Reliability and validity of the electronic version of the Hopkins verbal learning test-revised in middle-aged and elderly Chinese people.

Background: The aging population is increasing, making it essential to have a standardized, convenient, and valid electronic memory test that can be accessed online for older people and caregivers. The electronic version of the Hopkins Verbal Learning Test-Revised (HVLT-R) as a test with these advantages and its reliability and validity has not yet been tested. Thus, this study examined the reliability and validity of the electronic version of the HVLT-R in middle-aged and elderly Chinese people to provide a scientific basis for its future dissemination and use. Methods: We included 1,925 healthy participants aged over 40, among whom 38 were retested after 3-6 months. In addition, 65 participants completed both the pad and paper-and-pencil versions of the HVLT-R (PAP-HVLT-R). We also recruited 42 Alzheimer's disease (AD) patients, and 45 amnestic mild cognitive impairment (aMCI) patients. All participants completed the Pad-HVLT-R, the Hong Kong Brief Cognitive Test (HKBC), the Brief Visual Memory Test-Revised (BVMT-R), and the Logical Memory Test (LM). Results: (1) Reliability: the Cronbach's α value was 0.94, the split-half reliability was 0.96. The test-retest correlation coefficients were moderate, ranging from 0.38 to 0.65 for direct variables and 0.16 to 0.52 for derived variables; (2) Concurrent validity: the Pad-HVLT-R showed a moderate correlation with the HKBC and BVMT-R, with correlation coefficients between total recall of 0.41 and 0.54, and between long-delayed recall of 0.42 and 0.59, respectively. It also showed a high correlation with the LM, with correlation coefficients of 0.72 for total recall and 0.62 for long-delayed recall; (3) Convergent validity: the Pad-HVLT-R was moderately correlated with the PAP version, with correlation coefficients ranging from 0.29 to 0.53 for direct variables and 0.15 to 0.43 for derived variables; (4) Discriminant capacity: the Pad-HVLT-R was effective in differentiating AD patients, as demonstrated by the ROC analysis with AUC values of 0.834 and 0.934 for total recall and long-delayed recall, respectively. Conclusion: (1) The electronic version of HVLT-R has good reliability and validity in middle-aged and elderly Chinese people; (2) The electronic version of HVLT-R can be used as an effective tool to distinguish AD patients from healthy people.

Parietal-hippocampal rTMS improves cognitive function in Alzheimer's disease and increases dynamic functional connectivity of default mode network.

Parietal-hippocampal repetitive transcranial magnetic stimulation (rTMS) improves cognitive function in Alzheimer's disease (AD), however, the underlying therapeutic mechanism has not been elucidated. A double-blind, randomized, sham-controlled parietal-hippocampal rTMS trial (five sessions/week for a total of 10 sessions) of mild-to-moderate AD patients was conducted in the study. High-frequency rTMS was applied to a subject-specific left lateral parietal region with the highest functional connectivity with the hippocampus based on resting-state fMRI. A multimodal MRI scan and a complete neuropsychological battery of tests were conducted at baseline, immediately after the intervention and 12-week follow-up after the rTMS treatment. Compared to sham treatment (n = 27), patients undergoing active rTMS treatment (n = 29) showed higher Mini Mental State Examination (MMSE) score and dynamic functional connectivity (dFC) magnitude of the default mode network (DMN) after two weeks of rTMS treatment, but not at 12-week follow-up. A significant positive correlation was observed between changes in MMSE and changes in the dFC magnitude of DMN in patients who underwent active-rTMS treatment, but not in those who received sham-rTMS treatment. The findings of the current study indicate that fMRI-guided rTMS treatment improves cognitive function of AD patients in the short term, and DMN functional connectivity contributes to therapeutic effectiveness of rTMS.

Inferring the Individual Psychopathologic Deficits With Structural Connectivity in a Longitudinal Cohort of Schizophrenia.

The prediction of schizophrenia-related psychopathologic deficits is exceedingly important in the fields of psychiatry and clinical practice. However, objective association of the brain structure alterations to the illness clinical symptoms is challenging. Although, schizophrenia has been characterized as a brain dysconnectivity syndrome, evidence accounting for neuroanatomical network alterations remain scarce. Moreover, the absence of generalized connectome biomarkers for the assessment of illness progression further perplexes the prediction of long-term symptom severity. In this paper, a combination of individualized prediction models with quantitative graph theoretical analysis was adopted, providing a comprehensive appreciation of the extent to which the brain network properties are affected over time in schizophrenia. Specifically, Connectome-based Prediction Models were employed on Structural Connectivity (SC) features, efficiently capturing individual network-related differences, while identifying the anatomical connectivity disturbances contributing to the prediction of psychopathological deficits. Our results demonstrated distinctions among widespread cortical circuits responsible for different domains of symptoms, indicating the complex neural mechanisms underlying schizophrenia. Furthermore, the generated models were able to significantly predict changes of symptoms using SC features at follow-up, while the preserved SC features suggested an association with improved positive and overall symptoms. Moreover, cross-sectional significant deficits were observed in network efficiency and a progressive aberration of global integration in patients compared to healthy controls, representing a group-consensus pathological map, while supporting the dysconnectivity hypothesis.

Impact of depression on the quality of sleep and immune functions in patients with coronary artery disease.

Background: The risk of major depressive disorder (MDD) and insomnia is higher in patients with coronary heart disease (CHD) than in the general population. In addition, immune inflammation may be a shared aetiological factor for mental disorders and CHD. However, it is unclear whether MDD is associated with poor sleep quality and cell-mediated immune function in patients with CHD. Aims: This study investigated the impact of depression on sleep quality and cell-mediated immune functions in patients with CHD and examined discriminative factors in patients with CHD with and without MDD. Methods: This cross-sectional retrospective study was conducted at the Zhejiang University School of Medicine affiliated with Sir Run Run Shaw Hospital. The study population consisted of 84 patients with CHD assigned to two groups based on their Hamilton Depression Rating Scale (HAMD) score (CHD with MDD (HAMD score of ≥10) vs without MDD). Subjective sleep quality, systemic inflammatory response and cell-mediated immune functions were assessed in patients with CHD with (n=50) and without (n=34) MDD using the Pittsburgh Sleep Quality Index (PSQI), routine blood tests and flow cytometry. The relationships between variables were ascertained using Pearson's product-moment, and linear discriminant analysis was used to explore the discriminative factors between groups. Results: Patients with CHD with MDD had significantly poorer sleep quality than those without MDD (Z=-6.864, p<0.001). The Systemic Inflammation Index (SII) and CD4+/CD8+ T-cell ratios were higher in patients with CHD with MDD than in those without MDD (Z=-3.249, p=0.001). Patients with CHD with MDD had fewer CD3+CD8+ and CD3+ T cells (Z=3.422, p=0.001) than those without MDD (t=2.032, p=0.045). Furthermore, patients with CHD with MDD may be differentiated from those without MDD using the PSQI, SII and T-cell levels, as these variables correctly classified the depressed and non-depressed groups with an accuracy of 96.4%. Conclusions: MDD may be responsible for poor sleep quality, increased cell-mediated immunity and SII in patients with CHD, which are discriminative factors for CHD in the depressive state. Clinicians should be aware of these interactions, as treatment for depressive symptoms may also improve CHD prognosis.

Reduced Plasma Estradiol Levels are Associated with Sleep Apnea in Depressed Peri- and Post-Menopausal Women.

OBJECTIVE: This study aimed at investigating the correlation between estradiol and sleep apnea among women with major depressive disorders during the perimenopausal and postmenopausal periods. METHODS: A total of 84 perimenopausal and postmenopausal women diagnosed with depression, and who had been subjected to whole-night polysomnography (PSG) were retrospectively studied. They were assigned into two groups based on the presence of OSA (apnea-hypopnea index (AHI)≥5) (OSA vs non-OSA). The correlation between estradiol levels and apnea-hypopnea index were assessed by logistic regression models after adjusting for age, body mass index (BMI), Hamilton Depression Rating Scale (HAMD), Pittsburgh Sleep Quality Index (PSQI), apnea frequency and progesterone. RESULTS: Among the 84 patients, 45.23% had OSA. Estradiol levels were significantly elevated in non-OSA than in OSA patients (p<0.05). Univariate analysis revealed that elevated estradiol levels are associated with reduced odds of OSA (odds ratio [OR] 0.92, 95% confidence interval [CI] 0.875-0.966, p = 0.001). Multivariate analyses showed that low estradiol levels (OR = 0.859, 95% CI 0.826-0.991, p = 0.031), higher HAMD scores (OR = 1.212, 95% CI 1.012-1.453, p = 0.037), higher apnea frequency (OR = 2.493, 95% CI 1.389-4.473, p = 0.002) and higher BMI (OR=1.635, 95% CI 1.136-2.353, p = 0.008) are correlated with OSA. CONCLUSION: The ratio of depressed perimenopausal to postmenopausal women comorbid OSA was high. Higher BMI, low estradiol levels, high apnea frequency and high HAMD scores were correlated with OSA diagnosis and could be potential diagnostic markers for OSA in depressed perimenopausal and postmenopausal women. Reduced estradiol levels were correlated with an increased risk of OSA among depressed perimenopausal and postmenopausal women.

Precision Repetitive Transcranial Magnetic Stimulation Over the Left Parietal Cortex Improves Memory in Alzheimer's Disease: A Randomized, Double-Blind, Sham-Controlled Study.

OBJECTIVE: We aim to study the effect of precision repetitive transcranial magnetic stimulation (rTMS) over the left parietal cortex on the memory and cognitive function in Alzheimer's disease (AD). METHODS: Based on the resting-state functional magnetic resonance imaging, the left parietal cortex site with the highest functional connectivity to the hippocampus was selected as the target of rTMS treatment. Sixty-nine AD patients were randomized to either rTMS or sham treatment (five sessions/week for a total of 10 sessions). The Mini-Mental State Examination (MMSE), 12-Word Philadelphia Verbal Learning Test (PVLT), and Clinical Dementia Rating (CDR) were assessed at baseline and after the last session. RESULTS: After a 2-week treatment, compared to patients in the sham group, those in the rTMS group scored significantly higher on PVLT total score and its immediate recall subscale score. Moreover, in the rTMS group, there were significant improvements after the 2-week treatment, which were manifested in MMSE total score and its time orientation and recall subscale scores, as well as PVLT total score and its immediate recall and short delay recall subscale scores. In the sham group, the PVLT total score was significantly improved. CONCLUSION: The target site of the left parietal cortex can improve AD patients' cognitive function, especially memory, providing a potential therapy.

Safety and Efficacy of Donepezil 10 mg/day in Patients with Mild to Moderate Alzheimer's Disease.

BACKGROUND: Efficacy and dose-effect relationship of donepezil for treating patients with Alzheimer's disease (AD) have been proven. However, few studies focused on the safety of donepezil, particularly in Chinese patients. OBJECTIVE: To assess the safety of donepezil 10 mg/day in Chinese patients with mild-to-moderate AD. METHODS: In this single-arm, prospective, multicenter trial, 241 patients with mild to moderate AD who had been treated with donepezil 5 mg/day for at least 4 weeks were enrolled. All patients received donepezil 10 mg/day for 20 weeks. Primary outcome was the incidence of adverse events (AEs). Safety profile was evaluated by physical examinations including vital signs and weight, clinical laboratory tests and electrocardiograms, and also correlation analysis between AEs and APOE genotypes. RESULTS: 241 patients were enrolled. Of which, 38.59% patients experienced at least one AE and 17.43% discontinued due to AEs. Most AEs were mild to moderate, with diarrhea, vomiting, and nausea the most frequently reported. Risk of AEs was significantly increased by concomitant use of drugs for cardiovascular and cerebrovascular diseases. Mean changes in heart rate and corrected QT relative to baseline were -1.08±6.02 beat/min (p = 0.009) and -3.91±18.68 ms (p = 0.0062) at week 4 and -1.48 beat/min±7.18 (p = 0.0028) and -0.66 ms±19.66 (p = 0.6561) at week 20, respectively. There were no significant changes in other vital sign parameters. Patients' MMSE scores improved significantly after treatment (p = 0.0038), especially for non-APOEɛ4 allele carriers and patients ≤75 years. CONCLUSION: Donepezil 10 mg/day can be tolerated and is effective in Chinese patients with mild-to-moderate AD.

Connectome analysis of functional and structural hemispheric brain networks in major depressive disorder.

Neuroimaging studies have shown topological disruptions of both functional and structural whole-brain networks in major depressive disorder (MDD). This study examined common and specific alterations between these two types of networks and whether the alterations were differentially involved in the two hemispheres. Multimodal MRI data were collected from 35 MDD patients and 35 healthy controls, whose functional and structural hemispheric networks were constructed, characterized, and compared. We found that functional brain networks were profoundly altered at multiple levels, while structural brain networks were largely intact in patients with MDD. Specifically, the functional alterations included decreases in intra-hemispheric (left and right) and inter-hemispheric (heterotopic) functional connectivity; decreases in local, global and normalized global efficiency for both hemispheric networks; increases in normalized local efficiency for the left hemispheric networks; and decreases in intra-hemispheric integration and inter-hemispheric communication in the dorsolateral superior frontal gyrus, anterior cingulate gyrus and hippocampus. Regarding hemispheric asymmetry, largely similar patterns were observed between the functional and structural networks: the right hemisphere was over-connected and more efficient than the left hemisphere globally; the occipital and partial regions exhibited leftward asymmetry, and the frontal and temporal sites showed rightward lateralization with regard to regional connectivity profiles locally. Finally, the functional-structural coupling of intra-hemispheric connections was significantly decreased and correlated with the disease severity in the patients. Overall, this study demonstrates modality- and hemisphere-dependent and invariant network alterations in MDD, which are helpful for understanding elaborate and characteristic patterns of integrative dysfunction in this disease.

Spatiotemporal, metabolic, and therapeutic characterization of altered functional connectivity in major depressive disorder.

Although imbalanced functional integration has been increasingly reported in major depressive disorder (MDD), there still lacks a general framework to characterize common characteristic and origin shared by the integrative disturbances. Here we examined spatial selectivity, temporal uniqueness, metabolic basis, and therapeutic response of altered functional connectivity (FC) in MDD by analyzing both cross-sectional and longitudinal multimodal functional magnetic resonance imaging data from 35 patients and 34 demographically matched healthy controls. First, based on a voxel-wise, data-driven, graph-based degree centrality approach, the bilateral anterior cingulate gyri, middle frontal gyri and superior frontal gyri, and the right parahippocampal gyrus were robustly identified to show decreased FC in MDD. Further spatiotemporal analyses revealed that these regions exhibited hub-like features and were selectively located in limbic and default mode networks spatially and, relative to other areas in the brain, exhibited unique, frequency-dependent oscillation power (stronger within 0.01-0.027 Hz and weaker within 0.027-0.073 Hz) and less dynamical variability of whole-brain FC profiles temporally. Moreover, a cross-modality fusion analysis showed that all MDD-related FC impairments were associated with reduced cerebral blood flow (CBF); however, there existed multiple regions that showed reduced CBF but had intact FC in the patients, which resulted in a decreased FC-CBF coupling and implied an earlier emergence of reduced CBF than impaired FC in MDD. Finally, the disrupted FC in MDD gradually recovered over the course of drug treatment (2 and 12 weeks). Altogether, these findings could help establish a general framework to provide mechanistic insights into integrative dysfunctions in MDD.

Relationship of Mean Platelet Volume To MDD: A Retrospective Study.

BACKGROUND: Results of numerous studies show that major depressive disorder (MDD) is associated with a chronic low-grade inflammation, but the underlying mechanism remains unclear. AIM: To compare the results of blood cell analysis of MDD patients with healthy controls, and explore the potential value of it as an indicator of immune-inflammation in MDD, especially the mean platelet volume. METHODS: 103 MDD patients and 106 healthy controls with matched age and gender were recruited. We collected peripheral blood samples from both groups and gathered basic data. For comparison of normally distributed data (age, body mass index, lymphocyte count, white blood cell count, red blood cell count, hematocrit, platelet count and mean corpuscular volume) between groups, single t-test were used; and for comparison of non-normally distributed data (Neutrophil count, neutrophil count, platelet/ lymphocyte ratio, hemoglobin, red blood cell distribution width, mean platelet volume, mean hemoglobin concentration, mean hemoglobin and platelet distribution width), we used Mann-Whitney U-test. RESULTS: Compared with healthy controls, the MDD groups showed significantly higher white blood cell count (F=0.443, p=0.004), plateletcrit (F=8.3, p<0.001), neutrophil and lymphocyte ratio (Z=-6.063, p<0.001), neutrophil count (Z=-5.062, p<0.001), platelet/lymphocyte ratio (Z=-2.469, p=0.014), red blood cell distribution width (Z=-2.481, p=0.013) and mean platelet volume (Z=-2.668, p=0.008). In addition they had significantly lower hemoglobin (Z=-3.876, p<0.001), mean hemoglobin amount (Z=-3.005, p=0.003), red blood cell count (F=0.248, p<0.001), lymphocyte count (F=3.826, p=0.004) and hematocrit (F=0.000, p>0.001). CONCLUSIONS: The results suggest that serum inflammatory response probably exists in people with MDD, and indicators of blood analysis especially mean platelet volume have a potential value as biomarker for inflammation.

Evaluation of the risk factors of depressive disorders comorbid with obstructive sleep apnea.

OBJECTIVE: Overlap of obstructive sleep apnea (OSA) complicates diagnosis of depressive disorder and renders antidepressant treatment challenging. Previous studies have reported that the incidence of OSA is higher in patients with depression than in the general population. The purpose of this article was to investigate clinical risk factors to predict OSA in depression disorders. METHODS: A total of 115 patients diagnosed with major depressive disorder (MDD) and bipolar disorder (in a major depressive episode), who underwent overnight polysomnography, were studied retrospectively. They were divided into two groups: non-OSA and OSA. The patients who had apnea-hypopnea index (AHI) <5 were defined as the non-OSA group, whereas the OSA group was defined as those with an AHI ≥5. Logistic regression was used to analyze the association among AHI and clinical factors, including sex, age, body mass index (BMI), Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale, Pittsburgh Sleep Quality Index (PSQI), and diagnosis (MDD or bipolar disorder [in a major depressive episode]). RESULTS: In 115 patients, 51.3% had OSA. Logistic regression analysis showed significant associations between AHI and diagnosis (MDD or bipolar disorder [in a major depressive episode]), BMI, HAMD, and PSQI (P<0.05). CONCLUSION: The findings of our study suggested that the rate of depression being comorbid with OSA is remarkably high and revealed that there is a high rate of undetected OSA among depressive disorder patients and untreated OSA among mood disorder patients. The clinical risk factors (diagnosis [MDD or bipolar disorder {in a major depressive episode}], BMI, HAMD, and PSQI) could predict AHI or OSA diagnosis and contribute to OSA screening in depressive disorder patients.

Sympathetic skin response and R-R interval variation in the assessment of clinical remission of bipolar disorder.

For our retrospective study, we chose patients who met the inclusion criteria for bipolar disorder (BD) according to the ICD-10. We conducted correlation analyses between scale scores and SSR and RRIV values before and after 1 year ±1 month of treatment. Our results suggest that the feet SSR latency and R% can be used as an indicator of clinical BD remission. The scales have high sensitivity and low specificity in assessing BD remission.

A Case Report of Psychoactive Drugs Aggravating and Alleviating Meige Syndrome.

The present case report described a 61-year-old female patient who was diagnosed as Meige syndrome with double eyelid spasm, anxiety and insomnia. After she was treated with psychoactive drugs, it was found that clonazepam tablets in the benzodiazepine class and dopamine antagonist olanzapine tablets aggravated double eyelid spasm; while eszopiclone tablets as a specificity γ-aminobutyric acid receptor binding drug alleviated this condition. The present case suggests that psychoactive drugs have both positive and negative effects on treating Meige syndrome. As for the patients who also have emotion disorder, their conditions should be observed carefully when choosing which psychoactive drug to use. The specificity γ-aminobutyric acid receptor binding drugs should be the prime choice, such as eszopiclone.

Regional Coherence Changes in Alzheimer's Disease Patients with Depressive Symptoms: A Resting-State Functional MRI Study.

Alzheimer's disease (AD) is characterized by progressive cognitive decline along with neuropsychiatric symptoms including depression and psychosis. Depression is a common psychiatric disorder occurring in people across the lifespan. Accumulating evidence indicates that depression may be a prodrome and/or a "risk factor" for AD. However, whether AD and depression share a common pathophysiological pathway is still unclear. The aim of this study was to identify regional alterations in brain function associated with depressive symptoms in mild AD patients. Thirty-two mild AD patients were evaluated using the Neuropsychiatric Inventory and Hamilton Depression Rating Scale, and were divided into two groups: 15 AD patients with depressive symptoms (D-AD) and 17 non-depressed AD (nD-AD) patients. Using the approach of regional homogeneity (ReHo), we characterized resting-state regional brain activity in D-AD and nD-AD patients. Compared with nD-AD patients, D-AD patients showed decreased ReHo in the right precentral gyrus, right superior frontal gyrus, right middle frontal gyrus, and right inferior frontal cortex. Our findings show regional brain activity alterations in D-AD patients. Thus, D-AD pathogenesis may be attributed to abnormal neural activity in multiple brain regions.

Sub-hubs of baseline functional brain networks are related to early improvement following two-week pharmacological therapy for major depressive disorder.

Accumulating evidence suggests that early improvement after two-week antidepressant treatment is predictive of later outcomes of patients with major depressive disorder (MDD); however, whether this early improvement is associated with baseline neural architecture remains largely unknown. Utilizing resting-state functional MRI data and graph-based network approaches, this study calculated voxel-wise degree centrality maps for 24 MDD patients at baseline and linked them with changes in the Hamilton Rating Scale for Depression (HAMD) scores after two weeks of medication. Six clusters exhibited significant correlations of their baseline degree centrality with treatment-induced HAMD changes for the patients, which were mainly categorized into the posterior default-mode network (i.e., the left precuneus, supramarginal gyrus, middle temporal gyrus, and right angular gyrus) and frontal regions. Receiver operating characteristic curve and logistic regression analyses convergently revealed excellent performance of these regions in discriminating the early improvement status for the patients, especially the angular gyrus (sensitivity and specificity of 100%). Moreover, the angular gyrus was identified as the optimal regressor as determined by stepwise regression. Interestingly, these regions possessed higher centrality than others in the brain (P < 10(-3)) although they were not the most highly connected hubs. Finally, we demonstrate a high reproducibility of our findings across several factors (e.g., threshold choice, anatomical distance, and temporal cutting) in our analyses. Together, these preliminary exploratory analyses demonstrate the potential of neuroimaging-based network analysis in predicting the early therapeutic improvement of MDD patients and have important implications in guiding earlier personalized therapeutic regimens for possible treatment-refractory depression.

Effect of enoxaparin and aspirin on hemodynamic disturbances after global cerebral ischemia in rats.

STUDY AIM: Whether patients benefit from anticoagulation or anti-platelet agents when subjected to global ischemia is controversial. In this study we assessed the effect of enoxaparin and aspirin on hemodynamic disturbances following global ischemia in rats. METHODS: Twenty-minute global ischemia was induced by four-vessel occlusion in Sprague-Dawley rats. Enoxaparin (1.5 mg/kg, i.v.) was administered 4 min before or after ischemia, and aspirin (40 mg/kg, i.p.) was administered twice, 18 and 1.5 h before ischemia. Parietal cortical cerebral blood flow was measured in real time with a laser Doppler flowmeter, and activated partial thromboplastin time (APTT) and prothrombin time (PT) were measured. Three phenomena of hemodynamic disturbance: no-reflow, hyperperfusion, and hypoperfusion, were assessed after 20-min global ischemia. RESULTS: No significant differences in PT values were found; in contrast, the APTT values were shortened markedly by 20-min ischemia, which indicated activation of the endogenous coagulation system. The shortened APTT was markedly prevented by enoxaparin administered before ischemia. No-reflow was partly mitigated by administration of enoxaparin or aspirin before ischemia. Hypoperfusion was almost fully blocked by aspirin, and the hypoperfusion value was increased and hypoperfusion duration was shortened by enoxaparin administered 4 min before or after ischemia. CONCLUSION: These results indicate that enoxaparin and aspirin have protective effects against cerebral hemodynamic disturbances induced by global ischemia in rats.

[The properties and research methods of pannexins].

The gene encoding pannexin is a new gap junction family member discovered in 2000. Recent studies indicated that pannexin protein can form hemichannel on the membrane or intercellular gap junction channel, which is involved in many physiological and pathological activities. Here, we make a review of the latest research progress on the expression and cellular localization, the channel properties and the research methods of pannexins in an attempt to provide some evidences and methodological references to further investigation on the physiological and pathological functions of pannexin.