The Golgi apparatus: Site for convergence of COVID-19 brain fog and Alzheimer's disease?
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ABSTRACT:
SUBMITTER: Wang Y
PROVIDER: S-EPMC9587685 | biostudies-literature | 2022 Oct
REPOSITORIES: biostudies-literature
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The Golgi apparatus: Site for convergence of COVID-19 brain fog and Alzheimer's disease?
Molecular neurodegeneration 20221021 1
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Project description:Brain fog is a kind of mental problem, similar to chronic fatigue syndrome, and appears about 3 months after the infection with COVID-19 and lasts up to 9 months. The maximum magnitude of the third wave of COVID-19 in Poland was in April 2021. The research referred here aimed at carrying out the investigation comprising the electrophysiological analysis of the patients who suffered from COVID-19 and had symptoms of brain fog (sub-cohort A), suffered from COVID-19 and did not have symptoms of brain fog (sub-cohort B), and the control group that had no COVID-19 and no symptoms (sub-cohort C). The aim of this article was to examine whether there are differences in the brain cortical activity of these three sub-cohorts and, if possible differentiate and classify them using the machine-learning tools. he dense array electroencephalographic amplifier with 256 electrodes was used for recordings. The event-related potentials were chosen as we expected to find the differences in the patients' responses to three different mental tasks arranged in the experiments commonly known in experimental psychology: face recognition, digit span, and task switching. These potentials were plotted for all three patients' sub-cohorts and all three experiments. The cross-correlation method was used to find differences, and, in fact, such differences manifested themselves in the shape of event-related potentials on the cognitive electrodes. The discussion of such differences will be presented; however, an explanation of such differences would require the recruitment of a much larger cohort. In the classification problem, the avalanche analysis for feature extractions from the resting state signal and linear discriminant analysis for classification were used. The differences between sub-cohorts in such signals were expected to be found. Machine-learning tools were used, as finding the differences with eyes seemed impossible. Indeed, the A&B vs. C, B&C vs. A, A vs. B, A vs. C, and B vs. C classification tasks were performed, and the efficiency of around 60-70% was achieved. In future, probably there will be pandemics again due to the imbalance in the natural environment, resulting in the decreasing number of species, temperature increase, and climate change-generated migrations. The research can help to predict brain fog after the COVID-19 recovery and prepare the patients for better convalescence. Shortening the time of brain fog recovery will be beneficial not only for the patients but also for social conditions.
| S-EPMC9947499 | biostudies-literature
Project description:This case report highlights a unique case of brain fog in a COVID-19 patient suggesting COVID-19's neurotropic nature. COVID-19 is associated with a long-COVID syndrome that presents with cognitive decline and fatigue. Recent studies show the emergence of a novel syndrome known as post-acute COVID syndrome or long COVID, which constitutes a variety of symptoms that continue for four weeks following the onset of a COVID-19 diagnosis. Numerous post-COVID patients experience both short and long-lasting symptoms affecting several organs, including the brain, which includes being unconscious, bradyphrenia, or amnesia. This long COVID status comprises of "brain fog", which, coupled with neuro-cognitive effects, has a significant role in prolonging the recovery phase. The pathogenesis of brain fog is currently unknown. One of the leading causes might be the involvement of neuroinflammation due to mast cells stimulated by pathogenic and stress stimuli. This in turn, triggers the release of mediators that activate microglia, causing inflammation in the hypothalamus. Its ability to invade the nervous system through trans-neural or hematogenous mechanisms is possibly the chief cause behind the presenting symptoms. This case report highlights a unique case of brain fog in a COVID-19 patient suggesting COVID-19's neurotropic nature and how it may lead to neurologic complications such as meningitis, encephalitis, and Guillain-Barré syndrome.
| S-EPMC10105897 | biostudies-literature
Project description:We investigated the frequency of brain fog in a large cohort of patients with documented coronavirus disease-2019 (COVID-19) who have survived the illness. We also scrutinized the potential risk factors associated with the development of brain fog. Adult patients (18-55 years of age), who were referred to the healthcare facilities anywhere in Fars province from February 19, 2020 to November 20, 2020 were included. All patients had a confirmed COVID-19 diagnosis. In a phone call, at least 3 months after their discharge from the hospital, we obtained their current information. A questionnaire was specifically designed for data collection. In total, 2696 patients had the inclusion criteria; 1680 (62.3%) people reported long COVID syndrome (LCS). LCS-associated brain fog was reported by 194 (7.2%) patients. Female sex (odds ratio [OR]: 1.4), respiratory problems at the onset (OR: 1.9), and intensive care unit (ICU) admission (OR: 1.7) were significantly associated with reporting chronic post-COVID "brain fog" by the patients. In this large population-based study, we report that chronic post-COVID "brain fog" has significant associations with sex (female), respiratory symptoms at the onset, and the severity of the illness (ICU admission).
| S-EPMC8662118 | biostudies-literature
Project description:Polygenic risk scores (PRS) have been widely adopted as a tool for measuring common variant liability and they have been shown to predict lifetime risk of Alzheimer's disease (AD) development. However, the relationship between PRS and AD pathogenesis is largely unknown. To this end, we performed a differential gene-expression and associated disrupted biological pathway analyses of AD PRS vs. case/controls in human brain-derived cohort sample (cerebellum/temporal cortex; MayoRNAseq). The results highlighted already implicated mechanisms: immune and stress response, lipids, fatty acids and cholesterol metabolisms, endosome and cellular/neuronal death, being disrupted biological pathways in both case/controls and PRS, as well as previously less well characterised processes such as cellular structures, mitochondrial respiration and secretion. Despite heterogeneity in terms of differentially expressed genes in case/controls vs. PRS, there was a consensus of commonly disrupted biological mechanisms. Glia and microglia-related terms were also significantly disrupted, albeit not being the top disrupted Gene Ontology terms. GWAS implicated genes were significantly and in their majority, up-regulated in response to different PRS among the temporal cortex samples, suggesting potential common regulatory mechanisms. Tissue specificity in terms of disrupted biological pathways in temporal cortex vs. cerebellum was observed in relation to PRS, but limited tissue specificity when the datasets were analysed as case/controls. The largely common biological mechanisms between a case/control classification and in association with PRS suggests that PRS stratification can be used for studies where suitable case/control samples are not available or the selection of individuals with high and low PRS in clinical trials.
| S-EPMC10005937 | biostudies-literature
Project description:The coronavirus disease 2019 (COVID-19) remains an epidemic worldwide. Most patients suffer residual symptoms, the so-called "Long COVID," which includes respiratory and neuropsychiatric symptoms. Brain Fog, one of the symptoms of Long COVID, is a major public health issue because it can impair patients' quality of life even after recovery from the disease. However, neither the pathogenesis nor the treatment of this condition remains unknown. We focused on serum ferritin levels in this study and collected information on the onset of Brain Fog through questionnaires and found that high ferritin levels during hospitalization were associated with the occurrence of Brain Fog. In addition, we excluded confounders as far as possible using propensity score analyses and found that ferritin was independently associated with Brain Fog in most of the models. We conducted phase analysis and evaluated the interaction of each phase with ferritin levels and Brain Fog. We found a positive correlation between serum ferritin levels during hospitalization and Brain Fog after COVID-19. High ferritin levels in patients with Brain Fog may reflect the contribution of chronic inflammation in the development of Brain Fog. This study provides a novel insight into the pathogenic mechanism of Brain Fog after COVID-19.
| S-EPMC10421912 | biostudies-literature
Project description:ObjectivesLimited research exists on COVID-19 associated brain fog, and on the long-term cognitive and psychiatric sequelae in racially and ethnically diverse patients. We characterize the neuropsychological sequelae of post-acute COVID-19 in a diverse cohort and investigate whether COVID-19 clinical severity remains associated with brain fog and cognitive deficits approximately 2 years post infection.MethodsA cross-sectional study of patients with a history of COVID-19 hospitalization (March-September 2020). COVID-19 clinical severity was indexed using the National Early Warning Score 2 and a comprehensive neuropsychological tele-battery was administered 2 years post discharge. Pearson's r correlations assessed association, while independent sample t-tests examined group differences. Significant outcomes were further analyzed using multiple regression and ANCOVAs, adjusting for key covariates.ResultsIn 41 adult patients (19 female, 30 Hispanic, 13 Black, mean age of 65 (SD = 15), COVID-19 level of severity was associated with greater number of endorsed brain fog symptoms (Pearson's r = .34, 95% CI [.04, .59]), worse overall cognitive functioning (global cognition: r = -.36, 95% CI [-.61, -.05]) and reduced performance on an attention and working memory task (digit span backwards: r = -.41, 95% CI [-.66, -.09]) at 2-year follow-up. Brain fog symptoms most associated with COVID-19 severity included difficulty focusing (r = .46, 95% CI [.18, .67]), detached (r = .41, 95% CI [.12, .64]) and feeling sleepy (r = .40, 95% CI [.11, .63]). Patients' cognitive performance was generally below average (global cognition z-score: M = -.96, SD = .66), with group differences based on sex and ethnicity evidenced on individual cognitive tests.DiscussionThis study emphasizes the importance of continued research on the long-term effects of COVID-19 infection on neuropsychological outcomes, particularly among underrepresented, health-disparate groups. Greater understanding of these associations could improve detection and treatment of those at increased risk of cognitive decline or impairment.
| S-EPMC11361661 | biostudies-literature
Project description:BackgroundAge represents the largest risk factor for Alzheimer's disease (AD) but is typically treated as a covariate. Still, there are similarities between brain regions affected in AD and those showing accelerated decline in normal aging, suggesting that the distinction between the two might fall on a spectrum.ObjectiveOur goal was to identify regions showing accelerated atrophy across the brain and investigate whether these overlapped with regions involved in AD or where related to amyloid.MethodsWe used a longitudinal sample of 137 healthy older adults from the Alzheimer's Disease Neuroimaging Initiative (ADNI), who underwent magnetic resonance imaging (MRI). In addition, a total of 79 participants also had longitudinal positron emission tomography (PET) data. We computed linear-mixed effects models for brain regions declining faster than the average to investigate variability in the rate of change.Results23 regions displayed a 0.5 standard deviation (SD) above average decline over 2 years. Of these, 52% overlapped with regions showing similar decline in a matched AD sample. Beyond this, the left precuneus, right superior frontal, transverse temporal, and superior temporal sulcus showed accelerated decline. Lastly, atrophy in the precuneus was associated with increased amyloid load.ConclusionsAccelerated decline in normal aging might contribute to the detection of early signs of AD among healthy individuals.
| S-EPMC11745547 | biostudies-literature
Project description:Post-acute sequelae of SARS-CoV-2 (PASC) is a poorly understood condition with significant impact on quality of life. We aimed to better understand the lived experiences of patients with PASC, focusing on the impact of cognitive complaints ("brain fog") and fatigue on (1) daily activities, (2) work/employment, and (3) interpersonal relationships. We conducted semi-structured qualitative interviews with 15 patients of a Midwestern academic hospital's post-COVID-19 clinic. We audio-recorded, transcribed, and analyzed interviews thematically using a combined deductive-inductive approach and collected participants' characteristics from chart review. Participants frequently used descriptive and metaphorical language to describe symptoms that were relapsing-remitting and unpredictable. Fatigue and brain fog affected all domains and identified subthemes included symptoms' synergistic effects, difficulty with multitasking, lack of support, poor self-perception, and fear of loss of income and employment. Personal relationships were affected with change of responsibilities, difficulty parenting, social isolation, and guilt due to the burdens placed on family. Furthermore, underlying social stigma contributed to negative emotions, which significantly affected emotional and mental health. Our findings highlight PASC's negative impact on patients' daily lives. Providers can better support COVID-19 survivors during their recovery by identifying their needs in a sensitive and timely manner.
| S-EPMC9737348 | biostudies-literature
Project description:Background: There is still a need for studies on the quality of life (QoL) at work among COVID-19 survivors. Therefore, we aimed to evaluate the association between the brain fog symptoms and the QoL at work in non-hospitalized patients with previous SARS-CoV-2 infection. Methods: Three hundred non-hospitalized patients (79.33% women; median age, 36 years; interquartile range, 30-48 years) were included in the final analysis. An anonymous neuropsychological questionnaire containing eight different questions on the presence of brain fog symptoms in four time intervals, i.e., pre-COVID-19 and 0-4, 4-12, and >12 weeks after infection, was retrospectively introduced to patients and staff of the University Hospital in Krakow. Additionally, a four-point Likert scale was used to evaluate QoL at work in four time periods. Included were participants aged ≥ 18 years in whom the diagnosis of COVID-19 was confirmed by the RT-PCR from nasopharyngeal swab and the first symptoms occurred no earlier than 3 months before the completion of the questionnaire. Results: Before SARS-CoV-2 infection, 28.00% (n = 84) of patients reported poor QoL at work. Within 4, 4-12, and >12 weeks after infection, a decrease in QoL was observed in 75.67% (n = 227), 65.00% (n = 195), and 53.66% (n = 161) of patients, respectively (p < 0.001). With increasing deterioration of the QoL at work, the number of brain fog symptoms increased, and patients with severe QoL impairment exhibited a median of five symptoms for <4, 4-12, and >12 weeks post-COVID-19. In the multivariable logistic regression model, predictors of the deterioration of the QoL at work depended on the time from COVID-19 onset; in the acute phase of the disease (<4 weeks), it was predicted by impairment in remembering information from the past (OR 1.88, 95%CI: 1.18-3.00, p = 0.008) and multitasking (OR 1.96, 95%CI: 1.48-2.58, p < 0.001). Furthermore, an impairment in the QoL at work 4-12 weeks and >12 weeks after COVID-19 was independently associated with age (OR 0.46, 95%CI: 0.25-0.85, p = 0.014 and OR 1.03, 95%CI: 1.01-1.05, p = 0.025, respectively), problems with multitasking (OR 2.05, 95%CI: 1.40-3.01, p < 0.001 and OR 1.75, 95%CI: 1.15-2.66, p = 0.009, respectively), answering questions in an understandable/unambiguous manner (OR 1.99, 95%CI: 1.27-3.14, p = 0.003 and OR 2.00, 95%CI: 1.47-2.36, p = 0.001, respectively), and, only for the >12 week interval, problems with remembering information from the past (OR 2.21, 95%CI: 1.24-3.92, p = 0.007). Conclusions: Certain brain fog symptoms, such as impaired memory or multitasking, are predictors of a poorer QoL at work not only during the acute phase of COVID-19 but also within more than 12 weeks after the onset of infection.
| S-EPMC9564568 | biostudies-literature
Project description:Neuritic plaques are one of the major pathological hallmarks of Alzheimer's disease. They are formed by the aggregation of extracellular amyloid-β protein (Aβ), which is derived from the sequential cleavage of amyloid-β precursor protein (APP) by β- and γ-secretase. BACE1 is the main β-secretase in the pathogenic process of Alzheimer's disease, which is believed to be a rate-limiting step of Aβ production. Presenilin 1 (PS1) is the active center of the γ-secretase that participates in the APP hydrolysis process. Mutations in the PS1 gene (PSEN1) are the most common cause of early onset familial Alzheimer's disease (FAD). The PSEN1 mutations can alter the activity of γ-secretase on the cleavage of APP. Previous studies have shown that PSEN1 mutations increase the expression and activity of BACE1 and that BACE1 expression and activity are elevated in the brains of PSEN1 mutant knock-in mice, compared with wild-type mice, as well as in the cerebral cortex of FAD patients carrying PSEN1 mutations, compared with sporadic AD patients and controls. Here, we used a Psen1 knockout cell line and a PS1 inhibitor to show that PS1 affects the expression of BACE1 in vitro. Furthermore, we used sucrose gradient fractionation combined with western blotting to analyze the distribution of BACE1, combined with a time-lapse technique to show that PS1 upregulates the distribution and trafficking of BACE1 in the endoplasmic reticulum, Golgi, and endosomes. More importantly, we found that the PSEN1 mutant S170F increases the distribution of BACE1 in the endoplasmic reticulum and changes the ratio of mature BACE1 in the trans-Golgi network. The effect of PSEN1 mutations on BACE1 may contribute to determining the phenotype of early onset FAD.
| S-EPMC9782474 | biostudies-literature