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October 23, 2023
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Article

Unraveling brain fog in post-COVID syndrome: Relationship between subjective cognitive complaints and cognitive function, fatigue, and neuropsychiatric symptoms

Publicated to: EUROPEAN JOURNAL OF NEUROLOGY. 32 (1): - 2025-01-01 32(1), DOI: 10.1111/ene.16084

Authors:

Delgado-Alonso, C; Díez-Cirarda, M; Pagán, J; Pérez-Izquierdo, C; Oliver-Mas, S; Fernández-Romero, L; Martínez-Petit, A; Valles-Salgado, M; Gil-Moreno, M; Yus, M; Matías-Guiu, J; Ayala, J; Matias-Guiu, JA
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Affiliations

CENTRO INVEST. SIMULACIÓN COMPUTACIONAL. Universidad Politécnica de Madrid - Author
Hosp Clin San Carlos, Dept Neurol, C Prof Martin Lagos, Madrid 28040, Spain - Author
Univ Complutense Madrid, Hosp Clin San Carlos, Hlth Res Inst San Carlos IdISCC, Dept Neurol, Madrid, Spain - Author
Univ Complutense Madrid, Hosp Clin San Carlos, Hlth Res Inst San Carlos IdISCC, Dept Radiol, Madrid, Spain - Author
Univ Complutense, Dept Automat Architecture & Automat, Madrid, Spain - Author
Univ Extremadura, Univ Ctr Plasencia, Dept Agron & Forestry Environm Engn, Plasencia, Spain - Author
Universidad Complutense de Madrid - Author
Universidad de Extremadura - Author
Universidad Politécnica de Madrid - Author
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Abstract

Background and purpose: “Brain fog” is a frequent and disabling symptom that can occur after SARS-CoV-2 infection. However, its clinical characteristics and the relationships among brain fog and objective cognitive function, fatigue, and neuropsychiatric symptoms (depression, anxiety) are still unclear. In this study, we aimed to examine the characteristics of brain fog and to understand how fatigue, cognitive performance, and neuropsychiatric symptoms and the mutual relationships among these variables influence subjective cognitive complaints. Methods: A total of 170 patients with cognitive complaints in the context of post-COVID syndrome were evaluated using a comprehensive neuropsychological protocol. The FLEI scale was used to characterize subjective cognitive complaints. Correlation analysis, regression machine-learning algorithms, and mediation analysis were calculated. Results: Cognitive complaints were mainly attention and episodic memory symptoms, while executive functions (planning) issues were less often reported. The FLEI scale, a mental ability questionnaire, showed high correlations with a fatigue scale and moderate correlations with the Stroop test, and anxiety and depressive symptoms. Random forest algorithms showed an R2 value of 0.409 for the prediction of FLEI score, with several cognitive tests, fatigue and depression being the best variables used in the prediction. Mediation analysis showed that fatigue was the main mediator between objective and subjective cognition, while the effect of depression was indirect and mediated through fatigue. Conclusions: Brain fog associated with COVID-19 is mainly characterized by attention and episodic memory, and fatigue, which is the main mediator between objective and subjective cognition. Our findings contribute to understanding the pathophysiology of brain fog and emphasize the need to unravel the main mechanisms underlying brain fog, considering several aspects.
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Keywords

covid-19depressionfatiguelong covidscaleCognitiveCovid-19DepressionFatigueImpairmentLong covid

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal EUROPEAN JOURNAL OF NEUROLOGY due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2025, it was in position 59/286, thus managing to position itself as a Q1 (Primer Cuartil), in the category Clinical Neurology.

Independientemente del impacto esperado determinado por el canal de difusión, es importante destacar el impacto real observado de la propia aportación.

Según las diferentes agencias de indexación, el número de citas acumuladas por esta publicación hasta la fecha 2026-04-26:

  • Google Scholar: 9
  • WoS: 20
  • Scopus: 20
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Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2026-04-26:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 68.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 67 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 166.
  • The number of mentions on the social network X (formerly Twitter): 133 (Altmetric).
  • The number of mentions in news outlets: 11 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
  • Assignment of a Handle/URN as an identifier within the deposit in the Institutional Repository: https://oa.upm.es/93732/

As a result of the publication of the work in the institutional repository, statistical usage data has been obtained that reflects its impact. In terms of dissemination, we can state that, as of

  • Views: 32
  • Downloads: 25
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Project objectives

Los objetivos perseguidos en esta aportación fueron analizar las características clínicas del fenómeno denominado "brain fog" en el síndrome post-COVID, determinar la relación entre las quejas cognitivas subjetivas y el rendimiento cognitivo objetivo, evaluar la influencia de la fatiga y los síntomas neuropsiquiátricos (depresión y ansiedad) en dichas quejas, caracterizar las correlaciones entre las variables cognitivas, la fatiga y los síntomas emocionales mediante análisis estadísticos y algoritmos de aprendizaje automático, y establecer el papel mediador de la fatiga en la relación entre la cognición objetiva y subjetiva. Además, se buscó contribuir a la comprensión de la fisiopatología del "brain fog" para identificar los mecanismos subyacentes que lo explican.
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Most relevant results

El estudio analiza las características del “brain fog” en el síndrome post-COVID y su relación con la función cognitiva, fatiga y síntomas neuropsiquiátricos. Los resultados más relevantes son: (1) las quejas cognitivas se centran principalmente en síntomas de atención y memoria episódica, siendo menos frecuentes los problemas en funciones ejecutivas como la planificación; (2) la escala FLEI mostró correlaciones altas con la fatiga y moderadas con el test de Stroop, ansiedad y depresión; (3) los algoritmos de random forest predijeron la puntuación FLEI con un R2 de 0.409, destacando pruebas cognitivas, fatiga y depresión como variables clave; (4) el análisis de mediación indicó que la fatiga es el principal mediador entre la cognición objetiva y subjetiva, mientras que la depresión actúa indirectamente a través de la fatiga.
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