Mild respiratory SARS-CoV-2 infection can cause multi-lineage cellular dysregulation and myelin loss in the brain

Survivors of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection frequently experience lingering neurological symptoms, including impairment in attention, concentration, speed of information processing and memory. This long-COVID cognitive syndrome shares many features with the syndrome of cancer therapy-related cognitive impairment (CRCI). Neuroinflammation, particularly microglial reactivity and consequent dysregulation of hippocampal neurogenesis and oligodendrocyte lineage cells, is central to CRCI. We hypothesized that similar cellular mechanisms may contribute to the persistent neurological symptoms associated with even mild SARS-CoV-2 respiratory infection. Here, we explored neuroinflammation caused by mild respiratory SARS-CoV-2 infection, without neuroinvasion, and effects on hippocampal neurogenesis and the oligodendroglial lineage. Using a mouse model of mild respiratory SARS-CoV-2 infection induced by intranasal SARS-CoV-2 delivery, we found white matter-selective microglial reactivity, a pattern observed in CRCI. Human brain tissue from 9 individuals with COVID-19 or SARS-CoV-2 infection exhibits the same pattern of prominent white matter-selective microglial reactivity. In mice, pro-inflammatory CSF cytokines/chemokines were elevated for at least 7-weeks post-infection; among the chemokines demonstrating persistent elevation is CCL11, which is associated with impairments in neurogenesis and cognitive function. Humans experiencing long-COVID with cognitive symptoms (48 subjects) similarly demonstrate elevated CCL11 levels compared to those with long-COVID who lack cognitive symptoms (15 subjects). Impaired hippocampal neurogenesis, decreased oligodendrocytes and myelin loss in subcortical white matter were evident at 1 week, and persisted until at least 7 weeks, following mild respiratory SARS-CoV-2 infection in mice. Taken together, the findings presented here illustrate striking similarities between neuropathophysiology after cancer therapy and after SARS-CoV-2 infection, and elucidate cellular deficits that may contribute to lasting neurological symptoms following even mild SARS-CoV-2 infection.

Characterization of cognitive impairment in adult polyglucosan body disease

Adult polyglucosan body disease (APBD) is a rare but probably underdiagnosed autosomal recessive neurodegenerative disorder due to pathogenic variants in GBE1. The phenotype is characterized by neurogenic bladder dysfunction, spastic paraplegia, and axonal neuropathy. Additionally, cognitive symptoms and dementia have been reported in APBD but have not been studied systematically. Using exome sequencing, we identified two previously unreported bi-allelic missense GBE1 variants in a patient with severe memory impairment along with the typical non-cognitive symptoms. We were able to confirm a reduction of GBE1 activity in blood lymphocytes. To characterize the neuropsychological profile of patients suffering from APBD, we conducted a systematic review of cognitive impairment in this rare disease. Analysis of 24 cases and case series (in total 58 patients) showed that executive deficits and memory impairment are the most common cognitive symptoms in APBD.

Psychometric Properties of Screening Questionnaires To Detect Depression In Primary Healthcare Setting In Rural Ethiopia

Background: Much of the research about the validity of depression screening questionnaires is on criterion validity. Evidence is scarce on the concurrent, convergent and construct validity of these measures, particularly from low-income countries. This study aimed to evaluate the psychometric properties of depression screening questionnaires in primary healthcare (PHC) in rural Ethiopia. Methods: A facility-based cross-sectional study was conducted with 587 participants recruited from patients attending three PHC facilities and two Holy water sites. The psychometric properties of five mental health screening questionnaires were evaluated: the nine item Patient Health Questionnaire (PHQ-9), the two item version of PHQ-9 (PHQ-2), a version of PHQ-9 with two added items of irritability and noise intolerance (PHQ-11), the Patient Health Questionnaire-15 (PHQ-15), and the World Health Organization-Five Well-being Index (WHO-5). Clinical diagnosis of depression was ascertained by psychiatrists using a semi-structured interview. We analyzed data using exploratory factor analysis, Spearman’s rank order correlation coefficient (Rho), the Mann Whitney test of the equality of medians, univariate logistic regression and Cronbach’s alpha. Results: PHQ-9, PHQ-11 and WHO-5 were found to be unidimensional, with items in each scale highly loading onto one factor (factor loadings ranging from 0.64 to 0.87). The items of each instrument were internally consistent, with Cronbach’s alpha ranging from 0.72 (PHQ-2) to 0.89 (PHQ-11). Scores for all screening scales were moderately or highly correlated with each other (Rho= 0.58 to 0.98) and moderately correlated with anxiety and disability scores. Median scores of all screening scales were significantly higher in those diagnosed with depression. The association of items measuring emotional and cognitive symptoms with the diagnosis of depression was stronger than the association with items measuring somatic symptoms. Irritability and noise intolerance had higher association with depression diagnosis than PHQ-9 items. Conclusion: Emotional and cognitive symptoms are more useful than somatic symptoms to predict the diagnosis of depression. Irritability and noise intolerance are more useful to detect depression. Future research should focus on testing the unidimensionality of PHQ-9, PHQ-11 and WHO-5 using confirmatory factor analysis; establishing the criterion validity of PHQ-11 and WHO-5; and on assessing test-retest reliability of all the measures.

Feasibility of online PD SAFEx™ exercise rehabilitation for symptom improvements of Parkinson’s disease: A pilot study

BACKGROUND: Parkinson’s Disease (PD) is a neurodegenerative disorder affecting both motor and cognitive symptoms. While medications show some improvement in motor symptoms, cognitive symptoms can worsen. In-person exercise programs, such as PD SAFEx™, are an important adjunct therapy in improving symptoms. However, coronavirus disease 2019 (COVID-19) limited in-person exercise interventions. Therefore, there is a need to investigate the effectiveness of online exercise delivery. OBJECTIVE: To identify (1) whether an online exercise intervention can achieve similar results to an identical in-person intervention and (2) if online PD SAFEx™ can alter the cognitive decline of PD patients. METHODS: 20 participants with idiopathic PD participated in a 12-week online PD SAFEx™ program and were compared to 73 participants from in-person PD SAFEx™. The primary outcome measure was the Unified Parkinson’s Disease Rating Scale-III measured before/after intervention. Three secondary cognitive measures were collected with the online group. RESULTS: Main effect of time on UPDRS-III scores of both groups were found (F(1,92) = 35.555, p < 0.001). No interaction was found between in-person and online groups (F(1,1) = 0.052, p = 0.820). TMT B in the online group showed significant improvements in executive function (F(1,17) = 7.095, p = 0.016). CONCLUSIONS: Online and in-person PD SAFEx™ both achieved clinically significant UPDRS-III improvement and are statistically equivalent. Online PD SAFEx™ reduced cognitive symptoms seen during COVID-19.

Assessment of the physical and emotional health concerning the students' physical activity during the COVID-19 pandemic

Introduction. SARS CoV-2 caused the third global pandemic and by applying quarantine / isolation / lockdown, the movement was restricted, the physical contact between people was reduced, the physical activity was low, but the activities using electronic devices at home were frequent. The aim of the study was to assess the physical and emotional health in relation to the physical activities done during quarantine/ isolation during the pandemic. Material and method. The study was cross-sectional and consisted of completing an online questionnaire. It was conducted in a period of 6 months and it included 334 students. In order to point out the symptoms caused by quarantine / isolation/ lockdown, we considered it useful for students to participate by completing an online questionnaire about physical activities, physical health and emotional state, related to the implications of participating in online courses. Results. The questions in this questionnaire were grouped on the following aspects: physical activity, physical health, emotional state, all in the context of the pandemic period, including the period in which the academic activity was online. Thus, in the first year, there is a positive correlation between physical condition, physical activity, emotional signs and cognitive ones. In the second year, the positive correlation is present between the physical and the affective signs, whereas the negative correlation is between the affective signs, the cognitive ones and the physical activity. In the third year, the positive correlation is obvious between the affective signs, the cognitive ones and the physical activity, whereas the negative one between the physical and cognitive signs, as well as between the physical activity and the cognitive and physical signs. Discussions. There is a link between emotional and cognitive symptoms and physical health. Fear, anxiety, behavioral disorders, and limited physical activity among students during this period can be a public health issue. Conclusions. The COVID-19 pandemic affected the physical and mental state, with a greater resonance for youth, especially pupils and students. Many of them had emotional, behavioral, physical and cognitive symptoms. These symptoms are found to a greater extent in students in the final years, due to the social impact, social and professional integration. Keywords: physical health, mental state, students,

Long-Term Cognitive Dysfunction in Cancer Survivors

Cancer-related cognitive impairment (CRCI) is a frequent side effect experienced by an increasing number of cancer survivors with a significant impact on their quality of life. Different definitions and means of evaluation have been used in available literature; hence the exact incidence of CRCI remains unknown. CRCI can be described as cognitive symptoms reported by cancer patients in self-reported questionnaires or as cognitive changes evaluated by formal neuropsychological tests. Nevertheless, association between cognitive symptoms and objectively assessed cognitive changes is relatively weak or absent. Studies have focused especially on breast cancer patients, but CRCI has been reported in multiple types of cancer, including colorectal, lung, ovarian, prostate, testicular cancer and hematological malignancies. While CRCI has been associated with various treatment modalities, including radiotherapy, chemotherapy, hormone therapy and novel systemic therapies, it has been also detected prior to cancer treatment. Therefore, the effects of cancer itself with or without the psychological distress may be involved in the pathogenesis of CRCI as a result of altered coping mechanisms after cancer diagnosis. The development of CRCI is probably multifactorial and the exact mechanisms are currently not completely understood. Possible risk factors include administered treatment, genetic predisposition, age and psychological factors such as anxiety, depression or fatigue. Multiple mechanisms are suggested to be responsible for CRCI, including direct neurotoxic injury of systemic treatment and radiation while other indirect contributing mechanisms are hypothesized. Chronic neuroinflammation mediated by active innate immune system, DNA-damage or endothelial dysfunction is hypothesized to be a central mechanism of CRCI pathogenesis. There is increasing evidence of potential plasma (e.g., damage associated molecular patterns, inflammatory components, circulating microRNAs, exosomes, short-chain fatty acids, and others), cerebrospinal fluid and radiological biomarkers of cognitive dysfunction in cancer patients. Discovery of biomarkers of cognitive impairment is crucial for early identification of cancer patients at increased risk for the development of CRCI or development of treatment strategies to lower the burden of CRCI on long-term quality of life. This review summarizes current literature on CRCI with a focus on long-term effects of different cancer treatments, possible risk factors, mechanisms and promising biomarkers.

Relationship Between Self-Reported Concomitant Depressive and Anxiety Symptoms and the Post-Concussion Symptoms Scale (PCSS)

ABSTRACT Objectives: The current study explored how affective disturbances, particularly concomitant anxiety and depressive symptoms, impact baseline symptom self-reporting on the Post-Concussion Symptoms Scale (PCSS) in college athletes. Methods: Athletes were separated into four groups (Healthy Control (HC) (n = 581), Depression Only (n = 136), Anxiety Only (n = 54), Concomitant Depression/Anxiety (n = 62)) based on their anxiety and depression scores. Groups were compared on Total PCSS Score as well as 5 PCSS Symptom Cluster scores (Cognitive, Physical, Affective, Sleep, and Headache). Results: The three affective groups reported significantly greater symptomatology than HCs, with the Concomitant group showing the highest symptomatology scores across all clusters. The depressive symptoms only group also reported significantly elevated symptomatology, compared to HCs, on every symptom cluster except headache. The anxiety symptoms only group differed from HCs on only the cognitive symptoms cluster. Additionally, the Concomitant group reported significantly increased PCSS symptomatology, in terms of total scores and all 5 symptom clusters, compared to the depressive symptoms only and anxiety symptoms only groups. Conclusions: Our findings suggest that athletes experiencing concomitant depressive/anxiety symptoms report significantly greater levels of symptomatology across all 5 PCSS symptom clusters compared to HCs. Further, results suggest that athletes experiencing concomitant affective disturbance tend to report greater symptomatology than those with only one affective disturbance. These findings are important because, despite the absence of concussion, the concomitant group demonstrated significantly elevated symptomatology at baseline. Thus, future comparisons with post-concussion data should account for this increased symptomatology, as test results may be skewed by affective disturbances at baseline.

Assessment of Cognitive Symptoms in Brain Bank-Registered Control Subjects: Feasibility and Utility of a Telephone-Based Screening

Background: For neuroscience research, the study of brain tissue of neurologically unimpaired subjects is crucial to interpret findings in neurodegenerative diseases. Sub-optimal neurological follow-up and the presence of neuropathological lesions in supposedly asymptomatic subjects casts doubt as to whether these subjects present an undetected underlying neurodegenerative disease or are resilient to neurodegeneration. Objective: We aimed to assess whether the control donors registered in the Neurological Tissue Bank-Hospital Clínic-IDIBAPS (NTB-HCI) are still free of cognitive symptoms at follow-up and to evaluate the feasibility and utility of a telephone-based screening. Methods: All control subjects older than 65 years registered at the NTB-HCI database were selected for the study. After a structured telephone interview, those subjects already diagnosed with a neurological disease were excluded. Then, a cognitive screening was performed, including the telephone version of the Mini-Mental State Examination (t-MMSE) and the eight-item interview (AD-8) to the subject and to one informant. Results: In total, 73.8% of the registered donors collaborated in the study. Only 21.4% had at least one of the three cognitive screening tools impaired, and 2.7% had a profile highly suggestive of cognitive impairment. AD-8i correlated moderately with t-MMSE. Conclusion: Telephone-based neurologic screening in control donors is feasible and was within the normal range in most of the subjects in our cohort. Albeit, the involvement of neurologists and periodic neurological screenings are desirable in a control subjects brain donor program, AD8-i could be used to screen the control’s neurological status in the absence of accurate clinical data at the time of the death.