Association between household size and risk of incident dementia in the UK Biobank study.

Currently, the relationship between household size and incident dementia, along with the underlying neurobiological mechanisms, remains unclear. This prospective cohort study was based on UK Biobank participants aged ≥ 50 years without a history of dementia. The linear and non-linear longitudinal association was assessed using Cox proportional hazards regression and restricted cubic spline models. Additionally, the potential mechanisms driven by brain structures were investigated by linear regression models. We included 275,629 participants (mean age at baseline 60.45 years [SD 5.39]). Over a mean follow-up of 9.5 years, 6031 individuals developed all-cause dementia. Multivariable analyses revealed that smaller household size was associated with an increased risk of all-cause dementia (HR, 1.06; 95% CI 1.02-1.09), vascular dementia (HR, 1.08; 95% CI 1.01-1.15), and non-Alzheimer's disease non-vascular dementia (HR, 1.09; 95% CI 1.03-1.14). No significant association was observed for Alzheimer's disease. Restricted cubic splines demonstrated a reversed J-shaped relationship between household size and all-cause and cause-specific dementia. Additionally, substantial associations existed between household size and brain structures. Our findings suggest that small household size is a risk factor for dementia. Additionally, brain structural differences related to household size support these associations. Household size may thus be a potential modifiable risk factor for dementia.

An NIR-IIb emissive transmembrane voltage nano-indicator for the optical monitoring of electrophysiological activities in vivo.

In vivo transmembrane-voltage detection reflected the electrophysiological activities of the biological system, which is crucial for the diagnosis of neuronal disease. Traditional implanted electrodes can only monitor limited regions and induce relatively large tissue damage. Despite emerging monitoring methods based on optical imaging have access to signal recording in a larger area, the recording wavelength of less than 1000 nm seriously weakens the detection depth and resolution in vivo. Herein, a Förster resonance energy transfer (FRET)-based nano-indicator, NaYbF4:Er@NaYF4@Cy7.5@DPPC (Cy7.5-ErNP) with emission in the near-infrared IIb biological window (NIR-IIb, 1500-1700 nm) is developed for transmembrane-voltage detection. Cy7.5 dye is found to be voltage-sensitive and is employed as the energy donor for the energy transfer to the lanthanide nanoparticle, NaYbF4:Er@NaYF4 (ErNP), which works as the acceptor to achieve electrophysiological signal responsive NIR-IIb luminescence. Benefiting from the high penetration and low scattering of NIR-IIb luminescence, the Cy7.5-ErNP enables both the visualization of action potential in vitro and monitoring of Mesial Temporal lobe epilepsy (mTLE) disease in vivo. This work presents a concept for leveraging the lanthanide luminescent nanoprobes to visualize electrophysiological activity in vivo, which facilitates the development of an optical nano-indicator for the diagnosis of neurological disorders.

Enhancing radiosensitivity in triple-negative breast cancer through targeting ELOB.

Enhancing radiotherapy sensitivity is crucial for improving treatment outcomes in triple-negative breast cancer (TNBC) patients. In this study, we investigated the potential of targeting Elongin B (ELOB) to enhance radiotherapy efficacy in TNBC. Analysis of TNBC patient cohorts revealed a significant association between high ELOB expression and poor prognosis in patients who received radiation therapy. Mechanistically, we found that ELOB plays a pivotal role in regulating mitochondrial function via modulating mitochondrial DNA expression and activities of respiratory chain complexes. Targeting ELOB effectively modulated mitochondrial function, leading to enhanced radiosensitivity in TNBC cells. Our findings highlight the importance of ELOB as a potential therapeutic target for improving radiotherapy outcomes in TNBC. Further exploration of ELOB's role in enhancing radiotherapy efficacy may provide valuable insights for developing novel treatment strategies for TNBC patients.

Vestibular-evoked myogenic potential abnormalities in Parkinson's disease with freezing of gait.

BACKGROUND: Vestibular dysfunction is closely associated with the pathophysiology of Parkinson's disease (PD) accompanied by freezing of gait (FOG); however, evidence supporting this clinical association is lacking. Vestibular-evoked myogenic potentials (VEMPs) have been widely acknowledged as a crucial electrophysiological parameter in the clinical evaluation of vestibular function. OBJECTIVE: The present study investigated the possible correlation of FOG occurrence with VEMP observations in patients diagnosed with PD. METHODS: Altogether, 95 idiopathic PD patients were recruited into the present cross-sectional study. All patients underwent motor and non-motor assessments using serial scales. In addition, the electrophysiological vestibular evaluation was conducted, which included cervical (cVEMP) and ocular VEMP (oVEMP) assessments. Furthermore, the correlations of bilateral c/oVEMP absence with clinical phenotypes, especially FOG, among the PD patients were analyzed. RESULTS: Among the 95 patients with PD, 44 (46.3%) had bilateral oVEMP absence and 23 (24.2%) had bilateral cVEMP absence, respectively. The proportions of patients with bilateral oVEMP absence (77.8% vs 30.9%, p = 0.004) and bilateral cVEMP absence (44.4% vs 19.5%, p = 0.035) were higher in the patient group exhibiting FOG than in the group without FOG. Following the adjustment of confounding variables, bilateral oVEMP absence (OR = 8.544, p = 0.007), rather than bilateral cVEMP absence, was shown to independently predict FOG occurrence in patients with PD. CONCLUSION: The close correlation between bilateral oVEMP absence and FOG in PD patients sheds new light on the possible role of central vestibular/upper brainstem dysfunction in FOG development in patients with PD.

The Synergistic Effect Study of Lipopolysaccharide (LPS) and A53T-α-Synuclein: Intranasal LPS Exposure on the A53T-α-Synuclein Transgenic Mouse Model of Parkinson's Disease.

Aging and interactions between genetic and environmental factors are believed to be involved the chronic development of Parkinson's disease (PD). Among PD patients, abnormally aggregated α-synuclein is a major component of the Lewy body. Generally, the intranasal route is believed to be a gate way to the brain, and it assists environmental neurotoxins in entering the brain and is related to anosmia during early PD. The current study applies the chronic intranasal application of lipopolysaccharides (LPS) in 4-, 8-, 12- and 16-month-old A53T-α-synuclein (A53T-α-Syn) transgenic C57BL/6 mice at 2-day intervals for a 2-month period, for evaluating the behavioral, pathological, and biochemical changes and microglial activation in these animals. According to our results, after intranasal administration of LPS, A53T-α-Syn mice showed severe progressive anosmia, hypokinesia, selective dopaminergic (DAergic) neuronal losses, decreased striatal dopamine (DA) level, and enhanced α-synuclein accumulation within the substantia nigra (SN) in an age-dependent way. In addition, we found obvious NF-кB activation, Nurr1 inhibition, IL-1ß, and TNF-α generation within the microglia of the SN. Conversely, the wild-type (WT) mice showed mild, whereas A53T-α-Syn mice had moderate PD-like changes among the old mice. This study demonstrated the synergistic effect of intranasal LPS and α-synuclein burden on PD development. Its underlying mechanism may be associated with Nurr1 inhibition within microglia and the amplification of CNS neuroinflammation. The mice with multiple factors, including aging, neuroinflammation, and α-synuclein mutation, have played a significant role in enhancing our understanding of how inflammation and α-synuclein mutation contribute to the neurodegeneration observed in PD.

Altered neurovascular coupling in migraine without aura.

Neurovascular coupling (NVC) provides new insights into migraine, a neurological disorder impacting over one billion people worldwide. This study compared NVC and cerebral blood flow (CBF) in patients with migraine without aura (MwoA) and healthy controls. About 55 MwoA patients in the interictal phase and 40 age- and sex-matched healthy controls underwent resting-state functional magnetic resonance imaging and arterial spin-labeling perfusion imaging scans. The CBF and resting-state neuronal activity indicators, including the amplitudes of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), and degree centrality (DC), were calculated for each participant. The global and regional NVCs were assessed using cross-voxel CBF-neuronal activity correlations and CBF/neuronal activity ratios. Patients with MwoA showed increased CBF/ALFF ratios in the left media, superior and inferior frontal gyri, and anterior cingulate gyrus, increased CBF/DC ratios in the left middle and inferior frontal gyri, and increased CBF/ReHo ratios in the right corpus callosum and right posterior cingulate gyrus. Lower CBF/ALFF ratios in the right rectal gyrus, the left orbital gyrus, the right inferior frontal gyrus, and the right superior temporal gyrus were also found in the MwoA patients. Furthermore, the CBF/ALFF ratios in the inferior frontal and superior temporal gyri were positively correlated with the Headache Impact Test scores and Hamilton anxiety scale scores in the MwoA patients. These findings provide evidence for the theory that abnormal NVC contributes to MwoA.

Simultaneous ischemic regions targeting and BBB crossing strategy to harness extracellular vesicles for therapeutic delivery in ischemic stroke.

Extracellular vesicles (EVs) derived from adipose-derived stem cells (ADSC-EVs) hold great promise for ischemic stroke treatment, but their therapeutic efficacy is greatly limited due to insufficient targeting ability. Previous reports focused on single ischemic targeting or blood-brain barrier (BBB) penetration, precise delivery to the brain parenchyma has not been fully considered. This study leveraged the targeting ability of RGD peptide and the cell penetrating ability of Angiopep-2 peptide to deliver ADSC-EVs precisely to the impaired brain parenchyma. We found that dual-modified EVs (RA-EVs) significantly enhanced the transcellular permeability across BBB in vitro, and not only targeted ischemic blood vessels but also achieved rapid accumulation in the ischemic lesion area after intravenous administration in vivo. RA-EVs further decreased the infarct volume, apoptosis, BBB disruption, and neurobehavioral deficits. RNA sequencing revealed the molecular regulation mechanism after administration. These findings demonstrate that dual-modification optimizes brain parenchymal targeting and highlights the significance of recruitment and penetration as a previously unidentified strategy for harnessing EVs for therapeutic delivery in ischemic stroke.

Near Infrared Emissive Lanthanide Luminescence Nanoparticle Used in Early Diagnosis and Brain Temperature Detection for Ischemic Stroke.

Ischemic stroke (IS) is one of the most dangerous medical conditions resulting in high mortality and morbidity. The increased brain temperature after IS is closely related to prognosis, making it highly significant for the early diagnosis and the progression evaluation of IS. Herein, a temperature-responsive near infrared (NIR) emissive lanthanide luminescence nanoparticle is developed for the early diagnosis and brain temperature detection of IS. After intravenous injection, the nanoparticles can pass through the damaged blood-brain barrier of the ischemic region, allowing the extravasation and enrichment of nanoparticles into the ischemic brain tissue. The NIR luminescence signals of the nanoparticles are used not only to judge the location and severity of the cerebral ischemic injury but also to report the brain temperature variation in the ischemic area through a visualized way. The results show that the designed nanoparticles can be used for the early diagnosis of ischemic stroke and minimally invasive temperature detection of cerebral ischemic tissues in transient middle cerebral artery occlusion mice model, which is expected to make the clinical diagnosis of ischemic stroke more rapid and convenient, more accurately evaluate the state of brain injury in stroke patients and also guide stroke hypothermia treatment.

Altered resting-state effective connectivity of trigeminal vascular system in migraine without aura: A spectral dynamic causal modeling study.

BACKGROUND: The trigeminal vascular system is an important part of the anatomical and physiological basis of migraine. The effective connectivity (EC) among the regions of interest (ROIs) in the trigeminal vascular system involved in migraine without aura (MWoA) remains unclear. METHODS: In this cross-sectional study, 48 patients (mean [SD] age 38.06 [10.35] years; male, 14/48 [29%]) with MWoA during the interictal phase and 48 healthy controls of similar age and sex (mean [SD] age 38.96 [10.96] years; male, 14/48 [29%]) underwent resting-state functional magnetic resonance imaging (fMRI). Dynamic causal modeling analysis was conducted to investigate directional EC among ROIs in the trigeminal vascular system including the bilateral brainstem, the primary somatosensory cortex (S1), the thalamus, and the insula. RESULTS: Compared with the healthy control group, MWoA represented significantly reduced EC from the left brainstem (Brainstem.L) to the left insula (MWoA: mean [SD] -0.16 [0.36]; healthy controls: mean [SD] 0.11 [0.41]; Pcorrected = 0.021), reduced EC from the Brainstem.L to the right insula (MWoA: mean [SD] -0.15 [0.39]; healthy controls: mean [SD] 0.03 [0.35]; Pcorrected = 0.021), and decreased EC from the left thalamus (Thalamus.L) to the Brainstem.L (MWoA: mean [SD] -0.13 [0.56]; healthy controls: mean [SD] 0.10 [0.45]; Pcorrected = 0.021). Altered EC parameters were not significantly correlated with MWoA clinical data. CONCLUSION: These results further provide increasing evidence that disturbed homeostasis of the trigeminovascular nociceptive pathway is involved in the pathophysiological mechanisms of migraine. Patients with MWoA exhibited a regional interaction distinct from healthy controls in the neural pathway of the Bilateral Insula-Brainstem.L-Thalamus.L, which may shed light on the future understanding of brain mechanisms for MWoA. Future brain-based interventions are suggested to consider the dysregulation in the Bilateral Insula-Brainstem.L-Thalamus.L circuits.

Clinical characteristics and outcome of COVID-19 patients with Parkinson's disease: a hospital-based case-control study in Shanghai, China.

Background: Clinical manifestations of Parkinson's disease (PD) after Corona Virus Disease 2019 (COVID-19) infection are poorly investigated. Objective: We aimed to explore the clinical features and outcomes of hospitalized PD patients with COVID-19. Methods: A total of 48 PD patients and 96 age-and sex-matched non-PD patients were included. Demographics, clinical characteristics and outcomes were compared between two groups. Results: PD patients with COVID-19 were elderly (76.69 ± 9.21 years) with advanced stage (H-Y stage 3-5 as 65.3%). They had less clinical symptoms (nasal obstruction, etc.), more proportions of severe/critical COVID-19 clinical classification (22.9 vs. 1.0%, p < 0.001), receiving oxygen (29.2 vs. 11.5%, p = 0.011), antibiotics (39.6 vs. 21.9%, p = 0.031) therapies, as well as longer hospitalization duration (11.39 vs. 8.32, p = 0.001) and higher mortality (8.3% vs. 1.0%, p = 0.001) relative to those without PD. Laboratory results showed that the PD group had higher white blood cell counts (6.29 vs. 5.16*109, p = 0.001), neutrophil-to-lymphocyte ratio (3.14 vs. 2.11, p < 0.001) and C-reactive protein level (12.34 vs. 3.19, p < 0.001). Conclusion: PD patients with COVID-19 have insidious clinical manifestation, elevated proinflammatory markers and are prone to the development of severe/critical condition, contributing to a relatively poor prognosis. Early identification and active treatment of COVID-19 are pivotal to advanced PD patients during the pandemic.

Effect of the serum 25-hydroxyvitamin D level on risk for short-term residual dizziness after successful repositioning in benign paroxysmal positional vertigo stratified by sex and onset age.

Objective: A low serum 25-hydroxyvitamin D (25(OH)D) level is relevant to both the occurrence and recurrence of benign paroxysmal positional vertigo (BPPV). However, whether it also contributes to residual dizziness (RD) after successful repositioning maneuvers is unknown. Therefore, this study aimed to explore the correlation between the serum 25(OH)D level and short-term RD severity in patients with BPPV after successful repositioning maneuvers. Methods: In total, 251 patients with BPPV after successful repositioning were enrolled and prospectively followed up for 1 week (W1). Serum 25(OH)D values were detected by chemiluminescence immunoassay at enrollment (W0). In addition, we explored the relationship between 25(OH)D values at baseline and RD severity at W1 in different subgroups stratified by sex and onset age (early-onset, ≤50 years; late-onset, >50 years). Results: The serum 25(OH)D level of female patients was significantly lower than that of male patients (15.9 ± 6.8 vs. 19.8 ± 6.6 ng/ml, p < 0.001). Its level also decreased in early-onset patients compared to late-onset ones (15.3 ± 5.9 vs. 18.0 ± 7.3 ng/ml, p = 0.003). In addition, early-onset female patients had lower 25(OH)D values than late-onset female patients (14.0 ± 5.5 vs. 17.1 ± 7.2 ng/ml, p = 0.004). However, this difference was not observed between early- and late-onset male patients. Among early-onset female patients, the 25(OH)D values of the moderate-to-severe RD group were lower than those of the minor or no RD group (10.9 ± 3.3 vs. 14.7 ± 5.7 vs. 15.0 ± 5.9 ng/ml, p = 0.046). Multivariate analysis found that decreased 25(OH)D values were related to the occurrence of moderate-to-severe RD in early-onset female patients (OR = 0.801; p = 0.022). This effect did not exist in late-onset female or male patients with BPPV. Conclusions: Age and sex differences in serum 25(OH)D levels exist in patients with BPPV. A decreased 25(OH)D level in early-onset female patients may increase the odds of moderate-to-severe RD 1 week after successful repositioning maneuvers.

Ginkgo biloba extract EGb 761® improves cognition and overall condition after ischemic stroke: Results from a pilot randomized trial.

Background: Patients who experienced an ischemic stroke are at risk for cognitive impairment. Quantified Ginkgo biloba extract EGb 761® has been used to treat cognitive dysfunction, functional impairment and neuropsychiatric symptoms in mild cognitive impairment and dementia. Objectives: To assess the cognitive-related effects of EGb 761® treatment in patients after acute ischemic stroke, as well as the feasibility of patient selection and outcome measures. Methods: We conducted a randomized, multicentric, open-label trial at 7 centers in China. Patients scoring 20 or lower on the National Institutes of Health Stroke Scale were enrolled between 7 and 14 days after stroke onset and randomly assigned to receive 240 mg per day of EGb 761® or no additional therapy for 24 weeks in a 1:1 ratio. Both groups received standard treatments for the prevention of recurrent stroke during the trial. General cognitive function and a battery of cognitive tests for sub-domains were evaluated at 24 weeks. All patients were monitored for adverse events. Results: 201 patients ≥50 years old were included, with 100 assigned to the EGb 761® group and 101 to the reference group. The mean change from baseline on the global cognitive function as assessed by the Montreal Cognitive Assessment score was 2.92 in the EGb 761® group and 1.33 in the reference group (between-group difference: 1.59 points; 95% confidence interval [CI], 0.51 to 2.67; p < 0.005). For cognitive domains, EGb 761® showed greater effects on the Hopkins Verbal Learning Test Total Recall (EGb 761® change 1.40 vs. reference -0.49) and Form 1 of the Shape Trail Test (EGb 761® change -38.2 vs. reference -15.6). Potentially EGb 761®-related adverse events occurred in no more than 3% of patients. Conclusion: Over the 24-week period, EGb 761® treatment improved overall cognitive performance among patients with mild to moderate ischemic stroke. Our findings provide valuable recommendations for the design of future trials, including the criteria for patient selection. Clinical Trial Registration: www.isrctn.com, identifier ISRCTN11815543.

Altered Spontaneous Brain Activity in Poststroke Aphasia: A Resting-State fMRI Study.

PURPOSE: Brain areas frequently implicated in language recovery after stroke comprise perilesional sites in the left hemisphere and homotopic regions in the right hemisphere. However, the neuronal mechanisms underlying language restoration are still largely unclear. METHODS AND MATERIALS: In the present study, we investigated the brain function in 15 patients with poststroke aphasia and 30 matched control subjects by combining the regional homogeneity (ReHo) and amplitudes of low-frequency fluctuation (ALFF) analysis methods based on resting-state fMRI. RESULTS: Compared to the control subjects, the patients with aphasia exhibited increased ReHo and ALFF values in the ipsilateral perilesional areas and increased ReHo in the contralesional right middle frontal gyrus. CONCLUSIONS: The increased spontaneous brain activity in patients with poststroke aphasia during the recovery period, specifically in the ipsilateral perilesional regions and the homologous language regions of the right hemisphere, has potential implications for the treatment of patients with aphasia.

Neurological Manifestations of hospitalized patients with mild to moderate infection with SARS-CoV-2 Omicron variant in Shanghai, China.

BACKGROUND: Accumulating studies demonstrated that patients with coronavirus disease 2019(COVID-19) could develop a variety of neurological manifestations and long-term neurological sequelae, which may be different from the strains. At the peak of the Omicron variant outbreak in Shanghai, China, no relevant epidemiological data about neurological manifestations associated with this strain was reported. OBJECTIVE: To investigate neurological manifestations and related clinical features in patients with mild to moderate COVID-19 patients with Omicron variant. METHODS: A self-designed clinical information registration form was used to gather the neurological manifestations of mild to moderate COVID-19 patients admitted to a designated hospital in Shanghai from April 18, 2022 to June 1, 2022. Demographics, clinical presentations, laboratory findings, treatments and clinical outcomes were compared between patients with and without neurological manifestations. RESULTS: One hundred sixty-nine(48.1 %) of 351 patients diagnosed with mild to moderate COVID-19 exhibited neurological manifestations, the most common of which were fatigue/weakness(25.1 %) and myalgia(20.7 %), whereas acute cerebrovascular disease(0.9 %), impaired consciousness(0.6 %) and seizure(0.6 %) were rare. Younger age(p = 0.001), female gender(p = 0.026) and without anticoagulant medication(p = 0.042) were associated with increasing proportions of neurological manifestations as revealed by multivariate logistic regressions. Patients with neurological manifestations had lower creatine kinase and myoglobin levels, as well as higher proportion of patchy shadowing on chest scan. Vaccination status, clinical classification of COVID-19 and clinical outcomes were similar between the two groups. CONCLUSIONS: Nearly half of the involved patients have neurological manifestations which were relatively subjective and closely associated with younger age, female gender and without anticoagulation. Patients with neurologic manifestations may be accompanied by increased lung patchy shadowing.

Effect of the Shanghai Stroke Service System (4S) on the quality of stroke care and outcomes: A prospective quality improvement project.

BACKGROUND: In China, disparities in the quality of stroke care still exist and implementing quality improvement is still a challenge. AIM: The aim of the study was to determine whether the intervention by Shanghai Stroke Service System (4S) has helped improve adherence to stroke care guidelines and patient outcome. METHODS: The 4S is a regional stroke network with real-time data extraction among its 61 stroke centers in Shanghai. A total of 11 key performance indicators (KPIs) were evaluated. The primary outcomes were a composite measure and an all-or-none measure of adherence to 11 KPIs. The secondary outcomes were length of hospital stay and in-hospital mortality. RESULTS: The study enrolled 92,395 patients (mean age 69.0 ± 12.5 years, 65.2% men) with acute ischemic stroke hospitalized within 7 days of onset in Shanghai from January 2015 to December 2020. More patients received guideline recommended care between 2018 and 2020 than those between 2015 and 2017 (composite measure 87.1% vs 83.6%; absolute difference 2.9%, 95% confidence interval (CI) = [2.7%, 3.2%], p < 0.001; all-or-none measure 49.2% vs 44.8% patients; absolute difference 3.5%, 95% CI = [2.7%, 4.2%], p < 0.001). Further analysis of individual KPIs showed an absolute increase in six KPIs ranging from 3.4% to 8.9% (p < 0.001 for all comparisons). Compared with 2015-2017, hospital length of stay was shorter (10.95 vs 11.90 days; absolute difference -1.08, 95% CI = [-1.18, -0.99], p < 0.001), and in-hospital mortality was significantly reduced (risk ratio (RR) = 0.88, 95% CI = [0.79, 0.98], p = 0.01) in 2018-2020. CONCLUSION: The 4S intervention was associated with increased adherence to the stroke care guidelines, which further translated to improved clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02735226.

REM sleep behavior disorder correlates with constipation in de novo Chinese Parkinson's disease patients.

BACKGROUND: Constipation, rapid eye movement sleep behavior disorder (RBD) and hyposmia are common prodromal symptoms of Parkinson's disease (PD), and they may represent two distinct types of disease origin, from the body or the brain. Our study aimed to compare the clinical characteristics of de novo PD patients with and without constipation and identify which prodromal symptoms were associated with constipation. METHODS: A total of 111 de novo, drug-naïve Chinese PD patients were consecutively enrolled from Jan 2017 to Sept 2021. Patients were classified into PD with and without constipation based on item 5 of the Scales for Outcomes in Parkinson's disease-Autonomic Dysfunction (SCOPA-AUT). The demographic data, motor, and non-motor symptoms were compared between the two groups. The associated factors of constipation were analyzed by the multivariate logistic regression analysis. RESULTS: In total, 44.1% (n = 49) of de novo PD patients had constipation. PD patients with constipation were older (p = 0.028), had higher proportions of Hoehn and Yahr (H-Y) stage [Formula: see text] 2 (p = 0.002), clinical possible RBD (cpRBD) (p = 0.002) and depression (p = 0.023), as well as marginal increase of hyposmia (p = 0.058) and freezing of gait (p = 0.069). After adjusting for H-Y stage and other confounding factors, cpRBD (OR = 3.508, p = 0.009), rather than hyposmia or depression, was closely related to constipation in de novo Chinese PD patients. CONCLUSIONS: RBD is closely associated with constipation in de novo Chinese PD patients. Our results support the theory that prodromal symptoms that represent the same pathological origin are closely related to each other.

Microstructural Differences of the Cerebellum-Thalamus-Basal Ganglia-Limbic Cortex in Patients with Somatic Symptom Disorders: a Diffusion Kurtosis Imaging Study.

Somatic symp tom disorders (SSDs) are a group of psychiatric disorders characterized by persistent disproportionate concern and obsessive behaviors regarding physical conditions. Currently, SSDs lack effective treatments and their pathophysiology is unclear. In this paper, we aimed to examine microstructural abnormalities in the brains of patients with SSD using diffusion kurtosis imaging (DKI) and to investigate the correlation between these abnormalities and clinical indicators. Diffusion kurtosis images were acquired from 30 patients with SSD and 30 healthy controls (HCs). Whole-brain maps of multiple diffusion measures, including fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), mean diffusivity (MD), mean kurtosis (MK), radial kurtosis (RK), and axial kurtosis (AK), were calculated. To analyze differences between the two groups, nonparametric permutation testing with 10,000 randomized permutations and threshold-free cluster enhancement was used with family-wise error-corrected p values < 0.05 as the threshold for statistical significance. Then, the correlations between significant changes in these diffusion measures and clinical factors were examined. Compared to HCs, patients with SSD had significantly higher FA, MK, and RK and significantly lower MD and RD in the cerebellum, thalamus, basal ganglia, and limbic cortex. The FA in the left caudate and the pontine crossing tract were negatively correlated with disease duration; the MD and the RD in the genu of the corpus callosum were positively correlated with disease duration. Our findings highlight the role of the cerebellum-thalamus-basal ganglia-limbic cortex pathway, especially the cerebellum, in SSDs and enhance our understanding of the pathogenesis of SSDs.

Oculomotor impairments in de novo Parkinson's disease.

Objective: Reliable electrophysiological indicators are urgently needed in the precise evaluation of Parkinson's disease (PD). It is still elusive whether oculomotor performance is impaired or has clinical value in early PD. This study aims to explore oculomotor performance in newly diagnosed, drug-naïve PD and its correlation with clinical phenotype. Methods: Seventy-five patients with de novo PD, 75 patients with essential tremor (ET), and 46 gender-and age-matched healthy controls (HCs) were included in this cross-sectional study. All subjects underwent oculomotor test via videonystagmography. Visually guided saccade latency, saccadic accuracy and gain in smooth pursuit eye movement (SPEM) at three frequencies of the horizontal axis were compared among the three groups. Patients with PD also received detailed motor and non-motor evaluation by serial scales. The association between key oculomotor parameters and clinical phenotypes were explored in PD patients. Results: Both de novo PD and ET patients showed prolonged saccadic latency and decreased saccadic accuracy relative to HCs. SPEM gain in PD was uniformly reduced at each frequency. SPEM gain at 0.4 Hz was also decreased in ET compared with HCs. However, there was no significant difference of oculomotor parameters between de novo PD and ET patients. Furthermore, prolonged saccadic latency was correlated with long disease duration, whereas decreased SPEM gain was associated with severe motor symptoms in de novo PD patients. Conclusion: Ocular movements are impaired in de novo, drug naïve PD patients; these changes could be indicators for disease progression in PD.

Clinical characteristics and short-term recovery of hyposmia in hospitalized non-severe COVID-19 patients with Omicron variant in Shanghai, China.

Background: Olfactory dysfunction is a common neurological symptom of Corona Virus Disease 2019(COVID-19). Little is known about hyposmia after COVID-19 infection with Omicron variant in Chinese population. Objective: To investigate the incidence, clinical characteristics and recovery of hyposmia in hospitalized non-severe COVID-19 patients with Omicron variant in Shanghai, China. Methods: Three hundred and forty-nine Chinese non-severe COVID-19 patients with Omicron variant were consecutively enrolled in a designated hospital to investigate the incidence of hyposmia in hospitalization and the recovery rate 1 month later. The visual assessment scale (VAS) was used to evaluate the severity of hyposmia. We compared the demographic, clinical features and treatment outcomes, as well as laboratory parameters between patients with and without hyposmia. Results: The cross-sectional survey showed that 22 (6.3%) hospitalized patients with non-severe COVID-19 had hyposmia. Patients with hyposmia were younger (61.5 vs. 72.0, p = 0.002), had more related clinical symptoms (sore throat, cough, poor appetite, diarrhea, myalgia and taste impairment, etc.), a higher proportion of moderate clinical type (31.8 vs. 13.5%, p = 0.028) and longer duration of hospitalization (11 vs. 8 days, p = 0.027) than those without hyposmia. Whereas, there were no significant differences regarding gender, comorbidity and nucleic acid conversion time between the two groups. Laboratory subgroup analyses demonstrated that patients with hyposmia had slightly low serum IL-6 and TNF-α levels. However, both of the levels were not associated with hyposmia occurrence in multivariate regression analyses. Further follow-up study disclosed that 16 of 22 (72.7%) hyposmia patients had recovered olfaction 1 month later. Serum IL-6 and TNF-α levels were similar between hyposmia recovered patients and those with persistent hyposmia. Conclusion: Although the incidence of hyposmia after Omicron variant infection is relatively low and the short-term recovery rate is quite high, patients with hyposmia are prone to have a higher proportion of both upper and lower respiratory tract involvements, gastrointestinal and neurological symptoms, contributing to a longer duration of hospitalization.