Background and Aim: Alzheimer's disease (AD) is the most common type of dementia and presents with metabolic perturbations early in the disease process. In order to explore biomarkers useful in predicting early AD, we compared serum metabolites among patients suffering different stages of AD. Methods: We recruited 107 participants including 23 healthy controls (HC), 21 amnestic mild cognitive impairment (aMCI), 24 non-amnestic mild cognitive impairment (naMCI) and 39 AD patients. Via liquid chromatography-mass spectrometry based serum untargeted lipidomics analysis, we compared differences in serum lipid metabolites among these patient groups and further elucidated biomarkers that differentiate aMCI from HC. Results: There were significant differences of serum lipid metabolites among the groups, and 20 metabolites were obtained under negative ion mode from HC and aMCI comparison. Notably, 16:3 cholesteryl ester, ganglioside GM3 (d18:1/9z-18:1) and neuromedin B were associated with cognition and increased the predictive effect of aMCI to 0.98 as revealed by random forest classifier. The prediction model composed of MoCA score, 16:3 cholesteryl ester and ganglioside GM3 (d18:1/9z-18:1) had good predictive performance for aMCI. Glycerophospholipid metabolism was a pathway common among HC/aMCI and aMCI/AD groups. Conclusion: This study provides preliminary evidence highlighting that 16:3 cholesteryl ester were useful for AD disease monitoring while ganglioside GM3 (d18:1/9z-18:1) and neuromedin B discriminated aMCI from HC, which can probably be applied in clinic for early predicting of AD.

Objective: Intractable epilepsy and uncontrolled seizures could affect cardiac function and the autonomic nerve system with a negative impact on children's growth. The aim of this study was to investigate the variability and complexity of cardiac autonomic function in pre-school children with pediatric intractable epilepsy (PIE). Methods: Twenty four-hour Holter electrocardiograms (ECGs) from 93 patients and 46 healthy control subjects aged 3-6 years were analyzed by the methods of traditional heart rate variability (HRV), multiscale entropy (MSE), and Kurths-Wessel symbolization entropy (KWSE). Receiver operating characteristic (ROC) curve analysis was used to estimate the overall discrimination ability. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) models were also analyzed. Results: Pre-school children with PIE had significantly lower HRV measurements than healthy controls in time (Mean_RR, SDRR, RMSSD, pNN50) and frequency (VLF, LF, HF, LF/HF, TP) domains. For the MSE analysis, area 1_5 in awake state was lower, and areas 6_15 and 6_20 in sleep state were higher in PIE with a significant statistical difference. KWSE in the PIE group was also inferior to that in healthy controls. In ROC curve analysis, pNN50 had the greatest discriminatory power for PIE. Based on both NRI and IDI models, the combination of MSE indices (wake: area1_5 and sleep: area6_20) and KWSE (m = 2, τ = 1, α = 0.16) with traditional HRV measures had greater discriminatory power than any of the single HRV measures. Significance: Impaired HRV and complexity were found in pre-school children with PIE. HRV, MSE, and KWSE could discriminate patients with PIE from subjects with normal cardiac complexity. These findings suggested that the MSE and KWSE methods may be helpful for assessing and understanding heart rate dynamics in younger children with epilepsy.

Background: Phosphatidylinositol binding clathrin assembly protein (PICALM) rs541458 C allele has been identified and validated to be associated with a reduction of Alzheimer's disease (AD) risk. Nevertheless, the exact mechanisms through which the variant exert its disease-relevant association remain to be elucidated. This study is to determine whether PICALM rs541458 polymorphism modulates functional magnetic resonance imaging measured brain spontaneous activity in older adults with amnestic mild cognitive impairment (aMCI). Methods: Thirty five aMCI patients and twenty six healthy controls (HC) were enrolled in this study. Each individual was genotyped for rs541458 and scanned with resting-state functional magnetic resonance imaging. Each group was divided into two subgroups (C carriers and TT genotype). Brain activity was measured with amplitude of low-frequency fluctuation (ALFF). Results: The aMCI patients showed decreased ALFF in left inferior frontal gyrus, superior temporal gyrus and insula, while increased ALFF in right cuneus, calcarine, and bilateral posterior cingulate and precuneus. A significant interaction between diagnosis (aMCI vs. HC) and PICALM rs541458 genotype (C carriers vs. TT) on ALFF was observed mainly in the right frontal lobe, with aMCI C carriers and TT genotype in HC showing significantly lower ALFF than HC C carriers. While only negative correlation between ALFF and verbal fluency test was found in HC C carriers (r = -0.543, p = 0.030). Conclusions: This study provided preliminary evidences that PICALM rs541458 variations may modulate the spontaneous brain activity in aMCI patients.

Objectives: A combined approach of behavioral characteristics and network properties was applied to explore the effect of repetitive transcranial magnetic stimulation (rTMS) on disorders of consciousness (DOC) and to observe changes in brain network connections before and after the stimulation. Methods: A total of 7 DOC patients and 11 healthy controls were enrolled. The study was designed as a randomized, sham-controlled study. All DOC patients were given 20 Hz rTMS real and sham stimuli to the left M1 region, with each stimulus lasting for 5 consecutive working days and the interval between two stimuli being 1 week. Coma Recovery Scale-Revised (CRS-R) and resting state functional MRI data before and after stimuli were collected. The functional connection (FC) of the default mode network and the frontoparietal network were chosen as the central target to compare differences in network connections between the DOC group and the normal control group. For DOC patients, changes in behavior and brain function before and after real and sham stimuli were also assessed as a group and individually. Results: (1). The overall analyses showed no significant changes of CRS-R scores or brain FC following real or sham rTMS stimuli in the DOC patients. However, real rTMS stimuli tended to enhance the FC of nodes in left lateral parietal cortex (LPC), left inferior temporal cortex (ITC) and right dorsolateral prefrontal cortex (DLPFC). (2). The individual analyses showed one minimally conscious state (MCS) patient presented with a obviously increased CRS-R score following real rTMS stimuli, and a visibly enhanced connectivity was observed in the nodes of left LPC, left ITC and right DLPFC of this patient. Conclusion: Our findings did not provide sufficient evidence of therapeutic effect of 20 Hz rTMS over the left M1 in DOC. However, MCS patients shortly after brain injury may possibly benefit from rTMS. Reconstruction of the left LPC, the left ITC and the right DLPFC may be the brain networking foundation of improvements in consciousness from rTMS.

Object: To explore the post-hemispherotomy seizure outcome and its prognostic predictors in children with refractory epilepsy. Methods: We reviewed 83 consecutive child patients with refractory epilepsy who underwent a hemispherectomy from June 2014 to January 2017 at our Pediatric Epilepsy Center. Demographic, clinical, EEG, neuroimaging, and surgical data were collected. Seizure outcome data were collected via outpatient clinics as well as telephone visits and were graded according to Engel criteria. Logistic regression model and Cox proportional hazard regression model were, respectively, applied to explore the related factors predicting the seizure outcomes of children after a hemispherotomy. Results: Of the 83 patients, 55 (63.2%) were male. The mean seizure onset age was 1.9 years (0-8.7 years), and the mean surgery age was 5 years (0.8-14 years). At a mean follow-up of 3 years, 69 children (83.1%) were seizure free, and 14 (16.9%) exhibited seizure recurrence. In a univariate analysis, whether or not considering follow-up time, a non-lateralized interictal EEG pattern, bilateral PET abnormalities and acute postoperative seizures (APOS) could all predict poor seizure outcomes post-hemispherotomy. Bilateral PET abnormalities were independently correlated with unfavorable seizure outcomes in the multivariate Logistic regression analysis (Odds ratio(OR) = 13.05, 95%CI = 1.52-112.29, P = 0.019) and in the multivariate Cox proportional hazard analysis(OR = 13.99, 95%CI = 2.75-71.17, P = 0.001). Conclusions: Child epileptic patients with bilateral PET abnormalities may have poor seizure outcomes after a hemispherotomy procedure. This study will facilitate better candidate selection for hemispherotomies and early identification of unfavorable seizure outcomes.