Search

Background and purpose: White matter hyperintensities (WMHs) are associated with cognitive deficits and worse clinical outcomes in dementia, but rare studies have been carried out of cognitive impairment in Lewy body disease (CI‐LB) patients. The objective was to investigate the associations between WMHs and clinical manifestations in patients with CI‐LB. Methods: In this retrospective multicentre cohort study, 929 patients (486 with dementia with Lewy bodies [DLB], 262 with Parkinson's disease dementia [PDD], 74 with mild cognitive impairment [MCI] with Lewy bodies [MCI‐LB] and 107 with Parkinson's disease with MCI [PD‐MCI]) were analysed from 22 memory clinics between January 2018 and June 2022. Demographic and clinical data were collected by reviewing medical records. WMHs were semi‐quantified according to the Fazekas method. Associations between WMHs and clinical manifestations were investigated by multivariate linear or logistic regression models. Results: Dementia with Lewy bodies patients had the highest Fazekas scores compared with PDD, MCI‐LB and PD‐MCI. Multivariable regressions showed the Fazekas score was positively associated with the scores of Unified Parkinson's Disease Rating Scale Part III (p = 0.001), Hoehn−Yahn stage (p = 0.004) and total Neuropsychiatric Inventory (p = 0.001) in MCI‐LB and PD‐MCI patients. In patients with DLB and PDD, Fazekas scores were associated with the absence of rapid eye movement sleep behaviour disorder (p = 0.041) and scores of Unified Parkinson's Disease Rating Scale Part III (p < 0.001), Hoehn−Yahn stage (p < 0.001) and the Montreal Cognitive Assessment (p = 0.014). Conclusion: White matter hyperintensity burden of DLB was higher than for PDD, MCI‐LB and PD‐MCI. The greater WMH burden was significantly associated with poorer cognitive performance, worse motor function and more severe neuropsychiatric symptoms in CI‐LB. [ABSTRACT FROM AUTHOR]

Background: Lewy body dementia is the second most common neurodegenerative dementia, but data concerning the onset age and clinical features in the prodromal stage remain limited in China.Objective: To investigate the associations between onset age and clinical manifestations of cognitive impairment with Lewy bodies in a large-sample cohort.Methods: We included 74 patients with mild cognitive impairment with Lewy bodies (MCI-LB), 533 patients with dementia with Lewy bodies (DLB), 118 patients with Parkinson's disease with MCI (PD-MCI), and 313 patients with Parkinson's disease dementia (PDD) in this multicenter cohort from 22 memory clinics of China from 1 January 2018 to 31 March 2022. The onset age, clinical manifestations, and neuropsychological assessments were recorded and analyzed after reviewing the medical records.Results: The average onset age of memory loss was 68.28 (±7.00) years, and parkinsonism happened 2.00 (±1.24) years later for patients with MCI-LB. The average onset age of parkinsonism was 60.56 (±8.96) years, and the memory loss happened 3.49 (±3.02) years later for patients with PD-MCI. Rapid eye movement sleep behavior disorder and visual hallucinations were frequently reported in MCI-LB, DLB, and PDD, while visual hallucinations were least frequently reported in PD-MCI. Lower scores of MMSE and depression, and higher scores of activities of daily living and delusions, were independently associated with older onset age in DLB.Conclusion: The onset of PD-MCI precedes MCI-LB, and memory loss occurs 3 years after parkinsonism. The onset age is associated with cognition and neuropsychiatric symptoms in process. [ABSTRACT FROM AUTHOR]

Introduction: Geriatric symptoms are common in dementia cases, while few studies have focused on these symptoms in Lewy body dementia (LBD). The purpose of this study is to investigate the distributions of Apolipoprotein E (APOE) ε4 and geriatric symptoms, and explore their associaitons in Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD).Methods: A retrospective study with 185 mild-moderate probable DLB (n = 93) and PDD (n = 92) patients was assigned. Demographic and clinical characteristics, neuropsychological assessments, and APOE genotypes were recorded. Description, correlation and logistic regression models were used to analyze the presence of geriatric symptom complaints and their associations with APOE ε4.Results: DLB patients displayed more frequency of fluctuating cognition, visual hallucination, rapid eye movement sleep behavior disorder, delusion, depression, anxiety, apathy, and loss of appetite, whereas the PDD cases had constipation, fear of falling, and insomnia more frequently. The APOE ε4 allele was more common in DLB than PDD (29.9% vs. 7.0%, p < 0.001), and the patients with DLB + APOE ε4 (+) were presented more delusions (p = 0.005) and apathy (p = 0.007) than patients with PDD + APOE ε4 (+). We also found that the APOE ε4 allele was significantly associated with hyperhidrosis (OR = 3.472, 95%CI: 1.082-11.144, p = 0.036) and depression (OR = 3.002, 95%CI: 1.079-8.353, p = 0.035) in DLB patients, while there were no significant associations between APOE ε4 allele and the age at visit, the age at onset, scores of MDS-UPDRS III, H&Y stage, ADL, MMSE, MOCA and NPI, as well as the presences of fluctuating cognition, VH, parkinsonism and RBD in both groups.Conclusion: The presence and co-incidence of geriatric symptoms are common in patients with mild-moderate LBD. The presence of APOE ε4 allele is associated with hyperhidrosis and depression, but not global cognition, activitives of daily life, motor function and other neuropsychitric symptoms in DLB. These findings improve the awareness of geriatric symptoms, and contribute to the healthcare management of mild-moderate DLB and PDD. [ABSTRACT FROM AUTHOR]

Objective: Parkinson's disease (PD) is the second most common neurodegenerative disorder worldwide. Mitochondrial dysfunction is suspected as one of the pathogenic mechanisms of PD. Growth/differentiation Factor-15 (GDF15) has been reported to affect mitochondrial function in PD. However, the relationship between mitochondrial function and GDF15 induction has not been explained well. Hence, we aimed to reveal the effect of GDF15 induction on SH-SY5Y cells with rotenone toxicity, a cell model of PD. Methods: SH-SY5Y cells were exposed to 1 μM rotenone as a PD model. Cells were transfected with a GDF15-overexpression plasmid and empty vector. We then analyzed the expression level of GDF15, BCL-2/BAX, P53, PGC1-α, α-syn, and TH in GDF15-overexpressing cells by western blotting, enzyme-linked immunosorbent assay, and quantitative real-time polymerase chain reaction. The cytotoxicity of rotenone was measured by CCK-8 assays. Cell apoptosis was detected by flow cytometric and TUNEL assays. The effect of GDF15 on oxidative stress and mitochondrial function was revealed using DCFH-DA, mito-SOX, and JC-10 assays and a Seahorse XF Cell Mito Stress Test. Results: GDF15 protected rotenone-treated SH-SY5Y cells from toxicity by preserving mitochondrial function and decreasing apoptosis, during which GDF15 might function by influencing PGC1α through the regulation of p53. In addition, GDF15 overexpression could improve Akt and mTOR phosphorylation, leading to PI3K/Akt/mTOR pathway activation. However, these protective effects were eliminated when cells were treated with the PI3K/Akt specific inhibitor LY294002. Conclusion: Our findings suggest that GDF15 can protect mitochondrial function and inhibit apoptosis in SH-SY5Y cells after exposure to rotenone by upregulating PGC1α via p53. These properties might comprise its anti-apoptotic effects, mediated by the PI3K/Akt/mTOR signaling pathway. [ABSTRACT FROM AUTHOR]

Genetic factors are thought to play an important role in the pathogenesis of Parkinson's disease (PD), particularly early-onset PD. The PRKN gene is the primary disease-causing gene for early-onset PD. The details of its functions remain unclear. This study identified novel compound heterozygous variants (p.T240K and p.L272R) of the PRKN gene in a Han-Chinese family with early-onset PD. This finding is helpful in the genetic diagnosis of PD and also the functional research of the PRKN gene. [ABSTRACT FROM AUTHOR]

Background: Non-motor symptoms are common in Parkinson's disease (PD) and can even be used as part of the supportive criteria for diagnosis. Chronic inflammation is involved in every stage of PD. Disorders of the immune system affect the peripheral blood. Whether the humoral immune response is associated with the non-motor symptoms of PD remains unknown. Methods: Mann–Whitney tests and Bonferroni correction were used to compare the serum levels of IgG, IgA, IgM, C3, and C4 between 180 sporadic PD patients and 187 healthy controls. Multiple regression models were conducted to assess the associations among these indicators of humoral immunity and the clinical features of PD patients. Results: Male PD patients had lower levels of C3 and C4 than healthy controls [0.87 (0.22) vs. 0.96 (0.19); 0.19 (0.06) vs. 0.22 (0.07), respectively, Pc < 0.01] and lower levels of C3 than female PD patients [0.87 (0.22) vs. 1.02 (0.23), Pc < 0.01]. Patients suffering from attention/memory problems had significantly lower levels of IgA and C3 than those without these problems [1.92 (1.21) vs. 2.57 (0.76); 0.89 (0.24) vs. 0.97 (0.24), respectively, Pc < 0.04]. In addition, serum IgG levels were negatively associated with mood/cognition problem scores and were positively associated with gastrointestinal tract problem scores (adjusted R 2 = 0.063, F = 1.805, p = 0.038). Serum C3 levels were negatively associated with being male, age, and sleep/fatigue problem scores (adjusted R 2 = 0.123, F = 2.678, p = 0.001). Conclusion: The peripheral humoral immune response might be correlated with the non-motor symptoms of PD. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effect of minocycline in rats with rotenone-induced Parkinson's disease (PD). The open field test was performed to determine the motor ability of the rats. Double immunofluorescence staining was used to detect the expression of tyrosine hydroxylase (TH) and Nurr1 in the substantia nigra (SN) of rats. The relative protein levels of TH, Nurr1, and the total- and phosphorylated-cAMP-response element binding protein (CREB) were determined by western blot analysis. The production of reactive oxygen species (ROS) and nitric oxide (NO) was detected by commercial kits. After exposure to rotenone for 28 days, rats exhibited decreased ambulation and rearing frequency and prolonged immobility time with loss of TH positive neurons in the SN. The phosphorylation levels of CREB and Nurr1 expression decreased significantly accompanied with the release of ROS and NO. Minocycline alleviated the motor deficits of rats lesioned by rotenone and elevated the expression of TH, as well as suppressing the release of ROS and NO in the SN. That was in line with the elevated phosphorylation levels of CREB and Nurr1 expression. In conclusion, our present study showed minocycline protected against neurotoxicity in a rotenone-induced rat model of PD, which was correlated with upregulation of Nurr1. [ABSTRACT FROM AUTHOR]

Azadirachta indica has previously been demonstrated to act as a multi‑functional medicinal plant for >2,000 years in India, and its neighboring countries. Currently, it is considered a natural resource with great value used in industrial product development and as a medicine for various types of diseases. The present study investigated the neuroprotective effects of Azadirachta indica which improved functional recovery in the 6‑hydroxydopamine induced rat Parkinson's disease (PD) model. Catalase, glutathione‑peroxidase, tumor necrosis factor‑α, interleukin (IL)‑1β, IL‑6, nuclear factor (NF)‑κB p65, inducible nitric oxide synthase (iNOS) and AChE activity levels were analyzed via ELISA. Western blotting was used to analyze B cell lymphoma‑2 associated X protein (Bax), cytochrome c and p53 protein expression. Treatment with Azadirachta indica significantly decreased the PD‑induced rotational behavior in rats. PD‑induced catalase, glutathione‑peroxidase, iNOS activity and iNOS protein expression were significantly suppressed by treatment with Azadirachta indica. Inflammatory factors, acetylcholinesterase activity and cyclo‑oxygenase‑2 protein expression levels were additionally significantly suppressed by treatment with Azadirachta indica. The protein expression levels of Bax, cytochrome c and p53 were decreased and caspase‑3 and caspase‑9 activities diminished, with treatment with Azadirachta indica. Therefore, Azadirachta indica was demonstrated to exhibit neuroprotective antioxidative and anti‑apoptotic effects in Parkinson's disease. [ABSTRACT FROM AUTHOR]

Background: Growth differentiation factor 15 (GDF15) has been shown to be protective for dopaminergic neurons in animal and ex vivo experiments. However, little is known about its effect on the human body. Objective: This study investigated associations between serum GDF15 levels and clinical parameters in patients with Parkinson disease (PD). Methods: Idiopathic PD patients ( n = 104) and age-matched controls ( n = 88) were enrolled. Serum GDF15 levels were measured by human enzyme-linked immunosorbent assay. Univariate and multivariate analyses investigated correlations between GDF15 and clinical characteristics, including disease severity by the Unified PD Rating Scale (UPDRS)-III. The diagnostic value of GDF15 was evaluated by receiveroperating characteristic curve (ROC) analysis. Results: The serum GDF15 levels of the PD patients were significantly higher than those of the healthy controls. In PD patients, serum GDF15 levels in men were significantly higher than in women. GDF15 levels correlated with age, gender, disease duration, and UPDRS-III score. After adjusting for confounding factors, multiple linear regression analysis showed that the serum GDF15 level (β = 0.015, p = 0.001) was an independent risk factor for UPDRS-III score. In ROC analysis, GDF15 achieved an area under the curve of 0.86 for the identification of PD, with a sensitivity of 71.15% and a specificity of 87.50%. Conclusion: GDF15 may be a potential biomarker for the diagnosis and monitoring of motor severity in PD. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is the common age-related neurodegenerative disorder. Sensitive, noninvasive biomarkers that facilitate PD diagnosis and stage assignment are currently unavailable. This study aims to investigate the potential of 16 previous reported PD-associated miRNAs as novel biomarkers for PD. The expression of 16 serum miRNAs was measured by quantitative reverse transcriptase polymerase chain reaction in 138 PD patients and 112 control populations. Analyses were undertaken to assess the specificity and sensitivity of miRNAs to predict PD. In addition, the relationship between deregulated miRNAs and Part III of the United Parkinson's Disease Rating Scale (UPDRS-III) and Part V of the UPDRS (UPDRS-V; the modified Hoehn and Yahr staging of PD) in PD patients was also assessed. It was found that the serums miR-29c, miR-146a, miR-214, and miR-221 were significantly decreased in PD patients compared with healthy control populations. In addition, serum miR-221 was positively correlated with UPDRS-III ( r = .4702) and UPDRS-V ( r = .4788) score in PD patients. Furthermore, the receiver operating characteristic result of serum miR-221 for prediction of PD was 0.787. Our preliminary findings indicate that downregulated serum miR-221 might be a potential biomarker for PD evaluation. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To test the usefulness of the Parkinson''s disease sleep scale (PDSS) in identifying sleep disorders in the clinical practice setting. Methods: Sixty-two PD patients were evaluated with the PDSS and the Epworth sleepiness scale (ESS). A cut-off of less than five for each PDSS item as an indicator of substantial sleep disturbance was chosen. If the ESS was equal to or greater than eight, patients were referred to a sleep disorder specialist and possible polysomnography. Results: The mean total PDSS score was 104.7±21.5,which correlated with the mean Hoehn and Yahr score (1.9±0.9) as well as the mean ESS score (9.7±4.7). A significant correlation was also found between the ESS score and several items of the PDSS. Conclusions: The PDSS was useful in identifying sleep disturbances which were not previously diagnosed, such as sleep maintenance insomnia and excessive daytime sleepiness. Problems with the PDSS include ambiguities of some questions, lack of quantification and an inability to identify specific sleep disturbances such as sleep apnea. [Copyright &y& Elsevier]

• I-proteasome is activated under oxidative stress induced by rotenone in SH-SY5Y cells. • PSMB9 knockdown aggravated accumulation of α-syn, release of ROS, modulating antigen presentation related proteins. • I-proteasome may play a neuroprotective role. This study investigated the expression and role of immunoproteasome (i-proteasome) in a cell model of Parkinson's disease (PD). The cytotoxicity of rotenone was measured by CCK-8 assay. The i-proteasome β1i subunit PSMB9 was suppressed by a specific shRNA or transfected with an overexpression plasmid in the SH-SY5Y cells. Under the exposure to rotenone or not, the expression of constitutive proteasome β subunits, i-proteasome βi subunits, antigen presentation related proteins, α-syn and TH were detected by Western blot in PSMB9-silenced or -overexpressed cells, and the proteasomal activities were detected by fluorogenic peptide substrates. The location of i-proteasome βi subunits and α-syn were detected by immunofluorescence staining. The levels of ROS, GSH and MDA were measured by commercial kits. Cell apoptosis was detected by flow cytometry. Besides impairing the constitutive proteasomes, rotenone induced the expression of βi subunits of i-proteasome and antigen presentation related proteins such as TAP1, TAP2 and MHC-I. Silencing or overexpressing PSMB9 had no obvious effect on the levels of other subunits, but could regulate the chymotrypsin-like activity of 20S proteasome and the expression of TAP1, TAP2 and MHC-I. Three βi subunits (PSMB9, PSMB10, PSMB8) of i-proteasome were all co-localized with α-syn. PSMB9 knockdown aggravated accumulation of α-syn, degradation of TH, release of ROS, increased level of MDA, decreased level of GSH and eventually promoted apoptosis in SH-SY5Y cells after rotenone treatment, while over-expression of PSMB9 could attenuate these toxic effects of rotenone. I-proteasome is activated in SH-SY5Y cells treated with rotenone and may play a neuroprotective role. [ABSTRACT FROM AUTHOR]

Parkinson’s disease (PD) features selective loss of dopaminergic neurons of the substantia nigra pars compacta accompanied by the accumulation and aggregation of alpha-synuclein in Lewy bodies. PTEN induced putative kinase 1 gene ( PINK1 ) mutations are the second most common genetic cause of autosomal recessive early-onset Parkinson’s disease (EOPD). A single nucleotide deletion in PINK1 exon 8 (c.1557delG) was identified in a consanguineous Chinese family with EOPD. The homozygous deletion was co-segregated with disease in the family and resulted in a frameshift after codon 520 with a premature termination at codon 522 (p.K520RfsX3). These findings have significant implications on genetic counseling for the family and may be helpful in considering potential pathogenesis-targeted and disease-modifying strategies which should further improve patient quality of life. [ABSTRACT FROM AUTHOR]

• A rat model of Parkinson's disease (PD) was induced by rotenone. • Immunoproteasome (PSMB9 and PSMB8) were markedly up-regulated in the PD rat model. • Antigen presentation-related proteins were significantly up-regulated in PD rat model. • Immunoproteasome and antigen presentation pathways were activated in PD rat model. The study was to investigate whether immunoproteasome (i-proteasome) and its downstream pathway are related to the pathogenesis of Parkinson's disease (PD). Rats were treated with rotenone showed significant weight loss and dyskinesia, which is consistent with the degeneration of TH-positive neurons and the activation of Iba-1-positive microglia/macrophages. Two major catalytic subunits of i-proteasome (PSMB9 and PSMB8) were seldom expressed in rat substantia nigra (SN) under normal condition, but they were significantly up-regulated with the release of TNF-α and IFN-γ after exposure to rotenone. In addition, compared with control group, the antigen presentation-related proteins antigen peptide transporter (TAP) 1, TAP2, major histocompatibility complex (MHC)-I and MHC-II levels were significantly up-regulated in rotenone group, which was in line with the accumulation of α-syn. These findings suggested that i-proteasome and antigen presentation pathways (related proteins) were upregulated by rotenone in a PD rat model. [ABSTRACT FROM AUTHOR]

Summary: We conducted a cross-sectional analysis with 901 Parkinson''s disease (PD) patients in China to understand the epidemiological characteristics of PD pain among Chinese patients. In addition, we searched PubMed and the China Hospital Knowledge Database for epidemiological studies of pain and fatigue among PD patients from 1999 to 2011 to understand the prevalence of these symptoms around the world and associated clinical features. The 901 PD cases were recruited from 42 university affiliated hospitals randomly selected from seven provincial capitals across four economic regions of China. We documented motor and non-motor symptoms via clinical examinations and questionnaire surveys. Using logistic regression models, we evaluated factors that were associated with PD pain among these Chinese patients. Of the 901 Chinese patients, 269 (29.9%) had PD-related pain. After adjusting for confounders, only dyskinesias (OR = 2.66) and depression (OR = 2.88) were independently associated with PD pain. The literature search identified a total of 16 eligible studies on PD-pain and 19 on PD fatigue with various tools for symptom assessment. The data suggest a crude prevalence of 33.7% for PD pain in Asia and 79.4% in Northern Europe; the prevalence for PD fatigue was 35.4% in Northern Europe and 59.1% in Western Europe. Interestingly, Northern-European PD patients reported the highest prevalence of pain, but the lowest prevalence of fatigue. These studies suggest that motor complications and depression are likely key predictors for PD pain, while disease severity, depression and sleep disturbance are associated with PD fatigue. More studies with standardized methods would be needed to better understand the prevalence of PD pain and fatigue across various regions of the world. [Copyright &y& Elsevier]