Plasma Extracellular Vesicle α-Synuclein Level in Patients with Parkinson’s Disease

Background: The most established pathognomonic protein of Parkinson’s disease (PD), α-synuclein, is extensively investigated for disease diagnosis and prognosis; however, investigations into whether the free form of α-synuclein in the blood functions as a PD biomarker have not been fruitful. Extracellular vesicles (EVs) secreted from cells and present in blood transport molecules are novel platforms for biomarker identification. In blood EVs, α-synuclein originates predominantly from the brain without the interference of the blood–brain barrier. The present study investigated the role of plasma EV-borne α-synuclein as a biomarker of PD. Methods: Patients with mild to moderate stages of PD (n = 116) and individuals without PD (n = 46) were recruited to serve as the PD study group and the control group, respectively. Plasma EVs were isolated, and immunomagnetic reduction–based immunoassay was used to assess EV α-synuclein levels. Conventional statistical analysis was performed using SPSS 25.0, and p < 0.05 was considered significant. Results: Compared with controls, we observed significantly lower plasma EV α-synuclein levels in the patients with PD (PD: 56.0 ± 3.7 fg/mL vs. control: 74.5 ± 4.3 fg/mL, p = 0.009), and the significance remained after adjustment for age and sex. Plasma EV α-synuclein levels in the patients with PD did not correlate with age, disease duration, Part I and II scores of the Unified Parkinson’s Disease Rating Scale (UPDRS), or the Mini-Mental State Examination scores. However, such levels were significantly correlated with UPDRS Part III score, which assesses motor dysfunction. Furthermore, the severity of akinetic-rigidity symptoms, but not tremor, was inversely associated with plasma EV α-synuclein level. Conclusion: Plasma EV α-synuclein was significantly different between the control and PD group and was associated with akinetic-rigidity symptom severity in patients with PD. This study corroborates the possible diagnostic and subtyping roles of plasma EV α-synuclein in patients with PD, and it further provides a basis for this protein’s clinical relevance and feasibility as a PD biomarker.

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

npj Parkinson s Disease ◽

10.1038/s41531-021-00225-3 ◽

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.

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

10.21203/rs.3.rs-112941/v1 ◽

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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Donepezil for mild cognitive impairment in Parkinson’s disease

Scientific Reports ◽

10.1038/s41598-021-84243-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kyoungwon Baik ◽

Seon Myeong Kim ◽

Jin Ho Jung ◽

Yang Hyun Lee ◽

Seok Jong Chung ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Treatment Group ◽

Outcome Measures ◽

Rating Scale ◽

Secondary Outcome ◽

Control Group ◽

Significant Difference

AbstractWe investigated the efficacy of donepezil for mild cognitive impairment in Parkinson’s disease (PD-MCI). This was a prospective, non-randomized, open-label, two-arm study. Eighty PD-MCI patients were assigned to either a treatment or control group. The treatment group received donepezil for 48 weeks. The primary outcome measures were the Korean version of Mini-Mental State Exam and Montreal Cognitive Assessment scores. Secondary outcome measures were the Clinical Dementia Rating, Unified Parkinson’s Disease Rating Scale part III, Clinical Global Impression scores. Progression of dementia was assessed at 48-week. Comprehensive neuropsychological tests and electroencephalography (EEG) were performed at baseline and after 48 weeks. The spectral power ratio of the theta to beta2 band (TB2R) in the electroencephalogram was analyzed. There was no significant difference in the primary and secondary outcome measures between the two groups. However, the treatment group showed a significant decrease in TB2R at bilateral frontotemporoparietal channels compared to the control group. Although we could not demonstrate improvements in the cognitive functions, donepezil treatment had a modulatory effect on the EEG in PD-MCI patients. EEG might be a sensitive biomarker for detecting changes in PD-MCI after donepezil treatment.

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Parkinson’s Disease Motor Symptom Progression Slowed with Multisensory Dance Learning over 3-Years: A Preliminary Longitudinal Investigation

Brain Sciences ◽

10.3390/brainsci11070895 ◽

2021 ◽

Vol 11 (7) ◽

pp. 895

Author(s):

Karolina A. Bearss ◽

Joseph F. X. DeSouza

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Daily Living ◽

Rating Scale ◽

Motor Impairment ◽

Motor Dysfunction ◽

Motor Symptom ◽

Significant Group ◽

Rate Of Decline ◽

Symptom Progression

Parkinson’s disease (PD) is a neurodegenerative disease that has a fast progression of motor dysfunction within the first 5 years of diagnosis, showing an annual motor rate of decline of the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) between 5.2 and 8.9 points. We aimed to determine both motor and non-motor PD symptom progression while participating in dance classes once per week over a period of three years. Longitudinal data was assessed for a total of 32 people with PD using MDS-UPDRS scores. Daily motor rate of decline was zero (slope = 0.000146) in PD-Dancers, indicating no motor impairment, whereas the PD-Reference group showed the expected motor decline across three years (p < 0.01). Similarly, non-motor aspects of daily living, motor experiences of daily living, and motor complications showed no significant decline. A significant group (PD-Dancers and PD-Reference) by days interaction showed that PD who train once per week have less motor impairment (M = 18.75) than PD-References who do not train (M = 24.61) over time (p < 0.05). Training is effective at slowing both motor and non-motor PD symptoms over three years as shown in decreased scores of the MDS-UPDRS.

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Association between White Matter Lesions and Non-Motor Symptoms in Parkinson Disease

Neurodegenerative Diseases ◽

10.1159/000489311 ◽

2018 ◽

Vol 18 (2-3) ◽

pp. 127-132 ◽

Cited By ~ 3

Author(s):

Jeong-Yoon Lee ◽

Ji Sun Kim ◽

Wooyoung Jang ◽

Jinse Park ◽

Eungseok Oh ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

White Matter ◽

Parkinson Disease ◽

Cognitive Dysfunction ◽

Rating Scale ◽

White Matter Lesions ◽

Motor Dysfunction ◽

Motor Symptoms ◽

Non Motor Symptoms

Background: There are only few studies exploring the relationship between white matter lesions (WMLs) and non-motor symptoms in Parkinson disease (PD). This study aimed to investigate the association between WMLs and the severity of non-motor symptoms in PD. Methods: The severity of motor dysfunction, cognitive impairment, and non-motor symptoms was assessed by various scales in 105 PD patients. We used a visual semiquantitative rating scale and divided the subjects into four groups: no, mild, moderate, and severe WMLs. We compared the means of all scores between the four groups and analyzed the association between the severity of WMLs and the specific domain of non-motor symptoms. Results: The non-motor symptoms as assessed by the Non-Motor Symptoms Scale, Parkinson’s Disease Questionnaire (PDQ-39), Parkinson’s Disease Sleep Scale, Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Neuropsychiatric Inventory (NPI), and Parkinson Fatigue Scale (PFS) were significantly worse in the patients with moderate and severe WMLs than in those without WMLs. Compared with the no WML group, the scores for motor dysfunction were significantly higher in the mild, moderate, and severe WML groups. The scores for cognitive dysfunction were significantly higher in the patients with severe WMLs than in those without WMLs. The severity of WMLs showed linear associations with PFS, BDI, BAI, NPI, and PDQ-39 scores. The severity of WMLs also correlated linearly with scores for motor and cognitive dysfunction. Conclusions: Among the non-motor symptoms, fatigue, depression, anxiety, and quality of life were significantly affected by WMLs in PD. Confirmation of the possible role of WMLs in non-motor symptoms associated with PD in a prospective manner may be crucial not only for understanding non-motor symptoms but also for the development of treatment strategies.

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Stereopsis Deficits in Parkinson’s Disease and Their Clinical Implications

10.21203/rs.3.rs-106032/v1 ◽

2020 ◽

Author(s):

Fang Ba ◽

Tina T. Sang ◽

Jaleh Fatehi ◽

Wenjing He ◽

Emanuel Mostofi ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Disease Severity ◽

Rating Scale ◽

Disease Status ◽

Cognitive Status ◽

Control Group ◽

Motor Disorder ◽

Healthy Control ◽

Stereo Acuity

Abstract Background: Parkinson's disease (PD) is not exclusively a motor disorder. Among non-motor features, PD patients possess sensory visual dysfunctions. Stereopsis deficit can significantly impact patients' motor performance. However, it is not routinely tested, and its significance is under-investigated. Studying stereopsis using reliable 3D stimuli may help determine its implications in disease status in PD.The objective of the study is to investigate stereopsis abnormalities in PD with reliable and more physiological tools, and their correlation with indicators of PD severity. Methods: Twenty-four healthy control and 20 PD participants were first evaluated for visual acuity, visual field, contrast acuity, and stereoperception with 2D and Titmus stereotests, followed by the assessment with the 3D active shutter system. The correlation between stereopsis and disease severity, Unified Parkinson’s disease rating scale motor scores (UPDRS-III), levodopa equivalent daily dose (LEDD), course of disease and cognitive status were evaluated using univariate regression models. Results: Screening visual tests did not reveal any differences between PD and control group. With the 3D active shutter system, PD patients demonstrated significantly worse stereopsis (i.e p=0.002, 26 seconds of arc). There was a trend that UPDRS-III and LEDD negatively correlate with the stereo acuity, suggesting poorer stereoperception is related to disease severity. Preserved cognitive function correlated with more intact stereo acuity. Conclusion: With more reliable and physiological tools, PD patients exhibit poorer stereopsis. These deficits reflected PD motor and cognitive status. How stereopsis relates to gait, fall risks and navigation warrants more investigations in the future.

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Palmitate and Stearate are Increased in the Plasma in a 6-OHDA Model of Parkinson’s Disease

Metabolites ◽

10.3390/metabo9020031 ◽

2019 ◽

Vol 9 (2) ◽

pp. 31 ◽

Cited By ~ 1

Author(s):

Anuri Shah ◽

Pei Han ◽

Mung-Yee Wong ◽

Raymond Chang ◽

Cristina Legido-Quigley

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Stearic Acid ◽

Palmitic Acid ◽

Neurodegenerative Disorder ◽

Motor Dysfunction ◽

Substantia Nigra Pars Compacta ◽

Control Group ◽

Sprague Dawley ◽

Curative Therapy

Introduction: Parkinson’s disease (PD) is the second most common neurodegenerative disorder, without any widely available curative therapy. Metabolomics is a powerful tool which can be used to identify unexpected pathway-related disease progression and pathophysiological mechanisms. In this study, metabolomics in brain, plasma and liver was investigated in an experimental PD model, to discover small molecules that are associated with dopaminergic cell loss. Methods: Sprague Dawley (SD) rats were injected unilaterally with 6-hydroxydopamine (6-OHDA) or saline for the vehicle control group into the medial forebrain bundle (MFB) to induce loss of dopaminergic neurons in the substantia nigra pars compacta. Plasma, midbrain and liver samples were collected for metabolic profiling. Multivariate and univariate analyses revealed metabolites that were altered in the PD group. Results: In plasma, palmitic acid (q = 3.72 × 10−2, FC = 1.81) and stearic acid (q = 3.84 × 10−2, FC = 2.15), were found to be increased in the PD group. Palmitic acid (q = 3.5 × 10−2) and stearic acid (q = 2.7 × 10−2) correlated with test scores indicative of motor dysfunction. Monopalmitin (q = 4.8 × 10−2, FC = −11.7), monostearin (q = 3.72 × 10−2, FC = −15.1) and myo-inositol (q = 3.81 × 10−2, FC = −3.32), were reduced in the midbrain. The liver did not have altered levels of these molecules. Conclusion: Our results show that saturated free fatty acids, their monoglycerides and myo-inositol metabolism in the midbrain and enteric circulation are associated with 6-OHDA-induced PD pathology.

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Visuospatial cognitive tests for the evaluation of patients with Parkinson's disease

Dementia & Neuropsychologia ◽

10.1590/s1980-57642009dn20300007 ◽

2008 ◽

Vol 2 (3) ◽

pp. 201-205 ◽

Cited By ~ 3

Author(s):

Marina Ceres Silva Pena ◽

Emmanuelle Silva Tavares Sobreira ◽

Carolina Pinto Souza ◽

Guiomar Nascimento Oliveira ◽

Vitor Tumas ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Rating Scale ◽

Control Group ◽

Cognitive Changes ◽

Daily Life Activities ◽

Drawing Task ◽

Medium Level ◽

Visuospatial Functions ◽

Visual Organization

Abstract Parkinson's disease (PD) is a neurological disorder characterized by motor disturbances, neuropsychological symptoms and cognitive changes, including cases of dementia. The most frequently described cognitive changes in these patients involve executive and visuospatial functions, which are very important for the execution of daily life activities. Objective: To compare different tests used to examine visuospatial functions in patients with PD. Methods: Thirty-five patients (21 women) with PD symptoms (medicated and "on") and mean schooling of 5.5±4.2 years were examined using the following tests: Mini-Mental State Examination (MMSE), Dementia Rating Scale (DRS), Scales of Outcomes of Parkinson's Disease (SCOPA-COG), Hooper Visual Organization Test (HVOT), Judgment of Line Orientation, Form V (JLO), and Clock drawing task - CLOX (1 and 2). Results: The mean MMSE score was 24.8±3.03 and 54.8% of the patients performed correctly in the copy of a pentagon drawing, with a medium-level performance in most tests. Good correlations were detected between JLO versus SCOPA Assembling patterns (0.67), JLO versus HVOT (0.56), JLO versus CLOX2 (0.64), SCOPA Figure Composition versus HVOT (0.54), CLOX1 versus CLOX2 (0.43), and DRS Construction versus CLOX2 (0.42). Discussion: Although correlations were detected, not all were strong, probably because the tests employed do not measure solely visuospatial functions, but also other skills such as attention, motor ability and executive functions. A limitation of the present study was the lack of a control group for the establishment of adequate standards for this population.

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Apathy in patients with Parkinson’s disease following deep brain stimulation of the subthalamic nucleus

CNS Spectrums ◽

10.1017/s1092852916000171 ◽

2016 ◽

Vol 21 (3) ◽

pp. 258-264 ◽

Cited By ~ 10

Author(s):

Isabel Hindle Fisher ◽

Hardev S. Pall ◽

Rosalind D. Mitchell ◽

Jamilla Kausar ◽

Andrea E. Cavanna

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Deep Brain Stimulation ◽

Subthalamic Nucleus ◽

Brain Stimulation ◽

Rating Scale ◽

Control Group ◽

Stn Dbs ◽

Deep Brain ◽

Stimulation Of

ObjectiveApathy has been reported as a possible adverse effect of deep brain stimulation of the subthalamic nucleus (STN-DBS). We investigated the prevalence and severity of apathy in 22 patients with Parkinson’s disease (PD) who underwent STN-DBS, as well as the effects of apathy on quality of life (QOL).MethodsAll patients were assessed with the Lille Apathy Rating Scale (LARS), the Apathy Scale (AS), and the Parkinson’s Disease Questionnaire and were compared to a control group of 38 patients on pharmacotherapy alone.ResultsThere were no significant differences in the prevalence or severity of apathy between patients who had undergone STN-DBS and those on pharmacotherapy alone. Significant correlations were observed between poorer QOL and degree of apathy, as measured by the LARS (p<0.001) and the AS (p=0.021). PD-related disability also correlated with both apathy ratings (p<0.001 and p=0.017, respectively).ConclusionOur findings suggest that STN-DBS is not necessarily associated with apathy in the PD population; however, more severe apathy appears to be associated with a higher level of disability due to PD and worse QOL, but no other clinico-demographic characteristics.

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Gut microbiota in Parkinson’s disease patients: hospital-based study

The Egyptian Journal of Neurology Psychiatry and Neurosurgery ◽

10.1186/s41983-021-00407-z ◽

2021 ◽

Vol 57 (1) ◽

Author(s):

Eman M. Khedr ◽

Anwar M. Ali ◽

Enas Deaf ◽

Hebatallah M. Hassan ◽

Ahmed Alaa ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Lactic Acid ◽

Gut Microbiota ◽

Rating Scale ◽

Pesticide Exposure ◽

Age Of Onset ◽

Significant Negative Correlation ◽

Control Group ◽

Dominant Type

Abstract Background Parkinson’s disease (PD) is one of the most common neurodegenerative diseases. There is accumulating evidence that link gut microbiota to symptomatology and pathophysiology of PD. The aim of this study was to describe the pattern of gut microbiota and its association with PD and identify the effect of environmental factors on gut microbiota. This case–control study included 46 patients diagnosed as Parkinson’s disease (PD) and 31 healthy volunteers age and sex matched. Detailed history including age of onset, duration of disease, environmental risk factors, diet data, treatment, Unified Parkinson’s Disease Rating Scale (UPDRS), and gastrointestinal tract (GIT) domain of Non‐Motor Symptoms Scale (NMSS) were assessed. After extraction of bacterial DNA from the fecal samples, bacterial abundance was quantified by qPCR using 16S rRNA group-specific primers. Results Significant high abundance of Clostridium cluster IV, Akkermansia, Bifidobacterium, and lactic acid bacteria were found in the PD group compared with the control group (P < 0.001, 0.04, 0.02 and < 0.001, respectively), while Firmicutes were significantly less abundant in the PD group (P < 0.001) compared with the control group. The naive PD patients had significant abundance of Bifidobacterium, and lactic acid compared with control group. Interestingly, Akkermansia was more abundant in treated than untreated patients. There were significant associations between pesticide exposure and Bifidobacterium (P = 0.002), while no significant correlations between different gut microbiota and demographic, environment data, different rating scores or dominant type of PD. There was a significant negative correlation between the Bifidobacterium with the duration of illness (P = 0.012). Conclusion The present study highlighted a significant connection between PD and levels of certain types of gut microbiota, in support of a possible link between gut microbiota and a neurodegenerative cascade of PD.

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