Olfactory Dysfunction as a Marker for Cognitive Impairment in General Paresis of the Insane: A Clinical Study.

BACKGROUND General paresis of the insane (GPI) is characterized by cognitive impairment, neuropsychiatric symptoms, and brain structural abnormalities, mimicking many neuropsychiatric diseases. Olfactory dysfunction has been linked to cognitive decline and neuropsychiatric symptoms in numerous neuropsychiatric diseases. Nevertheless, it remains unclear whether patients with GPI experience olfactory dysfunction and whether olfactory dysfunction is associated with their clinical manifestations. MATERIAL AND METHODS Forty patients with GPI and 37 healthy controls (HCs) underwent the "Sniffin Sticks" test battery, Mini-Mental State Examination, and Neuropsychiatric Inventory to measure olfactory function, cognitive function, and neuropsychiatric symptoms, respectively. Brain structural abnormalities were evaluated using visual assessment scales including the medial temporal lobe atrophy (MTA) visual rating scale and Fazekas scale. RESULTS Compared with HCs, patients with GPI exhibited significant olfactory dysfunction, as indicated by deficits in the odor threshold (OT) (P=0.001), odor discrimination (OD) (P<0.001), and odor identification (OI) (P<0.001). In patients with GPI, the OI was positively correlated with cognitive function (r=0.57, P<0.001), but no significant correlation was found between olfactory function and neuropsychiatric symptoms, blood, or cerebrospinal fluid biomarkers (rapid plasma reagin circle card test and Treponema pallidum particle agglutination test), or brain structural abnormalities (MTA and Fazekas scale scores). Mediation analysis indicated that the impaired OI in patients with GPI was mediated by cognitive impairment and impaired OT respectively. CONCLUSIONS Patients with GPI exhibited overall olfactory dysfunction. OI is correlated with cognitive function and the impaired OI is mediated by cognitive impairment in patients with GPI. Thus, OI may serve as a marker for reflecting cognitive function in patients with GPI.

Capillary-driven microchip integrated with nickel phosphide hybrid-modified electrode for the electrochemical detection of glucose.

BACKGROUND: Transition metal phosphides with properties similar to platinum metal have received increasing attention for the non-enzymatic detection of glucose. However, the requirement of highly corrosive reagent during sample pretreatment would impose a potential risk to the human body, limiting their practical applications. RESULTS: In this study, we report a self-powered microfluidic device for the non-enzymatic detection of glucose using nickel phosphide (Ni2P) hybrid as the catalyst. The Ni2P hybrid is synthesized by pyrolysis of metal-organic framework (MOF)-based precursor and in-situ phosphating process, showing two linear detection ranges (1 µM-1 mM, 1 mM-6 mM) toward glucose with the detection limit of 0.32 µM. The good performance of Ni2P hybrid for glucose is attributed to the synergistic effect of Ni2P active sites and N-doped porous carbon matrix. The microchip is integrated with a NaOH-loaded paper pad and a capillary-based micropump, enabling the automatic NaOH redissolution and delivery of sample solution into the detection chamber. Under the optimized condition, the Ni2P hybrid-based microchip realized the detection of glucose in a user-friendly way. Besides, the feasibility of using this microchip for glucose detection in real serum samples has also been validated. SIGNIFICANCE: This article presents a facile fabrication method utilizing a MOF template to synthesize a Ni2P hybrid catalyst. By leveraging the synergy between the Ni2P active sites and the N-doped carbon matrix, an exceptional electrochemical detection performance for glucose has been achieved. Additionally, a self-powered chip device has been developed for convenient glucose detection based on the pre-established high pH environment on the chip.

Abnormalities in Electroencephalographic Microstates in Patients with Late-Life Depression.

Background: Late-life depression (LLD) is characterized by disrupted brain networks. Resting-state networks in the brain are composed of both stable and transient topological structures known as microstates, which reflect the dynamics of the neural activities. However, the specific pattern of EEG microstate in LLD remains unclear. Methods: Resting-state EEG were recorded for 31 patients with episodic LLD (eLLD), 20 patients with remitted LLD (rLLD) and 32 healthy controls (HCs) using a 64-channel cap. The clinical data of the patients were collected and the 17-Item Hamilton Rating Scale for Depression (HAMD) was used for symptom assessment. Duration, occurrence, time coverage and syntax of the four microstate classes (A-D) were calculated. Group differences in EEG microstates and the relationship between microstates parameters and clinical features were analyzed. Results: Compared with NC and patients with rLLD, patients with eLLD showed increased duration and time coverage of microstate class D. Besides, a decrease in occurrence of microstate C and transition probability between microstate B and C was observed. In addition, the time coverage of microstate D was positively correlated with the total score of HAMD, core symptoms, and miscellaneous items. Conclusion: These findings suggest that disrupted EEG microstates may be associated with the pathophysiology of LLD and may serve as potential state markers for the monitoring of the disease.

Static and dynamic functional connectivity of the habenula in late-life depression patient with suicidal ideation.

BACKGROUND: Suicide is one of the most lethal complications of late-life depression (LLD), and habenular dysfunction may be involved in depression-related suicidality and may serve as a potential target for alleviating suicidal ideation. This study aimed to investigate abnormal functional connectivity of the habenula in LLD patients with suicidal ideation. METHODS: One hundred twenty-seven patients with LLD (51 with suicidal ideation (LLD-S) and 76 without suicidal ideation (LLD-NS)) and 75 healthy controls (HCs) were recruited. The static functional connectivity (sFC) and dynamic functional connectivity (dFC) between the habenula and the whole brain were compared among the three groups, and correlation and moderation analyses were applied to investigate whether suicidal ideation moderated the relationships of habenular FC with depressive symptoms and cognitive impairment. RESULTS: The dFC between the right habenula and the left orbitofrontal cortex (OFC) increased in the following order: LLD-S > LLD-NS > control. No significant difference in the habenular sFC was found among the LLD-S, LLD-NS and control groups. The dFC between the right habenula and the left OFC was positively associated with global cognitive function and visuospatial skills, and the association between this dFC and visuospatial skills was moderated by suicidal ideation in patients with LLD. CONCLUSION: The increased variability in dFC between the right habenula and left OFC was more pronounced in the LLD-S group than in the LLD-NS group, and the association between habenular-OFC dFC and visuospatial skills was moderated by suicidal ideation in patients with LLD.

Abnormal levels of expression of microRNAs in peripheral blood of patients with traumatic brain injury are induced by microglial activation and correlated with severity of injury.

BACKGROUND: Microglia play a crucial role in regulating the progression of traumatic brain injury (TBI). In specific, microglia can self-activate and secrete various substances that exacerbate or alleviate the neuroimmune response to TBI. In addition, microRNAs (miRNAs) are involved in the functional regulation of microglia. However, molecular markers that reflect the dynamics of TBI have not yet been found in peripheral tissues. METHODS: Paired samples of peripheral blood were collected from patients with TBI before and after treatment. Next-generation sequencing and bioinformatics analysis were used to identify the main pathways and biological functions of TBI-related miRNAs in the samples. Moreover, lipopolysaccharide-treated human microglia were used to construct a cellular immune-activation model. This was combined with analysis of peripheral blood samples to screen for highly expressed miRNAs derived from activated microglia after TBI treatment. Quantitative reverse-transcriptase polymerase chain reaction was used to determine the expression levels of these miRNAs, allowing their relationship with the severity of TBI to be examined. Receiver operating characteristic (ROC) curves were constructed to analyse the clinical utility of these miRNAs for determining the extent of TBI. RESULTS: Sequencing results showed that 37 miRNAs were differentially expressed in peripheral blood samples from patients with TBI before and after treatment, with 17 miRNAs being upregulated and 20 miRNAs being downregulated after treatment. The expression profiles of these miRNAs were verified in microglial inflammation models and in the abovementioned peripheral blood samples. The results showed that hsa-miR-122-5p and hsa-miR-193b-3p were highly expressed in the peripheral blood of patients with TBI after treatment and that the expression levels of these miRNAs were correlated with the patients' scores on the Glasgow Coma Scale. ROC curve analysis revealed that abnormally high levels of expression of hsa-miR-122-5p and hsa-miR-193b-3p in peripheral blood have some clinical utility for distinguishing different extents of TBI and thus could serve as biomarkers of TBI. CONCLUSION: Abnormally high levels of expression of hsa-miR-122-5p and hsa-miR-193b-3p in the peripheral blood of patients with TBI were due to the activation of microglia and correlated with the severity of TBI. This discovery may help to increase understanding of the molecular pathology of TBI and guide the development of new strategies for TBI therapy based on microglial function.

Hypoxia-induced circRNAs encoded by PPARA are highly expressed in human cardiomyocytes and are potential clinical biomarkers of acute myocardial infarction.

BACKGROUND: Acute myocardial infarction (AMI) is a serious cardiovascular disease that adversely affects human health. Circular RNAs (circRNAs) are involved in the pathological and physiological processes of AMI, but the biological mechanism of their involvement and their clinical significance remain unknown. We aimed to identify circRNAs that are significantly associated with morbidity in the peripheral blood of patients with AMI and evaluate their diagnostic utility. METHODS: High-throughput sequencing was used to screen for differentially expressed circRNAs in peripheral blood samples obtained from five patients with AMI and five sex- and age-matched healthy controls. A series of bioinformatics tools and databases were used to determine the biological functional classification and pathway enrichment of the circRNAs based on data obtained from sequencing. A hypoxia model was established and used to evaluate the effect of hypoxia on circRNA expression in human cardiomyocytes. A cytoplasmic separation assay and enzyme resistance assay were employed to identify the biological characteristics of circRNA. Polymerase chain reaction validity testing and receiver operating characteristic (ROC) curve analysis were used to evaluate the utility of circRNA assessments in the diagnosis of AMI. RESULTS: A large number of circRNAs were found to be differentially expressed in the peripheral blood of patients with AMI, and significantly more of these circRNAs were highly expressed than lowly expressed. The genes encoding these circRNAs have a wide range of effects on various functions in the body. A hypoxic environment promoted the upregulation of circRNA expression in human cardiomyocytes, and hsa_circ_0116795 encoded by PPARA was highly expressed in the peripheral blood of the patients with AMI. In terms of biological characteristics, under physiological conditions, hsa_circ_0116795 (circ_PPARA) was mainly located in the cytoplasm of cardiomyocytes and found to be resistant to exonuclease. The ROC curve analysis showed that the expression levels of circ_PPARA in the peripheral blood of patients with AMI were significantly different from those in the peripheral blood of healthy controls. CONCLUSION: A large number of abnormally expressed circRNAs are detectable in the peripheral blood of patients with AMI. In particular, circ_PPARA is highly expressed in human myocardial cells under hypoxic conditions, and its biological characteristics indicate that it could be employed as a biomarker for the early diagnosis of AMI.

Altered resting-state brain oscillation and the associated cognitive impairments in late-life depression with different depressive severity: An EEG power spectrum and functional connectivity study.

OBJECTIVE: Cognitive impairments are prevalent in late-life depression (LLD). However, it remains unclear whether there are concurrent brain oscillation alterations in resting condition across varying level of depression severity. This cross-sectional study aims to investigate the characteristics of altered resting-state oscillations, including power spectrum and functional connectivity, and their association with the cognitive impairments in LLD with different depression severity. METHODS: A total of 65 patients with LLD and 40 elder participants without depression were recruited. Global cognition and subtle cognitive domains were evaluated. A five-minute resting-state electroencephalography (EEG) was conducted under eyes-closed conditions. Measurements included the ln-transformed absolute power for power spectrum analysis and the weighted phase lag index (wPLI) for functional connectivity analysis. RESULTS: Attentional and executive dysfunction were exhibited in Moderate-Severe LLD group. Enhanced posterior upper gamma power was observed in both LLD groups. Additionally, enhanced parietal and fronto-parietal/occipital theta connectivity were observed in Moderate-Severe LLD group, which were associated with the attentional impairment. LIMITATIONS: Limitations include a small sample size, concomitant medication use, and a relatively higher proportion of females. CONCLUSIONS: Current study observed aberrant brain activity patterns in LLD across different levels of depression severity, which were linked to cognitive impairments. The altered posterior brain oscillations may be trait marker of LLD. Moreover, cognitive impairments and associated connectivity alterations were exhibited in moderate-severe group, which may be a state-like marker of moderate-to severe LLD. The study deepens understanding of cognitive impairments with the associated oscillation changes, carrying implications for neuromodulation targets in LLD.

Disrupted functional connectivity of the habenula links psychomotor retardation and deficit of verbal fluency and working memory in late-life depression.

BACKGROUND: Functional abnormalities of the habenula in patients with depression have been demonstrated in an increasing number of studies, and the habenula is involved in cognitive processing. However, whether patients with late-life depression (LLD) exhibit disrupted habenular functional connectivity (FC) and whether habenular FC mediates the relationship between depressive symptoms and cognitive impairment remain unclear. METHODS: Overall, 127 patients with LLD and 75 healthy controls were recruited. The static and dynamic FC between the habenula and the whole brain was compared between LLD patients and healthy controls, and the relationships of habenular FC with depressive symptoms and cognitive impairment were explored by correlation and mediation analyses. RESULTS: Compared with the controls, patients with LLD exhibited decreased static FC between the right habenula and bilateral inferior frontal gyrus (IFG); there was no significant difference in dynamic FC of the habenula between the two groups. Additionally, the decreased static FC between the right habenula and IFG was associated with more severe depressive symptoms (especially psychomotor retardation) and cognitive impairment (language, memory, and visuospatial skills). Last, static FC between the right habenula and left IFG partially mediated the relationship between depressive symptoms (especially psychomotor retardation) and cognitive impairment (verbal fluency and working memory). CONCLUSIONS: Patients with LLD exhibited decreased static FC between the habenula and IFG but intact dynamic FC of the habenula. This decreased static FC mediated the relationship between depressive symptoms and cognitive impairment.

Lower Dorsal Lateral Prefrontal Cortex Functional Connectivity in Late-Life Depression With Suicidal Ideation.

OBJECTIVE: The dorsal lateral prefrontal cortex (DLPFC) has been identified as a neuromodulation target for alleviating suicidal ideation. Dysfunctional DLPFC has been implicated in suicidality in depression. This study aimed to investigate the functional connectivity (FC) of the DLPFC in late-life depression (LLD) with suicidal ideation. METHODS: Resting-state functional magnetic resonance imaging (fMRI) data from 32 LLD patients with suicidal ideation (LLD-S), 41 LLD patients without suicidal ideation (LLD-NS), and 54 healthy older adults (HOA) were analyzed using DLPFC seed-based FC analyses. Group differences in FC were examined, and machine learning was applied to explore the potential of DLPFC-FC for classifying LLD-S from LLD-NS. RESULTS: Abnormal DLPFC-FC patterns were observed in LLD-S, characterized by lower connectivity with the angular gyrus, precuneus, and superior frontal gyrus compared to LLD-NS and healthy controls. A classification model based on the identified DLPFC-FC achieved an accuracy of 75%. CONCLUSION: The lower FC of DLPFC networks may contribute to the neurobiological mechanism of suicidal ideation in late-life depression. These findings may facilitate suicide prevention for LLD by providing potential neuroimaging markers and network-based neuromodulation targets. However, further confirmation with larger sample sizes and experimental designs is warranted.

Relationships Among Short Self-Reported Sleep Duration, Cognitive Impairment, and Insular Functional Connectivity in Late-Life Depression.

BACKGROUND: Both late-life depression (LLD) and short sleep duration increase the risk of cognitive impairment. Increased insular resting-state functional connectivity (FC) has been reported in individuals with short sleep duration and dementia. OBJECTIVE: This study aimed to investigate whether short sleep duration is associated with impaired cognition and higher insular FC in patients with LLD. METHODS: This case- control study recruited 186 patients with LLD and 83 normal controls (NC), and comprehensive psychometric assessments, sleep duration reports and resting-state functional MRI scans (81 LLD patients and 54 NC) were conducted. RESULTS: Patients with LLD and short sleep duration (LLD-SS patients) exhibited more severe depressive symptoms and worse cognitive function than those with normal sleep duration (LLD-NS patients) and NC. LLD-SS patients exhibited higher FC between the bilateral insula and inferior frontal gyrus (IFG) pars triangularis than LLD-NS patients and NC, while LLD-NS patients exhibited lower FC than NC. Increased insular FC was correlated with short sleep duration, severe depressive symptoms, and slower information processing speeds. Furthermore, an additive effect was found between sleep duration and LLD on global cognition and insular FC. CONCLUSION: LLD-SS patients exhibited impaired cognition and increased insular FC. Abnormal FC in LLD-SS patients may be a therapeutic target for neuromodulation to improve sleep and cognitive performance and thus decrease the risk of dementia.

MiR-145 regulates steroidogenesis in mouse primary granulosa cells by targeting Arpc5 and subsequent cytoskeleton remodeling.

MicroRNA (miR)-145 is enriched in the follicular granulosa cells (GCs) of 3-week-old mice. Downregulating miR-145 inhibits the proliferation and differentiation of GCs and induces evident changes in their cytoskeleton. In this study, we examined how miR-145 induces cytoskeletal changes in mouse GCs and its potential mechanism in regulating GC steroidogenesis. We found that actin related protein 2/3 complex subunit 5 (Arpc5) is a target of miR-145. The miR-145 antagomir increased ARPC5 expression but not ß-ACTIN, ß-TUBULIN, and PAXILLIN expression. Arpc5 overexpression inhibited GC proliferation, differentiation, and progesterone synthesis. Furthermore, the expression of progesterone synthesis-associated enzymes was downregulated in the Arpc5 overexpression group, and the GC cytoskeleton exhibited evident changes. We conclude that Arpc5, a new target of miR-145, regulates primary GC proliferation and progesterone production by regulating the cytoskeleton remodeling.

Disrupted dynamic functional connectivity of hippocampal subregions mediated the slowed information processing speed in late-life depression.

BACKGROUND: Slowed information processing speed (IPS) is the core contributor to cognitive impairment in patients with late-life depression (LLD). The hippocampus is an important link between depression and dementia, and it may be involved in IPS slowing in LLD. However, the relationship between a slowed IPS and the dynamic activity and connectivity of hippocampal subregions in patients with LLD remains unclear. METHODS: One hundred thirty-four patients with LLD and 89 healthy controls were recruited. Sliding-window analysis was used to assess whole-brain dynamic functional connectivity (dFC), dynamic fractional amplitude of low-frequency fluctuations (dfALFF) and dynamic regional homogeneity (dReHo) for each hippocampal subregion seed. RESULTS: Cognitive impairment (global cognition, verbal memory, language, visual-spatial skill, executive function and working memory) in patients with LLD was mediated by their slowed IPS. Compared with the controls, patients with LLD exhibited decreased dFC between various hippocampal subregions and the frontal cortex and decreased dReho in the left rostral hippocampus. Additionally, most of the dFCs were negatively associated with the severity of depressive symptoms and were positively associated with various domains of cognitive function. Moreover, the dFC between the left rostral hippocampus and middle frontal gyrus exhibited a partial mediation effect on the relationships between the scores of depressive symptoms and IPS. CONCLUSIONS: Patients with LLD exhibited decreased dFC between the hippocampus and frontal cortex, and the decreased dFC between the left rostral hippocampus and right middle frontal gyrus was involved in the underlying neural substrate of the slowed IPS.

Identification of novel key genes associated with uterine corpus endometrial carcinoma progression and prognosis.

Background: Uterine corpus endometrial carcinoma (UCEC) is a common malignant cancer type which affects the health of women worldwide. However, its molecular mechanism has not been elucidated. Methods: To identify the hub modules and genes in UCEC associated with clinical phenotypes, the RNA sequencing data and clinical data of 543 UCEC samples were obtained from The Cancer Genome Atlas (TCGA) database and then subjected to weighted gene co-expression network analysis (WGCNA). To explore the potential biological function of the hub modules, Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted. Genes differentially expressed in UCEC were screened according to TCGA data using the "gdcDEAnalysis" package in R (The R Foundation for Statistical Computing). After intersecting with hub genes, the shared genes were used for further survival analyses. The relationship between gene expression level and clinical phenotype was analyzed in the TCGA-UCEC cohort in The University of ALabama at Birmingham CANcer data analysis Portal and the Human Protein Atlas. The microarray data set GSE17025 was also analyzed to validate the gene expression profiles. Results: There were 19 coexpression modules generated by WGCNA. Among them, 2 modules with 198 hub genes were highly correlated with clinical features (especially histologic grade and clinical stage). Meanwhile, 4,003 differentially expressed genes (DEGs) were screened out, and 164 DEGs overlapped with hub genes. Survival analyses revealed that high expression of GINS4 and low expression of ESR1 showed a trend of poor prognosis. Further analyses demonstrated that both messenger RNA (mRNA) and protein expression profiles of GINS4 and ESR1 were significantly associated with UCEC development and progression in TCGA and GSE17025 cohorts. Conclusions: Based on the integrated bioinformatic analyses, our data indicated that GINS4 and ESR1 might serve as potential prognostic markers and targets for UCEC therapy.

Comparison of recurrence rate and risk factors in patients with focal adenomyosis with and without medical treatment after conservative surgery.

OBJECTIVE: To compare the recurrence rate and risk factors between conservative surgery followed by medical treatments and conservative surgery-only in patients with focal adenomyosis. METHODS: This retrospective study was conducted in a single teaching hospital from May 2011 to October 2016. All eligible patients were identified into three groups: surgery-only group, surgery combined with gonadotropin-releasing hormone agonist (GnRHa), and a levonorgestrel-releasing intrauterine system (LNG-IUS) group. The recurrence rate and risk factors were compared among groups using Kaplan-Meier and Cox proportional hazards analyses. Receiver operating characteristic (ROC) curve analysis was applied to determine a cut-off value for identifying recurrence-related risk factors. RESULTS: A total of 249 postoperative patients with adenomyosis were included in the final analysis with a mean of 41 months of follow up. The recurrence rate at the long-term follow up was significantly lower in intervention groups than in the surgery-only group (P = 0.011). The Cox proportional hazards and ROC analyses showed that a menstrual cycle longer than 26 days (P = 0.026), diameter of lesions <6 cm (P = 0.030), and combination treatment using GnRHa (P = 0.039) or LNG-IUS (P = 0.007) were protective against relapse. The risk of recurrence was lower in patients with anterior (P = 0.034) or fundus (P = 0.038) adenomyosis. CONCLUSION: Postoperative therapy using GnRHa or LNG-IUS decreases the long-term relapse rate in women undergoing conservative surgery.

Differences in olfactory functional connectivity in early-onset depression and late-onset depression.

Background: Late-onset depression (LOD) and early-onset depression (EOD) exhibit different pathological mechanisms and clinical phenotypes, including different extents of olfactory dysfunction. However, the brain abnormalities underlying the differences in olfactory dysfunction between EOD and LOD remain unclear. Objective: The aim of this study was to compare the functional connectivity (FC) patterns of olfactory regions between EOD patients and LOD patients and examine their relationship with cognitive function. Methods: One hundred and five patients with EOD, 101 patients with LOD and 160 normal controls (NCs) were recruited for the present study. Participants underwent clinical assessment, olfactory testing, cognitive assessments, and magnetic resonance imaging. Eight regions of the primary and secondary olfactory regions were selected to investigate olfactory FC. Results: Patients with LOD exhibited decreased odor identification (OI) compared with patients with EOD and NCs. The LOD group exhibited decreased FC compared with the EOD and NC groups when primary and secondary olfactory regions were selected as the regions of interest (the piriform cortex, lateral entorhinal cortex, and orbital-frontal cortex). Additionally, these abnormal olfactory FCs were associated with decreased cognitive function scores and OI, and the FC between the left orbital-frontal cortex and left amygdala was a partial mediator of the relationship between global cognitive scores and OI. Conclusion: Overall, patients with LOD exhibited decreased FC in both the primary and secondary olfactory cortices compared with patients with EOD, and abnormal olfactory FC was associated with OI dysfunction and cognitive impairment. The FC between the orbital-frontal cortex and amygdala mediated the relationship between global cognitive function and OI.

Static and dynamic functional connectivity variability of the anterior-posterior hippocampus with subjective cognitive decline.

BACKGROUND: Subjective cognitive decline (SCD) is a putative Alzheimer's disease (AD) precursor without objective neuropsychological deficits. The hippocampus plays an important role in cognitive function and emotional responses and is generally aberrant in SCD. However, previous studies have mainly focused on static functional connectivity (sFC) by resting-state functional magnetic resonance imaging (fMRI) in SCD individuals, and it remains unclear whether hippocampal dynamic functional connectivity (dFC) changes exist in SCD and whether those changes are associated with subtle changes in cognitive function or affect. METHODS: Seventy SCD patients and 65 healthy controls were recruited. Demographic data, comprehensive neuropsychology assessments, and resting-state fMRI data were collected. The bilateral anterior and posterior hippocampi were selected as seeds to investigate the static and dynamic functional connectivity alterations in SCD. RESULTS: Compared to healthy controls, subjects with SCD exhibited: (1) decreased sFC between the left caudal hippocampus and left precuneus; (2) decreased dFC variability between the bilateral caudal hippocampus and precuneus; (3) increased dFC variability between the bilateral rostral hippocampus and caudate nucleus; and (4) increased dFC variability between the left rostral hippocampus and left olfactory cortex. Additionally, the attention scores were positively correlated with dFC variability between the left posterior hippocampus and left precuneus, and the dFC variability between the bilateral anterior hippocampus and caudate nucleus was positively correlated with depression scores and negatively correlated with global cognition scores. CONCLUSION: SCD individuals exhibited abnormal sFC and dFC in the anterior-posterior hippocampus, and abnormal dFC was more widespread than abnormal sFC. A combination of sFC and dFC provides a new perspective for exploring the brain pathophysiological mechanisms in SCD and offers potential neuroimaging biomarkers for the early diagnosis and intervention of AD.

Shared and specific dynamics of brain activity and connectivity in amnestic and nonamnestic mild cognitive impairment.

AIMS: The present study aimed to compare temporal variability in the spontaneous fluctuations of activity and connectivity between amnestic MCI (aMCI) and nonamnestic MCI (naMCI), which enhances the understanding of their different pathophysiologies and provides targets for individualized intervention. METHODS: Sixty-five naMCI and 48 aMCI subjects and 75 healthy controls were recruited. A sliding window analysis was used to evaluate the dynamic amplitude of low-frequency fluctuations (dALFF), dynamic regional homogeneity (dReHo), and dynamic functional connectivity (dFC). The caudal/rostral hippocampus was selected as the seeds for calculating dFC. RESULTS: Both aMCI and naMCI exhibited abnormal dALFF, dReHo, and hippocampal dFC compared with healthy controls. Compared with individuals with naMCI, those with aMCI exhibited (1) higher dALFF variability in the right putamen, left Rolandic operculum, and right middle cingulum, (2) lower dReHo variability in the right superior parietal lobule, and (3) lower dFC variability between the hippocampus and other regions (left superior occipital gyrus, middle frontal gyrus, inferior cerebellum, precuneus, and right superior frontal gyrus). Additionally, variability in dALFF, dReHo, and hippocampal dFC exhibited different associations with cognitive scores in aMCI and naMCI patients, respectively. Finally, dReHo variability in the right superior parietal lobule and dFC variability between the right caudal hippocampus and left inferior cerebellum exhibited partially mediated effects on the different memory scores between people with aMCI and naMCI. CONCLUSION: The aMCI and naMCI patients exhibited shared and specific patterns of dynamic brain activity and connectivity. The dReHo of the superior parietal lobule and dFC of the hippocampus-cerebellum contributed to the memory heterogeneity of MCI subtypes. Analyzing the temporal variability in the spontaneous fluctuations of brain activity and connectivity provided a new perspective for exploring the different pathophysiological mechanisms in MCI subtypes.

Elevated homocysteine levels, white matter abnormalities and cognitive impairment in patients with late-life depression.

Background: Cognitive impairment in late-life depression (LLD) is considered to be caused by neurodegenerative changes. Elevated homocysteine (Hcy) levels may be linked to cognitive abnormalities associated with LLD. The important role of white matter (WM) damage in cognitive impairment and pathogenesis in patients with LLD has been widely reported. However, no research has explored the interrelationships of these features in patients with LLD. Objective: The goal of the study was to examine the interrelationship between Hcy levels, cognition, and variations in WM microstructure detected by diffusion tensor imaging (DTI) in patients with LLD. Methods: We recruited 89 healthy controls (HCs) and 113 patients with LLD; then, we measured the plasma Hcy levels of participants in both groups. All individuals performed a battery of neuropsychological tests to measure cognitive ability. Seventy-four patients with LLD and 68 HCs experienced a DTI magnetic resonance imaging (MRI) scan. Results: Patients with LLD showed significantly lower fractional anisotropy (FA) values in the bilateral inferior longitudinal fasciculus than those of healthy participants. Only in LLD patients was Hcy concentration inversely associated to FA values in the forceps minor. Finally, multiple regression analyses showed that an interaction between Hcy levels and FA values in the right cingulum of the cingulate cortex and right inferior longitudinal fasciculus were independent contributors to the executive function of patients with LLD. Conclusion: Our results highlight the complex interplay between elevated homocysteine levels and WM abnormalities in the pathophysiology of LLD-related cognitive impairment, consistent with the neurodegeneration hypothesis.

Resting-state electroencephalography of neural oscillation and functional connectivity patterns in late-life depression.

BACKGROUND: The clinical manifestations of late-life depression (LLD) are highly heterogeneous. Currently, abnormal characteristics of resting-state electroencephalography (EEG) power and functional connectivity are considered trait markers of depressive symptoms in major depression. However, the relationship between EEG spectral features and functional connectivity in LLD remains unknown. METHODS: Forty-one patients with LLD and 44 participants without depression underwent an eyes-closed resting-state EEG. EEG power spectra, alpha asymmetry, and functional connectivity were calculated and analyzed. RESULTS: Although alpha frontal asymmetry and cortical functional connectivity between the two groups showed no significant differences, the LLD group exhibited abnormal neural oscillation patterns of higher beta frequency activity in the parietal, central, and occipital lobes while alpha activity was increased in the parietal central electrodes. LIMITATIONS: The number of EEG electrodes used in this study was low, and the sample size was limited. CONCLUSIONS: Increased alpha and beta frequency band powers were observed in patients with LLD. These abnormal patterns may be associated with a disturbed balance of cortical excitation, inhibition, and hyperactivity. In the future, a neurofeedback protocol based on the findings of neural oscillation patterns in certain types of LLD should be explored.

Altered Microstate Dynamics and Spatial Complexity in Late-Life Schizophrenia.

Background: Resting-state EEG microstate and omega complexity analyses have been widely used to explore deviant brain function in various neuropsychiatric disorders. This study aimed to investigate the features of microstate dynamics and spatial complexity in patients with late-life schizophrenia (LLS). Method: Microstate and omega complexity analyses were performed on resting-state EEG data from 39 in patients with LLS and compared with 40 elderly normal controls (NCs). Result: The duration of microstate classes A and D were significantly higher in patients with LLS compared with NCs. The occurrence of microstate classes A, B, and C was significantly lower in patients with LLS compared with NCs. LLS patients have a lower time coverage of microstate class A and a higher time coverage of class D than NCs. Transition probabilities from microstate class A to B and from class A to C were significantly lower in patients with LLS compared with NCs. Transition probabilities between microstate class B and D were significantly higher in patients with LLS compared with NCs. Global omega complexity and anterior omega complexity were significantly higher in patients with LLS compared with NCs. Conclusion: This study revealed an altered pattern of microstate dynamics and omega complexity in patients with LLS. This may reflect the disturbed neural basis underlying LLS and enhance the understanding of the pathophysiology of LLS.