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

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.