scholarly journals Deep nasal sinus cavity microbiota dysbiosis in Parkinson’s disease

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Gian Pal ◽  
Vivian Ramirez ◽  
Phillip A. Engen ◽  
Ankur Naqib ◽  
Christopher B. Forsyth ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Olfactory Bulb ◽  
Nasal Cavity ◽  
Amplicon Sequencing ◽  
Motor Symptom ◽  
Rrna Gene ◽  
Healthy Controls ◽  
Nasal Sinus ◽  
Severe Motor

AbstractOlfactory dysfunction is a pre-motor symptom of Parkinson’s disease (PD) that appears years prior to diagnosis and can affect quality of life in PD. Changes in microbiota community in deep nasal cavity near the olfactory bulb may trigger the olfactory bulb-mediated neuroinflammatory cascade and eventual dopamine loss in PD. To determine if the deep nasal cavity microbiota of PD is significantly altered in comparison to healthy controls, we characterized the microbiota of the deep nasal cavity using 16S rRNA gene amplicon sequencing in PD subjects and compared it to that of spousal and non-spousal healthy controls. Correlations between microbial taxa and PD symptom severity were also explored. Olfactory microbial communities of PD individuals were more similar to those of their spousal controls than to non-household controls. In direct comparison of PD and spousal controls and of PD and non-spousal controls, significantly differently abundant taxa were identified, and this included increased relative abundance of putative opportunistic-pathobiont species such as Moraxella catarrhalis. M. catarrhalis was also significantly correlated with more severe motor scores in PD subjects. This proof-of-concept study provides evidence that potential pathobionts are detected in the olfactory bulb and that a subset of changes in the PD microbiota community could be a consequence of unique environmental factors associated with PD living. We hypothesize that an altered deep nasal microbiota, characterized by a putative pro-inflammatory microbial community, could trigger neuroinflammation in PD.

scholarly journals The Role of the Western Diet and Oral Microbiota in Parkinson’s Disease

Nutrients ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 355
Author(s):  
Barbara Zapała ◽  
Tomasz Stefura ◽  
Tomasz Milewicz ◽  
Julia Wątor ◽  
Monika Piwowar ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Food Preferences ◽  
Amplicon Sequencing ◽  
Rrna Gene ◽  
Oral Microbiota ◽  
Healthy Controls ◽  
Increased Risk ◽  
Specific Food

The type of diet not only affects the composition of the oral microflora but is also one of the more critical factors associated with an increased risk of Parkinson’s disease, PD. This study compared diet preferences and oral microbiota profiles in patients with PD vs. healthy controls. This study compared the oral microbiota composition of 59 patients with PD and 108 healthy controls (without neurodegeneration) using 16S rRNA gene amplicon sequencing. According to results, oral microbiota in patients with PD is different compared from healthy controls. In particular, decreased abundance of Proteobacteria, Pastescibacteria, and Tenercutes was observed. The oral cavity of patients with PD was characterized by the high relative abundance of bacteria from the genera Prevotella, Streptococcus, and Lactobaccillus. There were also differences in food preferences between patients with PD and healthy controls, which revealed significantly higher intake of margarine, fish, red meat, cereals products, avocado, and olives in the patients with PD relative to healthy controls. Strong positive and negative correlations between specific food products and microbial taxa were identified.

scholarly journals Cross-frequency phase-amplitude coupling in repetitive movements in patients with Parkinson's disease

2021 ◽  
Author(s):  
Ruxue Gong ◽  
Christoph Mühlberg ◽  
Mirko Wegscheider ◽  
Christopher Fricke ◽  
Jost-Julian Rumpf ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Primary Motor Cortex ◽  
Premotor Cortex ◽  
Neuronal Population ◽  
Motor Symptom ◽  
Healthy Controls ◽  
Eeg Signals ◽  
Oscillatory Eeg ◽  
Phase Amplitude

Bradykinesia is a cardinal motor symptom in Parkinson's disease whose pathophysiology is incompletely understood. When signals are recorded from the cortex or scalp at rest, affected patients display enhanced phase-amplitude coupling between β (13-30Hz) and broadband γ (50-150Hz) oscillatory activities. However, it remains unclear whether and how abnormal phase-amplitude coupling is involved in slowing Parkinsonian movements during their execution. To address these questions, we analyzed high-density EEG signals recorded simultaneously with various motor activities and at rest in 19 patients with Parkinson's disease and 20 healthy controls. The motor tasks consisted of repetitive index finger pressing, and slow and fast tapping movements. Individual EEG source signals were computed for the premotor cortex, primary motor cortex, primary somatosensory cortex, and primary somatosensory complex. For the resting condition and the pressing task, phase-amplitude coupling averaged over the 4 motor regions and the entire movement period was larger in patients than in controls. In contrast, in all tapping tasks, state-related phase-amplitude coupling was similar between patients and controls. These findings were not aligned with motor performance and EMG data, which showed abnormalities in patients for tapping but not for pressing, suggesting that the strength of β-broadband γ phase-amplitude coupling during the movement period does not directly relate to Parkinsonian bradykinesia. Subsequently, we examined the dynamics of oscillatory EEG signals during motor transitions. When healthy controls performed the pressing task, dynamic phase-amplitude coupling increased shortly before pressing onset and decreased subsequently. A strikingly similar motif of coupling rise and decay was observed around the offset of pressing and around the onset of slow tapping, suggesting that such transient phase-amplitude coupling changes may be linked to transitions between different movement states - akin to preparatory states in dynamical systems theory of motor control. In patients, the modulation of phase-amplitude coupling was similar in (normally executed) pressing, but flattened in slow (abnormally executed) tapping compared to the controls. These deviations in phase-amplitude coupling around motor action transients may indicate dysfunctional evolution of neuronal population dynamics from the preparatory state to movement generation in Parkinson's disease. These findings may indicate that cross-frequency coupling is involved in the pathophysiology of bradykinesia in Parkinson's disease through its abnormal dynamic modulation.

scholarly journals Sensitivity and Specificity of the ECAS in Parkinson’s Disease and Progressive Supranuclear Palsy

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Jennifer A. Foley ◽  
Elaine H. Niven ◽  
Andrew Paget ◽  
Kailash P. Bhatia ◽  
Simon F. Farmer ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Progressive Supranuclear Palsy ◽  
Verbal Fluency ◽  
High Sensitivity ◽  
Healthy Controls ◽  
Diagnostic Challenge ◽  
Motor Disability ◽  
Severe Motor

Disentangling Parkinson’s disease (PD) and progressive supranuclear palsy (PSP) may be a diagnostic challenge. Cognitive signs may be useful, but existing screens are often insufficiently sensitive or unsuitable for assessing people with motor disorders. We investigated whether the newly developed ECAS, designed to be used with people with even severe motor disability, was sensitive to the cognitive impairment seen in PD and PSP and able to distinguish between these two disorders. Thirty patients with PD, 11 patients with PSP, and 40 healthy controls were assessed using the ECAS, as well as an extensive neuropsychological assessment. The ECAS detected cognitive impairment in 30% of the PD patients, all of whom fulfilled the diagnostic criteria for mild cognitive impairment. The ECAS was also able to detect cognitive impairment in PSP patients, with 81.8% of patients performing in the impaired range. The ECAS total score distinguished between the patients with PSP and healthy controls with high sensitivity (91.0) and specificity (86.8). Importantly, the ECAS was also able to distinguish between the two syndromes, with the measures of verbal fluency offering high sensitivity (82.0) and specificity (80.0). In sum, the ECAS is a quick, simple, and inexpensive test that can be used to support the differential diagnosis of PSP.

scholarly journals Progression of Nonmotor Symptoms in Parkinson’s Disease by Sex and Motor Laterality

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Zimple Kurlawala ◽  
Paul H. Shadowen ◽  
Joseph D. McMillan ◽  
Levi J Beverly ◽  
Robert P. Friedland
Keyword(s):  
Quality Of Life ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Motor Symptom ◽  
Motor Symptoms ◽  
Healthy Controls ◽  
Nonmotor Symptoms ◽  
Start Up ◽  
Progression Markers

Nonmotor symptoms (NMS) in Parkinson’s disease (PD) can start up to a decade before motor manifestations and strongly correlate with the quality of life. Understanding patterns of NMS can provide clues to the incipient site of PD pathology. Our goal was to systematically characterize the progression of NMS in PD (n = 489), compared to healthy controls, HC (n = 241), based on the sex of the subjects and laterality of motor symptom onset. Additionally, NMS experienced at the onset of PD were also compared to subjects with scans without dopaminergic deficit, SWEDD (n = 81). The Parkinson’s Progression Markers Initiative (PPMI) database was utilized to analyze several NMS scales. NMS experienced by PD and SWEDD cohorts were significantly higher than HC and both sex and laterality influenced several NMS scales at the onset of motor symptoms. Sex Differences. PD males experienced significant worsening of sexual, urinary, sleep, and cognitive functions compared to PD females. PD females reported significantly increased thermoregulatory dysfunction and anxious mood over 7 years and significantly more constipation during the first 4 years after PD onset. Laterality Differences. At onset, PD subjects with right-sided motor predominance reported significantly higher autonomic dysfunction. Subjects with left-sided motor predominance experienced significantly more anxious mood at onset which continued as Parkinson’s progressed. In conclusion, males experienced increased NMS burden in Parkinson’s disease. Laterality of motor symptoms did not significantly influence NMS progression, except anxious mood. We analyzed NMS in a large cohort of PD patients, and these data are valuable to improve PD patients’ quality of life by therapeutically alleviating nonmotor symptoms.

scholarly journals Reduction of spontaneous cortical beta bursts in Parkinson’s disease is linked to symptom severity

2019 ◽  
Author(s):  
Mikkel C. Vinding ◽  
Panagiota Tsitsi ◽  
Josefine Waldthaler ◽  
Robert Oostenveld ◽  
Martin Ingvar ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Time Series ◽  
Parkinson's Disease ◽  
Symptom Severity ◽  
Time Course ◽  
High Amplitude ◽  
Motor Symptom ◽  
Healthy Controls ◽  
Beta Band ◽  
Band Activity

AbstractParkinson’s disease is characterized by a gradual loss of dopaminergic neurons, which are associated with altered neuronal activity in the beta band (13-30 Hz). Assessing beta band activity typically involves transforming the time-series to get the power of the signal in the frequency-domain. Such transformation assumes that the time-series can be reduced to a combination of steady-state sine-and cosine waves. However, recent studies have suggested that this approach masks relevant biophysical features in the beta band activity—for example, that the beta band exhibits transient bursts of high-amplitude activity.In an exploratory study we used magnetoencephalography (MEG) to record cortical beta band activity to characterize how spontaneous cortical beta bursts manifest in Parkinson’s patients ON and OFF dopaminergic medication, and compare this to matched healthy controls. From three minutes of MEG data, we extracted the time-course of beta band activity from the sensorimotor cortex and characterized high-amplitude epochs in the signal to test if they exhibited burst like properties. We then compared the rate, duration, inter-burst interval, and peak amplitude of the high-amplitude epochs between the Parkinson’s patients and healthy controls.Our results show that Parkinson’s patients OFF medication had a 6-17% lower beta bursts rate compared to healthy controls, while both the duration and the amplitude of the bursts were the same for Parkinson’s patients and healthy controls and medicated state of the Parkinson’s patients. These data thus support the view that beta bursts are fundamental underlying features of beta band activity, and show that changes in cortical beta band power in PD can be explained primarily by changes in the underlying burst rate. Importantly, our results also revealed a relationship between beta bursts rate and motor symptom severity in PD: a lower burst rate scaled with increased in severity of bradykinesia and postural/kinetic tremor. Beta burst rate might thus serve as neuromarker for Parkinson’s disease that can help in the assessment of symptom severity in Parkinson’s disease or evaluate treatment effectiveness.

scholarly journals Reduction of spontaneous cortical beta bursts in Parkinson’s disease is linked to symptom severity

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Mikkel C Vinding ◽  
Panagiota Tsitsi ◽  
Josefine Waldthaler ◽  
Robert Oostenveld ◽  
Martin Ingvar ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Time Series ◽  
Parkinson's Disease ◽  
Sensorimotor Cortex ◽  
Symptom Severity ◽  
Time Course ◽  
Motor Symptom ◽  
Healthy Controls ◽  
Beta Band ◽  
Band Activity

Abstract Parkinson’s disease is characterized by a gradual loss of dopaminergic neurons, which is associated with altered neuronal activity in the beta-band (13–30 Hz). Assessing beta-band activity typically involves transforming the time-series to get the power of the signal in the frequency domain. Such transformation assumes that the time-series can be reduced to a combination of steady-state sine- and cosine waves. However, recent studies have suggested that this approach masks relevant biophysical features in the beta-band—for example, that the beta-band exhibits transient bursts of high-amplitude activity. In an exploratory study, we used magnetoencephalography to record beta-band activity from the sensorimotor cortex, to characterize how spontaneous cortical beta bursts manifest in Parkinson’s patients on and off dopaminergic medication, and compare this to matched healthy controls. We extracted the time-course of beta-band activity from the sensorimotor cortex and characterized bursts in the signal. We then compared the burst rate, duration, inter-burst interval and peak amplitude between the Parkinson’s patients and healthy controls. Our results show that Parkinson’s patients off medication had a 5–17% lower beta bursts rate compared to healthy controls, while both the duration and the amplitude of the bursts were the same for healthy controls and medicated state of the Parkinson’s patients. These data thus support the view that beta bursts are fundamental underlying features of beta-band activity, and show that changes in cortical beta-band power in Parkinson’s disease can be explained—primarily by changes in the underlying burst rate. Importantly, our results also revealed a relationship between beta burst rate and motor symptom severity in Parkinson’s disease: a lower burst rate scaled with increased severity of bradykinesia and postural/kinetic tremor. Beta burst rate might thus serve as a neuromarker for Parkinson’s disease that can help in the assessment of symptom severity in Parkinson’s disease or in the evaluation of treatment effectiveness.

scholarly journals Parkinson’s disease-associated alterations of the gut microbiome can invoke disease-relevant metabolic changes

2019 ◽  
Author(s):  
Federico Baldini ◽  
Johannes Hertel ◽  
Estelle Sandt ◽  
Cyrille C. Thinnes ◽  
Lorieza Neuberger-Castillo ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Gut Microbiome ◽  
Systemic Disease ◽  
Rrna Gene ◽  
Healthy Controls ◽  
Microbial Metabolites ◽  
Metabolic Modelling ◽  
Microbiome Composition ◽  
Relative Abundances

ABSTRACTParkinson’s disease (PD) is a systemic disease clinically defined by the degeneration of dopaminergic neurons in the brain. While alterations in the gut microbiome composition have been reported in PD, their functional consequences remain unclear. Herein, we first analysed the gut microbiome of patients and healthy controls by 16S rRNA gene sequencing of stool samples from the Luxembourg Parkinson’s study (n=147 typical PD cases, n=162 controls). All individuals underwent detailed clinical assessment, including neurological examinations and neuropsychological tests followed by self-reporting questionnaires. Second, we predicted the potential secretion for 129 microbial metabolites through personalised metabolic modelling using the microbiome data and genome-scale metabolic reconstructions of human gut microbes. Our key results include: 1. eight genera and nine species changed significantly in their relative abundances between PD patients and healthy controls. 2. PD-associated microbial patterns statistically depended on sex, age, BMI, and constipation. The relative abundances ofBilophilaandParaprevotellawere significantly associated with the Hoehn and Yahr staging after controlling for the disease duration. In contrast, dopaminergic medication had no detectable effect on the PD microbiome composition. 3. Personalised metabolic modelling of the gut microbiomes revealed PD-associated metabolic patterns in secretion potential of nine microbial metabolites in PD, including increased methionine and cysteinylglycine. The microbial pantothenic acid production potential was linked to the presence of specific non-motor symptoms and attributed to individual bacteria, such asAkkermansia muciniphilaandBilophila wardswarthia. Our results suggest that PD-associated alterations of gut microbiome could translate into functional differences affecting host metabolism and disease phenotype.

scholarly journals Oral Dysbiosis and Inflammation in Parkinson’s Disease

2021 ◽  
Vol 11 (2) ◽  
pp. 619-631
Author(s):  
Vanessa Fleury ◽  
Alkisti Zekeridou ◽  
Vladimir Lazarevic ◽  
Nadia Gaïa ◽  
Catherine Giannopoulou ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dental Plaque ◽  
Gingival Crevicular Fluid ◽  
Amplicon Sequencing ◽  
Interferon Γ ◽  
Oral Microbiome ◽  
Rrna Gene ◽  
Oral Microbiota ◽  
Tnf Α

Background: Oral microbiota has largely escaped attention in Parkinson’s disease (PD), despite its pivotal role in maintaining oral and systemic health. Objective: The aim of our study was to examine the composition of the oral microbiota and the degree of oral inflammation in PD. Methods: Twenty PD patients were compared to 20 healthy controls. Neurological, periodontal and dental examinations were performed as well as dental scaling and gingival crevicular fluid sampling for cytokines measurement (interleukine (IL)-1β, IL-6, IL-1 receptor antagonist (RA), interferon-γ and tumor necrosis factor (TNF)-α). Two months later, oral microbiota was sampled from saliva and subgingival dental plaque. A 16S rRNA gene amplicon sequencing was used to assess bacterial communities. Results: PD patients were in the early and mid-stage phases of their disease (Hoehn & Yahr 2–2.5). Dental and periodontal parameters did not differ between groups. The levels of IL-1β and IL-1RA were significantly increased in patients compared to controls with a trend for an increased level of TNF-α in patients. Both saliva and subgingival dental plaque microbiota differed between patients and controls. Streptococcus mutans, Kingella oralis, Actinomyces AFQC_s, Veillonella AFUJ_s, Scardovia, Lactobacillaceae, Negativicutes and Firmicutes were more abundant in patients, whereas Treponema KE332528_s, Lachnospiraceae AM420052_s, and phylum SR1 were less abundant. Conclusion: Our findings show that the oral microbiome is altered in early and mid-stage PD. Although PD patients had good dental and periodontal status, local inflammation was already present in the oral cavity. The relationship between oral dysbiosis, inflammation and the pathogenesis of PD requires further study.

Association of the Non-Motor Burden with Patterns of Striatal Dopamine Loss in de novo Parkinson’s Disease

2020 ◽  
Vol 10 (4) ◽  
pp. 1541-1549
Author(s):  
Seok Jong Chung ◽  
Sangwon Lee ◽  
Han Soo Yoo ◽  
Yang Hyun Lee ◽  
Hye Sun Lee ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
De Novo ◽  
Early Stage ◽  
Striatal Dopamine ◽  
Motor Deficits ◽  
Dopamine Depletion ◽  
Severe Motor ◽  
Severe Group ◽  
Striatal Dopamine Depletion

Background: Striatal dopamine deficits play a key role in the pathogenesis of Parkinson’s disease (PD), and several non-motor symptoms (NMSs) have a dopaminergic component. Objective: To investigate the association between early NMS burden and the patterns of striatal dopamine depletion in patients with de novo PD. Methods: We consecutively recruited 255 patients with drug-naïve early-stage PD who underwent 18F-FP-CIT PET scans. The NMS burden of each patient was assessed using the NMS Questionnaire (NMSQuest), and patients were divided into the mild NMS burden (PDNMS-mild) (NMSQuest score <6; n = 91) and severe NMS burden groups (PDNMS-severe) (NMSQuest score >9; n = 90). We compared the striatal dopamine transporter (DAT) activity between the groups. Results: Patients in the PDNMS-severe group had more severe parkinsonian motor signs than those in the PDNMS-mild group, despite comparable DAT activity in the posterior putamen. DAT activity was more severely depleted in the PDNMS-severe group in the caudate and anterior putamen compared to that in the PDMNS-mild group. The inter-sub-regional ratio of the associative/limbic striatum to the sensorimotor striatum was lower in the PDNMS-severe group, although this value itself lacked fair accuracy for distinguishing between the patients with different NMS burdens. Conclusion: This study demonstrated that PD patients with severe NMS burden exhibited severe motor deficits and relatively diffuse dopamine depletion throughout the striatum. These findings suggest that the level of NMS burden could be associated with distinct patterns of striatal dopamine depletion, which could possibly indicate the overall pathological burden in PD.

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