scholarly journals Hydrogen Sulfide Attenuates the Cognitive Dysfunction in Parkinson’s Disease Rats via Promoting Hippocampal Microglia M2 Polarization by Enhancement of Hippocampal Warburg Effect

2022 ◽  
Vol 2022 ◽  
pp. 1-18
Author(s):  
Qing Tian ◽  
Hui-Ling Tang ◽  
Yi-Yun Tang ◽  
Ping Zhang ◽  
Xuan Kang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Hydrogen Sulfide ◽  
Cognitive Impairment ◽  
Cognitive Function ◽  
Cognitive Dysfunction ◽  
Warburg Effect ◽  
M2 Polarization ◽  
Underlying Mechanisms ◽  
The Warburg Effect

Identification of innovative therapeutic targets for the treatment of cognitive impairment in Parkinson’s disease (PD) is urgently needed. Hydrogen sulfide (H2S) plays an important role in cognitive function. Therefore, this work is aimed at investigating whether H2S attenuates the cognitive impairment in PD and the underlying mechanisms. In the rotenone- (ROT-) established PD rat model, NaHS (a donor of H2S) attenuated the cognitive impairment and promoted microglia polarization from M1 towards M2 in the hippocampus of PD rats. NaHS also dramatically upregulated the Warburg effect in the hippocampus of PD rats. 2-Deoxyglucose (2-DG, an inhibitor of the Warburg effect) abolished NaHS-upregulated Warburg effect in the hippocampus of PD rats. Moreover, the inhibited hippocampal Warburg effect by 2-DG abrogated H2S-excited the enhancement of hippocampal microglia M2 polarization and the improvement of cognitive function in ROT-exposed rats. Our data demonstrated that H2S inhibits the cognitive dysfunction in PD via promoting microglia M2 polarization by enhancement of hippocampal Warburg effect.

scholarly journals Freezing of Gait in Parkinson’s Disease: Risk Factors, Their Interactions, and Associated Nonmotor Symptoms

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
David Gordon Lichter ◽  
Ralph Holmes Boring Benedict ◽  
Linda Ann Hershey
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Cognitive Dysfunction ◽  
Univariate Analysis ◽  
Freezing Of Gait ◽  
Motor Complications ◽  
Clinical Factors ◽  
Nonmotor Symptoms ◽  
Gait Score

Background. Freezing of gait (FOG) is a debilitating and incompletely understood symptom in Parkinson’s disease (PD). Objective. To determine the principal clinical factors predisposing to FOG in PD, their interactions, and associated nonmotor symptoms. Methods. 164 PD subjects were assessed in a cross-sectional retrospective study, using the MDS-UPDRS scale, MMSE, and Clinical Dementia Rating Scale. Clinical factors associated with FOG were determined using univariate analysis and nominal logistic regression. Receiver operating characteristic curves were computed, to obtain measures of sensitivity and specificity of predictors of FOG. Subgroups of patients with FOG were compared with those without FOG, based on defining aspects of their clinical phenotype. Results. Relative to non-FOG patients, those with FOG had a longer disease duration, higher PIGD and balance-gait score, higher LED, and more motor complications ( p < 0.0001 ) and were more likely to exhibit urinary dysfunction ( p < 0.0003 ), cognitive impairment, hallucinations, and psychosis ( p = 0.003 ). The balance-gait score and motor complications, at their optimum cutoff values, together predicted FOG with 86% accuracy. Interactions were noted between cognitive dysfunction and both the Bal-Gait score and motor complication status, cognitive impairment or dementia increasing the likelihood of FOG in subjects without motor complications ( p = 0.0009 ), but not in those with motor complications. Conclusions. Both disease and treatment-related factors, notably LED, influence the risk of FOG in PD, with a selective influence of cognitive dysfunction in patients with balance-gait disorder but not in those with motor fluctuations. These findings may help to inform clinical management and highlight distinct subgroups of patients with PD-FOG, which are likely to differ in their network pathophysiology.

scholarly journals Corneal nerve fiber loss relates to cognitive impairment in patients with Parkinson’s disease

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Ning-Ning Che ◽  
Qiu-Huan Jiang ◽  
Guan-Xiao Ding ◽  
Si-Yuan Chen ◽  
Zhen-Xiang Zhao ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Cognitive Function ◽  
Nerve Fiber ◽  
Rating Scale ◽  
Motor Dysfunction ◽  
Control Group ◽  
Corneal Confocal Microscopy ◽  
Corneal Nerve

AbstractCognitive impairment in Parkinson’s disease (PD) adversely influences quality of life. There is currently no available biomarker to predict cognitive decline in PD. Corneal confocal microscopy (CCM) has been used as a non-invasive tool for quantifying small nerve damage in PD. The present study investigated whether corneal nerve measures were associated with cognitive function in PD. Patients with PD were classified into those with normal cognitive function (PD-CN), mild cognitive impairment (PD-MCI), and dementia (PDD). Corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), and corneal nerve fiber length (CNFL) were quantified with CCM and compared with a control group. Sixty-five PD patients and thirty controls were studied. CNFD was decreased and CNBD was increased in PD patients compared to controls (P < 0.05). CNBD and CNBD/CNFD ratio was higher in PD-CN compared to controls. CNFD was positively correlated with the Montreal cognitive assessment (MoCA) score (r = 0.683, P < 0.001), but negatively associated with unified Parkinson disease rating scale (UPDRS)-part III (r = −0.481, P < 0.001) and total UPDRS scores (r = −0.401, P = 0.001) in PD patients. There was no correlation between CNFD and Levodopa equivalent daily dose (LEDD) (r = 0.176, P = 0.161). CNFD, CNBD, CNFL, and CNBD/CNFD ratio was lower with increasing Hoehn and Yahr stage. PD patients show evidence of corneal nerve loss compared with controls and corneal nerve parameters are associated with the severity of cognitive and motor dysfunction in PD. CCM could serve as an objective in vivo ophthalmic imaging technique to assess neurodegeneration in PD.

scholarly journals Relationship of Serum Tau Levels with Cognitive Functions and Factors Affecting The Cognitive Function Decrease in Parkinson's Disease Patients

2021 ◽  
Vol 5 (3) ◽  
pp. 539-545
Author(s):  
Meldayeni Busra ◽  
Yuliarni Syafrita ◽  
Hendra Permana
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Cognitive Function ◽  
Tau Protein ◽  
Significant Relationship ◽  
Education Level ◽  
Motor Symptom ◽  
Categorical Variables ◽  
The Relationship

Introduction: Cognitive impairment is a non-motor symptom of Parkinson's disease (PD) which occurs as the disease progresses and affects quality of life. Many efforts have been developed in early detection of cognitive disorders, one of which is the examination of tau protein biomarkers, where the tau protein that undergoes pathological changes to form neurofibrillary tangles (NFTs) is found in Alzheimer's disease and PD and plays a role in cognitive impairment. However, the role of tau in PD is still controversial. This study aims to assess the relationship between serum tau levels and cognitive function and the factors that affect cognitive function in PD patients. Methods: This cross-sectional design was conducted at the RSUP DR. M Djamil Padang. During the period March to August 2020, 62 research subjects were obtained. Cognitive function examination was carried out by using the MoCA-Ina test and examination of serum tau levels using the Elisa method. The relationship between categorical variables was tested by Chi square and differences in serum tau levels in the group with and without cognitive impairment were tested with the Mann Whitney test, considered statistically significant if the p value <0.05. Results: With Moca Ina examination, it was found that 67.7% of patients had impaired cognitive function. The mean serum tau level was 198.004 ± 162.69 ng / L.There was a significant relationship between education level and degree of disease with cognitive function (p <0.05) and there was no difference in mean serum tau levels between groups with and without cognitive impairment. Conclusion: There is a significant relationship between education level and degree of disease with cognitive function and there is no difference in mean serum tau protein levels between the cognitive impaired group and the cognitive normal group.

scholarly journals Features of GBA-associated Parkinson’s disease at presentation in the UK Tracking Parkinson’s study

2018 ◽  
Vol 89 (7) ◽  
pp. 702-709 ◽  
Author(s):  
Naveed Malek ◽  
Rimona S Weil ◽  
Catherine Bresner ◽  
Michael A Lawton ◽  
Katherine A Grosset ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Cognitive Function ◽  
Rating Scale ◽  
Disease Stage ◽  
Baseline Assessment ◽  
Mutation Carriers ◽  
Pathogenic Mutations ◽  
Motor Phenotype

ObjectivesTo examine the influence of the glucocerebrosidase (GBA) mutation carrier state on age at onset of Parkinson’s disease (PD), the motor phenotype and cognitive function at baseline assessment in a large cohort of UK patients. We also analysed the prevalence of mood and behavioural problems that may confound the assessment of cognitive function.MethodsWe prospectively recruited patients with PD in the Tracking Parkinson’s study. We fully sequenced the GBA gene in all recently diagnosed patients (≤3.5 years). We examined cognitive (Montreal Cognitive Assessment) and motor (Movement Disorder Society Unified Parkinson’s Disease Rating Scale part 3) function at a baseline assessment, at an average of 1.3 years after diagnosis. We used logistic regression to determine predictors of PD with mild cognitive impairment and PD with dementia.ResultsWe studied 1893 patients with PD: 48 (2.5%) were heterozygous carriers for known Gaucher’s disease (GD) causing pathogenic mutations; 117 (6.2%) had non-synonymous variants, previously associated with PD, and 28 (1.5%) patients carried variants of unknown significance in the GBA gene. L444P was the most common pathogenic GBA mutation. Patients with pathogenic GBA mutations were on average 5 years younger at disease onset compared with non-carriers (P=0.02). PD patients with GD-causing mutations did not have an increased family risk of PD. Patients with GBA mutations were more likely to present with the postural instability gait difficulty phenotype compared with non-carriers (P=0.02). Patients carrying pathogenic mutations in GBA had more advanced Hoehn and Yahr stage after adjustment for age and disease duration compared with non-carriers (P=0.005). There were no differences in cognitive function between GBA mutation carriers and non-carriers at this early disease stage.ConclusionsOur study confirms the influence of GBA mutations on the age of onset, disease severity and motor phenotype in patients with PD. Cognition did not differ between GBA mutation carriers and non-carriers at baseline, implying that cognitive impairment/dementia, reported in other studies at a later disease stage, is not present in recently diagnosed cases. This offers an important window of opportunity for potential disease-modifying therapy that may protect against the development of dementia in GBA-PD.Clinical trial registrationNCT02881099; Results.

scholarly journals Cognitive function in men with non-motor features of Parkinson’s disease

2021 ◽  
Vol 3 (1) ◽  
pp. e000112
Author(s):  
Mario H Flores-Torres ◽  
Katherine C Hughes ◽  
Samantha Molsberry ◽  
Xiang Gao ◽  
Jae H Kang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Cognitive Function ◽  
Cognitive Decline ◽  
Smoking Status ◽  
Cognitive Interview ◽  
Coffee Consumption ◽  
Subjective Cognitive Decline ◽  
Prodromal Phase

ObjectiveSubtle cognitive deficits can occur during the prodromal phase of Parkinson’s disease (PD), commonly in conjunction with hyposmia. However, little is known about the association between cognitive function and other features suggestive of prodromal PD. We evaluated the association of non-motor prodromal PD features, including hyposmia, constipation and probable REM sleep behaviour disorder (pRBD), with objective measures of cognitive function and self-reported cognitive decline.MethodsThe study population comprised 804 men who responded to a telephone cognitive interview in 2016–2017. Participants included 680 individuals with hyposmia, of whom 45 had confirmed PD, and 124 men without hyposmia. Among these men, we evaluated objective cognitive function and subjective cognitive decline to determine whether the presence of non-motor features of prodromal PD was associated with cognitive functioning. Analyses were adjusted for age, physical activity, body mass index, smoking status and coffee consumption.ResultsIndividuals with non-motor features of prodromal PD had worse objective and subjective cognitive performance relative to men without non-motor features. Cognitive impairment was particularly prevalent among individuals with concurrent hyposmia, pRBD and constipation (multivariate-adjusted OR=3.80; 95% CI 1.52 to 9.47 for objective poor cognitive function; OR=8.71; 95% CI 3.18 to 23.83 for subjective cognitive decline). As expected, both objective (OR=7.91) and subjective (OR=17.42) cognitive impairment were also more common among men with confirmed PD.ConclusionsOur study suggests that cognition is commonly affected in individuals with non-motor prodromal PD features, particularly when multiple of these features are present.

scholarly journals Corneal Nerve Fiber Loss Relates to Cognitive Impairment in Patients with Parkinson’s Disease

2020 ◽  
Author(s):  
Ning-Ning Che ◽  
Qiu-Huan Jiang ◽  
Guan-Xiao Ding ◽  
Si-Yuan Chen ◽  
Zhen-Xiang Zhao ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Cognitive Function ◽  
Nerve Fiber ◽  
Rating Scale ◽  
Motor Dysfunction ◽  
Control Group ◽  
Corneal Confocal Microscopy ◽  
Corneal Nerve

Abstract Background Cognitive impairment in Parkinson’s disease (PD) adversely influences quality of life. There is currently no available biomarker to predict cognitive decline in PD. PD involves both the central and peripheral nervous system and especially small fiber damage occurs in PD. Corneal confocal microscopy (CCM) has been used as a non-invasive tool for quantifying small nerve fibre damage in PD. The present study investigated whether corneal nerve measures were associated with cognitive function in PD. Methods Patients with PD were classified into those with normal cognitive function (PD-CN), mild cognitive impairment (PD-MCI), and dementia (PDD). Corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD) and corneal nerve fiber length (CNFL) were quantified with CCM and compared with a control group.Results Sixty-five PD patients (44.62% male; mean age 64.60±6.95 years; mean disease duration 4.63±2.53 years) and 30 controls (53.33% male; mean age 62.43±6.16 years) were studied. CNFD was decreased and CNBD was increased in PD patients compared to controls ( P <0.05). CNFD decreased progressively with decline in cognitive function in PD patients. CNBD and CNBD/CNFD ratio was higher in PD-CN compared to controls but decreased with worsening cognitive function in PD-MCI and PDD patients. CNFD correlated with the Montreal cognitive assessment (MoCA) score ( r =0.683, P <0.0001), unified Parkinson disease rating scale (UPDRS)-part III ( r =-0.481, P <0.0001) and total UPDRS scores ( r =-0.401, P <0.0001) in PD patients. CNFD, CNBD, CNFL were lower and CNBD/CNFD ratio was higher with increasing Hoehn and Yahr stage. There was no correlation between CNFD and Levodopa equivalent daily dose (LEDD) ( r =0.176, P =0.161). CNFD, CNBD and CNFL could discriminate between PD-MCI and PD-CN with an area under the curve (AUC) of 82.85%, 67.47%, and 78.74%, respectively. CNFD, CNBD and CNFL could discriminate between PDD and PD-CN with an AUC of 96.67%, 90.12% and 84.44%. A combination of all three CCM parameters further increased the AUC value. Conclusions PD patients show evidence of corneal nerve loss compared with controls and corneal nerve parameters are associated with the severity of cognitive and motor dysfunction in PD. CCM could serve as an objective in vivo ophthalmic imaging technique to assess neurodegeneration in PD.

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