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Objective: A large number of studies have found that the prevalence of cognitive impairment varies in different regions. However, data on cognitive impairment in the Chinese population is still lacking. The goal of this study was to assess the prevalence of cognitive impairment among the elderly in a region of China and explore the associated risk factors. Methods: We performed a population‐based cross‐sectional survey from April to June 2022. Residents come from three villages and six urban communities in the county‐level city of Liuyang in southern China (N = 3233) and the coverage rate of our study population reached 73%. Participants were assessed with a series of clinical examinations and neuropsychological measures. A total of 2598 participants were selected after filtering out those under 60 years old or with incomplete data. Patients with cognitive impairment included those with mild cognitive impairment (MCI) or dementia who met standard diagnostic criteria. Results: The prevalence of cognitive impairment, MCI, and dementia among participants aged 60 years and older were 21.48% (95% CI, 19.90–23.10), 15.70% (95% CI, 14.30–17.10), and 5.77 (95% CI, 4.90–6.70), respectively. And residents in villagers were more likely to have cognitive impairment than in urban communities (p < 0.001). Age growth and education level were independent influencing factors for cognitive impairment in all populations (p < 0.001). For lifestyles factors, both smoking and drinking reduced the risk of cognitive impairment (p < 0.05), but when further quantified, the link disappeared. Moreover, having cerebrovascular disease and severe vision impairment were risk factors (p < 0.05). Conclusion: A representative prevalence of cognitive impairment, MCI, and dementia was found in the elderly Han Chinese population in Southern China. And we further explored the role of known risk factors, particularly in physical activity, smoking, and alcohol consumption. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Whether the integration of eye‐tracking, gait, and corresponding dual‐task analysis can distinguish cognitive impairment (CI) patients from controls remains unclear. METHODS: One thousand four hundred eighty‐one participants, including 724 CI and 757 controls, were enrolled in this study. Eye movement and gait, combined with dual‐task patterns, were measured. The LightGBM machine learning models were constructed. RESULTS: A total of 105 gait and eye‐tracking features were extracted. Forty‐six parameters, including 32 gait and 14 eye‐tracking features, showed significant differences between two groups (P < 0.05). Of these, the Gait_3Back‐TurnTime and Dual‐task cost‐TurnTime patterns were significantly correlated with plasma phosphorylated tau 181 (p‐tau181) level. A model based on dual‐task gait, dual‐task smooth pursuit, prosaccade, and anti‐saccade achieved the best area under the receiver operating characteristics curve (AUC) of 0.987 for CI detection, while combined with p‐tau181, the model discriminated mild cognitive impairment from controls with an AUC of 0.824. DISCUSSION: Combining dual‐task gait and dual‐task eye‐tracking analysis is feasible for the detection of CI. Highlights: This is the first study to report the efficiency of integrated parameters of dual‐task gait and eye‐tracking for cognitive impairment (CI) detection in a large cohort.We identified 46 gait and eye‐tracking features associated with CI, and two were correlated to plasma phosphorylated tau 181.We constructed the model based on dual‐task gait, smooth pursuit, prosaccade, and anti‐saccade, achieving the best area under the curve of 0.987 for CI detection. [ABSTRACT FROM AUTHOR]

Background: Neuroinflammation might contribute to the pathogenesis of multiple systemic atrophy (MSA). However, specific alterations in the peripheral inflammatory and immune profiles of patients with MSA remain unclear. Objectives: To determine the peripheral inflammatory and immune profiles of patients with MSA and their potential value as biomarkers for facilitating clinical diagnosis and monitoring disease severity. Methods: This cross‐sectional study included 235, 240, and 235 patients with MSA, patients with Parkinson's disease (PD), and healthy controls (HCs), respectively. Inflammatory and immune parameters were measured in peripheral blood, differences between groups were assessed, and clusters were analyzed. Associations between the parameters and clinical characteristics of MSA were assessed using Spearman and partial correlation analyses. Results: Significant differences were observed especially in monocytes, neutrophils‐to‐lymphocyte ratio (NLR) and neutrophils‐to‐lymphocyte ratio (MPV) between MSA patients and HCs (P < 0.01). Monocytes and uric acid (UA) levels were also significantly different between the MSA and PD patients (P < 0.05). The combination of NLR and MPV distinguished MSA‐P patients from HCs (areas under the curve = 0.824). In addition, complement components C4 and C3 were significantly correlated with the Scale Outcomes in PD for Autonomic Symptoms and Wexner scale, whereas immunoglobulin G (IgG) was significantly correlated with scores of Unified Multiple System Atrophy Rating Scale (P < 0.05). Conclusions: In MSA patients, monocytes, NLR and MPV might serve as potential diagnostic biomarkers, whereas MLR, C3, C4, and IgG significantly correlate with disease severity. © 2023 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Introduction: Recently, chloride channel CLIC‐like 1 (CLCC1) was reported to be a novel ALS‐related gene. We aimed to screen CLCC1 variants in our ALS cohort and further explore the genotype–phenotype correlation of CLCC1‐related ALS. Methods: We screened rare damaging variants in CLCC1 from our cohorts of 1005 ALS patients and 1224 healthy controls with whole‐exome sequencing in Central South China. Fisher's exact test was conducted for association analysis at the entire gene level and single variant level. Results: In total, four heterozygous missense variants in CLCC1 were identified from four unrelated sporadic ALS patients and predicted to be putative pathogenic by in silico tools and protein model prediction, accounting for 0.40% of all patients (4/1005). The four variants were c.A275C (p.Q92P), c.G1139A (p.R380K), c.C1244T (p.T415M), and c.G1328A (p.R443Q), respectively, which had not been reported in ALS patients previously. Three of four variants were located in exon 10. Patients harboring CLCC1 variants seemed to share a group of similar clinical features, including earlier age at onset, rapid progression, spinal onset, and vulnerable cognitive status. Statistically, we did not find CLCC1 to be associated with the risk of ALS at the entire gene level or single variant level. Conclusion: Our findings further expanded the genetic and clinical spectrum of CLCC1‐related ALS and provided more genetic evidence for anion channel involvement in the pathogenesis of ALS, but further investigations are needed to verify our findings. [ABSTRACT FROM AUTHOR]

Objective Methods Results Interpretation Transcranial sonography (TCS) is a noninvasive neuroimaging technique, visualizing deep brain structures and the ventricular system. Although widely employed in diagnosing various movement disorders, such as Parkinson's disease and dystonia, by detecting disease‐specific abnormalities, the specific characteristics of the TCS in cerebellar ataxia remain inconclusive. We aimed to assess the potential value of TCS in patients with cerebellar ataxias for disease diagnosis and severity assessment.TCS on patients with genetic and acquired cerebellar ataxia, including 94 with spinocerebellar ataxias (SCAs) containing 10 asymptomatic carriers, 95 with cerebellar subtype of multiple system atrophy (MSA‐C), and 100 healthy controls (HC), was conducted. Assessments included third ventricle width, substantia nigra (SN) and lentiform nucleus (LN) echogenicity, along with comprehensive clinical evaluations and genetic testing.The study revealed significant TCS abnormalities in patients with cerebellar ataxia, such as enlarged third ventricle widths and elevated rates of hyperechogenic SN and LN. TCS showed high accuracy in distinguishing patients with SCA or MSA‐C from HC, with an AUC of 0.870 and 0.931, respectively. TCS abnormalities aided in identifying asymptomatic SCA carriers, effectively differentiating them from HC, with an AUC of 0.725. Furthermore, third ventricle width was significantly correlated with SARA and ICARS scores in patients with SCA3 and SCOPA‐AUT scores in patients with MSA‐C. The SN area and SARA or ICARS scores in patients with SCA3 were also positively correlated.Our findings illustrate remarkable TCS abnormalities in patients with cerebellar ataxia, serving as potential biomarkers for clinical diagnosis and progression assessment. [ABSTRACT FROM AUTHOR]

There is an obvious clinical-pathological overlap between essential tremor and some known tremor-associated short tandem repeat expansion disorders. The aim is to analyse whether these short tandem repeat genes, including ATXN1 , ATXN2 , ATXN3 , CACNA1A , ATXN7 , ATXN8OS , ATXN10 , PPP2R2B , TBP , BEAN1 , NOP56 , DAB1 , ATN1 , SADM12 and FMR1 , are associated with familial essential tremor patients. Genetic analysis of repeat sizes in tremor-associated short tandem repeat expansions was performed in a large cohort of 515 familial essential tremor probands and 300 controls. The demographic and clinical features among carriers of pathogenic expansions, intermediate repeats and non-carriers were compared. A total of 18 out of 515 (18/515, 3.7%) patients were found to have repeats expansions, including 12 cases (12/515, 2.5%) with intermediate repeat expansions (one ATXN1 , eight TBP , two FMR1 , one ATN1 ), and six cases (6/515, 1.2%) with pathogenic expansions (one ATXN1 , one ATXN2 , one ATXN8OS , one PPP2R2B , one FMR1 , one SAMD12 ). There were no statistically significant differences in intermediate repeats compared to healthy controls. Furthermore, there were no significant differences in demographics and clinical features among individuals with pathogenic expansions, intermediate repeat expansions carriers and non-carriers. Our study indicates that the intermediate repeat expansion in tremor-associated short tandem repeat expansions does not pose an increased risk for essential tremor, and rare pathogenic expansion carriers have been found in the familial essential tremor cohort. The diagnosis of essential tremor based solely on clinical symptoms remains a challenge in distinguishing it from known short tandem repeat expansions diseases with overlapping clinical-pathological features., Competing Interests: The authors report no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background and Purpose: The role of GGC repeat expansions within NOTCH2NLC in Parkinson's disease (PD) and the substantia nigra (SN) dopaminergic neuron remains unclear. Here, we profile the NOTCH2NLC GGC repeat expansions in a large cohort of patients with PD. We also investigate the role of GGC repeat expansions within NOTCH2NLC in the dopaminergic neurodegeneration of SN., Methods: A total of 2,522 patients diagnosed with PD and 1,085 health controls were analyzed for the repeat expansions of NOTCH2NLC by repeat-primed PCR and GC-rich PCR assay. Furthermore, the effects of GGC repeat expansions in NOTCH2NLC on dopaminergic neurons were investigated by using recombinant adeno-associated virus (AAV)-mediated overexpression of NOTCH2NLC with 98 GGC repeats in the SN of mice by stereotactic injection., Results: Four PD pedigrees (4/333, 1.2%) and three sporadic PD patients (3/2189, 0.14%) were identified with pathogenic GGC repeat expansions (larger than 60 GGC repeats) in the NOTCH2NLC gene, while eight PD patients and one healthy control were identified with intermediate GGC repeat expansions ranging from 41 to 60 repeats. No significant difference was observed in the distribution of intermediate NOTCH2NLC GGC repeat expansions between PD cases and controls (Fisher's exact test p-value = 0.29). Skin biopsy showed P62-positive intranuclear NOTCH2NLC-polyGlycine (polyG) inclusions in the skin nerve fibers of patient. Expanded GGC repeats in NOTCH2NLC produced widespread intranuclear and perinuclear polyG inclusions, which led to a severe loss of dopaminergic neurons in the SN. Consistently, polyG inclusions were presented in the SN of EIIa-NOTCH2NLC-(GGC)98 transgenic mice and also led to dopaminergic neuron loss in the SN., Conclusions: Overall, our findings provide strong evidence that GGC repeat expansions within NOTCH2NLC contribute to the pathogenesis of PD and cause degeneration of nigral dopaminergic neurons., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Introduction: Whether the integration of eye-tracking, gait, and corresponding dual-task analysis can distinguish cognitive impairment (CI) patients from controls remains unclear., Methods: One thousand four hundred eighty-one participants, including 724 CI and 757 controls, were enrolled in this study. Eye movement and gait, combined with dual-task patterns, were measured. The LightGBM machine learning models were constructed., Results: A total of 105 gait and eye-tracking features were extracted. Forty-six parameters, including 32 gait and 14 eye-tracking features, showed significant differences between two groups (P < 0.05). Of these, the Gait&#95;3Back-TurnTime and Dual-task cost-TurnTime patterns were significantly correlated with plasma phosphorylated tau 181 (p-tau181) level. A model based on dual-task gait, dual-task smooth pursuit, prosaccade, and anti-saccade achieved the best area under the receiver operating characteristics curve (AUC) of 0.987 for CI detection, while combined with p-tau181, the model discriminated mild cognitive impairment from controls with an AUC of 0.824., Discussion: Combining dual-task gait and dual-task eye-tracking analysis is feasible for the detection of CI., Highlights: This is the first study to report the efficiency of integrated parameters of dual-task gait and eye-tracking for cognitive impairment (CI) detection in a large cohort. We identified 46 gait and eye-tracking features associated with CI, and two were correlated to plasma phosphorylated tau 181. We constructed the model based on dual-task gait, smooth pursuit, prosaccade, and anti-saccade, achieving the best area under the curve of 0.987 for CI detection., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Mutations in the microrchidia CW-type zinc finger protein 2 (MORC2) gene are the causative agent of Charcot-Marie-Tooth disease type 2Z (CMT2Z), and the hotspot mutation p.S87L is associated with a more severe spinal muscular atrophy-like clinical phenotype. The aims of this study were to determine the mechanism of the severe phenotype caused by the MORC2 p.S87L mutation and to explore potential treatment strategies. Epithelial cells were isolated from urine samples from a spinal muscular atrophy (SMA)-like patient (MORC2 p.S87L), a CMT2Z patient (MORC2 p.Q400R), and a healthy control and induced to generate pluripotent stem cells, which were then differentiated into motor neuron precursor cells. Next-generation RNA sequencing followed by KEGG pathway enrichment analysis revealed that differentially expressed genes involved in the PI3K/Akt and MAPK/ERK signaling pathways were enriched in the p.S87L SMA-like patient group and were significantly downregulated in induced pluripotent stem cells. Reduced proliferation was observed in the induced pluripotent stem cells and motor neuron precursor cells derived from the p.S87L SMA-like patient group compared with the CMT2Z patient group and the healthy control. G0/G1 phase cell cycle arrest was observed in induced pluripotent stem cells derived from the p.S87L SMA-like patient. MORC2 p.S87L-specific antisense oligonucleotides (p.S87L-ASO-targeting) showed significant efficacy in improving cell proliferation and activating the PI3K/Akt and MAPK/ERK pathways in induced pluripotent stem cells. However, p.S87L-ASO-targeting did not rescue proliferation of motor neuron precursor cells. These findings suggest that downregulation of the PI3K/Akt and MAPK/ERK signaling pathways leading to reduced cell proliferation and G0/G1 phase cell cycle arrest in induced pluripotent stem cells might be the underlying mechanism of the severe p.S87L SMA-like phenotype. p.S87L-ASO-targeting treatment can alleviate disordered cell proliferation in the early stage of pluripotent stem cell induction., Competing Interests: None