“Brain Fog” by COVID-19 or Alzheimer’s Disease? A Case Report

Matías‐Guiu, Jordi A.; Delgado‐Alonso, Cristina; Yus, Miguel; Polidura, Carmen; Gómez-Ruiz, Natividad; Valles‐Salgado, María; Ortega‐Madueño, Isabel; Cabrera‐Martín, María Nieves; Matías‐Guiu, Jorge

doi:10.3389/fpsyg.2021.724022

Cited by 21 publications

(12 citation statements)

References 48 publications

(54 reference statements)

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“…Patients with Parkinson’s disease (PD) showed worsened motor and nonmotor symptoms after being diagnosed with COVID-19 [ 22 ]. Meanwhile, several case reports described the development of acute parkinsonism, AD, or amyotrophic lateral sclerosis (ALS) following COVID-19 [ 23 – 25 ]. However, the observational studies might be biased by unavoidable confounding factors, and cannot determine causation.…”

Section: Introductionmentioning

confidence: 99%

COVID-19 and risk of neurodegenerative disorders: A Mendelian randomization study

Liu

Lin

et al. 2022

Transl Psychiatry

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Emerging evidence has suggested a close correlation between COVID-19 and neurodegenerative disorders. However, whether there exists a causal association and the effect direction remains unknown. To examine the causative role of COVID-19 in the risk of neurodegenerative disorders, we estimated their genetic correlation, and then conducted a two-sample Mendelian randomization analysis using summary statistics from genome-wide association studies of susceptibility, hospitalization, and severity of COVID-19, as well as six major neurodegenerative disorders including Alzheimer’s disease (AD), amyotrophic lateral sclerosis, frontotemporal dementia, Lewy body dementia, multiple sclerosis, and Parkinson’s disease. We identified a significant and positive genetic correlation between hospitalization of COVID-19 and AD (genetic correlation: 0.23, P = 8.36E–07). Meanwhile, hospitalization of COVID-19 was significantly associated with a higher risk of AD (OR: 1.02, 95% CI: 1.01–1.03, P: 1.19E–03). Consistently, susceptibility (OR: 1.05, 95% CI: 1.01–1.09, P: 9.30E–03) and severity (OR: 1.01, 95% CI: 1.00–1.02, P: 0.012) of COVID-19 were nominally associated with higher risk of AD. The results were robust under all sensitivity analyses. These results demonstrated that COVID-19 could increase the risk of AD. Future development of preventive or therapeutic interventions could attach importance to this to alleviate the complications of COVID-19.

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Section: Introductionmentioning

confidence: 99%

COVID-19 and risk of neurodegenerative disorders: A Mendelian randomization study

Liu

Lin

et al. 2022

Transl Psychiatry

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“…In addition, our results indicated that AD has the highest number of overlapping GO biological processes (COVID-19 ∩ Disease) that can be modulated by SARS-CoV-2 through virus–host PPIs, whereas Epilepsy has the lowest number of overlapping processes, Figure 3 A. Cognitive symptoms, such as memory impairment and brain fog, are commonly reported after COVID-19 and memory problems are also a major symptom of AD [ 71 , 72 , 109 ]. A recent case study has shown that a patient that had cognitive symptoms after COVID-19 had increased CSF biomarkers associated with AD [ 110 ]. In addition, elevated levels of serum neurodegenerative biomarkers similarly to those observed in AD have been found in hospitalized COVID-19 patients [ 100 ].…”

Section: Discussionmentioning

confidence: 99%

Systems Bioinformatics Reveals Possible Relationship between COVID-19 and the Development of Neurological Diseases and Neuropsychiatric Disorders

Onisiforou

Spyrou²

2022

Viruses

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Coronavirus Disease 2019 (COVID-19) is associated with increased incidence of neurological diseases and neuropsychiatric disorders after infection, but how it contributes to their development remains under investigation. Here, we investigate the possible relationship between COVID-19 and the development of ten neurological disorders and three neuropsychiatric disorders by exploring two pathological mechanisms: (i) dysregulation of host biological processes via virus–host protein–protein interactions (PPIs), and (ii) autoreactivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epitopes with host “self” proteins via molecular mimicry. We also identify potential genetic risk factors which in combination with SARS-CoV-2 infection might lead to disease development. Our analysis indicated that neurodegenerative diseases (NDs) have a higher number of disease-associated biological processes that can be modulated by SARS-CoV-2 via virus–host PPIs than neuropsychiatric disorders. The sequence similarity analysis indicated the presence of several matching 5-mer and/or 6-mer linear motifs between SARS-CoV-2 epitopes with autoreactive epitopes found in Alzheimer’s Disease (AD), Parkinson’s Disease (PD), Myasthenia Gravis (MG) and Multiple Sclerosis (MS). The results include autoreactive epitopes that recognize amyloid-beta precursor protein (APP), microtubule-associated protein tau (MAPT), acetylcholine receptors, glial fibrillary acidic protein (GFAP), neurofilament light polypeptide (NfL) and major myelin proteins. Altogether, our results suggest that there might be an increased risk for the development of NDs after COVID-19 both via autoreactivity and virus–host PPIs.

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“…On the one hand, this supports the consistency of the cognitive impairment post-COVID syndrome, which has a relatively characteristic cognitive profile characterized by attention/processing speed deficits with or without associated episodic memory and executive function deficits. This has important implications for the differential diagnosis because the identification of patients after COVID-19 displaying other cognitive profiles with a predominant impairment of other cognitive domains beyond attention/processing speed (e.g., visuospatial, language) should suggest alternative diagnoses [19]. On the other hand, clustering analysis may be helpful in determining the optimal cutoff points for patient classification following an unsupervised strategy.…”

Section: Discussionmentioning

confidence: 99%

Development of criteria for cognitive dysfunction in post-COVID syndrome: the IC-CoDi-COVID approach

Matías‐Guiu

Herrera

González-Nosti

et al. 2022

Preprint

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BackgroundWe aimed to develop objective criteria for cognitive dysfunction associated with the post-COVID syndrome.MethodsFour hundred and four patients with post-COVID syndrome from two centers were evaluated with comprehensive neuropsychological batteries. The International Classification for Cognitive Disorders in Epilepsy (IC-CoDE) framework was adapted and implemented. A complementary data-driven approach based on unsupervised machine-learning clustering algorithms was also used to evaluate the optimal classification and cutoff points.ResultsAccording to the developed criteria, 41.2% and 17.3% of the sample were classified as having at least one cognitive domain impaired using -1 and -1.5 standard deviations as cutoff points. Attention/processing speed was the most frequently impaired domain. There were no differences in base rates of cognitive impairment between the two centers. Clustering analysis revealed two clusters according to the severity of cognitive impairment, but there was no difference in cognitive profiles. Cognitive impairment was associated with younger age and lower education levels, but not hospitalization.ConclusionsWe propose a harmonization of the criteria to define and classify cognitive impairment in the post-COVID syndrome. These criteria may be extrapolated to other neuropsychological batteries and settings, contributing to the diagnosis of cognitive deficits after COVID-19 and facilitating multicenter studies to guide biomarker investigation and therapies.

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“Brain Fog” by COVID-19 or Alzheimer’s Disease? A Case Report

Cited by 21 publications

References 48 publications

COVID-19 and risk of neurodegenerative disorders: A Mendelian randomization study

COVID-19 and risk of neurodegenerative disorders: A Mendelian randomization study

Systems Bioinformatics Reveals Possible Relationship between COVID-19 and the Development of Neurological Diseases and Neuropsychiatric Disorders

Development of criteria for cognitive dysfunction in post-COVID syndrome: the IC-CoDi-COVID approach

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