Panel of Genetic Variations as a Potential Non-invasive Biomarker for Early Diagnosis of Alzheimer's Disease

Alzheimer's disease (AD) is the most prevalent form of dementia. Biomarkers such as levels of amyloid beta (Aβ) in cerebrospinal fluid and ApoE genotyping were suggested for the diagnosis of AD, however, the result is either non-conclusive or with invasive procedure. Genome-wide association studies (GWASs) for AD suggested single nucleotide polymorphisms (SNPs) in many genes are associated with the risk of AD, but each only contributed with small effect to the disease. By incorporating a panel of established genetic susceptibility factors, the risk of an individual in getting AD could be better estimated. Further research will be required to reveal if adding to the current well-developed clinical diagnosis protocol, the accuracy and specificity of diagnosis of AD would be greatly improved and if this might also be beneficial in identifying pre-symptomatic AD patients for early diagnosis and intervention of the disease

Pengaruh Good Corporate Governance terhadap Efisiensi Pengelolaan Badan Usaha Milik Negara

This study aims to examine the effect of Good Corporate Governance as measured by the board of directors, independent board of commissioners and public ownership on the management efficiency of State- Owned Enterprises. The type of research used is a type of quantitative research. This study uses secondary data obtained from the annual financial reports of state-owned enterprises. The population in this study is State- Owned Enterprises from 2017-2022. The method used in sampling is purposive sampling method so that a sample of 11 companies is obtained. The analysis technique used in this research is panel data regression analysis with the selected regression model, namely the Random Effect Model (REM) using the Eviews 12 program. The results of this study indicate that the independent board of directors and board of commissioners variables have no effect on the management efficiency of State-Owned Enterprises. Meanwhile, the public ownership variable has a positive effect on the management efficiency of State-Owned Enterprises.Penelitian ini bertujuan untuk menguji pengaruh dari penerapan Good Corporate Governance yang diukur dengan dewan direksi, dewan komisaris independen dan kepemilikan publik terhadap efisiensi pengelolaan Badan Usaha Milik Negara. Jenis penelitian yang digunakan adalah jenis penelitian kuantitatif. Penelitian ini menggunakan data sekunder yang diperoleh dari laporan keuangan tahunan Badan Usaha Milik Negara. Populasi dalam penelitian ini adalah Badan Usaha Milik Negara dari tahun 2017-2022. Metode yang digunakan dalam pengambilan sampel adalah metode purposive sampling sehingga diperoleh sampel sebanyak 11 perusahaan. Teknik analisis yang digunakan dalam penelitian ini menggunakan analisis regresi data panel dengan model regresi yang terpilih yaitu Random Effect Model (REM) menggunakan alat bantuan program Eviews 12. Hasil penelitian ini menunjukkan bahwa variabel dewan direksi dan dewan komisaris independen tidak berpengaruh positif terhadap efisiensi pengelolaan Badan usaha Milik Negara. Sedangkan variabel kepemilikan publik berpengaruh positif terhadap efisiensi pengelolaan Badan usaha Milik Negara

Relationship between cortical thickness and neuropsychological performance in normal older adults and those with mild cognitive impairment

Mild cognitive impairment (MCI) has been extensively investigated in recent decades to identify groups with a high risk of dementia and to establish effective prevention methods during this period. Neuropsychological performance and cortical thickness are two important biomarkers used to predict progression from MCI to dementia. This study compares the cortical thickness and neuropsychological performance in people with MCI and cognitively healthy older adults. We further focus on the relationship between cortical thickness and neuropsychological performance in these two groups. Forty-nine participants with MCI and 40 cognitively healthy older adults were recruited. Cortical thickness was analysed with semiautomatic software, Freesurfer. The analysis reveals that the cortical thickness in the left caudal anterior cingulate (p=0.041), lateral occipital (p=0.009) and right superior temporal (p=0.047) areas were significantly thinner in the MCI group after adjustment for age and education. Almost all neuropsychological test results (with the exception of forward digit span) were significantly correlated to cortical thickness in the MCI group after adjustment for age, gender and education. In contrast, only the score on the Category Verbal Fluency Test and the forward digit span were found to have significant inverse correlations to cortical thickness in the control group of cognitively healthy older adults. The study results suggest that cortical thinning in the temporal region reflects the global change in cognition in subjects with MCI and may be useful to predict progression of MCI to Alzheimer's disease. The different pattern in the correlation of cortical thickness to the neuropsychological performance of patients with MCI from the healthy control subjects may be explained by the hypothesis of MCI as a disconnection syndrome

Would transcranial direct current stimulation (tDCS) enhance the effects of working memory training in older adults with mild neurocognitive disorder due to Alzheimer’s disease: study protocol for a randomized controlled trial

© 2015 Cheng et al. Background: There has been longstanding interesting in cognitive training for older adults with cognitive impairment. In this study, we will investigate the effects of working memory training, and explore augmentation strategies that could possibly consolidate the effects in older adults with mild neurocognitive disorder. Transcranial direct current stimulation (tDCS) has been demonstrated to affect the neuronal excitability and reported to enhance memory performance. As tDCS may also modulate cognitive function through changes in neuroplastic response, it would be adopted as an augmentation strategy for working memory training in the present study. Methods/Design: This is a 4-week intervention double-blind randomized controlled trial (RCT) of tDCS. Chinese older adults (aged 60 to 90 years) with mild neurocognitive disorder due to Alzheimer 's disease (DSM-5 criteria) would be randomized into a 4-week intervention of either tDCS-working memory (DCS-WM), tDCS-control cognitive training (DCS-CC), and sham tDCS-working memory (WM-CD) groups. The primary outcome would be working memory test - the n-back task performance and the Chinese version of the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog). Secondary outcomes would be test performance of specific cognitive domains and mood. Intention-to-treat analysis would be carried out. Changes of efficacy indicators with time and intervention would be tested with mixed effect models. Discussion: This study adopts the theory of neuroplasticity to evaluate the potential cognitive benefits of non-invasive electrical brain stimulation, working memory training and dual stimulation in older adults at risk of cognitive decline. It would also examine the tolerability, program adherence and adverse effects of this novel intervention. Information would be helpful for further research of dementia prevention studies. Trial registration: ChiCTR-TRC- 14005036Date of registration: 31 July 2014.published_or_final_versio

Effect of computerized cognitive training on mood, cognition, and serum brain-derived neurotrophic factor level in late-life depression — a pilot randomized controlled trial

BackgroundThe aim of this pilot randomized controlled trial was to test the feasibility of a computerized cognitive training targeting executive dysfunction in late-life depression and to investigate its impact on mood, cognition, and brain-derived neurotrophic factor (BDNF) levels.MethodsA total of 28 community-living Chinese individuals aged 55–75 with moderate-to-severe depression and cognitive symptoms (but without mild cognitive impairment or dementia) were recruited from a community centre in Hong Kong. Participants were randomly allocated to either the experimental (receiving computerized cognitive training) or the control group (receiving computer-based health education). Both programs lasted for one hour and were conducted twice a week for 6 weeks at the community centre. We assessed mood using the Hamilton Rating Scale for Depression (HAM-D) and Patient Health Questionaire-9 (PHQ-9), cognition using the Montreal Cognitive Assessment (MoCA), and serum BDNF levels at baseline and follow-up. We performed repeated measures analysis of variance to compare the differences in outcome changes between groups and correlation analysis to test if changes in mood and cognition correlated with changes in BDNF level.ResultsOur sample had a mean age of 66.8 (SD = 5.3) years, a mean HAM-D score of 19.4 (SD = 7.5), and a mean PHQ-9 score of 18.0 (SD = 6.3). No adverse effects were reported. Significant differences were observed between the experimental and control groups in changes in HAM-D (-8.4 vs. -2.9; group difference = -5.5; p = 0.01), PHQ-9 (-6.6 vs. -0.6; -6.0; p < 0.001), MoCA (1.4 vs. -1.3; 2.7; p = 0.001), and serum BDNF levels (in pg/ml; 2088.3 vs. -3277.4; 5365.6; p = 0.02). Additionally, changes in HAM-D, PHQ-9, and MoCA scores correlated significantly with changes in BDNF level.ConclusionWith computerized cognitive training improving mood and cognition and increasing serum BDNF levels in 6 weeks, it may serve as a safe and effective evidence-based alternative or adjuvant treatment for late-life depression.Clinical trial registrationhttps://www.chictr.org.cn/indexEN.html, identifier ChiCTR1900027029

Sacrocolpopexy without concomitant posterior repair improves posterior compartment defects

The aim of this study is to determine posterior compartment topography 1-year after sacrocolpopexy (SC). Women who had SC without concomitant anterior or posterior repairs for symptomatic pelvic organ prolapse (POP) were included. Vaginal topography was assessed at baseline and 1-year postoperatively using POP quantification (POPQ). At baseline, 24% had stage IV POP, 68% stage III, and 8% stage II. One year after surgery, 75% had stage 0/I POP, 24% stage II, and 1% stage III. 112 (75%) were objectively cured (stage 0 or I POP). Anterior compartment was the most common site of POP persistence or recurrence (Ba ≥ stage II in 23 women) followed by posterior compartment (Bp ≥ stage II in 12 women) and apex (C ≥ stage II in 2 women). In 1-year follow-up, SC without concomitant posterior repair restores posterior vaginal topography in the majority of women with undergoing SC

Gene expression analysis of glioblastomas identifies the major molecular basis for the prognostic benefit of younger age

<p>Abstract</p> <p>Background</p> <p>Glioblastomas are the most common primary brain tumour in adults. While the prognosis for patients is poor, gene expression profiling has detected signatures that can sub-classify GBMs relative to histopathology and clinical variables. One category of GBM defined by a gene expression signature is termed ProNeural (PN), and has substantially longer patient survival relative to other gene expression-based subtypes of GBMs. Age of onset is a major predictor of the length of patient survival where younger patients survive longer than older patients. The reason for this survival advantage has not been clear.</p> <p>Methods</p> <p>We collected 267 GBM CEL files and normalized them relative to other microarrays of the same Affymetrix platform. 377 probesets on U133A and U133 Plus 2.0 arrays were used in a gene voting strategy with 177 probesets of matching genes on older U95Av2 arrays. Kaplan-Meier curves and Cox proportional hazard analyses were applied in distinguishing survival differences between expression subtypes and age.</p> <p>Results</p> <p>This meta-analysis of published data in addition to new data confirms the existence of four distinct GBM expression-signatures. Further, patients with PN subtype GBMs had longer survival, as expected. However, the age of the patient at diagnosis is not predictive of survival time when controlled for the PN subtype.</p> <p>Conclusion</p> <p>The survival benefit of younger age is nullified when patients are stratified by gene expression group. Thus, the main cause of the age effect in GBMs is the more frequent occurrence of PN GBMs in younger patients relative to older patients.</p