Plasma Lipopolysaccharide-Binding Protein Reflects Risk and Progression of Parkinson’s Disease

2021 ◽  
pp. 1-11
Author(s):  
Szu-Ju Chen ◽  
Yu-Chiao Chi ◽  
Chang-Han Ho ◽  
Wei-Shiung Yang ◽  
Chin-Hsien Lin
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mmse Score ◽  
Binding Protein ◽  
Motor Score ◽  
Lipopolysaccharide Binding Protein ◽  
Cox Regression Analysis ◽  
Updrs Part ◽  
Lipopolysaccharide Binding

Background: Lipopolysaccharide-binding protein (LBP) presents bacterial endotoxin, lipopolysaccharides, to cellular surface pattern receptors for immune responses in the gut-brain axis of Parkinson’s disease (PD). Objective: We investigated whether plasma LBP levels were associated with PD severity and progression. Methods: This study included 397 participants (248 PD patients and 149 controls). We measured participants’ plasma levels of LBP and pro-inflammatory cytokines, including TNF-α, IL-6, andIL-17A. PD patients underwent motor and cognition evaluations at baseline and at a mean follow-up interval of 4.7±2.3 years. We assessed the progression of motor and cognition symptoms based on changes in the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part III motor score and Mini-Mental State Examination (MMSE) score, respectively. Results: Plasma LBP levels were lower in PD patients than controls (9.08±2.91 vs. 10.10±3.00μg/ml, p <  0.01). A multiple logistic regression model with adjustment for age, sex, and plasma cytokine levels revealed that reduced plasma LBP levels were associated with increased PD risk (odds ratio 0.816, [95% CI 0.717–0.929], p = 0.002). Among PD patients, LBP levels were correlated with MDS-UPDRS part III motor score after adjustment for confounders (coefficient = 0.636, p = 0.017), but not with MMSE score. Adjusted Cox regression analysis showed that higher plasma LBP levels associated with faster motor progression (adjusted hazard ratio 1.084 [95% CI 1.011–1.163], p = 0.024) during follow-up. Conclusion: Our results demonstrated that plasma LBP levels reflect risk, motor symptom severity and progression in patients with PD.

scholarly journals Intestinal Dysbiosis and Lowered Serum Lipopolysaccharide-Binding Protein in Parkinson’s Disease

PLoS ONE ◽  
2015 ◽  
Vol 10 (11) ◽  
pp. e0142164 ◽  
Author(s):  
Satoru Hasegawa ◽  
Sae Goto ◽  
Hirokazu Tsuji ◽  
Tatsuya Okuno ◽  
Takashi Asahara ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Binding Protein ◽  
Lipopolysaccharide Binding Protein ◽  
Intestinal Dysbiosis ◽  
Lipopolysaccharide Binding ◽  
Lowered Serum

scholarly journals Lipopolysaccharide-binding protein (LBP) can reverse the amyloid state of fibrin seen or induced in Parkinson’s disease: implications for its aetiology

2017 ◽  
Author(s):  
Etheresia Pretorius ◽  
Sthembile Mbotwe ◽  
Douglas B. Kell
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Blood Clotting ◽  
Binding Protein ◽  
Treatment Strategies ◽  
Lipopolysaccharide Binding Protein ◽  
Novel Treatment ◽  
Novel Treatment Strategies ◽  
Lipopolysaccharide Binding ◽  
Scanning Electron

AbstractThe thrombin-induced polymerisation of fibrinogen to form fibrin is well established as a late stage of blood clotting. In recent work, we showed that the presence of tiny amounts of bacterial lipopolysaccharide (LPS) could cause these clots to adopt an amyloid form, that could be observed via scanning electron microscopy (SEM) or via the fluorescence of thioflavin-T. This could be prevented by the prior addition of lipopolysaccharide-binding protein (LBP). We had also observed by SEM this unusual clotting in the blood of patients with Parkinson’s disease (PD). We here show that this too can be prevented by LBP, thereby implicating such inflammatory microbial cell wall products in the aetiology of the disease. This may lead to novel treatment strategies in PD designed to target microbes and their products.

scholarly journals Increased risk of Parkinson’s disease among patients with age-related macular degeneration

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Po-Yu Jay Chen ◽  
Lei Wan ◽  
Jung-Nien Lai ◽  
Chih Sheng Chen ◽  
Jamie Jiin-Yi Chen ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Macular Degeneration ◽  
Cox Regression ◽  
Age Related Macular Degeneration ◽  
Rank Test ◽  
Cox Regression Analysis ◽  
Age Related ◽  
Increased Risk

Abstract Background This study aimed to investigate the risk of Parkinson’s disease (PD) among patients with age-related macular degeneration (AMD) and its association with confounding comorbidities. Methods A population-based retrospective cohort study was conducted using Longitudinal Health Insurance Database 2000 (LHID2000). We established AMD and non-AMD cohorts from January 1, 2000 to December 31, 2012 to determine the diagnosis of PD. A total of 20,848 patients were enrolled, with 10,424 AMD patients and 10,424 controls matched for age, sex, and index year at a 1:1 ratio. The follow-up period was from the index date of AMD diagnosis to the diagnosis of PD, death, withdrawal from the insurance program, or end of 2013. Multivariable Cox regression analysis was performed to examine the hazard ratio (HR) and 95% confidence interval (CI) for the risk of PD between the AMD and non-AMD cohorts. Result After adjusting for potential confounders, there was a higher risk of developing PD in the AMD cohort than in the non-AMD cohort (adjusted HR = 1.35, 95% CI = 1.16–1.58). A significant association could be observed in both female (aHR = 1.42, 95% CI = 1.13–1.80) and male (aHR = 1.28, 95% CI = 1.05–1.57) patients, aged more than 60 years (60–69: aHR = 1.51, 95% CI = 1.09–2.09, 70–79: aHR = 1.30, 95% CI = 1.05–1.60; 80–100: aHR = 1.40, 95% CI = 1.01–1.95), and with more than one comorbidity (aHR = 1.40, 95% CI = 1.20–1.64). A significant association between increased risk of PD and AMD was observed among patients with comorbidities of osteoporosis (aHR = 1.68, 95% CI = 1.22–2.33), diabetes (aHR = 1.41, 95% CI = 1.12–1.78) and hypertension (aHR = 1.36, 95% CI = 1.15–1.62) and medications of statin (aHR = 1.42, 95% CI = 1.19–1.69) and calcium channel blocker (CCB) (aHR = 1.32, 95% CI = 1.11–1.58). The cumulative incidence of PD was significantly higher over the 12-year follow-up period in AMD cohort (log-rank test, p < 0.001). Conclusions Patients with AMD may exhibit a higher risk of PD than those without AMD.

scholarly journals Lockdown effects on Parkinson’s disease during COVID-19 pandemic: a pilot study

2021 ◽  
Author(s):  
Marika Falla ◽  
Alessandra Dodich ◽  
Costanza Papagno ◽  
Alessandro Gober ◽  
Pamela Narduzzi ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Pilot Study ◽  
Movement Disorder ◽  
Psychological Stress ◽  
Clinical Features ◽  
Nonmotor Symptoms ◽  
Web Based ◽  
Updrs Part

AbstractThe coronavirus-disease 2019 (COVID-19) outbreak precipitated prolonged lock-down measures. The subsequent social distancing, isolation, and reduction in mobility increased psychological stress, which may worsen Parkinson’s disease (PD). Therefore, telemedicine has been proposed to provide care to PD patients. To evaluate the effects of lock-down on motor and nonmotor symptoms in PD patients during the COVID-19 pandemic and the feasibility of telemedicine. Motor and nonmotor aspects were longitudinally assessed using structured questionnaires at baseline (in-person, February 2020) and at follow-up (remote web-based video, lock-down) evaluation. Of the seventeen PD patients evaluated at baseline, fourteen agreed to participate in, and completed follow-up evaluations. There was an impairment of nonmotor aspects measured with the MDS-UPDRS part I (p < 0.001) during lock-down. Nine patients participated independently in the telemedicine evaluation while five needed help from relatives. Our preliminary findings suggest an impairment of nonmotor symptoms in PD patients and support the feasibility and need for telemedicine in monitoring PD patients during the COVID-19 pandemic, to guarantee optimal assistance with reducing the burden of infection. Our findings also suggest that movement disorder clinics should be carefully considering socio-demographics and clinical features when developing telemedicine programs.

scholarly journals Plasma pS129-α-Synuclein Is a Surrogate Biofluid Marker of Motor Severity and Progression in Parkinson’s Disease

2019 ◽  
Vol 8 (10) ◽  
pp. 1601 ◽  
Author(s):  
Lin ◽  
Liu ◽  
Yang ◽  
Yang ◽  
Wu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Plasma Levels ◽  
Rating Scale ◽  
Surrogate Marker ◽  
Lewy Bodies ◽  
Motor Symptom ◽  
Rank Test ◽  
Updrs Part

Phosphorylated α-synuclein accounts for more than 90% of α-synuclein found in Lewy bodies of Parkinson’s disease (PD). We aimed to examine whether plasma Ser129-phosphorylated α-synuclein (pS129-α-synuclein) is a surrogate marker of PD progression. This prospective study enrolled 170 participants (122 PD patients, 68 controls). We measured plasma levels of total and pS129-α-synuclein using immunomagnetic reduction-based immunoassay. PD patients received evaluations of motor and cognition at baseline and at a mean follow-up interval of three years. Changes in the Movement Disorder Society revision of the Unified Parkinson’s Disease Rating Scale motor score (MDS-UPDRS part III) and Mini-Mental State Examination (MMSE) score were used to assess motor and cognition progression. Our results showed that plasma levels of total and pS129-α-synuclein were significantly higher in PD patients than controls (total: 1302.3 ± 886.6 fg/mL vs. 77.8 ± 36.6 fg/mL, p < 0.001; pS129-α-synuclein: 12.9 ± 8.7 fg/mL vs. 0.8 ± 0.6 fg/mL, p < 0.001), as was the pS129-α-synuclein/total α-synuclein ratio (2.8 ± 1.1% vs. 1.1 ± 0.6%, p = 0.01). Among PD patients, pS129-α-synuclein levels were higher with advanced motor stage (p < 0.001) and correlated with MDS-UPDRS part III scores (r = 0.27, 95% CI: 0.09–0.43, p = 0.004). However, we found no remarkable difference between PD patients with and without dementia (p = 0.75). After a mean follow-up of 3.5 ± 2.1 years, PD patients with baseline pS129-α-synuclein > 8.5 fg/mL were at higher risk of motor symptom progression of at least 3 points in the MDS-UPDRS part III scores than those with pS129-α-synuclein < 8.5 fg/mL (p = 0.03, log rank test). In conclusion, our data suggest that plasma pS129-α-synuclein levels correlate with motor severity and progression, but not cognitive decline, in patients with PD.

scholarly journals Olfactory Dysfunction Predicts Disease Progression in Parkinson’s Disease: A Longitudinal Study

2020 ◽  
Vol 14 ◽  
Author(s):  
Runcheng He ◽  
Yuwen Zhao ◽  
Yan He ◽  
Yangjie Zhou ◽  
Jinxia Yang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Disease Progression ◽  
Rating Scale ◽  
Mmse Score ◽  
Clinical Manifestations ◽  
Olfactory Dysfunction ◽  
Olfactory Function ◽  
Motor Symptom

Background and Objective:Olfactory dysfunction (hyposmia) is an important non-motor symptom of Parkinson’s disease (PD). To investigate the potential prognostic value of hyposmia as a marker for disease progression, we prospectively assessed clinical manifestations and longitudinal changes of hyposmic PD patients and normosmic ones.MethodsOlfactory function was evaluated with the Sniffin’ Sticks in PD patients at baseline. One hundred five hyposmic PD patients and 59 normosmic PD patients were enrolled and followed up for 2 years. They were subsequently evaluated at baseline and during follow-up periods with neurological and neuropsychological assessments. Clinical manifestations and disease progressions were compared between hyposmic and normosmic patients. In addition, the relationship between disease progressions and olfactory function was analyzed.ResultsOur study suggested that hyposmic PD patients and normosmic ones were similar in gender, age, education levels, age of onset, disease duration, and clinical features at baseline. Hyposmic PD patients exhibited more severe Unified Parkinson’s Disease Rating Scale Part II–III (UPDRS II-III) scores, higher levodopa equivalent dose (LED) needs, and poorer Mini-Mental State Examination (MMSE) score at follow-up visits compared to those in normosmic PD patients. Hyposmia also showed greater rates in the increase of LED needs, improvement of UPDRS III score, and deterioration of MMSE score. Both improvement of UPDRS III score and decline of MMSE score were associated with poorer odor identification.ConclusionOur prospective study demonstrated that hyposmic PD patients showed a relatively worse clinical course compared with normosmic patients. Olfactory dysfunction is a useful predictor of disease progression.

scholarly journals Evolution of Orofacial Symptoms and Disease Progression in Idiopathic Parkinson’s Disease: Longitudinal Data from the Jönköping Parkinson Registry

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Seyed-Mohammad Fereshtehnejad ◽  
Örjan Skogar ◽  
Johan Lökk
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Routine Care ◽  
Autonomic Disturbance ◽  
Advanced Stages ◽  
Male Sex ◽  
Late Stages ◽  
Updrs Part ◽  
Registry Database

Background. Orofacial symptoms are common in Parkinson’s disease (PD) both as initial manifestations and late markers of disease complications. We aimed to investigate the evolution of orofacial manifestations and their prognostic value throughout PD progression. Methods. Data was obtained from “Jönköping Parkinson Registry” database on routine care visits of 314 people with idiopathic PD in southern Sweden. Information on baseline symptomatology, orofacial features, UPDRS, and medications was recorded at baseline and during each follow-up visit within an average of 4.2 (range: 1–12) years. Results. Hypomimia, affected speech, drooling, and impaired swallowing were present in 37.3%/91.6%, 14.1%/65.5%, 11.7%/55.3%, and 10.2%/34.5% at baseline/follow-up, respectively. Male sex [OR = 2.4 (95% CI: 1.0–5.9)], UPDRS motor scores [OR = 1.2 (95% CI: 1.1–1.3)], dominant rigidity [OR = 5.2 (95% CI: 1.4–19.1)], and autonomic disturbance [OR = 3.4 (95% CI: 1.1–10.9)] were risk factors for drooling. Individuals with more severe orofacial burden at baseline had shorter median time to develop UPDRS-Part III > 28 [3rd tertile = 4.7 yr, 2nd tertile = 6.2 yr, and 1st tertile = 7.8 yr; p = 0.014]. Conclusions. Majority of people with PD manifest orofacial manifestations at either early or late stages of the disease. PD severity, symmetry of motor disturbances, and autonomic disorders correlate with orofacial symptoms. Individuals with more severe orofacial burden at baseline progressed faster to more advanced stages.

PREDICTORS OF INSTITUTIONALISATION IN PARKINSON'S DISEASE

2015 ◽  
Vol 86 (11) ◽  
pp. e4.87-e4
Author(s):  
Angus Macleod ◽  
Carl Counsell
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cox Regression ◽  
Mmse Score ◽  
Older Age ◽  
Community Based ◽  
Free Survival ◽  
Kaplan Meier ◽  
Lost To Follow Up

BackgroundInstitutionalisation (entry to nursing home, or other place of residential care) is an important outcome in PD. We investigated frequency of, and baseline predictors of, institutionalisation in Parkinson's disease (PD).MethodsWe identified all new cases of PD in Aberdeen, UK, over 4.5 years using multiple, community-based ascertainment methods. Age-sex matched community-based controls were also recruited. Participants were seen annually and place of residence at each follow-up or before death were ascertained, together with date of entry to institution. Kaplan–Meier institution-free survival probabilities were plotted. Potential baseline predictors were investigated using Cox regression.Results198 PD patients and 260 controls were recruited. One patient and one control were institutionalised before diagnosis. One patient and four controls were lost to follow-up. 44 (22%) PD patients and 19 (7%) controls were institutionalised during mean 6.1 years follow-up. Hazards of institutionalisation were higher in PD than controls (HR 3.72 [2.16–6.39]). Older age (HR 1.05 [1.01–1.09]), lower MMSE score (HR 0.88 [0.79–0.98]), and baseline dependence (HR 2.48 [1.18–5.25]) were independently associated with institutionalisation.ConclusionsInstitutionalisation was higher in PD than controls. Older age, poorer cognition and being dependent at diagnosis led to increased institutionalisation.

scholarly journals Focused Ultrasound Thalamotomy in Tremor Dominant Parkinson’s Disease: Long-Term Results

2021 ◽  
pp. 1-8
Author(s):  
Alon Sinai ◽  
Maria Nassar ◽  
Elliot Sprecher ◽  
Marius Constantinescu ◽  
Menashe Zaaroor ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Focused Ultrasound ◽  
Rating Scale ◽  
Long Term Results ◽  
Disease Rating ◽  
Updrs Part ◽  
Clinical Rating Scale

Background: MRI-guided focused ultrasound (FUS) has established short-term efficacy in tremor relief. Objective: We report our long-term experience of treating tremor with unilateral FUS unilateral VIM-thalamotomy in tremor dominant Parkinson’s disease (TDPD) patients. Methods: We report outcome of FUS thalamotomy in TDPD patients with 1–5 years of follow-up. Outcomes: tremor reduction assessed with Clinical Rating Scale for Tremor (CRST) and Unified Parkinson’s Disease Rating Scale (UPDRS part III) overall and in the treated hemibody and safety. Results: Twenty-six TDPD patients completed 1–5 years of follow-up (median follow-up 36 months, range 12–60 months). Median age was 60 years (range 46–79), with median disease duration of 6 years (range 2–16). Immediately, treatment resulted in 100%improvement in tremor in the treated arm in 23 patients and 90%improvement in 3 patients. In 15 patients with leg tremor, 2 patients with chin tremor and 1 patient with head tremor, tremor was significantly improved. Up to 5 years, median CRST score, median UPDRS score, overall and in treated hemibody, decreased significantly as compared with baseline (p <  0.0001). In 2 patients tremor returned completely and in 8 patients there was partial return of tremor. Adverse events were mild and resolved within 3 months. At baseline 4 patients were not receiving any medication vs. 3 at last follow-up and 15 were not taking levodopa vs.9 at last follow-up. Conclusion: Unilateral FUS VIM-thalamotomy in TDPD patients was effective and safe and provided long-term tremor relief in most patients. FUS thalamotomy for tremor may delay initiation of levodopa treatment.

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