Objectives: To ascertain factors associated with worsening of psychiatric conditions during the coronavirus disease 2019 (COVID-19) pandemic.Methods: This study anonymously examined 2,734 psychiatric patients worldwide for worsening of their preexisting psychiatric conditions during the COVID-19 pandemic. An independent clinical investigation of 318 psychiatric patients from United States was used for verification.Results: Valid responses mainly from 12 featured countries indicated self-reported worsening of psychiatric conditions in two-thirds of the patients assessed that was through their significantly higher scores on scales for general psychological disturbance, posttraumatic stress disorder, and depression. Female gender, feeling no control of the situation, reporting dissatisfaction with the response of the state during the COVID-19 pandemic, and reduced interaction with family and friends increased the worsening of preexisting psychiatric conditions, whereas optimism, ability to share concerns with family and friends, and using social media like usual were associated with less worsening. An independent clinical investigation from the United States confirmed worsening of psychiatric conditions during the COVID-19 pandemic based on identification of new symptoms that necessitated clinical interventions such as dose adjustment or starting new medications in more than half of the patients.Conclusions: More than half of the patients are experiencing worsening of their psychiatric conditions during the COVID-19 pandemic.

Microglia, the resident immune cells of the brain, are increasingly implicated in the regulation of brain health and disease. Microglia perform multiple functions in the central nervous system, including surveillance, phagocytosis and release of a variety of soluble factors. Importantly, a majority of their functions are closely related to changes in their metabolism. This natural inter-dependency between core microglial properties and metabolism offers a unique opportunity to modulate microglial activities via nutritional or metabolic interventions. In this review, we examine the existing scientific literature to synthesize the hypothesis that microglial phagocytosis of amyloid beta (Aβ) aggregates in Alzheimer’s disease (AD) can be selectively enhanced via metabolic interventions. We first review the basics of microglial metabolism and the effects of common metabolites, such as glucose, lipids, ketone bodies, glutamine, pyruvate and lactate, on microglial inflammatory and phagocytic properties. Next, we examine the evidence for dysregulation of microglial metabolism in AD. This is followed by a review of in vivo studies on metabolic manipulation of microglial functions to ascertain their therapeutic potential in AD. Finally, we discuss the effects of metabolic factors on microglial phagocytosis of healthy synapses, a pathological process that also contributes to the progression of AD. We conclude by enlisting the current challenges that need to be addressed before strategies to harness microglial phagocytosis to clear pathological protein deposits in AD and other neurodegenerative disorders can be widely adopted.

Background: Despite an alarming rise in the global prevalence of dementia, the available modalities for improving cognition and mental wellbeing of dementia patients remain limited. Environmental enrichment is an experimental paradigm that has shown promising anti-depressive and memory-enhancing effects in pre-clinical studies. However, its clinical utility has remained limited due to the lack of effective implementation strategies. Objective: The primary objective of this study was to evaluate the usability (tolerability and interactivity) of a long-term virtual reality (VR)- based environmental enrichment training program in older adults with mild cognitive impairment (MCI) and mild dementia. A secondary objective was to assess the effect of VR-based environmental enrichment on stabilization of cognitive functioning and improvement of mental wellbeing in older adults with MCI and mild dementia. Methods: A total of seven participants (four patients with MCI and three with mild dementia) received biweekly VR-based environmental enrichment over a course of 6 months. The tolerability and interactivity of the participants in the VR training was serially assessed via virtual reality sickness questionnaire (VRSQ) and recording of input-error ratio. Cognitive functioning was assessed through Montreal cognitive assessment (MoCA) before and after the study. Mental wellbeing was assessed through Warwick-Edinburgh Mental Well Being Scale (WEMWBS). Results: VR-based environmental enrichment was well-tolerated by the patients with significant decrease in VRSQ scores (p < 0.01) and input-error ratio (p < 0.001) overtime. VR training was also effective in stabilization of MoCA scores over the course of therapy (non-significant difference in the MoCA scores before and after the therapy) and was associated with a trend (p < 0.1) towards improvement in WEMWBS scores between the first and the last assessments. Qualitative observations by the care-givers further corroborated a noticeable improvement in mental wellbeing of patients. Conclusions: This pilot study shows that VR can be a feasible, tolerable, and potentially effective tool in long-term support of older adults with MCI and mild dementia.

Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are two fatal neurodegenerative disorders with considerable clinical, pathological and genetic overlap. Both disorders are characterized by the accumulation of pathological protein aggregates that contain a number of proteins, most notably TAR DNA binding protein 43 kDa (TDP-43). Surprisingly, recent clinical studies suggest that dyslipidemia, high body mass index, and type 2 diabetes mellitus are associated with better clinical outcomes in ALS. Moreover, ALS and FTLD patients have a significantly lower incidence of cardiovascular disease, supporting the idea that an unfavorable metabolic profile may be beneficial in ALS and FTLD. The two most widely studied ALS/FTLD models, super-oxide dismutase 1 (SOD1) and TAR DNA binding protein of 43 kDA (TDP-43), reveal metabolic dysfunction and a positive effect of metabolic strategies on disease onset and/or progression. In addition, molecular studies reveal a role for ALS/FTLD-associated proteins in the regulation of cellular and whole-body metabolism. Here, we systematically evaluate these observations and discuss how changes in cellular glucose/lipid metabolism may result in abnormal protein aggregations in ALS and FTLD, which may have important implications for new treatment strategies for ALS/FTLD and possibly other neurodegenerative conditions.