The Relative Contribution of Plasma Homocysteine Levels vs. Traditional Risk Factors to the First Stroke: A Nested Case-Control Study in Rural China.

BACKGROUND: Approximately 75% of Chinese hypertensive patients have elevated homocysteine (Hcy). Its implication in risk assessment and prevention of the first stroke remains an important clinical and public health question. METHODS: This study was based on a community cohort recruited from 2016 to 2018 in the rural China. To maximize cost efficiency, we used a nested case-control design, including 3,533 first stroke cases and 3,533 controls matched for age ±1 years, sex, and village. Individual associations of tHcy and traditional risk factors with the first stroke were examined, and their population-attributable risks (PARs) were estimated. RESULTS: There was a significant dose-response association between first stroke and total Hcy (tHcy) levels, with adjusted odds ratios of 1.11 (95% CI: 0.97, 1.26) for tHcy 10-15 µmol/L and 1.44 (1.22, 1.69) for tHcy ≥ 15 µmol/L, all compared to tHcy < 10 µmol/L. A similar trend was found for ischemic and hemorrhagic stroke. tHcy and systolic blood pressure (SBP) were independently and additively associated with the risk of first stroke (tHcy: 1.06 [1.02, 1.1]; SBP: 1.13 [1.1, 1.16]; P-interaction, 0.889). Among the ten main risk factors examined, the top two contributors to the first stroke were SBP and tHcy, with PARs of 25.73 and 11.24%, respectively. CONCLUSIONS: Elevated tHcy is the second most important contributor and acts additively with SBP to increase the risk of the first stroke. This finding underscores the importance of screening and treating elevated tHcy along with traditional risk factors to further reduce the burden of the first stroke in the high-risk populations.

A Follow-up Study of Cerebral Microbleeds in Patients Who Received Stents for Symptomatic Cerebral Artery Stenosis.

BACKGROUND: The aims of this study were to explore (i) the dynamic changes in cerebral microbleeds (CMBs) in patients with symptomatic cerebral artery stenosis who received endovascular stent-assisted angioplasty and (ii) the risk factors associated with the new incidence of CMBs as well as whether CMBs increased the risk of vascular events in these patients. METHODS: Clinical information and magnetic resonance images were collected on admission and 3 months after endovascular stent-assisted angioplasty. Based on susceptibility-weighted imaging, the patients were divided into groups with or without newly developed CMBs, and between-group differences in risk factors were compared. We also compared whether CMBs increased the risk of vascular events among those patients. RESULTS: Seventy-three patients completed the relevant follow-up examinations. After an average follow-up period of 109 days, 7 (9.6%) patients showed new CMBs. A univariate analysis showed that the number of lacunar infarcts and the increase in systolic blood pressure were higher in patients with new CMBs than in those without new CMBs, and these differences were significant (P = 0.034, P = 0.001). Increased systolic blood pressure was an independent risk factor for developing new CMBs (P = 0.017). CONCLUSIONS: CMBs may be a continuously progressing cerebral small-vessel disease. The newly developed CMBs in patients with intracranial and/or extracranial stents were associated with increased systolic blood pressure but not with the number of baseline CMBs.

Retracted Article: LncRNA MALAT1 aggravates MPP-induced neuronal injury by regulating miR-212 in SH-SY5Y cells.

Parkinson's disease (PD) is the most common neurodegenerative disease and its incidence is rising. Long noncoding RNAs (lncRNAs) have been reported to have essential roles in development of PD. LncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is dysregulated in PD, while the role of MALAT1 and its mechanism in PD remain poorly understood. In this study, SH-SY5Y cells were exposed to 1-methyl-4-phenylpyridinium (MPP+) to induce a PD model in vitro. Then we explored the effect of MALAT1 on cell viability, apoptosis and inflammatory response as well as its interaction with miR-212 in MPP+-treated SH-SY5Y cells. The results showed that MALAT1 was up-regulated in MPP+-treated SH-SY5Y cells compared with that in the normal group. Overexpression of MALAT1 exacerbated MPP+-induced neuronal injury, uncovered by inhibition of cell viability and increase of cell apoptosis as well as inflammatory cytokine expressions in SH-SY5Y cells. However, knockdown of MALAT1 exerted the opposite effect in MPP+-treated SH-SY5Y cells. Moreover, MALAT1 was bound to miR-212 and negatively regulated the miR-212 level. Furthermore, addition of miR-212 ablated the regulatory effect of MALAT1 on MPP+-induced neuronal injury, as indicated by restoration of cell viability and lower apoptotic rate along with inflammatory cytokine levels in SH-SY5Y cells. Therefore, we concluded that MALAT1 exacerbated MPP+-induced neuronal injury through regulating cell viability, apoptosis and inflammatory cytokines by sponging miR-212, providing a novel theoretical foundation for application of MALAT1 in PD.

Sex differences in cognition among Chinese people with Parkinson's disease.

To investigate sex differences in cognitive function in Parkinson's disease patients, a cohort of 172 male patients and 139 female patients were recruited for this study. Their demographic and clinical features, including age, disease duration, education level, Unified Parkinson's Disease Rating Scale-III, Hoehn-Yahr Scale, activities of daily living, Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale score were recorded. The Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Wechsler Adult Intelligence Scale-Chinese Revision (WAIS-RC) and Wechsler Memory Scale-Chinese Revision (WMS-RC) scores were compared to distinguish the cognitive properties between the two groups. The MMSE values did not show a significant difference between the groups. However, the MoCA scores of male patients were significantly higher than those of female patients (adjusted p<0.05). The male group demonstrated better performances with respect to visuospatial function, naming and abstraction (adjusted p<0.05). The WAIS-RC data showed that female patients had lower scores in information, vocabulary, picture completion, block design and picture arrangement (adjusted p<0.05), and the WMS-RC data showed that 100-1 and cumulative addition abilities were significantly weaker in females than males (adjusted p<0.05). Cognitive disturbances were more prevalent and severe in women among Chinese Parkinson's disease patients.

RIT2 polymorphism is associated with Parkinson's disease in a Han Chinese population.

Recently, a meta-analysis including 5 large genome-wide association studies has identified rs12456492 variant of RIT2 gene as a novel risk locus for Parkinson's disease (PD) in Caucasian populations. However, the association between RIT2 polymorphism and PD risk has not been positively replicated in Asian population yet. We detected the genotypes of rs12456492 in 524 PD patients and 521 control subjects from a Han Chinese population. The allele and genotype distribution of rs12456492 variant were significantly different between PD patients and controls (allele p = 0.001, genotype p = 0.002). Logistic regression analysis showed that the G-carrying genotype (AG + GG) individuals exhibited a nearly 1.4-fold increased risk for PD compared with the AA genotype carriers (OR = 1.390; 95% confidence interval = 1.079-1.791; p = 0.011). Our data support that the carriage of G allele of rs12456492 variant of RIT2 gene significantly increases the risk for PD in Han Chinese population, suggesting a potential role of RIT2 in the etiology of PD.

Cerebrospinal fluid alpha-synuclein as a biomarker for Parkinson's disease diagnosis: a systematic review and meta-analysis.

To date, there are no definitive biomarkers for Parkinson's disease (PD) diagnosis. The detection of cerebrospinal fluid (CSF) alpha (α)-synuclein in PD patients has yielded promising but inconclusive results. To determine the performance of CSF α-synuclein as a diagnostic biomarker of PD and whether CSF α-synuclein can discriminate PD from other neurodegenerative diseases, a systematic search of all relevant studies investigating reproducible CSF α-synuclein quantification methods was conducted in electronic databases. A total of 17 studies that included 3311 patients were included in this systemic review and meta-analysis. The mean CSF α-synuclein concentration was significantly lower in PD patients compared to normal/neurological controls [weighted mean difference (WMD) -0.31; 95% CI, -0.45, -0.16; p < 0.0001] and patients with Alzheimer's disease (AD) [WMD -0.15; 95% CI, -0.26, -0.04; p < 0.0001]. There was no significant difference between PD patients and dementia with Lewy bodies (DLB) patients [WMD -0.03; 95% CI, -0.16, 0.09; p = 0.58] or patients with multiple system atrophy (MSA) [WMD 0.05; 95% CI, -0.04, 0.13; p = 0.25]. Sensitivity and specificity of CSF α-synuclein in the diagnosis of PD was 0.88 (95% CI, 0.84-0.91) and 0.40 (95% CI, 0.35-0.45), respectively. The positive and negative likelihood ratios of CSF α-synuclein in the diagnosis of PD were 1.41 (95% CI, 1.24-1.60), and 0.29 (95% CI, 0.15-0.56), respectively. The corresponding summary receiver operating characteristic (SROC) curve showed an area under the curve (AUC) of 0.73. The concentration of CSF α-synuclein may be a biomarker for the diagnosis of PD. The use of α-synuclein alone however is not sufficient as a single biomarker and it must therefore be used in conjunction with other documented and reliable biomarkers.

MCP-1 and CCR2 gene polymorphisms in Parkinson's disease in a Han Chinese cohort.

Monocyte chemoattractant protein-1 (MCP-1) and its receptor CC chemokine receptor-2 (CCR2) play important roles in neuroinflammation and they have been shown to be involved in Parkinson's disease (PD) pathogenesis. In addition, several studies have suggested a role for the MCP-1 and CCR2 genotypes in cognitive impairment and depression, which are common non-motor symptoms in PD patients. In this study, a cohort of 521 PD patients and 556 cases of healthy controls were recruited to investigate the association between the MCP-1 2518A/G (rs1064211) and CCR2 V64I (rs1799864) gene polymorphisms and PD risk in the Chinese population. We also analyze the influence of these genotypes on the cognitive function and depression in PD patients by comparing Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Wechsler Adult Intelligence Scale-Chinese Revision (WAIS-RC), Wechsler Memory Scale-Chinese Revision (WMS-RC) and Hamilton Depression Rating Scale (HAMD) ratings in 217 PD patients. Our results showed no significant differences in the genotype frequency between the PD group and the control group (P > 0.05). In addition, we also failed to find an influence of the MCP-1 and CCR2 genotypes on MMSE scores, MoCA scores, WAIS-RC scores, WMS-RC scores and HAMD scores in PD patients (P > 0.05). The MCP-1 and CCR2 gene polymorphisms may not be genetic risk factors for PD in the Han Chinese population, and they do not appear to influence cognitive function and depression in PD patients.

Triggering receptor expressed on myeloid cells 2 variants are rare in Parkinson's disease in a Han Chinese cohort.

Recent studies have reported that a rare nonsynonymous variant rs75932628-T in the TREM2 gene is associated with increased risk of Alzheimer's disease and Parkinson's disease (PD) in European-descended populations. However, the association between rare TREM2 mutations and PD risk remains unknown in Chinese population. We directly sequenced exon2 of TREM2 in a cohort of 476 PD patients and 432 healthy controls from a Han Chinese population. Rs75932628-T (p.R47H) was found in 0.2% of PD cases (1/476) but in none of the controls (0/432, p = 1.000), with a minor allele frequency of 0.06% among the 908 subjects. Our findings suggest that variants in exon2 of TREM2 are extremely rare, and it is not a genetic risk factor for PD in the southern Han Chinese population.