Association between Periodontitis and Mild Cognitive Impairment: A Systematic Review and Meta-Analysis.

INTRODUCTION: The connection between periodontitis and mild cognitive impairment (MCI) continues to receive attention. However, whether periodontitis is a risk factor for MCI remains still uncertain. This study aims to systematically analyze the available literature regarding the relationship between periodontitis and the risk of developing MCI and whether the periodontal health of MCI patients is poorer. METHODS: A literature search of PubMed, Scopus, Embase, and Web of Science databases was conducted to include all studies on the relationship between periodontitis and MCI from inception to April 2023. The studies were independently screened by 2 researchers, and those meeting the inclusion criteria were extracted and cross-checked. Pooled odds ratio (OR) or mean difference (MD) with 95% confidence intervals (CI) was calculated using either a fixed-effects or random-effects model. RESULTS: Seven studies with a total of 3,973 participants were included. Meta-analysis results showed a statistically significant higher incidence of MCI in patients with periodontitis (OR, 1.70 (95% CI: 1.24-2.32, p < 0.001) compared to healthy participants. A subgroup meta-analysis showed that the pooled OR for the risk of MCI in patients with severe periodontitis was 2.09 (95% CI: 1.49-2.92, p < 0.001). In addition, attachment loss (MD = 0.44, 95% CI: 0.12-0.75, p < 0.001) and plaque index (MD = 0.72, 95% CI: 0.50-0.93, p < 0.001) were higher in MCI patients compared with the control group, but the pocket probing depth (MD = 0.21, 95% CI: -0.08 to 0.49, p = 0.15) was not significantly different between the two groups. CONCLUSIONS: Patients with periodontitis are at a higher risk of developing MCI, and the periodontal health of MCI patients is generally compromised. However, further well-designed studies should be conducted to confirm this relationship between MCI and periodontitis.

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.

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.

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.

Physical condition and activity of daily living among aging inpatients with mental disorders in Guangzhou, China: a cross-sectional study.

BACKGROUND: The number of elderly with mental disorders is increasing, but few studies have been concerned with the physical condition and activities of daily living (ADL) of these patients. This study aims to describe the physical condition and ADL of patients with mental illnesses (PMI) from different age groups, which provides evidence to improve mental health services for PMI. METHODS: In this prospective cross-sectional study, the samples were divided into three groups of less than 60 years old (group 1), 60-74 years old (group 2), and over 75 years old (group 3) for comparison. Participants' ADL and physical condition were measure by Barthel Index (BI), Functional Activities Questionnaire (FAQ), Standardised swallowing assessment (SSA) and Short Form of Mini Nutrition Assessment (MNA-SF). The Brief Psychiatric Rating Scale (BPRS) and the Mini-Mental State Examination (MMSE) were used to measure psychological condition. RESULTS: Totally, 392 participants had been recruited, meanwhile 86% of them were diagnosed with at least one physical disease. There were statistically significant differences in the three groups of participants in BI (F = 50.603, P < 0.001), FAQ (F = 40.332, P < 0.001), SSA (F = 28.574, P < 0.001), and MNA-SF (F = 18.366, P < 0.001). Group 2 and group 3 had significantly lower scores in BI and FAQ than group 1, and the SSA scores were significantly higher than the participants in group 1. In the negative symptoms subscale of BPRS, the mean score of group 3 was significantly higher than groups 1 and 2. Negative symptom subscale has different degrees of correlation with BI (r = -0.537), FAQ (r = 0.643), SSA (r = 0.480), MNA (r = -0.325) and MMSE (r = 0.607). In addition, the participants with comorbidities were related to BI (r = -0.364). CONCLUSION: Somatic comorbidities play a pivotal role in the clinical characteristics of elderly patients with mental illness, thus greater effort should be paid to elderly patients suffering from mental illness with dysphagia, malnutrition, and cognitive decline. Further, the negative symptoms of elderly patients with mental disorders also deserve attention.

Structural and Functional Abnormalities of Olfactory-Related Regions in Subjective Cognitive Decline, Mild Cognitive Impairment, and Alzheimer's Disease.

BACKGROUND: Odor identification (OI) dysfunction is an early marker of Alzheimer's disease (AD), but it remains unclear how olfactory-related regions change from stages of subjective cognitive decline (SCD) and mild cognitive impairment (MCI) to AD dementia. METHODS: Two hundred and sixty-nine individuals were recruited in the present study. The olfactory-related regions were defined as the regions of interest, and the grey matter volume (GMV), low-frequency fluctuation, regional homogeneity (ReHo), and functional connectivity (FC) were compared for exploring the changing pattern of structural and functional abnormalities across AD, MCI, SCD, and normal controls. RESULTS: From the SCD, MCI to AD groups, the reduced GMV, increased low-frequency fluctuation, increased ReHo, and reduced FC of olfactory-related regions became increasingly severe, and only the degree of reduced GMV of hippocampus and caudate nucleus clearly distinguished the 3 groups. SCD participants exhibited reduced GMV (hippocampus, etc.), increased ReHo (caudate nucleus), and reduced FC (hippocampus-hippocampus and hippocampus-parahippocampus) in olfactory-related regions compared with normal controls. Additionally, reduced GMV of the bilateral hippocampus and increased ReHo of the right caudate nucleus were associated with OI dysfunction and global cognitive impairment, and they exhibited partially mediated effects on the relationships between OI and global cognition across all participants. CONCLUSION: Structural and functional abnormalities of olfactory-related regions present early with SCD and deepen with disease severity in the AD spectrum. The hippocampus and caudate nucleus may be the hub joining OI and cognitive function in the AD spectrum.

Cardiac Phenotype Characterization at MRI in Patients with Danon Disease: A Retrospective Multicenter Case Series.

Danon disease (DD) is a rare X-chromosome-linked dominant lysosomal glycogen storage disease. Its features have seldom been reported by using cardiac MRI. This case series aimed to evaluate cardiac features of DD on the basis of MRI observations from five centers in China. From January 2010 to May 2019, 16 patients with DD (13 male patients [81%]; median age, 19 years; age range, 14-44 years) underwent MRI. The most frequent DD cardiomyopathy manifestation was symmetric hypertrophy cardiomyopathy (HCM) phenotype (nine of 16; 56%), followed by asymmetric HCM phenotype (six of 16; 38%) and dilated cardiomyopathy phenotype (one of 16; 6%). The characteristic late gadolinium enhancement features included midbasal septum sparing (14 of 16; 88%) and apex involvement (16 of 16; 100%) with a base-to-apex increasing tendency, free wall involvement (15 of 16; 94%), and extensive subendocardium involvement (14 of 16; 88%). Abnormal T2 signal (seven of 16; 44%) and resting perfusion defect (14 of 16; 88%) were not uncommon in patients with DD. Furthermore, the cardiac MRI features of DD cohort in this study were compared with those of DD in previous literature and with genetically confirmed sarcomeric HCM.

Working memory associated with anti-suicidal ideation effect of repeated-dose intravenous ketamine in depressed patients.

Suicide is a tremendous threat to global public health, and a large number of people who committed suicide suffered the pain of mental diseases, especially major depressive disorder (MDD). Previous study showed that ketamine could reduce suicidal ideation (SI), potentially by improving the impaired working memory (WM). The objective of current study was to illuminate the relationship between WM and SI in MDD with repeated ketamine treatment. MDD patients with SI (n = 59) and without SI (n = 37) completed six intravenous infusions of ketamine (0.5 mg/kg over 40 min) over 12 days (Day 1, 3, 5, 8, 10 and 12). The severity of depressive symptoms, SI and WM were assessed at baseline, day 13 and day 26. We found that WM was significantly improved after 6 ketamine infusions (F = 161.284, p = 0.009) in a linear mixed model. Correlation analysis showed that the improvement of depressive symptom was significantly associated with WM at baseline (r = - 0.265, p = 0.042) and the reduction in SSI-part I was related to the change of WM (r = 0.276, p = 0.034) in the MDD patients with SI. Furthermore, Logistic regression analysis showed that improvement in WM might predict the anti-SI response of ketamine. Our findings suggest that the improvement of working memory may partly account for the anti-SI effect of ketamine, and intervention of improving working memory function may be capable of reducing suicidal ideation.

ECG-gated CT in Aortic Perivalvular Abscess: Comparison with Transesophageal Echocardiography and Intraoperative Findings.

Background The 2015 European Society of Cardiology guidelines acknowledged similar diagnostic performance of electrocardiography (ECG)-gated CT on perivalvular abscesses compared with transesophageal echocardiography (TEE), but data on ECG-gated CT remain insufficient. Purpose To determine the diagnostic performance of ECG-gated CT for assessing aortic root perivalvular abscesses and to compare it with TEE. Materials and Methods Between January 2008 and June 2019, the imaging records of surgically confirmed infective endocarditis were retrospectively reviewed for presence of aortic perivalvular abscesses, their extension, fistulization, vegetations, and valvular destruction. The diagnostic performance of ECG-gated CT was analyzed in all patients (part A) and in an noninferiority analysis (part B; δ = -10%) in patients undergoing TEE. Results A total of 178 patients (median age, 54 years [interquartile range, 15 years]; 147 men) were evaluated (CT, n = 178; TEE, n = 35). In part A, the sensitivity and specificity of CT were 70 of 71 (99% [95% confidence interval (CI): 96%, 100%]) and 102 of 107 (95% [95% CI: 91%, 99%]) for abscess; 65 of 68 (96% [95% CI: 91%, 100%]) and 107 of 110 (97% [95% CI: 94%, 100%]) for extension, 36 of 36 (100% [95% CI: 100%, 100%]) and 139 of 142 (98% [95% CI: 96%, 100%]) for fistulization, 153 of 160 (96% [95% CI: 93%, 99%]) and five of 18 (28% [95% CI: 7%, 49%]) for vegetations, and 90 of 90 (100% [95% CI: 100%, 100%]) and 24 of 88 (27% [95% CI: 18%, 37%]) for valvular destruction. In part B, ECG-gated CT had noninferior sensitivity compared with TEE for detecting abscess (difference, 14 percentage points [lower one-sided 95% CI: -4 percentage points]), extension (difference, 0 percentage points [lower one-sided 95% CI: 0 percentage points]), fistulization (difference, 0 percentage points [lower one-sided 95% CI: 0 percentage points]), and valvular destruction (difference, 5 percentage points [lower one-sided 95% CI: -4 percentage points]). Specificity of CT was inferior for demonstrating perivalvular abscess (difference, 5 percentage points [lower one-sided 95% CI: -11 percentage points]) and valvular destruction (difference, -62 percentage points [lower one-sided 95% CI: -92 percentage points]). ECG-gated CT had inferior sensitivity in detecting vegetations (difference, -6 percentage points [lower one-sided 95% CI: -14 percentage points]). Conclusion Electrocardiography-gated CT had noninferior sensitivity compared with transesophageal echocardiography for identification of aortic perivalvular abscesses, extension of these abscesses, fistulization, and valvular destruction but had inferior sensitivity in detection of vegetations. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Sakuma in this issue.

The prevalence of agranulocytosis and related death in clozapine-treated patients: a comprehensive meta-analysis of observational studies.

BACKGROUND: Clozapine treatment increases the risk of agranulocytosis, but findings on the epidemiology of agranulocytosis have been inconsistent. This meta-analysis examined the prevalence of agranulocytosis and related death in clozapine-treated patients. METHODS: A literature search in the international (PubMed, PsycINFO, and EMBASE) and Chinese (WanFang, Chinese National Knowledge Infrastructure, and Sinomed) databases was conducted. Prevalence estimates of agranulocytosis and related death in clozapine-treated patients were synthesized with the Comprehensive Meta-Analysis program using the random-effects model. RESULTS: Thirty-six studies with 260 948 clozapine-treated patients published between 1984 and 2018 were included in the meta-analysis. The overall prevalence of agranulocytosis and death caused by agranulocytosis were 0.4% (95% CI 0.3-0.6%) and 0.05% (95% CI 0.03-0.09%), respectively. The prevalence of agranulocytosis was moderated by sample size, study quality, year of publication, and that of data collection. CONCLUSIONS: The prevalence of clozapine-associated agranulocytosis is low. Agranulocytosis-related death appears rare.

Cardiovascular diseases and related risk factors accelerated cognitive deterioration in patients with late-life depression: a one-year prospective study.

OBJECTIVES: Cognitive impairment in late-life depression is common and associated with a higher risk of all-cause dementia. Late-life depression patients with comorbid cardiovascular diseases (CVDs) or related risk factors may experience higher risks of cognitive deterioration in the short term. We aim to investigate the effect of CVDs and their related risk factors on the cognitive function of patients with late-life depression. METHODS: A total of 148 participants were recruited (67 individuals with late-life depression and 81 normal controls). The presence of hypertension, coronary heart disease, diabetes mellitus, or hyperlipidemia was defined as the presence of comorbid CVDs or related risk factors. Global cognitive functions were assessed at baseline and after a one-year follow-up by the Mini-Mental State Examination (MMSE). Global cognitive deterioration was defined by the reliable change index (RCI) of the MMSE. RESULTS: Late-life depression patients with CVDs or related risk factors were associated with 6.8 times higher risk of global cognitive deterioration than those without any of these comorbidities at a one-year follow-up. This result remained robust after adjusting for age, gender, and changes in the Hamilton Depression Rating Scale (HAMD) scores. CONCLUSIONS: This study suggests that late-life depression patients with comorbid CVDs or their related risk factors showed a higher risk of cognitive deterioration in the short-term (one-year follow up). Given that CVDs and their related risk factors are currently modifiable, active treatment of these comorbidities may delay rapid cognitive deterioration in patients with late-life depression.

Concurrent benzodiazepine use in older adults treated with antidepressants in Asia.

ABSTRACTBackground:Little is known about the combined use of benzodiazepines and antidepressants in older psychiatric patients. This study examined the prescription pattern of concurrent benzodiazepines in older adults treated with antidepressants in Asia, and explored its demographic and clinical correlates. METHODS: The data of 955 older adults with any type of psychiatric disorders were extracted from the database of the Research on Asian Psychotropic Prescription Patterns for Antidepressants (REAP-AD) project. Demographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. Both univariate and multiple logistic regression analyses were performed. RESULTS: The proportion of benzodiazepine and antidepressant combination in this cohort was 44.3%. Multiple logistic regression analysis revealed that higher doses of antidepressants, younger age (<65 years), inpatients, public hospital, major comorbid medical conditions, antidepressant types, and country/territory were significantly associated with more frequent co-prescription of benzodiazepines and antidepressants. CONCLUSIONS: Nearly, half of the older adults treated with antidepressants in Asia are prescribed concurrent benzodiazepines. Given the potentially adverse effects of benzodiazepines, the rationale of benzodiazepines and antidepressants co-prescription needs to be revisited.

Cognitive Impairment and Structural Abnormalities in Late Life Depression with Olfactory Identification Impairment: an Alzheimer's Disease-Like Pattern.

Background: Late-life depression patients are at a high risk of developing Alzheimer's disease, and diminished olfactory identification is an indicator in early screening for Alzheimer's disease in the elderly. However, whether diminished olfactory identification is associated with risk of developing Alzheimer's disease in late-life depression patients remains unclear. Methods: One hundred and twenty-five late-life depression patients, 50 Alzheimer's disease patients, and 60 normal controls were continuously recruited. The participants underwent a clinical evaluation, olfactory test, neuropsychological assessment, and neuroimaging assessment. Results: The olfactory identification impairment in late-life depression patients was milder than that in Alzheimer's disease patients. Diminished olfactory identification was significantly correlated with worse cognitive performance (global function, memory language, executive function, and attention) and reduced grey matter volume (olfactory bulb and hippocampus) in the late-life depression patients. According to a multiple linear regression analysis, olfactory identification was significantly associated with the memory scores in late-life depression group (B=1.623, P<.001). The late-life depression with olfactory identification impairment group had worse cognitive performance (global, memory, language, and executive function) and more structural abnormalities in Alzheimer's disease-related regions than the late-life depression without olfactory identification impairment group, and global cognitive function and logical memory in the late-life depression without olfactory identification impairment group was intact. Reduced volume observed in many areas (hippocampus, precuneus, etc.) in the Alzheimer's disease group was also observed in late-life depression with olfactory identification impairment group but not in the late-life depression without olfactory identification impairment group. Conclusion: The patterns of cognitive impairment and structural abnormalities in late-life depression with olfactory identification impairment patients were similar to those in Alzheimer's disease; olfactory identification may help identify late-life depression patients who are at a high risk of developing Alzheimer's disease.

Physical comorbidities in older adults receiving antidepressants in Asia.

BACKGROUND: The present study explored the patterns of physical comorbidities and their associated demographic and clinical factors in older psychiatric patients prescribed with antidepressants in Asia. METHODS: Demographic and clinical information of 955 older adults were extracted from the database of the Research on Asian Psychotropic Prescription Patterns for Antidepressants (REAP-AD) project. Standardized data collection procedure was used to record demographic and clinical data. RESULTS: Proportion of physical comorbidities in this cohort was 44%. Multiple logistic regression analyses showed that older age (OR = 1.7, P < 0.001), higher number of depressive symptoms (OR = 1.09, P = 0.016), being treated in psychiatric hospital (OR = 0.5, P = 0.002), living in high income countries/territories (OR = 2.4, P = 0.002), use of benzodiazepines (OR = 1.4, P = 0.013) and diagnosis of 'other psychiatric disorders' (except mood, anxiety disorders and schizophrenia) (OR = 2.7, P < 0.001) were significantly associated with physical comorbidities. CONCLUSIONS: Physical comorbidities in older patients prescribed with antidepressants were common in Asia. Integrating physical care into the treatment of older psychiatric patients should be urgently considered.

Decreased intracellular [Ca2+ ] coincides with reduced expression of Dhprα1s, RyR1, and diaphragmatic dysfunction in a rat model of sepsis.

INTRODUCTION: Sepsis can cause decreased diaphragmatic contractility. Intracellular calcium as a second messenger is central to diaphragmatic contractility. However, changes in intracellular calcium concentration ([Ca2+ ]) and the distribution and co-localization of relevant calcium channels [dihydropyridine receptors, (DHPRα1s) and ryanodine receptors (RyR1)] remain unclear during sepsis. In this study we investigated the effect of changed intracellular [Ca2+ ] and expression and distribution of DHPRα1s and RyR1 on diaphragm function during sepsis. METHODS: We measured diaphragm contractility and isolated diaphragm muscle cells in a rat model of sepsis. The distribution and co-localization of DHPRα1s and RyR1 were determined using immunohistochemistry and immunofluorescence, whereas intracellular [Ca2+ ] was measured by confocal microscopy and fluorescence spectrophotometry. RESULTS: Septic rat diaphragm contractility, expression of DHPRα1s and RyR1, and intracellular [Ca2+ ] were significantly decreased in the rat sepsis model compared with controls. DISCUSSION: Decreased intracellular [Ca2+ ] coincides with diaphragmatic contractility and decreased expression of DHPRα1s and RyR1 in sepsis. Muscle Nerve 56: 1128-1136, 2017.

Neuropsychiatric Features of Neurosyphilis: Frequency, Relationship with the Severity of Cognitive Impairment and Comparison with Alzheimer Disease.

BACKGROUND: The pattern of neuropsychiatric features of patients with neurosyphilis and the impact of the severity of cognitive impairment on neuropsychiatric syndromes are unknown. OBJECTIVE: We aim to assess the neuropsychiatric features of patients with neurosyphilis, and compare the impact of the severity of cognitive impairment on the neuropsychiatric syndromes between neurosyphilis and Alzheimer disease (AD). METHODS: Neuropsychiatric symptoms and the degree of cognitive impairment were assessed in a case-control study of 91 neurosyphilis, 162 AD, 157 mild cognitive impairment, and 139 normal controls by the Neuropsychiatric Inventory (NPI) scale and Clinical Dementia Rating scale, respectively. Factor analysis was performed on the 12 NPI items. RESULTS: Factor analysis showed that patients with neurosyphilis showed more severe neuropsychiatric syndromes at the dementia stage than those neurosyphilis patients at the mild cognitive impairment stage, while neuropsychiatric manifestations were equally common among the different stages of dementia (all p < 0.05). Frontal lobe syndrome was more severe in patients with neurosyphilis than in patients with AD from the early mild cognitive impairment stage to the moderate dementia stage (all p < 0.01). CONCLUSIONS: Patients with neurosyphilis show different patterns of neuropsychiatric syndromes at the mild cognitive impairment and dementia stages, and differ from patients with AD.

In Vivo Targeted MR Imaging of Endogenous Neural Stem Cells in Ischemic Stroke.

Acute ischemic stroke remains a leading cause of death and disability. Endogenous neurogenesis enhanced via activation of neural stem cells (NSCs) could be a promising method for stroke treatment. In vivo targeted tracking is highly desirable for monitoring the dynamics of endogenous NSCs in stroke. Previously, we have successfully realized in vivo targeted MR imaging of endogenous NSCs in normal adult mice brains by using anti-CD15 antibody-conjugated superparamagnetic iron oxide nanoparticles (anti-CD15-SPIONs) as the molecular probe. Herein, we explore the performance of this molecular probe in targeted in vivo tracking of activated endogenous NSCs in ischemic stroke. Our study showed that intraventricular injection of anti-CD15-SPIONs could label activated endogenous NSCs in situ seven days after ischemic stroke, which were detected as enlarged areas of hypo-intense signals on MR imaging at 7.0 T. The treatment of cytosine arabinosine could inhibit the activation of endogenous NSCs, which was featured by the disappearance of areas of hypo-intense signals on MR imaging. Using anti-CD15-SPIONs as imaging probes, the dynamic process of activation of endogenous NSCs could be readily monitored by in vivo MR imaging. This targeted imaging strategy would be of great benefit to develop a new therapeutic strategy utilizing endogenous NSCs for ischemic stroke.

Diagnostic performance of CT and MRI in distinguishing intraductal papillary neoplasm of the bile duct from cholangiocarcinoma with intraductal papillary growth.

OBJECTIVES: We aimed to evaluate the diagnostic performance of CT and MRI for distinguishing intraductal papillary neoplasm of the bile duct (IPNB) from cholangiocarcinoma (CC) with intraductal papillary growth (IPG). METHODS: Forty-two patients with either IPNB or CC with IPG proven by histopathology were independently reviewed in retrospect. Strict criteria for diagnosis of IPNB included presence of the designated imaging features as follows: local dilatation of the bile duct, nodule within the dilated bile duct, growing along the interior wall of bile duct. Any lesion that was not consistent with the criteria was classified as CC with IPG. Sensitivity, specificity, positive and negative predictive values for characterization of IPNB were calculated, and k test was used to assess the level of agreement. RESULTS: Two imaging reviewers correctly identified 21 of 26 (80.8%) and 22 of 26 (84.6%) IPNB cases, respectively. Alternatively, they correctly identified 14 of 16 (87.5%) and 15 of 16 (93.8%) CC with IPG, respectively. Agreement between the two reviewers was perfect (k = 0.81) for the diagnosis of IPNB and differentiation from CC with IPG. CONCLUSIONS: By using our designated diagnostic criteria of CT and MRI, IPNB can be accurately identified and possible to be distinguished from CC with IPG. KEY POINTS: • IPNB can accurately be identified by using defined diagnostic criteria at CT/MRI. • IPNB has some characteristic CT and MR imaging features. • IPNB is a rare entity; up until now it might have been misdiagnosed.

Increasing variance of rich-club nodes distribution in early onset depression according to dynamic network.

Early onset depression (EOD) and late onset depression (LOD) are thought to have different pathogeneses, but lack of pathological evidence. In the current study we describe the dynamic rich-club properties of patients with EOD and LOD to address this question indirectly. We recruited 82 patients with late life depression (EOD 40, LOD 42) and 90 healthy controls. Memory, executive function and processing speed were measured, and resting-stage functional MRI was performed with all participants. We constructed a dynamic functional connectivity network and carried out rich-club and modularity analyses. Normalized mutual information (NMI) was applied to describe the variance in rich-club nodes distribution and partitioning. The NMI coefficient of rich club nodes distribution among the three groups was the lowest in the EOD patients (F = 4.298; P = 0.0151, FDR = 0.0231), which was positively correlated with rich-club connectivity (R = 0.886, P < 0.001) and negatively correlated with memory (R = -0.347, P = 0.038) in the EOD group. In the LOD patients, non-rich-club connectivity was positively correlated with memory (R = 0.353, P = 0.030 and R = 0.420, P = 0.009). Furthermore, local connectivity was positively correlated with processing speed in the LOD patients (R = 0.374, P = 0.021). The modular partition was different between the EOD patients and the HCs (P = 0.0013 < 0.05/3). The temporal instability of rich-club nodes was found in the EOD patients, but not the LOD patients, supporting the hypothesis that EOD and LOD result from different pathogenesis, and showing that the instability of the rich-club nodes across time might disrupt rich-club connectivity.

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.