Publications by authors named "Cheng-Jie Mao"

61 Publications

Cognition and transcranial sonography in Parkinson's disease patients with or without orthostatic hypotension.

Brain Behav 2021 Jul 21. Epub 2021 Jul 21.

Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, China.

Background: Orthostatic hypotension (OH) is a common nonmotor symptom in patients with Parkinson's disease (PD), with an incidence ranging from 14% to 54%.

Aims: This study explored changes in cognition and transcranial sonography (TCS) findings in patients with PD and OH.

Methods: We enrolled PD patients who visited the outpatient or inpatient department from 2017 to 2020. Blood pressure was measured in different positions, and demographic data were collected. Motor and nonmotor symptoms were evaluated using standard scales. A subset of 107 patients underwent TCS.

Results: We enrolled 66 PD-OH patients and 92 PD-no orthostatic hypotension (NOH) patients. There were no significant differences in gender, age, disease duration, or Hoehn and Yahr stage between groups. Binary logistic regression revealed age as an independent risk factor for OH in PD patients. There were statistically significant group differences in visuospatial and executive function and Unified Parkinson's Disease Rating Scale (UPDRS) I and II scores (p < .05). Among PD-OH patients, there was a statistically significant difference in UPDRS II and III scores between patients with or without clinical symptoms (p < .05). The substantia nigra (SN) area was significantly larger in PD-NOH patients (0.45 ± 0.18 cm ) than PD-OH patients (0.34 ± 0.16 cm ) (p < .05).

Conclusions: PD-OH patients had poorer visuospatial and executive function and lower UPDRS I and II scores compared with PD-NOH patients. Within the PD-OH group, there was no significant difference in cognition between patients with or without clinical symptoms. The difference in the SN area may indicate different subtypes of PD or a tendency to develop parkinsonism syndrome.
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http://dx.doi.org/10.1002/brb3.2252DOI Listing
July 2021

Association between homocysteine and third ventricle dilatation, mesencephalic area atrophy in Parkinson's disease with cognitive impairment.

J Clin Neurosci 2021 Aug 21;90:273-278. Epub 2021 Jun 21.

Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China.

Objectives: This study aimed to explore the association of homocysteine (Hcy) with third ventricle (V3) dilatation and mesencephalic area (MA) atrophy as determined by transcranial sonography (TCS) in Parkinson's disease (PD) with cognitive impairment.

Methods: The final statistical analysis included 101 PD patients and 20 age- and sex-matched controls. Using the Movement Disorder Society (MDS) level II criteria for PD with cognitive impairment, we categorized the PD patients into PD with normal cognition group (PD) and PD with cognitive impairment group (PDC). All subjects underwent TCS and laboratory analysis.

Results: The V3 width (r = 0.349, P = 0.005) and the MA (r = -0.484, P < 0.001) were significantly correlated with the Hcy concentration in the PDC patients. Binary logistic regression analysis revealed that age (OR [95% CI] = 1.114 [0.991-1.251], P = 0.002), and Hcy level (OR [95% CI] = 0.931 [0.752-1.153], P = 0.411) were independent risk factors for V3 dilatation. Hcy level (OR [95% CI] = 0.557 [0.323-0.967], P = 0.035) were independent risk factors for MA atrophy. After adjustment for confounding factors, the odds ratio of V3 dilatation was 3.50 (95% CI 1.054-11.399, P = 0.031) and the odds ratio of MA atrophy was 4.67 (95% CI 1.395-15.602, P = 0.012) in the patients with higher Hcy level compared with the lower level.

Conclusions: The results revealed a close association between the V3 width, MA and Hcy concentration in PD patients with cognitive impairment. We hypothesized that increased Hcy concentration played a significant role in the development of brain atrophy in PD with cognitive impairment.
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http://dx.doi.org/10.1016/j.jocn.2021.06.006DOI Listing
August 2021

Effect of Sleep-Disordered Breathing During Rapid Eye Movement Sleep and Non-Rapid Eye Movement sleep on Acute Ischemic Stroke.

J Stroke Cerebrovasc Dis 2021 Aug 12;30(8):105913. Epub 2021 Jun 12.

Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China; Department of Neurology, Taicang Affiliated Hospital of Soochow University, The first People's Hospital of Taicang, Taicang 215400, China; Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou 215123, China. Electronic address:

Objectives: Sleep-disordered breathing adversely impacts stroke outcomes. We investigated whether sleep-disordered breathing during rapid eye movement sleep and non-rapid eye movement sleep differentially influenced stroke outcomes.

Materials And Methods: Acute ischemic stroke patients who finished polysomnography within 14 days of stroke onset from April 2010 to August 2018 were reviewed. Patients were divided into four groups according to apnea-hypopnea index during rapid eye movement sleep and non-rapid eye movement sleep. The modified Rankin Scale was used to evaluate short-term outcome. During January and April 2019, another follow-up was performed for long-term outcomes, including stroke-specific quality-of-life scale, modified Rankin Scale, stroke recurrence and death.

Results: Of 140 patients reviewed, 109 were finally recruited. Although patients with sleep-disordered breathing during non-rapid eye movement sleep only and with sleep-disordered breathing during both rapid eye movement sleep and non-rapid eye movement sleep had higher apnea-hypopnea indices and more disrupted sleep structures, short-term and long-term outcomes did not significantly different between four groups. In Logistic regression analysis, apnea-hypopnea index (p = 0.013, OR 1.023, 95%CI 1.005-1.042) was found independently associated with short-term outcome. Rapid eye movement sleep latency (p = 0.045, OR 0.994, 95%CI 0.987-1.000) was found independently associated with quality of life. Apnea-hypopnea indices during rapid eye movement sleep or non-rapid eye movement sleep were not significantly associated with short-term or long-term outcomes.

Conclusions: Apnea-hypopnea index is an independent risk factor of short-term outcome of acute ischemic stroke while sleep-disordered breathing during rapid eye movement sleep and non-rapid eye movement sleep do not affect stroke outcomes differently.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.105913DOI Listing
August 2021

Sex and onset-age-related features of excessive daytime sleepiness and night-time sleep in patients with Parkinson's disease.

BMC Neurol 2021 Apr 19;21(1):165. Epub 2021 Apr 19.

Department of Neurology and Suzhou Clinical Research Center of Neurological Diseases, the Second Affiliated Hospital of Soochow University, Suzhou, 215004, Jiangsu Province, China.

Background: The clinical characteristics of Parkinson's disease (PD) differ between men and women, and late- and early-onset patients, including motor symptoms and some nonmotor symptoms, such as cognition, anxiety, and depression.

Objective: To explore the features of excessive daytime sleepiness (EDS) and night-time sleep quality in PD patients of different sexes and age at onset (AAO).

Methods: Demographic data and clinical characteristics of 586 PD patients were collected. Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI) were used to investigate the daytime drowsiness and nocturnal sleep. Multivariate logistic regression analysis was used to explore the risk factors of EDS and poor night-time sleep quality.

Results: Sleep disorders were common in PD patients. EDS was more prominent in men than in women. There was no significant difference in ESS scores between late-onset PD (LOPD) and early-onset PD. LOPD patients had a higher probability of poor night-time sleep quality. Male sex, disease duration, and depression were risk factors for EDS. In all patients of both sexes and all AAO, depression was a risk factor for poor night-time sleep.

Conclusion: More attention should be paid to sleep disorders of PD patients, especially male LOPD patients. Depression is a common risk factor for EDS and poor sleep quality in PD patients.
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http://dx.doi.org/10.1186/s12883-021-02192-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054359PMC
April 2021

Depression Induced by Chronic Unpredictable Mild Stress Increases Susceptibility to Parkinson's Disease in Mice via Neuroinflammation Mediated by P2X7 Receptor.

ACS Chem Neurosci 2021 04 18;12(7):1262-1272. Epub 2021 Mar 18.

Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China.

The relationship between depression and Parkinson's disease (PD) is complicated and still not fully understood. We investigated whether depression increased the susceptibility to PD and whether this resulted from neuroinflammation mediated by purinergic ligand-gated ion channel 7 receptor (P2X7R) of microglia in mice. Depression was induced by a 14-day chronic unpredictable mild stress (CUMS), and PD was induced by 1-day acute injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Before MPTP administration, some mice were given brilliant blue G (BBG), a P2X7R inhibitor. Changes in depression and motor function were assessed by sucrose preference, tail suspension, open field, and rotating rod tests. Differences in P2X7R, caspase-1, NLRP3 inflammasome, interleukin (IL)-1β, tyrosine hydroxylase (TH), and microglial activation among experimental groups were detected by immunofluorescence, immunohistochemistry, western blotting, and ELISA. CUMS-induced depression-like behavior, and MPTP induced PD in mice. CUMS mice had no motor dysfunction, but the dyskinesia and loss of TH-positive neurons in the substantia nigra after MPTP treatment were more serious than with MPTP treatment alone. With behavioral changes, neuroinflammatory markers, such as caspase-1, NLRP3 and IL-1β increased, and microglia were activated as well as expression of P2X7R increased. Additionally, BBG partly reversed the above abnormalities. Summarily, we suggest that CUMS aggravates dyskinesia and death of dopaminergic neurons in an MPTP-PD model via promoting activation of microglia and neuroinflammation, which may be mediated by P2X7R. Inhibition of P2X7R could be a new control strategy for PD associated with depression.
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http://dx.doi.org/10.1021/acschemneuro.1c00095DOI Listing
April 2021

Fatigue correlates with sleep disturbances in Parkinson disease.

Chin Med J (Engl) 2020 Dec 16;134(6):668-674. Epub 2020 Dec 16.

Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China.

Background: Many Parkinson disease (PD) patients complain about chronic fatigue and sleep disturbances during the night. The objective of this study is to determine the relationship between fatigue and sleep disturbances by using polysomnography (PSG) in PD patients.

Methods: Two hundred and thirty-two PD patients (152 with mild fatigue and 80 with severe fatigue) were recruited in this study. Demographic information and clinical symptoms were collected. Fatigue severity scale (FSS) was applied to evaluate the severity of fatigue, and PSG was conducted in all PD patients. FSS ≥4 was defined as severe fatigue, and FSS <4 was defined as mild fatigue. Multivariate logistic regression and linear regression models were used to investigate the associations between fatigue and sleep disturbances.

Results: Patients with severe fatigue tended to have a longer duration of disease, higher Unified Parkinson Disease Rating Scale score, more advanced Hoehn and Yahr stage, higher daily levodopa equivalent dose, worse depression, anxiety, and higher daytime sleepiness score. In addition, they had lower percentage of rapid eye movement (REM) sleep (P = 0.009) and were more likely to have REM sleep behavior disorder (RBD) (P = 0.018). Multivariate logistic regression analyses found that the presence of RBD and proportion of REM sleep were the independent predictors for fatigue. After the adjustment of age, sex, duration, body mass index, severity of disease, scores of Hamilton Rating Scale for Depression, Hamilton Anxiety Rating Scale, and other sleep disorders, proportion of REM sleep and degree of REM sleep without atonia in patients with PD were still associated with FSS score.

Conclusion: Considering the association between fatigue, RBD, and the altered sleep architecture, fatigue is a special subtype in PD and more studies should be focused on this debilitating symptom.
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http://dx.doi.org/10.1097/CM9.0000000000001303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990014PMC
December 2020

Shear wave elastography characteristics of upper limb muscle in rigidity-dominant Parkinson's disease.

Neurol Sci 2021 Feb 4. Epub 2021 Feb 4.

Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, China.

Background: Rigidity is one of the major manifestations of Parkinson's disease (PD), but no quantitative and objective imaging method has been developed to measure rigidity. Ultrasound shear wave elastography (SWE) can reflect the stiffness of tissue by providing a quantitative index. Thus, we conducted this study to evaluate the potential clinical value of SWE in assessing rigidity in PD.

Methods: A total of 63 subjects (44 patients with rigidity-dominant PD and 19 right-dominant-hand normal controls with matched age) were enrolled, and each underwent ultrasound SWE testing. The tests were conducted on the brachioradialis (BR) and biceps brachii (BB) on the more affected side in patients with PD and on the right side in normal controls. Differences in quantitative shear wave velocity (SWV) between patients with PD and normal controls were determined. The relationship of muscle SWV with joint rigidity, UPDRSIII, disease duration, sex, and age in patients with PD was analyzed. The intraclass correlation coefficient (ICC) was used to evaluate the reliability of SWE in assessing muscle stiffness in patients with PD.

Results: The mean SWVs of the BB and BR were higher in the PD group (3.65±0.46 and 4.62±0.89 m/s, respectively) than in normal controls (2.79±0.37 and 3.26±0.40 m/s, respectively). Stiffness in BR and BB was correlated with the upper-limb joint rigidity, UPDRSIII, and disease duration but not with sex or age in the PD group. The intraobserver correlation coefficients (ICCs) for interobserver and intraobserver variations in measuring SWV were 0.85 (95% confidence interval 0.56-0.95) and 0.85 (95% confidence interval 0.58-0.95), respectively, for BR and 0.90 (95% confidence interval 0.73-0.97) and 0.86 (95% confidence interval 0.61-0.95), respectively, for BB.

Conclusions: SWV is associated with joint rigidity and disease duration, indicating that SWE can be potentially used as an objective and quantitative tool for evaluating rigidity.
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http://dx.doi.org/10.1007/s10072-021-05088-3DOI Listing
February 2021

Correlations between retinal nerve fiber layer thickness and cognitive progression in Parkinson's disease: A longitudinal study.

Parkinsonism Relat Disord 2021 01 28;82:92-97. Epub 2020 Nov 28.

Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China; Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, China. Electronic address:

Background: Retinal abnormalities measured by optical coherence tomography (OCT) have been detected in both Parkinson's disease (PD) and Alzheimer's disease (AD). Cognitive impairment is not only found in AD, but 75-90% of PD patients will also develop dementia in the late stage of disease. We assessed whether baseline retinal nerve fiber layer (RNFL) thickness predicted worsening of cognitive status over time and the correlation between RNFL thickness and the detailed impaired cognitive domains in PD.

Methods: RNFL thickness was measured using high-definition OCT in 78 non-dementia PD patients. Clinical and cognitive assessments were performed at baseline and at 3.61 ± 0.65 years follow-up. Linear mixed-effects models were used to examine associations between RNFL thickness and the changes in cognitive test scores, after adjusting for age, sex, disease duration and education.

Results: Analysis of outcomes according to baseline RNFL tertiles showed worse performance in global cognitive tests, delayed memory, and executive functions in patients with a thin RNFL. During follow-up, greater cognitive deterioration was found in thin RNFL tertile patients. Lower baseline average RNFL thickness was associated with greater annualized decline in Mini-Mental State Examination and Montreal Cognitive Assessment.

Conclusion: The correlation between RNFL thickness and cognitive dysfunction suggests that OCT may be useful for predicting cognitive dysfunction in PD patients.
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http://dx.doi.org/10.1016/j.parkreldis.2020.11.025DOI Listing
January 2021

Low-Frequency Repetitive Transcranial Magnetic Stimulation over Right Dorsolateral Prefrontal Cortex in Parkinson's Disease.

Parkinsons Dis 2020 14;2020:7295414. Epub 2020 Sep 14.

Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China.

Background: Repetitive transcranial magnetic stimulation (rTMS) is a promising therapeutic tool for Parkinson's disease (PD), and many stimulation targets have been implicated. We aim to explore whether low-frequency rTMS over the right dorsolateral prefrontal cortex (DLPFC) improves motor and nonmotor symptoms of individuals with PD.

Methods: We conducted a randomized, single-blind, sham-controlled parallel trial to compare the effect of 10 consecutive daily sessions of 1 Hz rTMS over right DLPFC on individuals with idiopathic PD between active and sham rTMS group. Primary outcomes were changes in Unified Parkinson's Disease Rating Scale (UPDRS) part III and Nonmotor Symptom Questionnaire (NMSQ). Secondary outcomes were changes in UPDRS total score, Hamilton Rating Scale for Depression (HRSD), Pittsburgh Sleep Quality Index (PSQI), and Montreal Cognitive Assessment (MoCA). Assessments were completed at baseline, after treatment, and at 1 month, 3 months, and 6 months after treatment.

Results: A total of 33 participants with PD were randomized. All participants completed the study and no severe adverse effect was noticed. Compared to baseline, active rTMS showed significant improvements in UPDRS part III and NMSQ at 1 month. Change of scores on UPDRS part III, HRSD, and PSQI persisted for 3 months after rTMS intervention. The beneficial effect on cognitive performance assessed by MoCA was maintained for at least 6 months in the follow-up. No significant changes were observed in the group with sham rTMS.

Conclusions: Low-frequency rTMS of right DLPFC could be a potential selection in managing motor and nonmotor symptoms in PD.
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http://dx.doi.org/10.1155/2020/7295414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509565PMC
September 2020

Echogenicity Changes in Brainstem Raphe Detected by Transcranial Parenchymal Sonography and Clinical Characteristics in Parkinson's Disease.

Front Neurol 2020 7;11:821. Epub 2020 Aug 7.

Department of Neurology and Suzhou Clinical Research Center of Neurological Diseases, The Second Affiliated Hospital of Soochow University, Suzhou, China.

Decreased brainstem raphe (BR) echogenicity detected by transcranial parenchymal sonography (TCS) is associated with depression in psychiatric and neurologic diseases. However, previous studies focusing on the relationship between motor and non-motor symptoms and echogenicity changes in BR in patients with PD yielded controversial results. To investigate the relationship between echogenicity changes in BR detected by TCS and motor and a series of non-motor symptoms in patients with PD. Consecutive PD patients were recruited from the Second Affiliated Hospital of Soochow University. Demographic information and Motor and non-motor symptoms for all subjects were collected. TCS was used to detect the echogenicity changes in BR in PD patients. One hundred and thirty-five consecutive patients with PD were enrolled in the study. The BR abnormal rate was significantly higher in PD patients with anxiety ( = 0.003) or depression ( = 0.022) than patients without. Spearman correlation analyses showed that Hamilton Rating Scale for Depression(HRSD) ( = 0.274, = 0.002) and Parkinson's Disease Questionnaire 39-item(PDQ-39) ( = 0.208, = 0.034) scores were positively correlated with abnormal BR echogenicity. Multivariate logistic regression analyses showed that HRSD and HAMA scores were associated with BR hypoechogenicity, the corresponding odds ratios (confidence intervals) were 1.07 (95% CI, 1.01-1.13) and 1.10(1.01-1.18), respectively. However, the PDQ-39 score was not associated with BR hypoechogenicity. The abnormal reduction in BR echogenicity detected by TCS is associated with depression and anxiety, but not motor symptoms in PD patients.
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http://dx.doi.org/10.3389/fneur.2020.00821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426486PMC
August 2020

Association of inflammatory factors and aging in Parkinson's disease.

Neurosci Lett 2020 09 16;736:135259. Epub 2020 Jul 16.

Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China; Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, Jiangsu 215123, China; Parkinson Disease Center of Beijing Institute for Brain Disorders, Beijing, China.

Background: Parkinson's disease as a common neurodegenerative disease, has been found to be related to inflammation. So we observed the characteristics of inflammatory indexes in patients with Parkinson's disease and investigated the relationship between inflammatory cytokines and clinical characteristics. Emerging data may reveal novel neuroinflammatory pathways and identify new targets for treatment of Parkinson's disease.

Methods: We examined the inflammatory indexes in 183 patients and 89 healthy controls in association with clinical characteristics.

Results: Patients had significantly higher levels of monocytes, neutrophils, high-sensitivity C-reactive protein, and monocyte-to-high-density lipoprotein ratios (p < 0.01) and lower levels of lymphocytes (p = 0.02) than the controls. There were no significant differences in age, leukocytes, high-density lipoprotein, or neutrophil-lymphocyte ratios between the two groups (p > 0.05). Multivariate logistic regression analysis of these indicators revealed that lymphocyte level was a protective factor (p = 0.025, OR=-0.679), while high-sensitivity C-reactive protein level was a risk factor (p = 0.000, OR=1.168) for Parkinson's disease. High-sensitivity C-reactive protein levels were higher in older Parkinson's disease patients.

Conclusion: High-sensitivity C-reactive protein is positively related to the risk of Parkinson's disease, especially in aging patients. High-sensitivity C-reactive protein is a potential biomarker for disease progression and treatment response for Parkinson's disease.
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http://dx.doi.org/10.1016/j.neulet.2020.135259DOI Listing
September 2020

Substantia nigra echogenicity is associated with serum ferritin, gender and iron-related genes in Parkinson's disease.

Sci Rep 2020 05 26;10(1):8660. Epub 2020 May 26.

Department of Neurology, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.

Substantia nigra (SN) hyperechogenicity is present in most Parkinson's disease (PD) cases but is occasionally absent in some. To date, age, gender, disease severity, and other factors have been reported to be associated with SN hyperechogenicity in PD. Previous studies have discovered that excess iron deposition in the SN underlies its hyperechogenicity in PD, which may also indicate the involvement of genes associated with iron metabolism in hyperechogenicity. The objective of our study is to explore the potential associations between variants in iron metabolism-associated genes and SN echogenicity in Han Chinese PD. Demographic profiles, clinical data, SN echogenicity and genotypes were obtained from 221 Han Chinese PD individuals with a sufficient bone window. Serum ferritin levels were quantified in 92 of these individuals by immunochemical assay. We then compared factors between PD individuals with SN hyperechogenicity and those with SN hypoechogenicity to identify factors that predispose to SN hyperechogenicity. Of our 221 participants, 122 (55.2%) displayed SN hyperechogenicity, and 99 (44.8%) displayed SN hypoechogenicity. Gender and serum ferritin levels were found to be associated with SN hyperechogenicity. In total, 14 genes were included in the sequencing part. After data processing, 34 common single nucleotide polymorphisms were included in our further analyses. In our data, we also found a significantly higher frequency of PANK2 rs3737084 (genotype: OR = 2.07, P = 0.013; allele: OR = 2.51, P = 0.002) in the SN hyperechogenic group and a higher frequency of PLA2G6 rs731821 (genotype: OR = 0.45, P = 0.016; allele: OR = 0.44, P = 0.011) in the SN hypoechogenic group. However, neither of the two variants was found to be correlated with serum ferritin. This study demonstrated that genetic factors, serum ferritin level, and gender may explain the interindividual variability in SN echogenicity in PD. This is an explorative study, and further replication is warranted in larger samples and different populations.
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http://dx.doi.org/10.1038/s41598-020-65537-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7250839PMC
May 2020

Substantia nigra hyperechogenicity in Parkinson disease patients with leucine-rich repeat kinase 2 variants in the Chinese Han population.

Chin Med J (Engl) 2020 06;133(12):1483-1484

Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China.

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http://dx.doi.org/10.1097/CM9.0000000000000842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339339PMC
June 2020

Human iPSCs derived astrocytes rescue rotenone-induced mitochondrial dysfunction and dopaminergic neurodegeneration in vitro by donating functional mitochondria.

Transl Neurodegener 2020 04 24;9(1):13. Epub 2020 Apr 24.

Department of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA, 95817, USA.

Background: Parkinson's disease (PD) is one of the neurodegeneration diseases characterized by the gradual loss of dopaminergic (DA) neurons in the substantia nigra region of the brain. Substantial evidence indicates that at the cellular level mitochondrial dysfunction is a key factor leading to pathological features such as neuronal death and accumulation of misfolded α-synuclein aggregations. Autologous transplantation of healthy purified mitochondria has shown to attenuate phenotypes in vitro and in vivo models of PD. However, there are significant technical difficulties in obtaining large amounts of purified mitochondria with normal function. In addition, the half-life of mitochondria varies between days to a few weeks. Thus, identifying a continuous source of healthy mitochondria via intercellular mitochondrial transfer is an attractive option for therapeutic purposes. In this study, we asked whether iPSCs derived astrocytes can serve as a donor to provide functional mitochondria and rescue injured DA neurons after rotenone exposure in an in vitro model of PD.

Methods: We generated DA neurons and astrocytes from human iPSCs and hESCs. We established an astroglial-neuronal co-culture system to investigate the intercellular mitochondrial transfer, as well as the neuroprotective effect of mitochondrial transfer. We employed immunocytochemistry and FACS analysis to track mitochondria.

Results: We showed evidence that iPSCs-derived astrocytes or astrocytic conditioned media (ACM) can rescue DA neurons degeneration via intercellular mitochondrial transfer in a rotenone induced in vitro PD model. Specifically, we showed that iPSCs-derived astrocytes from health spontaneously release functional mitochondria into the media. Mito-Tracker Green tagged astrocytic mitochondria were detected in the ACM and were shown to be internalized by the injured neurons via a phospho-p38 depended pathway. Transferred mitochondria were able to significantly reverse DA neurodegeneration and axonal pruning following exposure to rotenone. When rotenone injured neurons were cultured in presence of ACM depleted of mitochondria (by ultrafiltration), the neuroprotective effects were abolished.

Conclusions: Our studies provide the proof of principle that iPSCs-derived astrocytes can act as mitochondria donor to the injured DA neurons and attenuate pathology. Using iPSCs derived astrocytes as a donor can provide a novel strategy that can be further developed for cellular therapy for PD.
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http://dx.doi.org/10.1186/s40035-020-00190-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325238PMC
April 2020

Reduced cortical arousability to nocturnal apneic episodes in patients with wake-up ischemic stroke.

Sleep Med 2020 02 19;66:252-258. Epub 2019 Sep 19.

Department of Neurology, Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China; Department of Sleeping Center, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China; Jiangsu Key Laboratory of Neuropsychiatric Diseases, Institute of Neuroscience, Soochow University, Suzhou 215123, China. Electronic address:

Study Objectives: Sleep breathing disorders (SBD) have been linked to wake-up stroke (WUS). Respiratory arousals have an important role in responding to danger during sleep, yet currently no studies have investigated respiratory arousability in WUS. In this study, we used a clinical tool to predict low respiratory arousal threshold (ArTH), and then compared respiratory arousability in patients with WUS and non-WUS.

Methods: We enrolled 119 patients with acute ischemic stroke and assigned them into WUS (n = 34) and non-WUS (n = 85) groups. All participants underwent polysomnography (PSG) during the acute phase of stroke. The respiratory ArTH predictive tool assigns one point for each of the following: apnea-hypopnea index (AHI) < 30/h, nadir oxygen saturation (SaO) > 82.5%, and fraction of hypopneas > 58.3%. An ArTH score ≥2 represents low respiratory ArTH.

Results: Our results reconfirmed the association between moderate-to-severe sleep apnea syndrome and WUS (OR 2.879, 95% CI 1.17-7.089, p = 0.021). Significantly fewer participants with obstructive sleep apnea (AHI ≥ 5/h) had low respiratory ArTH in the WUS group than in the non-WUS group (34.8% vs. 68.1%, respectively, p = 0.008). High respiratory ArTH was independently associated with WUS (OR 5.556, 95% CI 1.959-15.761, p = 0.001).

Conclusions: The correlation between SBD and WUS suggests that sleep apnea might induce acute physiological changes that trigger the onset of stroke. We show that reduced respiratory arousability is associated with WUS, and hypothesize that reduced cortical capability to generate respiratory arousal may have a role in triggering stroke during sleep.
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http://dx.doi.org/10.1016/j.sleep.2019.09.007DOI Listing
February 2020

Hypertension with Hyperhomocysteinemia Increases the Risk of Early Cognitive Impairment after First-Ever Ischemic Stroke.

Eur Neurol 2019 11;82(4-6):75-85. Epub 2019 Dec 11.

Department of Neurology, Second Affiliated Hospital of Soochow University, Suzhou, China,

Background: Hypertension and hyperhomocysteinemia (HHcy) are independent risk factors of stroke and are associated with each other. Although evidence suggests that they are related to cognitive impairment, the relationship between hypertension accompanied with HHcy and poststroke cognitive impairment (PSCI) is unclear.

Objective: To define the relationship between hypertension with HHcy and early cognitive impairment after acute cerebral infarction.

Materials And Methods: Our study enrolled 232 patients with acute first-ever ischemic stroke. Patients were assigned to 3 groups by blood pressure and homocysteine (Hcy) levels: hypertension with HHcy, simple hypertension, or control. Cognition was assessed by the Montreal cognitive assessment at admission and at 3- and 6-month follow-ups.

Results: The hypertension with HHcy group exhibited the highest incidence of early cognitive impairment (simple hypertension: p = 0.000; control: p = 0.000). This group also had lower visual space/executive scores than the simple hypertension group (p = 0.000) and lower delayed recall scores than the control group (p = 0.011). Multivariate analysis showed that hypertension with HHcy (OR 7.797; 95% CI 2.917-20.843; p = 0.000), the level of serum Hcy (OR 1.063; 95% CI 1.109-1.109; p = 0.005), education years (OR 0.797; 95% CI 0.722-0.880; p = 0.000), and Fazekas scale of leukoaraiosis (OR 1.648; 95% CI 1.239-2.191; p = 0.001) were independent influencing factors of early PSCI; however, simple hypertension (OR 1.183, 95% CI 0.208-6.737; p = 0.850) and simple HHcy (OR 1.112, 95% CI 0.181-6.810; p = 0.909) were not.

Conclusion: Patients with both hypertension and HHcy are at an increased risk of early cognitive impairment after acute first-ever ischemic stroke.
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http://dx.doi.org/10.1159/000504704DOI Listing
June 2020

Relationship between 25-Hydroxyvitamin D, bone density, and Parkinson's disease symptoms.

Acta Neurol Scand 2019 Oct 6;140(4):274-280. Epub 2019 Aug 6.

Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China.

Objectives: Vitamin D deficiency is widespread in patients with Parkinson's disease (PD). Our aim was to determine whether serum vitamin D levels correlated with bone mineral density (BMD) and non-motor symptoms in patients with PD.

Materials & Methods: A consecutive series of 182 patients with PD and 185 healthy controls were included. Serum 25-hydroxyvitamin D (25[OH]D) levels were measured by immunoassay, while BMD of the lumbar spine and femoral neck was measured by dual-energy X-ray absorptiometry. Associations between serum vitamin D levels and clinical data were evaluated using partial correlation analysis.

Results: Patients with PD had significantly lower serum 25(OH)D levels relative to healthy controls (49.75 ± 14.11 vs 43.40 ± 16.51, P < 0.001). Furthermore, PD patients with lower vitamin D levels had a significantly higher frequency of falls (P = 0.033) and insomnia (P = 0.015). They also had significantly higher scores for the Pittsburgh Sleep Quality Index (PSQI; P = 0.014), depression (P = 0.020), and anxiety (P = 0.009). Finally, patients with PD also had a significantly lower mean BMD of the lumbar spine (P = 0.011) and femoral neck (P < 0.001). After adjusting for age, sex, and body mass index, vitamin D levels significantly correlated with falls, insomnia, and scores for the PSQI, depression, and anxiety.

Conclusions: In patients with PD, vitamin D levels significantly correlated with falls and some non-motor symptoms. However, no associations were found between BMD and the serum 25(OH)D levels in patients with PD. Thus, vitamin D supplementation is a potential therapeutic for non-motor PD symptoms.
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http://dx.doi.org/10.1111/ane.13141DOI Listing
October 2019

Nicotine improved the olfactory impairment in MPTP-induced mouse model of Parkinson's disease.

Neurotoxicology 2019 07 10;73:175-182. Epub 2019 Apr 10.

Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China; Institute of Neuroscience, Soochow University, Suzhou, 215123, China; Department of Neurology, Suzhou Municipal Hospital of Nanjing Medical University, Suzhou, 215008, China. Electronic address:

Olfactory impairment is an early feature of patients with Parkinson's disease (PD). Retrospective epidemiological studies reported lower scores on the University of Pennsylvania Smell Identification Test (UPSIT) in non-smokers than smokers with PD and showed an inverse correlation between susceptibility to PD and a person's history of smoking. But the mechanisms by which cigarettes affect olfaction in PD are not fully understood. So we investigated the effect of nicotine on the olfactory function in 1-methyl-4-phenyl-1, 2, 3, 6 tetrahydropyridine (MPTP)-treated mice. We observed that nicotine improved locomotor activity and protection against dopaminergic neuron loss in the midbrain in MPTP-treated mice. Compared to controls, MPTP-treated mice showed a deficit of odor discrimination and odor detection, which were alleviated by nicotine treatment. But no significant changes were found in olfactory memory in MPTP-treated mice. Moreover, we detected a marked decrease of Choline acetyltransferase (ChAT) expression in the olfactory bulb (OB) in MPTP-treated mice, which was also attenuated by nicotine administration. In addition, nicotine ameliorated the loss of cholinergic neurons and dopaminergic innervation in the horizontal limb of the diagonal band (HDB), which is the primary origin of cholinergic input to the OB. Our results suggested that nicotine could improve the olfactory impairment by protecting cholinergic systems in the OB of MPTP-treated mice. And nicotine protection of cholinergic systems in the OB is relevant to attenuating dopaminergic neuron loss in the midbrain and HDB.
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http://dx.doi.org/10.1016/j.neuro.2019.02.008DOI Listing
July 2019

A Critical Role of Autophagy in Regulating Microglia Polarization in Neurodegeneration.

Front Aging Neurosci 2018 20;10:378. Epub 2018 Nov 20.

Department of Neurology, Suzhou Clinical Research Center of Neurological Disease, Suzhou Municipal Hospital of Nanjing Medical University, Suzhou, China.

Neuroinflammation and autophagy dysfunction are closely related to the development of neurodegeneration such as Parkinson's disease (PD). However, the role of autophagy in microglia polarization and neuroinflammation is poorly understood. TNF-α, which is highly toxic to dopaminergic neurons, is implicated as a major mediator of neuroinflammation in PD. In this study, we found that TNF-α resulted in an impairment of autophagic flux in microglia. Concomitantly, an increase of M1 marker (iNOS/NO, IL-1β, and IL-6) expression and reduction of M2 marker (Arginase1, Ym1/2, and IL-10) were observed in TNF-α challenged microglia. Upregulation of autophagy via serum deprivation or pharmacologic activators (rapamycin and resveratrol) promoted microglia polarization toward M2 phenotype, as evidenced by suppressed M1 and elevated M2 gene expression, while inhibition of autophagy with 3-MA or Atg5 siRNA consistently aggravated the M1 polarization induced by TNF-α. Moreover, Atg5 knockdown alone was sufficient to trigger microglia activation toward M1 status. More important, TNF-α stimulated microglia conditioned medium caused neurotoxicity when added to neuronal cells. The neurotoxicity was further aggravated when Atg5 knockdown in BV2 cells but alleviated when microglia pretreatment with rapamycin. Activation of AKT/mTOR signaling may contribute to the changes of autophagy and inflammation as the AKT specific inhibitor perifosine prevented the increase of LC3II (an autophagic marker) in TNF-α stimulated microglia. Taking together, our results demonstrate that TNF-α inhibits autophagy in microglia through AKT/mTOR signaling pathway, and autophagy enhancement can promote microglia polarization toward M2 phenotype and inflammation resolution.
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http://dx.doi.org/10.3389/fnagi.2018.00378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6256089PMC
November 2018

Genetic analysis of LRRK2 in Parkinson's disease in Han Chinese population.

Neurobiol Aging 2018 12 4;72:187.e5-187.e10. Epub 2018 Jul 4.

Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China; Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, China; Parkinson Disease Center of Beijing Institute for Brain Disorders, Beijing, China. Electronic address:

Mutations in Leucine-rich repeat kinase 2 (LRRK2) are recognized as the most frequent genetic factors contributing to Parkinson's disease (PD). The aim of our study was to explore LRRK2 variants in PD patients within the mainland Han Chinese population. The whole coding regions of LRRK2 from 296 PD patients were sequenced by targeted regions sequencing and exome sequencing. Eighteen rare variants were identified in 27 PD patients, and 13 of them (M100T, L153W, A459S, S722N, R792K, C925Y, R981K, S1007T, V1447M, R1677S, N2308D, N2313S, and S2350I) were firstly reported in PD. We also tried to explore the genotype-phenotype associations of LRRK2 variants in our data and found that PD with common and rare LRRK2 variants was more likely to have motor fluctuation and nonmotor symptoms. The identification of novel variants in LRRK2 suggests that this gene plays an important role in the pathogenesis and phenotype of PD in Han Chinese population, and our data also rang the alarm bell-more attention should be paid to the whole coding regions of LRRK2.
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http://dx.doi.org/10.1016/j.neurobiolaging.2018.06.036DOI Listing
December 2018

Analysis of nocturnal hypokinesia and sleep quality in Parkinson's disease.

J Clin Neurosci 2018 Aug 13;54:96-101. Epub 2018 Jun 13.

Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China; Institute of Neuroscience, Soochow University, Suzhou 215123, China. Electronic address:

Nocturnal hypokinesia/akinesia and sleep disorder are believed to be common in Parkinson's disease (PD), but are often underestimated. To date, only a few studies have focused on nocturnal symptoms related to motor function and sleep quality in PD patients, and the assessments were based mainly on the subjective descriptions of the patients. In this study, we assessed the relationships between motor symptoms and sleep quality in 29 PD patients (17 PD patients reporting impaired bed mobility (IBM) and 12 patients without IBM). All the participants were monitored using multisite inertial sensors and polysomnography in sleep-monitoring rooms for whole night. Compared with PD-IBM patients, PD+IBM patients tended to have fewer turning-over episodes and smaller degree turns. Meanwhile, PD+IBM patients had worse Pittsburgh Sleep Quality Index (PSQI) and Parkinson's Disease Sleep Scale (PDSS) scores, and less total sleep time (TST) than PD-IBM patients. Spearman correlation analyses found that the number of turning-over events showed negative correlations with disease duration (r = -0.378, P < 0.05) and Unified Parkinson's Disease Rating Scale (UPDRS) axial scores (r = -0.370, P < 0.05). Moreover, TST (r = 0.505, p < 0.05) and sleep efficiency (SE) (r = 0.473, p < 0.05) positively correlated with the number of turns in bed. Multivariate linear regression analyses showed that UPDRS axial scores and the number of turns were significantly associated with TST (both p < 0.05). In conclusion, the number of turns in bed and UPDRS axial scores were two significant factors affecting sleep quality. Multisite inertial sensors can be used to quantitatively evaluate nocturnal motor functions in PD patients.
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http://dx.doi.org/10.1016/j.jocn.2018.06.016DOI Listing
August 2018

Effect of Rapid Eye Movement Sleep Behavior Disorder on Obstructive Sleep Apnea Severity and Cognition of Parkinson's Disease Patients.

Chin Med J (Engl) 2018 Apr;131(8):899-906

Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China.

Background: Rapid eye movement (REM) sleep behavior disorder (RBD) and obstructive sleep apnea (OSA) are the most common sleep disorders in Parkinson's disease (PD). The aim of this study was to identify whether RBD could alleviate OSA severity in PD patients and its effect on cognitive impairment.

Methods: From February 2014 to May 2017, we recruited 174 PD patients from the Second Affiliated Hospital of Soochow University, all of whom underwent polysomnography (PSG). We collected clinical data, PSG results, and compared information between patients with and without RBD or OSA by analysis of covariance. We also investigated the effect of these sleep disorders on cognitive impairment using linear regression.

Results: We grouped participants as follows: PD only (n = 53), PD + OSA (n = 29), PD + RBD (n = 61), and PD + RBD + OSA (n = 31). Minimum oxygen saturation (SaO) during whole sleep and in REM sleep was higher in PD + RBD + OSA patients than that in PD + OSA patients. PD + RBD patients had worse Mini-Mental Status Examination and Montreal Cognitive Assessment (MoCA) scores than those in the PD group (P < 0.001), especially in visuospatial/executive, attention, and memory functions. The PD + OSA group performed worse than the PD group in the delayed recall domain. After adjusting for age, sex, body mass index, education, disease severity, and other sleep disorders, MoCA was negatively associated with OSA (β = -0.736, P = 0.043) and RBD (β = -2.575,P < 0.001). The severity of RBD (tonic/phasic electromyography activity) and OSA (apnea-hypopnea index/oxygen desaturation index/minimum SaO) were also associated with MoCA. The adjusted β values of RBD-related parameters were higher than that for OSA.

Conclusions: We found that RBD alleviated OSA severity; however, RBD and OSA together exacerbated PD cognitive impairment. Further studies are needed to evaluate whether OSA treatment can improve cognition in PD.
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http://dx.doi.org/10.4103/0366-6999.229888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5912054PMC
April 2018

Investigation of non-motor symptoms in first-degree relatives of patients with Parkinson's disease.

Parkinsonism Relat Disord 2018 07 27;52:62-68. Epub 2018 Mar 27.

Department of Neurology, Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China; Institute of Neuroscience, Soochow University, Suzhou, Jiangsu, China. Electronic address:

Objective: Non-motor symptoms (NMS) are important prodromal characteristics of Parkinson's disease (PD). However, the incidence of NMS in first-degree relatives, such as siblings of PD patients, is still unknown.

Methods: A total of 98 PD patients of the Affiliated Hospital of Yangzhou University were recruited; 210 siblings of these patients were included in a first-degree relatives (FDR) group and 250 healthy individuals were included in a control group. Various scales were used to assess NMS, including depression, anxiety, cognitive function, sleep status, constipation, daytime sleepiness, Rapid-Eye-Movement Sleep Behavior Disorder (RBD), and Restless Legs Syndrome (RLS).

Results: NMS were more common in the PD group than the control group. The incidence of anxiety (OR = 3.434, 95%CI: 2.058-5.731, P < 0.001), depression (OR = 2.438, 95%CI: 1.289-4.609, P = 0.005), and RBD (OR = 4.120, 95%CI: 1.897-8.945, P < 0.001) was higher in the FDR group than the control group. There were non-significant differences in constipation, cognitive impairment, sleep disorder, daytime sleepiness, and RLS between the two groups. The incidence of RLS in FDR of PD with an age of onset <60 years was higher than in the controls (OR = 2.273, 95%CI: 1.107-4.667, P = 0.023).

Conclusions: Siblings of PD are more likely to suffer from anxiety, depression and RBD than the general population. RLS is more common in siblings of PD with onset age<60 than in the general population. It is speculated that PD patients and their siblings have common pathogenic genetic factors and early living environment for neurodegeneration.
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http://dx.doi.org/10.1016/j.parkreldis.2018.03.021DOI Listing
July 2018

A novel p.L216I mutation in the glucocerebrosidase gene is associated with Parkinson's disease in Han Chinese patients.

Neurosci Lett 2018 05 9;674:66-69. Epub 2018 Mar 9.

Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China; Institute of Neuroscience, Soochow University, Suzhou 215123, China; Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Soochow University, Suzhou, China; Parkinson Disease Center of Beijing Institute for Brain Disorders, Beijing, China. Electronic address:

Objectives: Pathogenic mutations in the glucocerebrosidase (GBA) gene are associated with Parkinson's disease (PD), of which L444P and N370S are the most frequently observed in patients with PD. The aim of this study was to systematically explore variations in the coding regions of GBA in Han Chinese patients with PD, as well as to expand the GBA mutation spectrum.

Material And Methods: A total of 213 Han Chinese patients with PD and 348 controls were enrolled in the study. Whole coding regions of GBA were captured and sequenced by target region sequencing. Sanger sequencing was also used to confirm the identified variants.

Results: We identified a novel variant (c. C646A; p.L216I; NM_001171811.1) of GBA in two unrelated patients, which was not observed in the controls. Both patients had early-onset PD and neither exhibited any motor-related symptoms. However, we did not find an L444P or N370S mutations in our patients.

Conclusions: The p.L216I mutation is a novel GBA mutation, which we identified in two Han Chinese patients with PD. The patients exhibited similar characteristics, which differed from those seen in patients with other GBA mutations. Future work is needed to investigate this mutation further, as well as larger cohort studies to explore other GBA mutations associated with PD in the Han Chinese and in other populations.
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http://dx.doi.org/10.1016/j.neulet.2018.03.017DOI Listing
May 2018

Progressive Changes in the Retinal Structure of Patients with Parkinson's Disease.

J Parkinsons Dis 2018 ;8(1):85-92

Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China.

Background: Many optical coherence tomography (OCT) studies have reported alterations in the retinal nerve fiber layer (RNFL) in Parkinson's disease (PD) and other neurodegenerative diseases. However, whether retinal alterations are a biomarker for PD is still controversial.

Objective: To investigate potential correlations between PD and morphological changes in retina using OCT and to determine its usefulness as a biomarker of disease progression in PD.

Methods: We performed a cross-sectional study on patients with PD (N = 37) and age-matched controls (N = 42), followed by a longitudinal study of the PD patients (N = 22) over approximately 2.5 years.

Results: The average retinal nerve fiber layer (RNFL) thickness (p < 0.001), total macular thickness (p = 0.001), and macular volume (p = 0.001) were decreased in PD patients compared to controls and had further decreased at the follow-up visit (p < 0.05 for all). The average RNFL thickness and the total thickness of macular were negatively correlated with age in PD patients at baseline. Linear regression analysis revealed that age (p = 0.002, p = 0.003, respectively) and LEDD (p = 0.011, p = 0.013, respectively) were correlated to total thickness and volume of macular in 22 PD patients in the follow-up study. However, no correlation was found between RNFL and other parameters.

Conclusions: PD progression is associated with pronounced retinal structure changes, which can be quantified by OCT. Patterns of RNFL and macular damage detected by the noninvasive technology of OCT can be a useful biomarker for evaluating the progression of PD.
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http://dx.doi.org/10.3233/JPD-171184DOI Listing
October 2019

Poor nighttime sleep is positively associated with dyskinesia in Parkinson's disease patients.

Parkinsonism Relat Disord 2018 03 21;48:68-73. Epub 2017 Dec 21.

Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, the Second Affiliated Hospital of Soochow University, Suzhou 215004, China; Institute of Neuroscience, Soochow University, Suzhou 215123 China. Electronic address:

Background: Dyskinesia is a troublesome complication of long-term dopaminergic medications in Parkinson's disease (PD) patients. Many factors are reported to be associated with dyskinesia in PD.

Objective: To investigate the association between sleep quality and dyskinesia in patients with PD.

Methods: Four hundred twenty-five patients with PD were enrolled in this study. Demographic information was collected. Unified Parkinson's Disease Rating Scale (UPDRS) and Hoehn and Yahr (H-Y) stage scale were also performed. Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI) were applied to evaluate daytime sleepiness and overall nighttime sleep quality, respectively, in PD patients.

Results: Patients with dyskinesia tended to have a longer duration of disease, higher daily levodopa-equivalent dose (LED), H-Y stage, UPDRS II and PSQI score, and a higher percentage of levodopa treatment than those without dyskinesia. After adjusting for age, sex, age at onset of PD, disease duration, UPDRS I, UPDRS II, UPDRS III, cigarette smoking, use of different antiparkinsonian drugs, phenotype, daily LED, and restless leg syndrome (RLS), PSQI score was still associated with dyskinesia, with corresponding ORs 1.111 (95% CI, 1.004-1.229) as a continuous variable, and 2.469 (95% CI, 1.051-5.800) as a categorical variable, respectively. Further analysis of PSQI components showed that subjective sleep quality and sleep latency were associated with dyskinesia in PD patients.

Conclusions: Our data showed that poor nighttime sleep is positively associated with dyskinesia in PD patients. Attention to the management of nighttime sleep quality may be beneficial to dyskinesia in patients with PD.
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http://dx.doi.org/10.1016/j.parkreldis.2017.12.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5949046PMC
March 2018

Serum sodium and chloride are inversely associated with dyskinesia in Parkinson's disease patients.

Brain Behav 2017 12 9;7(12):e00867. Epub 2017 Nov 9.

Department of Neurology and Suzhou Clinical Research Center of Neurological Diseasethe Second Affiliated Hospital of Soochow University Suzhou China.

Objective: We aim to report and evaluate the associations between serum sodium and chloride and dyskinesia in patients with Parkinson's disease. One hundred and two patients with Parkinson's disease were enrolled in this study.

Methods: Patients' serum electrolytes including sodium, calcium, potassium, magnesium, and chloride were measured. Other demographic information was collected, and Unified Parkinson's disease rating scale and Hoehn and Yahr stage scale were also performed.

Results: Patients with dyskinesia tended to have longer duration of disease, higher daily levodopa-equivalent dose, and Hoehn-Yahr stage, with lower serum sodium than those without dyskinesia. Spearman correlation analyses showed that serum sodium inversely correlated with duration of disease ( = -.218, =.028), and positively correlated with serum chloride levels ( = .565, <.001). Univariate logistic regression analysis found that duration of disease, daily levodopa-equivalent dose, serum sodium, and serum chloride were associated with dyskinesia in Parkinson's disease patients (<.05 for all). After adjusting for age, sex, age at onset of Parkinson's disease, medical history, and other covariates, serum sodium and chloride were still associated with dyskinesia, with corresponding Odd ratios 0.783 (95% confidence intervals, 0.642-0.955) and 0.796 (95% confidence intervals, 0.652-0.972), respectively.

Conclusion: Our findings indicated that serum sodium and chloride levels were inversely associated with dyskinesia in patients with Parkinson's disease. Further studies with large samples and range of serum sodium and chloride are needed.
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http://dx.doi.org/10.1002/brb3.867DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5745246PMC
December 2017

Serum Response Factor Promotes Dopaminergic Neuron Survival via Activation of Beclin 1-Dependent Autophagy.

Neuroscience 2018 02 28;371:288-295. Epub 2017 Nov 28.

Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China; Institute of Neuroscience, Soochow University, Suzhou 215123, China. Electronic address:

Serum response factor (SRF), a transcription factor highly expressed in neurons, is involved in neuronal survival and the pathogenesis of some neurodegenerative disorders. The ablation of SRF renders the midbrain dopaminergic (DA) neurons vulnerable to 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine-induced neurotoxicity, however, the underlying mechanisms remain poorly understood. Here, we report decreased SRF levels in the substantia nigra (SN) of rotenone-treated rats that was associated with the loss of tyrosine hydroxylase (TH)-positive neurons. SRF expression was also reduced in rotenone-treated PC12 cells in vitro. In addition, Srf knockdown augmented rotenone-induced toxicity in PC12 cells. In contrast, overexpression of Srf attenuated the cells' sensitivity to rotenone and alleviated rotenone-induced α-synuclein accumulation. The protective effect of SRF was abolished when the expression of autophagy-related proteins Beclin 1 and Atg5 was suppressed. These results suggested that SRF may promote DA neuron survival by regulating autophagy, and thus serves as a critical molecule in PD progression.
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http://dx.doi.org/10.1016/j.neuroscience.2017.11.040DOI Listing
February 2018

Odor selectivity of hyposmia and cognitive impairment in patients with Parkinson's disease.

Clin Interv Aging 2017 9;12:1637-1644. Epub 2017 Oct 9.

Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, the Second Affiliated Hospital of Soochow University.

Objective: Hyposmia is one of the earliest non-motor features of Parkinson's disease (PD) and can precede the onset of motor symptoms by years. Most of the current olfactory detection tests are targeted at Western populations. The exact relationship between hyposmia and cognitive impairment is unknown. The purpose of the study was to find bromines that can effectively identify olfactory dysfunction and investigate the relationship between hyposmia and cognitive function in early, non-demented, drug-naïve patients with PD in the People's Republic of China.

Methods: Sixty-three early, non-demented, drug-naïve patients with PD and 55 healthy controls were enrolled in the study. The T&T olfactometer and a Chinese version of Montreal Cognitive Assessment (MoCA) were applied to assess subjects' olfactory and cognitive functions. Patients with PD also completed the Modified Unified Parkinson's disease-rating scale (UPDRS) and Hoehn and Yahr (H&Y) scale.

Results: Patients with PD had lower scores of visuospatial and executive function (=0.000), attention (=0.03), and delayed recall (=0.001) than controls. β-phenylethyl alcohol (floral smell, smell of rose petals) and isovaleric acid (smell of sweat, stuffy socks) were more sensitive for identifying hyposmia in patients with PD than three other odors. Multivariate logistic regression analysis showed that impaired visuospatial and executive function was associated with hyposmia (=0.013), but was independent of other PD-associated variables.

Conclusion: Hyposmia was common in early, non-demented, drug-naïve PD patients. β-Phenylethyl alcohol and isovaleric acid were more superior for identifying hyposmia in early non-demented Chinese patients with PD. Hyposmia was associated with impaired visuospatial and executive function in patients with PD. Further prospective studies that apply a series of neuropsychological tests and functional magnetic resonance imaging methods in large samples in multicenter studies are needed to confirm our findings and to investigate the relationship between hyposmia and cognitive function with disease progression in patients with PD.
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http://dx.doi.org/10.2147/CIA.S147588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5640420PMC
April 2018
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