Predicting risk of dementia among the elderly with major depressive disorder in remission: A prospective study.

OBJECTIVES: Cognitive impairment and change are a focus of research into late-life depression. The aims of this 5-year prospective study were (1) to observe cognitive status change; (2) to investigate the rate and risk ratio of dementia or cognitive decline; and (3) to examine the cognitive domain predictors for conversion to dementia within 5 years among a clinical cohort with remitted major depressive disorder (MDD). METHODS: The study cohort included 130 elderly persons with late-life remitted MDD and 100 normal controls. Comprehensive neuropsychological tests were conducted to determine cognitive domain status. Diagnoses of mild cognitive impairment (MCI) and dementia were made at baseline and at a follow-up visit at the 5-year point. In total, 98 cases and 55 normal controls completed the 5-year follow-up assessment. RESULTS: Of the study cohort with late-life remitted MDD, 28.6% had MCI and 25.5% developed dementia within 5 years. Patients with late-life remitted MDD had an approximate 3 times higher risk of subsequent cognitive decline as compared with the normal controls. Information-processing speed (p = 0.009) and memory (p = 0.041) could predict subsequent progression to dementia within 5 years among patients with MDD. CONCLUSIONS: This study demonstrated that compared with the general elderly population, elderly patients with depression have more significant impairment in cognitive function after 5 years. Further, we found that in depressed patients, deficits in information-processing speed and memory domains were highly suggestive of progression to dementia within 5 years.

Effect of cranial electrotherapy stimulation as an add-on therapy on late-life generalized anxiety disorder: An open-label study.

INTRODUCTION: Cranial electrotherapy stimulation (CES) is beneficial in reducing anxiety in psychiatric patients. However, no studies have reported on elderly patients with generalized anxiety disorders (GAD). This study aimed to determine the efficacy and safety of a 6-week CES intervention for late-life GAD. MATERIALS AND METHODS: This single-arm pilot study assessed 6-week CES treatment (Alpha-Stim AID) for late-life GAD and 4-week follow-up post intervention. The Hamilton Rating Scale for Anxiety (HAMA) and Beck Anxiety Inventory (BAI) were used as baseline and outcome measures at weeks 4, 6, and 10, respectively. Treatment response was defined as 50 % or more reduction of the HAMA score and remission was defined as a of score ≤7 on the HAMA. Other measures included depression, sleep quality, and quality of life assessment. RESULTS: We included participants (n = 27) aged 68.0 ± 5.0 years, 81.5 % of whom were female. Fifteen (55.6 %), 18 (66.7 %), and 15 (55.6 %) patients were concurrently treated with antidepressants, BZDs, and antipsychotics, respectively. Intention-to-treat (ITT) analysis revealed a significant decrease in HAMA scores from baseline (20.96 ± 3.30) to week 6 (12.26 ± 7.09) and one-month (12.85 ± 7.08) follow-up at W10 (all p < 0.001). The response and remission rates were 33.3 %, 40.7 %, and 48.1 % and 25.9 %, 29.6 %, and 25.9 % at W4, W6, and W10, respectively. The CES improved depression and sleep conditions as measured by the Beck Depression Inventory-II and Pittsburgh Sleep Quality Index. CONCLUSION: CES clinically reduces symptoms of anxiety and depression and may improve sleep quality in late-life GAD. Future randomized controlled study is needed.

Application of blood-based biomarkers of Alzheimer's disease in clinical practice: Recommendations from Taiwan Dementia Society.

Blood-based biomarkers (BBM) are potentially powerful tools that assist in the biological diagnosis of Alzheimer's disease (AD) in vivo with minimal invasiveness, relatively low cost, and good accessibility. This review summarizes current evidence for using BBMs in AD, focusing on amyloid, tau, and biomarkers for neurodegeneration. Blood-based phosphorylated tau and the Aß42/Aß40 ratio showed consistent concordance with brain pathology measured by CSF or PET in the research setting. In addition, glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) are neurodegenerative biomarkers that show the potential to assist in the differential diagnosis of AD. Other pathology-specific biomarkers, such as α-synuclein and TAR DNA-binding protein 43 (TDP-43), can potentially detect AD concurrent pathology. Based on current evidence, the working group from the Taiwan Dementia Society (TDS) achieved consensus recommendations on the appropriate use of BBMs for AD in clinical practice. BBMs may assist clinical diagnosis and prognosis in AD subjects with cognitive symptoms; however, the results should be interpreted by dementia specialists and combining biochemical, neuropsychological, and neuroimaging information. Further studies are needed to evaluate BBMs' real-world performance and potential impact on clinical decision-making.

Cerebral Semaphorin3D is a novel risk factor for age-associated cognitive impairment.

BACKGROUND: We previously reported that miR-195 exerts neuroprotection by inhibiting Sema3A and cerebral miR-195 levels decreased with age, both of which urged us to explore the role of miR-195 and miR-195-regulated Sema3 family members in age-associated dementia. METHODS: miR-195a KO mice were used to assess the effect of miR-195 on aging and cognitive functions. Sema3D was predicted as a miR-195 target by TargetScan and then verified by luciferase reporter assay, while effects of Sema3D and miR-195 on neural senescence were assessed by beta-galactosidase and dendritic spine density. Cerebral Sema3D was over-expressed by lentivirus and suppressed by si-RNA, and effects of over-expression of Sema3D and knockdown of miR-195 on cognitive functions were assessed by Morris Water Maze, Y-maze, and open field test. The effect of Sema3D on lifespan was assessed in Drosophila. Sema3D inhibitor was developed using homology modeling and virtual screening. One-way and two-way repeated measures ANOVA were applied to assess longitudinal data on mouse cognitive tests. RESULTS: Cognitive impairment and reduced density of dendritic spine were observed in miR-195a knockout mice. Sema3D was identified to be a direct target of miR-195 and a possible contributor to age-associated neurodegeneration as Sema3D levels showed age-dependent increase in rodent brains. Injection of Sema3D-expressing lentivirus caused significant memory deficits while silencing hippocampal Sema3D improved cognition. Repeated injections of Sema3D-expressing lentivirus to elevate cerebral Sema3D for 10 weeks revealed a time-dependent decline of working memory. More importantly, analysis of the data on the Gene Expression Omnibus database showed that Sema3D levels were significantly higher in dementia patients than normal controls (p < 0.001). Over-expression of homolog Sema3D gene in the nervous system of Drosophila reduced locomotor activity and lifespan by 25%. Mechanistically, Sema3D might reduce stemness and number of neural stem cells and potentially disrupt neuronal autophagy. Rapamycin restored density of dendritic spines in the hippocampus from mice injected with Sema3D lentivirus. Our novel small molecule increased viability of Sema3D-treated neurons and might improve autophagy efficiency, which suggested Sema3D could be a potential drug target. Video Abstract CONCLUSION: Our results highlight the importance of Sema3D in age-associated dementia. Sema3D could be a novel drug target for dementia treatment.

[Medication rules of Chinese herbal compound prescriptions for treating angina in national patent database based on multiple data mining].

This study explored the medication rules of Chinese herbal compound prescriptions for the treatment of angina based on the Chinese herbal compound patents in the patent database of the China National Intellectual Property Administration. The data of eligible Chinese herbal compound patents for the treatment of angina were collected from the patent database of the China National Intellectual Property Administration from database inception to November 10, 2022, and subjected to data modeling, analysis of main syndromes, medication frequency analysis, cluster analysis, association rule analysis, and data visualization by using Excel 2021, IBM SPSS Statistics 26.0, IBM SPSS Modeler 18.0, Cytoscape 3.9.1, and Rstudio R 4.2.2.2 to explore the medication rules for angina. The study included 636 pieces of patent data for angina that met the inclusion criteria, involving 815 drugs, with a total frequency of 6 586. The most common main syndromes were blood stasis obstructing the heart syndrome(222, 34.91%) and Qi deficiency and blood stasis syndrome(112, 17.61%). The top 10 most frequently used drugs were Salviae Miltiorrhizae Radix et Rhizoma, Chuanxiong Rhizoma, Notoginseng Radix et Rhizoma, Astragali Radix, Angelicae Sinensis Radix, Carthami Flos, Glycyrrhizae Radix et Rhizoma, Ginseng Radix et Rhizoma, Borneolum Syntheticum, and Corydalis Rhizoma. High-frequency drugs included blood-activating and stasis-resolving drugs(1 197, 18.17%) and deficiency-tonifying drugs(809, 12.28%). Cluster analysis identified eight drug combinations, including five new prescriptions suitable for clinical use and new drug development, and three drug pairs. The core drug combination of Salviae Miltiorrhizae Radix et Rhizoma-Chuanxiong Rhizoma-Carthami Flos was identified through the complex co-occurrence network analysis of Chinese medicines. Association rule analysis yielded a total of 17 rules, including 13 drug pairs and 4 tripartite combinations. Common drug pairs included Salviae Miltiorrhizae Radix et Rhizoma-Chuanxiong Rhizoma(support degree 25.79%, confidence coefficient 69.49%, lift 1.30) and Salviae Miltiorrhizae Radix et Rhizoma-Notoginseng Radix et Rhizoma(support degree 22.01%, confidence coefficient 61.95%, lift 1.16). Common tripartite combinations included Salviae Miltiorrhizae Radix et Rhizoma-Chuanxiong Rhizoma-Astragali Radix(support degree 10.85%, confidence coefficient 73.40%, lift 1.37) and Salviae Miltiorrhizae Radix et Rhizoma-Chuanxiong Rhizoma-Notoginseng Radix et Rhizoma(support degree 10.69%, confidence coefficient 79.07%, lift 1.48). The results showed that the underlying pathogenesis of angina involved blood stasis obstructing the heart and Qi deficiency and blood stasis. The overall nature of the disease was characterized as asthenia in origin and sthenia in superficiality. In the prescription formulation, blood-activating and stasis-resolving drugs, such as Salviae Miltiorrhizae Radix et Rhizoma, Chuanxiong Rhizoma, and Carthami Flos were often used to resolve the excess manifestation, which were combined with tonifying drugs such as Astragali Radix, Angelicae Sinensis Radix, Glycyrrhizae Radix et Rhizoma, and Ginseng Radix et Rhizoma to reinforce the deficiency. The syndrome, pathogenesis, disease nature, and medication were consistent with clinical practice. Additionally, the new compound prescriptions and drug combinations derived from the multiple data mining in this study could provide references and insights for the clinical diagnosis and treatment of angina and the development of new drugs.

Neuropsychiatric symptoms and mortality among patients with mild cognitive impairment and dementia due to Alzheimer's disease.

BACKGROUND: Neuropsychiatric symptoms (NPS) could increase mortality risk in people with dementia due to Alzheimer's disease (AD). However, whether NPS affects mortality risk in people with mild cognitive impairment (MCI) and whether any specific syndrome of NPS influences this risk are still unclear. METHODS: In total, 984 participants with dementia due to AD, 338 with MCI, and 365 controls were enrolled. Over a mean of 5-year follow-up, cause of death data were obtained from the Ministry of Health and Welfare in Taiwan. NPS were assessed using Neuropsychiatric Inventory Questionnaire (NPI-Q), and psychosis, mood, and frontal domain scores were determined. Survival analyses were conducted to determine the hazard ratio (HR) of death. RESULTS: In controlled analyses, HR of death for AD was 2.19 (95% confidence interval [CI] = 1.29-3.71) compared with the control group, whereas no statistical significance was noted for the MCI group. A high NPI-Q score (above the median score) increased mortality risk for both the MCI and AD groups, with HRs of 2.32 (95% CI = 1.07-5.03) and 2.60 (95% CI = 1.51-4.47), respectively. Among NPI-Q domain scores, only high mood domain, but not psychosis or frontal domain, scores increased death risk for both the MCI (HR = 2.89, 95% CI = 1.00-8.51) and AD (HR = 2.59, 95% CI = 1.47-4.55) groups. CONCLUSION: Mortality risk is high for patients with AD. Not only for AD, patients with MCI presenting with NPS, particularly mood symptoms, have high death risk.

Sensitivity and Specificity of the Saint Louis University Mental Status Examination to Detect Mild Cognitive Impairment and Dementia in Chinese Population.

INTRODUCTION: The Saint Louis University Mental Status (SLUMS) examination is a common screening instrument to detect mild cognitive impairment (MCI) in Western countries. However, further work is needed to identify optimal SLUMS cutoff scores for screening MCI and dementia in Chinese populations. OBJECTIVE: The aim of this study was to evaluate the utility and diagnostic accuracy of the SLUMS examination in the diagnosis of dementia and MCI in Chinese population. METHODS: A cross-sectional multicenter design was conducted. Patients were recruited from the outpatient department of our neurology and psychiatric clinics. The establishment of the gold standard for the SLUMS-Chinese version (SLUMS-C) to detect MCI and dementia was based on the clinical criteria of the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) and related neuropsychological testing conducted by 3 certified dementia specialists. The consistency of the diagnosis process and administering SLUMS-C were established prior to the beginning of the study. Data were analyzed, and sensitivity, specificity, and areas under the curve (AUCs) were calculated. RESULTS: A total of 367 subjects were recruited. The SLUMS-C did not show satisfactory AUCs for the preliminary detection of normal cognitive status and MCI by different educational levels (all AUC 0.32-0.54). However, the SLUMS-C showed acceptable AUCs for the preliminary detection of dementia by different educational levels (all AUC 0.78-0.81). An educational level of senior high school showed the best cutoff, sensitivity, and specificity. The SLUMS-C scores to detect dementia for individuals with at least high school education and less than high school education were <24 and 22, respectively. CONCLUSIONS: Our results indicate that the SLUMS-C could be a beneficial and convenient screening instrument to detect dementia in Chinese population. After community screening, a comprehensive clinical evaluation including cognitive assessment, functional status, corroborative history, and imaging confirmation is needed.

Genetics of neuropsychiatric symptoms in patients with Alzheimer's disease: A 1-year follow-up study.

AIM: The aim of this study was to investigate the associations between candidate gene variants and domains of neuropsychiatric symptoms (NPS) and the changes in these associations over a 1-year period. METHODS: Seven hundred and ninety-three Taiwanese participants (47.8% female) with Alzheimer's disease (AD) were enrolled. Genes associated with a risk of developing AD were selected as candidate genes. NPS were assessed using the Neuropsychiatric Inventory Questionnaire (NPI-Q), and the NPI-Q total score and sub-scores for the Psychosis, Mood, and Frontal Syndrome domains were calculated. RESULTS: Patients with AD and the APOE ε4 allele exhibited more obvious symptoms of psychosis. Mood symptoms were associated with CD33 rs3865444 and EPHA1 rs11767557, and frontal symptoms were associated with SORL1 rs3824968. A 1-year Time × Alleles interaction effect of CD33 rs3865444 on mood symptoms was discerned. CONCLUSION: Risk genes of AD, which are also associated with NPS, are APOE ε4 for psychosis, CD33 and EPHA1 for mood symptoms, and SORL1 for frontal symptoms. The association between CD33 and mood symptoms is dynamic and could change over 1 year; however, the results should be interpreted with caution because corrections for multiple comparisons were not performed.

Association of brain white matter lesions and atrophy with cognitive function in chronic kidney disease.

OBJECTIVES: Cognitive impairment is common in patients with chronic kidney disease (CKD), possibly leading to poor outcomes. However, the correlation between brain structural abnormalities and cognitive impairment remains unclear. The aim of this study was to investigate the impairment of specific cognitive domains and their association with brain structural abnormalities. METHODS: Patients with CKD of at least stage 3 who were not on hemodialysis were enrolled. All participants underwent comprehensive neuropsychological testing in five cognitive domains. Ventricular atrophy, sulcal atrophy, medial temporal atrophy, and white matter changes were assessed using brain magnetic resonance imaging according to standard protocols. RESULTS: Eighty-seven patients and 50 controls were enrolled. Patients with CKD exhibited decreased cognitive function relative to controls. Compared with patients with stage 3 CKD, those with advanced stage (stages 4 or 5) had poorer cognitive performance, more pronounced white matter hyperintensity (WMH) and more severe ventricular atrophy. Among CKD patients, executive function (ß = -.23, P = .043) and attention (ß = -.29, P = .004) were associated with WMH in controlled analyses. However, no cognitive impairment was associated with ventricular atrophy. CONCLUSION: Patients with CKD exhibited cognitive impairment and brain structural abnormalities including WMH and general brain atrophy. Impairment of attention and executive dysfunction were associated with WMH.

Association between altered neurochemical metabolites and apathy in patients with Alzheimer's disease.

ABSTRACTBackground:Apathy is a condition characterized by a lack of motivation that manifests in emotional, behavioral, and cognitive domains. Although previous studies have indicated that apathy is associated with frontal lesions, few studies have focused on the different subdomains of apathy, and no in vivo human biochemical data have been obtained to examine the neurochemical changes related to apathy in patients with Alzheimer's disease (AD). Thus, we investigated the frontal neurochemical alterations related to apathy among patients with AD using proton magnetic resonance spectroscopy (1H MRS). METHODS: Apathy was assessed through the Apathy Evaluation Scale (AES). 1H MRS was performed to measure neurochemical metabolite levels in the anterior cingulate region and right orbitofrontal region. Associations between neurochemical metabolites and the total score and subscores of each domain of the AES were analyzed. RESULTS: Altogether, 36 patients completed the study. Patients with lower N-acetylaspartate/creatine ratios (NAA/Cr) in the anterior cingulate region demonstrated higher total apathy scores (ß = -0.56, p = 0.003) with adjustments for age, gender, educational level, dementia severity, and depression severity. In a further analysis, a lower NAA/Cr in the anterior cingulate region was associated with all subdomains of apathy, including cognition (ß = -0.43, p = 0.028), behavior (ß = -0.55, p = 0.002), and emotion (ß = -0.50, p = 0.005). No statistically significant associations were discovered in the right orbitofrontal region. CONCLUSIONS: Our results suggest that apathy, in each of its cognitive, behavioral, or emotional subdomains is associated with brain neurochemical alterations in the anterior cingulate region. Abnormal neuronal integrity over the anterior cingulate cortex may exhibit a central role in causing all aspects of apathy in patients with AD.

ALDH2 modulated changes in cytokine levels and cognitive function in bipolar disorder: A 12-week follow-up study.

OBJECTIVES: We investigated the association of the aldehyde dehydrogenase 2 ( ALDH2) polymorphism (rs671), which is involved with the dopaminergic function, and with changes in cytokine levels and cognitive function, in a 12-week follow-up study in patients with bipolar disorder. METHODS: Patients with a first diagnosis of bipolar disorder were recruited. Symptom severity and levels of plasma cytokines (tumor necrosis factor α, C-reactive protein, interleukin 6 and transforming growth factor ß1) were examined during weeks 0, 1, 2, 4, 8 and 12. Neurocognitive function was evaluated at baseline and endpoint. The ALDH2 polymorphism genotype was determined. RESULTS: A total of 541 patients with bipolar disorder were recruited, and 355 (65.6%) completed the 12-week follow-up. A multiple linear regression analysis showed a significant ( p = 0.000226) association between the ALDH2 polymorphism and changes in C-reactive protein levels. Different aspects of cognitive function improved in patients with different ALDH2 genotypes. Only patients with the ALDH2*1*1 genotype showed significant correlations between improvement of cognitive function and increased transforming growth factor -ß1. CONCLUSION: The ALDH2 gene might influence changes in cytokine levels and cognitive performance in patients with bipolar disorder. Additionally, changes in cytokine levels and cognitive function were correlated only in patients with specific ALDH2 genotypes.

Prevalence and clinical correlates of flunitrazepam-related complex sleep behaviors.

AIM: Complex sleep behaviors (CSB) are often associated with the use of hypnotic drugs. This study investigated the prevalence and correlates of CSB among psychiatric patients who were given flunitrazepam. METHODS: From June 2011 to May 2012, a total of 268 psychiatric outpatients who had received flunitrazepam for at least 3 months were enrolled. Data on occurrence of CSB, demographic characteristics, flunitrazepam dosage and duration of use, psychiatric diagnoses, physical illnesses, and alcohol use were collected. Logistic regression analysis was used to examine the clinical correlates of CSB. RESULTS: Sixty-six participants (24.6%) reported experiencing CSB. Logistic regression analysis showed that a high dosage (>2 mg/day) of flunitrazepam (odds ratio [OR] = 1.941, 95% confidence interval [CI] = 1.090-3.455, P = 0.024) and alcohol use (OR = 1.948, 95%CI = 1.023-3.709, P = 0.042) were significantly associated with the occurrence of CSB. Sex, age, duration of flunitrazepam use, psychiatric diagnoses, and physical illnesses were not significantly associated with the occurrence of CSB. CONCLUSION: CSB among flunitrazepam users should be monitored routinely, especially among those receiving a high dosage who also consume alcohol.

Comparison of LCModel and SAGE in Analysis of Brain Metabolite Concentrations-A study of Patients with Mild Cognitive Impairment.

PURPOSE: The purpose of this study was to compare brain metabolite concentration ratios determined by LCModel and Spectroscopy Analysis by General Electric (SAGE) quantitative methods to elucidate the advantages and disadvantages of each method. MATERIALS AND METHODS: A total of 10 healthy volunteers and 10 patients with mild cognitive impairment (MCI) were recruited in this study. A point-resolved spectroscopy (PRESS) sequence was used to obtain the brain magnetic resonance spectroscopy (MRS) spectra of the volunteers and patients, as well as the General Electric (GE) MRS-HD-sphere phantom. The brain metabolite concentration ratios were estimated based on the peak area obtained from both LCModel and SAGE software. Three brain regions were sampled for each volunteer or patient, and 20 replicates were acquired at different times for the phantom analysis. RESULTS: The metabolite ratios of the GE phantom were estimated to be myo-inositol (mI)/creatine (Cr): 0.70 ± 0.01, choline (Cho)/Cr: 0.37 ± 0.00, N-acetylaspartate (NAA)/Cr: 1.26 ± 0.02, and NAA/mI: 1.81 ± 0.04 by LCModel, and mI/Cr: 0.88 ± 0.15, Cho/Cr: 0.35 ± 0.01, NAA/Cr: 1.33 ± 0.03, and NAA/mI: 1.55 ± 0.26 by SAGE. In the healthy volunteers and MCI patients, the ratios of mI/Cr and Cho/Cr estimated by LCModel were higher than those estimated by SAGE. In contrast, the ratio of NAA/Cr estimated by LCModel was lower than that estimated by SAGE. CONCLUSION: Both methods were acceptable in estimating brain metabolite concentration ratios. However, LCModel was marginally more accurate than SAGE because of its full automation, basis set, and user independency.

Beta-amyloid deposition and cognitive function in patients with major depressive disorder with different subtypes of mild cognitive impairment: (18)F-florbetapir (AV-45/Amyvid) PET study.

PURPOSE: The objective of this study was to evaluate the amyloid burden, as assessed by (18)F-florbetapir (AV-45/Amyvid) positron emission tomography PET, in patients with major depressive disorder (MDD) with different subtypes of mild cognitive impairment (MCI) and the relationship between amyloid burden and cognition in MDD patients. METHODS: The study included 55 MDD patients without dementia and 21 healthy control subjects (HCs) who were assessed using a comprehensive cognitive test battery and (18)F-florbetapir PET imaging. The standardized uptake value ratios (SUVR) in eight cortical regions using the whole cerebellum as reference region were determined and voxel-wise comparisons between the HC and MDD groups were performed. Vascular risk factors, serum homocysteine level and the apolipoprotein E (ApoE) genotype were also determined. RESULTS: Among the 55 MDD patients, 22 (40.0 %) had MCI, 12 (21.8 %) non-amnestic MCI (naMCI) and 10 (18.2 %) amnestic MCI (aMCI). The MDD patients with aMCI had the highest relative (18)F-florbetapir uptake in all cortical regions, and a significant difference in relative (18)F-florbetapir uptake was found in the parietal region as compared with that in naMCI subjects (P < 0.05) and HCs (P < 0.01). Voxel-wise analyses revealed significantly increased relative (18)F-florbetapir uptake in the MDD patients with aMCI and naMCI in the frontal, parietal, temporal and occipital areas (P < 0.005). The global cortical SUVR was significantly negatively correlated with MMSE score (r = -0.342, P = 0.010) and memory function (r = -0.328, P = 0.015). The negative correlation between the global SUVR and memory in the MDD patients remained significant in multiple regression analyses that included age, educational level, ApoE genotype, and depression severity (ß = -3.607, t = -2.874, P = 0.006). CONCLUSION: We found preliminary evidence of brain beta-amyloid deposition in MDD patients with different subtypes of MCI. Our findings in MDD patients support the hypothesis that a higher amyloid burden is associated with a poorer memory performance. We also observed a high prevalence of MCI among elderly depressed patients, and depressed patients with MCI exhibited heterogeneously elevated (18)F-florbetapir retention as compared with depressed patients without MCI. The higher amyloid burden in the aMCI patients suggests that these patients may also be more likely to develop Alzheimer's disease than other patients diagnosed with major depression.

Loganin possesses neuroprotective properties, restores SMN protein and activates protein synthesis positive regulator Akt/mTOR in experimental models of spinal muscular atrophy.

Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease characterized by motor neurons degeneration and muscular atrophy. There is no effective SMA treatment. Loganin is a botanical candidate with anti-inflammatory, anti-oxidant, glucose-lowering and anti-diabetic nephropathy activities. The aim of this study is to investigate the potential protective effects of loganin on SMA using two cellular models, SMN-deficient NSC34 cells and SMA patient fibroblasts, and an animal disease model, SMAΔ7 mice. In SMN-deficient NSC34 cells, loganin increased cell viability, neurite length, and expressions of SMN, Gemin2, SMN-Gemin2 complex, p-Akt, p-GSK-3ß, p-CREB, BDNF and Bcl-2. However, both AG1024 (IGF-1 R antagonist) and IGF-1 R siRNA attenuated the protective effects of loganin on SMN level and cell viability in SMN-deficient NSC34 cells. In SMA patient fibroblasts, loganin up-regulated levels of SMN, FL-SMN2, and Gemins, increased numbers of SMN-containing nuclear gems, modulated splicing factors, and up-regulated p-Akt. Furthermore, in the brain, spinal cord and gastrocnemius muscle of SMAΔ7 mice, loganin up-regulated the expressions of SMN and p-Akt. Results from righting reflex and hind-limb suspension tests indicated loganin improved muscle strength of SMAΔ7 mice; moreover, loganin activated Akt/mTOR signal and inhibited atrogin-1/MuRF-1 signal in gastrocnemius muscle of SMAΔ7 mice. Loganin also increased body weight, but the average lifespan of loganin (20mg/kg/day)-treated SMA mice was 16.80±0.73 days, while saline-treated SMA mice was 10.91±0.96 days. In conclusion, the present results demonstrate that loganin provides benefits to SMA therapeutics via improving SMN restoration, muscle strength and body weight. IGF-1 plays an important role in loganin neuroprotection. Loganin can be therefore a valuable complementary candidate for treatment of neuromuscular diseases via regulation of muscle protein synthesis and neuroprotection.

Association of homocysteine level and vascular burden and cognitive function in middle-aged and older adults with chronic kidney disease.

OBJECTIVES: Patients with chronic kidney disease (CKD) have been found to have cognitive impairment. However, the core features and clinical correlates of cognitive impairment are still unclear. Elevated homocysteine levels are present in CKD, and this is a risk factor for cognitive impairment and vascular diseases in the general population. Thus, this study investigated the core domains of cognitive impairment and investigated the associations of homocysteine level and vascular burden with cognitive function in patients with CKD. METHODS: Patients with CKD aged ≥ 50 years and age- and sex-matched normal comparisons were enrolled. The total fasting serum homocysteine level was measured. Vascular burden was assessed using the Framingham Cardiovascular Risk Scale. Cognitive function was evaluated using comprehensive neuropsychological tests. RESULTS: A total of 230 patients with CKD and 92 comparisons completed the study. Memory impairment and executive dysfunction were identified as core features of cognitive impairment in the CKD patients. Among the patients with CKD, higher serum homocysteine levels (ß = -0.17, p = 0.035) and higher Framingham Cardiovascular Risk Scale scores (ß = -0.18, p = 0.013) were correlated with poor executive function independently. However, an association with memory function was not noted. Our results showed that an elevated homocysteine level and an increased vascular burden were independently associated with executive function, but not memory, in CKD patients. CONCLUSIONS: This findings suggested the co-existence of vascular and non-vascular hypotheses regarding executive dysfunction in CKD patients. Meanwhile, other risk factors related to CKD itself should be investigated in the future. Copyright © 2015 John Wiley & Sons, Ltd.

Changes of Explicit and Implicit Stigma in Medical Students during Psychiatric Clerkship.

OBJECTIVE: This study examines the differences in explicit and implicit stigma between medical and non-medical undergraduate students at baseline; the changes of explicit and implicit stigma in medical undergraduate and non-medical undergraduate students after a 1-month psychiatric clerkship and 1-month follow-up period; and the differences in the changes of explicit and implicit stigma between medical and non-medical undergraduate students. METHODS: Seventy-two medical undergraduate students and 64 non-medical undergraduate students were enrolled. All participants were interviewed at intake and after 1 month. The Taiwanese version of the Stigma Assessment Scale and the Implicit Association Test were used to measure the participants' explicit and implicit stigma. RESULTS: Neither explicit nor implicit stigma differed between two groups at baseline. The medical, but not the non-medical, undergraduate students had a significant decrease in explicit stigma during the 1-month period of follow-up. Neither the medical nor the non-medical undergraduate students exhibited a significant change in implicit stigma during the one-month of follow-up, however. There was an interactive effect between group and time on explicit stigma but not on implicit stigma. CONCLUSION: Explicit but not implicit stigma toward mental illness decreased in the medical undergraduate students after a psychiatric clerkship. Further study is needed to examine how to improve implicit stigma toward mental illness.

Bidirectional associations between family factors and Internet addiction among adolescents in a prospective investigation.

AIMS: This study aimed at evaluating the effect of family factors on the occurrence of Internet addiction and determining whether Internet addiction could make any difference in the family function. METHODS: A total of 2293 adolescents in grade 7 participated in the study. We assessed their Internet addiction, family function, and family factors with a 1-year follow up. RESULTS: In the prospective investigation, inter-parental conflict predicted the incidence of Internet addiction 1 year later in forward regression analysis, followed by not living with mother and allowance to use Internet more than 2 h per day by parents or caregiver. The inter-parental conflict and allowance to use Internet more than 2 h per day also predicted the incidence in girls. Not cared for by parents and family APGAR score predicted the incidence of Internet addiction among boys. The prospective investigation demonstrated that the incidence group had more decreased scores on family APGAR than did the non-addiction group in the 1-year follow-up. This effect was significant only among girls. CONCLUSIONS: Inter-parental conflict and inadequate regulation of unessential Internet use predicted risk of Internet addiction, particularly among adolescent girls. Family intervention to prevent inter-parental conflict and promote family function and Internet regulation were necessary to prevent Internet addiction. Among adolescents with Internet addiction, it is necessary to pay attention to deterioration of family function, particularly among girls.

Brain correlates of response inhibition in Internet gaming disorder.

AIMS: The present study aimed to evaluate the brain correlates of response inhibition among subjects with Internet gaming disorder (IGD). METHODS: For this purpose, 15 men with IGD for at least 1 year, and 15 controls with no history of IGD were recruited to perform the Go/Nogo task under functional magnetic resonance imaging investigation. Prior to scanning, the subjects were assessed using the Chen Internet Addiction Scale and the Barrett Impulsivity Scale. RESULTS: The control group exhibited activation of the right supplement motor area (SMA), dorsolateral prefrontal cortex, and caudate for response inhibition. However, the IGD group had a higher impulsivity and lower activity of the right SMA/pre-SMA in comparison to the control group. CONCLUSIONS: The results obtained suggest that dysfunctional activation of the SMA for response inhibition is one of the candidate mechanisms of IGD.

One-year follow up of PTSD and depression in elderly aboriginal people in Taiwan after Typhoon Morakot.

AIM: This paper describes a 1-year follow-up of post-traumatic stress disorder (PTSD) symptomatology and depression in an elderly minority population who experienced Typhoon Morakot in Taiwan. METHODS: The PTSD Symptom Scale--Interview and the 10-item short form Center for Epidemiological Studies Depression Scale were used to examine PTSD symptomatology and depression in 120 victims at 3-6 months and in 88 victims (73.3% reinterview rate) at 11-12 months after the disaster. Further, we looked for associations between stress, prognosis, and development of PTSD symptomatology and depression. RESULTS: The prevalence of PTSD symptomatology decreased from 29.2% (35/120) at 3-6 months to 15.9% (14/88) at 11-12 months. The prevalence of depression, however, increased from 43.3% (52/120) to 46.6% (41/88). No factor was associated with follow-up PTSD symptomatology, and only the level of education was related to follow-up depression. Generally, the risk factors of age, sex, symptomatology of PTSD and depression at baseline, and stressor of unemployment predicted new-onset or chronic PTSD symptomatology and depression. Delayed-onset depression 48.0% (24/50) was more common than delayed-onset PTSD symptomatology 11.3% (7/62). Chronic and delayed-onset PTSD symptomatology were more easily developed with depression. CONCLUSION: Although PTSD and depression were separate consequences of trauma, they emerged and affected mental health together. We documented the courses of PTSD and depression among elderly aboriginal people, and the possible effects of demographic, symptomatology, and adverse life stressors were discussed.