamine oxidase B (MAO-B) inhibitors are used to control Parkinson’s disease (PD). Selegiline, rasagiline, and safinamide are widely used as MAO-B inhibitors worldwide. Although these drugs inhibit MAO-B, there are pharmacological and chemical differences, such as the inhibitory activity, the non-dopaminergic properties in safinamide, and the amphetamine-like structure in selegiline. MAO-B inhibitors may differ in adverse events (AEs). However, differences in actual practical clinics are not fully investigated. A retrospective study was conducted using FAERS, the largest database of spontaneous adverse events. AE signals for MAO-B inhibitors, including selegiline, rasagiline, and safinamide, were detected using the reporting odds ratio method and compared. Hypocomplementemia, hepatic cyst, hepatic function abnormal, liver disorder and cholangitis were detected for selegiline as drug-specific signals. The amphetamine effect was not confirmed for any of the three MAO-B inhibitors. The tyramine reaction was detected as an AE signal only for rasagiline. Moreover, the REM sleep behavior disorder was not detected as an AE signal for safinamide, suggesting that non-dopaminergic effects might be beneficial. Considering the differences in AEs for MAO-B inhibitors will assist with the appropriate PD medication.