scholarly journals Gut bacterial tyrosine decarboxylase gene abundance associates with disease duration, medication exposure, and gastrointestinal symptoms in a longitudinal cohort of Parkinson's disease patients.

Author(s):  
Sebastiaan P van Kessel ◽  
Petri Auvinen ◽  
Filip Scheperjans ◽  
Sahar El Aidy

Gut microbiota influences the clinical response of a wide variety of orally administered drugs. However, the underlying mechanisms by which drug-microbiota interactions occur are still obscure. Previously, we reported that tyrosine decarboxylating (TDC) bacteria may restrict the levels of levodopa reaching the circulation in patients with Parkinson's disease (PD). We observed a significant positive association between disease duration and the abundance of the bacterial tdc-gene. The question arises whether increased exposure to anti-PD medication could affect the abundance of bacterial TDC, to ultimately impact drug efficacy. To this end, we investigated the potential association between anti-PD drug exposure and bacterial tdc-gene abundance over a time period of two years in a longitudinal cohort of PD patients and healthy controls. Our data reveal significant associations between tdc-gene abundance, anti-PD medication, and gastrointestinal symptoms and warrants further research on the effect of anti-PD medication on microbial changes and gastrointestinal-function.

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Sebastiaan P. van Kessel ◽  
Petri Auvinen ◽  
Filip Scheperjans ◽  
Sahar El Aidy

AbstractGut microbiota influences the clinical response of a wide variety of orally administered drugs. However, the underlying mechanisms through which drug–microbiota interactions occur are still obscure. Previously, we reported that tyrosine decarboxylating (TDC) bacteria may restrict the levels of levodopa reaching circulation in patients with Parkinson’s disease (PD). We observed a significant positive association between disease duration and the abundance of the bacterial tdc-gene. The question arises whether increased exposure to anti-PD medication could affect the abundance of bacterial TDC, to ultimately impact drug efficacy. To this end, we investigated the potential association between anti-PD drug exposure and bacterial tdc-gene abundance over a period of 2 years in a longitudinal cohort of PD patients and healthy controls. Our data reveal significant associations between tdc-gene abundance, several anti-PD medications, including entacapone, rasagiline, pramipexole, and ropinirole but not levodopa, and gastrointestinal symptoms, warranting further research on the effect of anti-PD medication on microbial changes and gastrointestinal function.


2019 ◽  
Vol 34 (6) ◽  
pp. 963-963
Author(s):  
M Nakhla ◽  
J Filoteo ◽  
C Pluim ◽  
A Cabrera Tuazon ◽  
N Whiteley ◽  
...  

Abstract Individuals with Parkinson’s disease (PD) frequently experience cognitive and functional difficulties, even in the absence of dementia. However, there is limited understanding of the relationship between specific cognitive abilities and functional skills, such as financial management, in these individuals. Understanding the potential impact of cognition on financial skills in non-demented PD will help discern neuropsychological predictors of real-world performance. 171 non-demented PD patients were administered a comprehensive neuropsychological battery including a measure of financial skills (University of California San Diego Performance-Based Skills Assessment; UPSA). Composite scores were created for five cognitive domains: [1] memory, [2] language, [3] executive function, [4] attention, and [5] visuospatial function. Bivariate correlations and hierarchical regressions were conducted to evaluate the associations between UPSA and cognition. There was a significant, positive association between financial skills performance and executive function, memory, attention, and language (r = .165 – .265; all p’s < .04), but not visuospatial function (r = .071, p = .37). Controlling for demographic factors, multiple linear regressions revealed that higher levels of executive function significantly predicted better UPSA performance (B = .323, p < .01). Findings suggest that several cognitive abilities are associated with adequate financial management, but that executive function, above and beyond other cognitive abilities, is the best predictor of this particular skill in non-demented PD. The assessment of cognition – specifically executive function – may be useful in identifying PD patients who may be at risk for financial management difficulties. Furthermore, findings have implications for the implementation of executive function-based interventions for the enhancement of everyday financial tasks in non-demented PD.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Stefano Romano ◽  
George M. Savva ◽  
Janis R. Bedarf ◽  
Ian G. Charles ◽  
Falk Hildebrand ◽  
...  

AbstractThe gut microbiota is emerging as an important modulator of neurodegenerative diseases, and accumulating evidence has linked gut microbes to Parkinson’s disease (PD) symptomatology and pathophysiology. PD is often preceded by gastrointestinal symptoms and alterations of the enteric nervous system accompany the disease. Several studies have analyzed the gut microbiome in PD, but a consensus on the features of the PD-specific microbiota is missing. Here, we conduct a meta-analysis re-analyzing the ten currently available 16S microbiome datasets to investigate whether common alterations in the gut microbiota of PD patients exist across cohorts. We found significant alterations in the PD-associated microbiome, which are robust to study-specific technical heterogeneities, although differences in microbiome structure between PD and controls are small. Enrichment of the genera Lactobacillus, Akkermansia, and Bifidobacterium and depletion of bacteria belonging to the Lachnospiraceae family and the Faecalibacterium genus, both important short-chain fatty acids producers, emerged as the most consistent PD gut microbiome alterations. This dysbiosis might result in a pro-inflammatory status which could be linked to the recurrent gastrointestinal symptoms affecting PD patients.


Author(s):  
Gladis Yohana Arboleda-Montealegre ◽  
Roberto Cano-de-la-Cuerda ◽  
César Fernández-de-las-Peñas ◽  
Carlos Sanchez-Camarero ◽  
Ricardo Ortega-Santiago

Background: Parkinson’s disease (PD) is the most common neurodegenerative disorder associated with motor and nonmotor symptoms. Drooling, one of the nonmotor symptoms, can be present in 70–80% of patients with PD. The aim of this paper is to study the characteristics of PD patients with drooling compared to those without in terms of age, gender, disease duration, stage of the disease, swallowing difficulties, and health-related quality of life; methods: a cross-sectional study was conducted. The sample was divided into two groups: PD with drooling (n = 32) and PD without drooling (n = 30). Age, gender, disease duration and Hoehn & Yahr (H & Y) stage, Sialorrhea Clinical Scale for Parkinson’s Disease (SCS-PD), the 10-item Eating Assessment Tool (EAT-10), and the 39-item Parkinson’s Disease Questionnaire (PDQ-39) were compared between groups; Results: 62 individuals with PD, 40 men and 22 women (mean age 73 ± 8 years), were included. Overall, 32 patients reported drooling, and 30 did not exhibit it. The ANCOVA found significant differences between groups for the EAT-10 score (0.83, 95% CI = 5.62–9.03; p = 0.016) and SCS-PD score (1.48, 95% CI = 0.86–6.81; p < 0.001). Analysis of the PDQ-39 scores revealed no significant differences between groups for the PDQ-39 total score (p > 0.057) and in all subscales. The inclusion of gender, age, disease duration, and H & Y as covariates did not influence the results (all p > 0.05). Conclusions: drooling is related to swallowing difficulties assessed with EAT-10 but not with health-related quality of life assessed with PDQ-39 in PD patients with drooling compared to PD patients without it. Age, gender, duration of the disease, and the H & Y state of PD patients with and without drooling seem to be similar.


2021 ◽  
pp. 1-8
Author(s):  
Alice K. Silbergleit ◽  
Lonni Schultz ◽  
Kendra Hamilton ◽  
Peter A. LeWitt ◽  
Christos Sidiropoulos

Background: Hypokinetic dysarthria and dysphagia are known features of Parkinson’s disease; however, self-perception of their handicapping effects on emotional, physical, and functional aspects of quality of life over disease duration is less understood. Objective: 1) Based upon patient self-perception, to determine the relationship of the handicapping effects of dysphagia and dysphonia with time since diagnosis in individuals with Parkinson’s disease; 2)To determine if there is a relationship between voice and swallowing handicap throughout the course of Parkinson’s disease. Method: 277 subjects completed the Dysphagia Handicap Index and the Voice Handicap Index. Subjects were divided into three groups based on disease duration: 0–4 years, 5–9 years, and 10 + years. Results: Subjects in the longer duration group identified significantly greater perceptions of voice and swallowing handicap compared to the shorter duration groups. There was a significant positive correlation between the DHI and VHI. Conclusion: Self-perception of swallowing and voice handicap in Parkinson’s disease are associated with later stages of disease and progress in a linear fashion. Self-perception of voice and swallowing handicap parallel each other throughout disease progression in Parkinson’s disease. Individuals may be able to compensate for changes in voice and swallowing early while sensory perceptual feedback is intact. Results support early targeted questioning of patient self-perception of voice and swallowing handicap as identification of one problem indicates awareness of the other, thus creating an opportunity for early treatment and maintenance of swallowing and communication quality of life for as long as possible.


Brain ◽  
2021 ◽  
Author(s):  
Qing Wang ◽  
Yuqi Luo ◽  
K Ray Chaudhuri ◽  
Richard Reynolds ◽  
Eng-King Tan ◽  
...  

Abstract Parkinson's disease is a common neurodegenerative disease in which gastrointestinal symptoms may appear prior to motor symptoms. The gut microbiota of patients with Parkinson's disease shows unique changes, which may be used as early biomarkers of disease. Alteration in gut microbiota composition may be related to the cause or effect of motor or non-motor symptoms, but the specific pathogenic mechanisms are unclear. The gut microbiota and its metabolites have been suggested to be involved in the pathogenesis of Parkinson's disease by regulating neuroinflammation, barrier function and neurotransmitter activity. There is bidirectional communication between the enteric nervous system and the central nervous system, and the microbiota-gut-brain axis may provide a pathway for the transmission of α-synuclein. We highlight recent discoveries and alterations of the gut microbiota in Parkinson's disease, and highlight current mechanistic insights on the microbiota-gut-brain axis in disease pathophysiology. We discuss the interactions between production and transmission of α-synuclein and gut inflammation and neuroinflammation. In addition, we also draw attention to diet modification, use of probiotics and prebiotics and fecal microbiota transplantation as potential therapeutic approaches that may lead to a new treatment paradigm for Parkinson's disease.


2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Yoshiki Takamatsu ◽  
Masayo Fujita ◽  
Gilbert J. Ho ◽  
Ryoko Wada ◽  
Shuei Sugama ◽  
...  

Lewy body diseases, such as Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), are associated with a wide range of nonmotor symptoms (NMS), including cognitive impairment, depression and anxiety, sleep disorders, gastrointestinal symptoms, and autonomic failure. The reason why such diverse and disabling NMS have not been weeded out but have persisted across evolution is unknown. As such, one possibility would be that the NMS might be somehow beneficial during development and/or reproductive stages, a possibility consistent with our recent view as to the evolvability of amyloidogenic proteins (APs) such as α-synuclein (αS) and amyloid-β (Aβ) in the brain. Based on the heterogeneity of protofibrillar AP forms in terms of structure and cytotoxicity, we recently proposed that APs might act as vehicles to deliver information regarding diverse internal and environmental stressors. Also, we defined evolvability to be an epigenetic phenomenon whereby APs are transgenerationally transmitted from parents to offspring to cope with future brain stressors in the offspring, likely benefitting the offspring. In this context, the main objective is to discuss whether NMS might be relevant to evolvability. According to this view, information regarding NMS may be transgenerationally transmitted by heterogeneous APs to offspring, preventing or attenuating the stresses related to such symptoms. On the other hand, NMS associated with Lewy body pathology might manifest through an aging-associated antagonistic pleiotropy mechanism. Given that NMS are not only specific to Lewy body diseases but also displayed in other disorders, including amyotrophic lateral sclerosis (ALS) and Huntington’s disease (HD), these conditions might share common mechanisms related to evolvability. This might give insight into novel therapy strategies based on antagonistic pleiotropy rather than on individual NMS from which to develop disease-modifying therapies.


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