INSIDER: Interpretable sparse matrix decomposition for RNA expression data analysis.

RNA sequencing (RNA-Seq) is widely used to capture transcriptome dynamics across tissues, biological entities, and conditions. Currently, few or no methods can handle multiple biological variables (e.g., tissues/ phenotypes) and their interactions simultaneously, while also achieving dimension reduction (DR). We propose INSIDER, a general and flexible statistical framework based on matrix factorization, which is freely available at https://github.com/kai0511/insider. INSIDER decomposes variation from different biological variables and their interactions into a shared low-rank latent space. Particularly, it introduces the elastic net penalty to induce sparsity while considering the grouping effects of genes. It can achieve DR of high-dimensional data (of > = 3 dimensions), as opposed to conventional methods (e.g., PCA/NMF) which generally only handle 2D data (e.g., sample × expression). Besides, it enables computing 'adjusted' expression profiles for specific biological variables while controlling variation from other variables. INSIDER is computationally efficient and accommodates missing data. INSIDER also performed similarly or outperformed a close competing method, SDA, as shown in simulations and can handle complex missing data in RNA-Seq data. Moreover, unlike SDA, it can be used when the data cannot be structured into a tensor. Lastly, we demonstrate its usefulness via real data analysis, including clustering donors for disease subtyping, revealing neuro-development trajectory using the BrainSpan data, and uncovering biological processes contributing to variables of interest (e.g., disease status and tissue) and their interactions.

Clinical and radiomic features for predicting the treatment response of repetitive transcranial magnetic stimulation in major neurocognitive disorder: Results from a randomized controlled trial.

Image-guided repetitive transcranial magnetic stimulation (rTMS) has shown clinical effectiveness in senior adults with co-occurring depression and cognitive impairment, yet the imaging markers for predicting the treatment response are less investigated. In this clinical trial, we examined the efficacy and sustainability of 10 Hz rTMS for the treatment of depression and cognitive impairment in major neurocognitive disorder (NCD) patients and tested the predictive values of imaging-informed radiomic features in response to rTMS treatment. Fifty-five major NCD patients with depression were randomly assigned to receive a 3-week rTMS treatment of either active 10 Hz rTMS (n = 27) or sham rTMS (n = 28). Left dorsolateral prefrontal cortex (DLPFC) was the predefined treatment target. Based on individual structural magnetic resonance imaging scans, surface-based analysis was conducted to quantitatively measure the baseline radiomic features of left DLPFC. Severity of depression, global cognition and the serum brain-derived neurotrophic factor (BDNF) level were evaluated at baseline, 3-, 6- and 12-week follow-ups. Logistic regression analysis revealed that advanced age, higher baseline cognition and randomized group were associated with the remission of depression. Increased cortical thickness and gyrification in left DLPFC were the significant predictors of clinical remission and cognitive enhancement. A 3-week course of 10 Hz rTMS is an effective adjuvant treatment for rapid ameliorating depressive symptoms and enhancing cognitive function. Pre-treatment radiomic features of the stimulation target can predict the response to rTMS treatment in major NCD. Cortical thickness and folding of treatment target may serve as imaging markers to detect the responders. ChiCTR-IOR-16008191, registered on March 30, 2016.

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

Background: The 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. Methods: A 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. Results: Our 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. Conclusion: With 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 registration: https://www.chictr.org.cn/indexEN.html, identifier ChiCTR1900027029.

Common mental disorders during the COVID-19 pandemic in Hong Kong: Age-related differences and implications for dementia risk.

Background: The COVID-19 pandemic has imposed a profound negative impact on the mental health and wellbeing of societies and individuals worldwide. Older adults may be more vulnerable to the mental health effects of the pandemic, either directly from the infection itself or indirectly through the preventive measures. However, the existing literature on mental health in the older age groups has not been consistent so far. The aim of this study was therefore to assess the prevalence of common mental disorders (CMD; including depression and anxiety disorders) given their association with dementia risk, and to further examine age-related differences between older (≥60 years old) and younger (18-59 years old) adult's psychological status during the COVID-19 pandemic. Method: This was a secondary analysis of a cross-sectional survey-study conducted during the second wave of COVID-19 pandemic in Hong Kong. The survey was disseminated through different social media platforms to the general population and included sociodemographic questions, self-reported physical health, and previous encounter with SARS or COVID-19. CMD was the primary outcome and was assessed using the 6-item Kessler Scale. A total of 1030 adults fulfilled inclusion criteria. Results: The prevalence of CMD during the pandemic was 16.1%. Compared to younger adults, older adults were significantly less likely to have a CMD (unadjusted OR = 0.07, 95% CI = 0.02-0.30, p < 0.001), with 18.1% of younger adults having CMD compared to 1.6% in the older cohort. Age differences remained significant after controlling for sociodemographic factors, physical health, and previous encounter with SARS or COVID-19 (adjusted OR = 0.12, 95% CI = 0.02-0.57, p = 0.008). Conclusion: Common mental disorders are highly prevalent during the COVID-19 pandemic in Hong Kong, though older adults appeared to be less affected mentally. Present findings highlight the urgent need to implement measures and strategies to mitigate the mental health problems, with particular attention to the younger cohort. Given their association with higher dementia risk, early detection and treatment of depression and anxiety disorders will be of critical importance in providing some relief to the already pressurized dementia burden in the longer term.

Do people with mental health problems have lower adherence to precautionary measures in COVID-19 pandemic? A cross-sectional observational study in Hong Kong.

OBJECTIVES: Mental health problems are prevalent during the COVID-19 pandemic, but their effect on adherence to precautionary measures is not well understood. Given that psychological morbidities are associated with lower treatment adherence, and that precautionary measures are important in containing the spread of COVID-19, this study aims to determine if people with mental health problems have lower adherence to precautionary measures against COVID-19. DESIGN: We conducted a cross-sectional territory-wide online survey between 17 June and 31 July 2020 during the COVID-19 pandemic. Clinically significant mental health problems, adherence to precautionary behaviours, and confounding factors such as sociodemographic factors and self-reported physical health were assessed. SETTING: The link to the questionnaire was disseminated to the general population in all 18 districts of Hong Kong using various social media platforms. PARTICIPANTS: 1036 individuals completed the survey. Of them, 1030 met the inclusion criteria of being adult Hong Kong residents. PRIMARY OUTCOME: Adherence to precautionary measures against COVID-19, including wearing face mask, frequent handwashing, household disinfection, social distancing, minimising unnecessary travel, and stocking up on food and daily essentials. RESULTS: Of the 1030 participants, 166 (16.1%) had clinically significant mental health problems. Interestingly, they were more likely to stock up on food and daily essentials during the pandemic (7 (4.2%) vs 15 (1.7%), p=0.04; unadjusted OR=2.49, 95% CI=1.00 to 6.21, p<0.05) and had a lesser tendency to stop social distancing even if the pandemic subsides (86 (51.8%) vs 513 (59.4%), p=0.07; unadjusted OR=0.74, 95% CI=0.53 to 1.03, p=0.07). The latter association remained significant after adjusting for the confounding factors (adjusted OR=0.68, 95% CI=0.48 to 0.96, p=0.03). CONCLUSIONS: Contrary to our hypothesis, people who are mentally unwell might go beyond the recommended precautionary measures. Our findings highlight the need to identify mental health problems and provide care and support for those who might go too far with precautionary measures. TRIAL REGISTRATION NUMBER: ChiCTR 2000033936.

Randomized controlled trial of TDCS on cognition in 201 seniors with mild neurocognitive disorder.

OBJECTIVE: To examine the efficacy and safety of combined transcranial direct current stimulation (tDCS) and working memory training (WMT) in enhancing the cognitive functions for individuals with mild neurocognitive disorder due to AD (NCD-AD). METHODS: In this double-blind, sham-controlled randomized clinical trial (RCT), 201 patients with NCD-AD were randomly assigned for a 4-week intervention of either a combination of tDCS and WMT, sham tDCS and WMT, or tDCS and control cognitive training (CCT). Global cognition and domain-specific cognitive function were assessed before and after the intervention with Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog), category verbal fluency test, logical memory, digit, and visual span tests. RESULTS: Study participants did not show intervention group differences in baseline demographics, or cognitive characteristics (ANOVA). Cognitive enhancement was found across three groups after 4 weeks intervention. Combined tDCS-WMT group showed significantly greater improvement compared with single-modality groups in delayed recall (P = 0.043, η2  = 0.036) and working memory capacity (P = 0.04, η2  = 0.038) at 4th week, and logical memory at 12th week (P = 0.042, η2  = 0.037). Adverse events, including skin lesions (2.2%), were similar between groups. INTERPRETATION: tDCS or WMT could be a safe, feasible, and effective intervention for individuals with NCD-AD. A combination of tDCS and WMT presents greater cognitive enhancement, which may highlight the potential synergistic effects of combined modality intervention on cognition.