Brain Fog reconsidered. Objectifying subjective cognitive impairment following COVID-19 infection.

Introduction Subjective cognitive impairment is frequently reported after COVID-19 infection. This study aims to assess objective impairment in attention, memory and executive functions among these patients. Further, we investigated potential determinants of objective cognitive impairment.

Methods In this cross-sectional study, standardized neuropsychological testing (Vienna Testing System), assessment of cognitive symptom aggravation, psychiatric anamnesis and psychometrics (BDI-II, Fatigue Severity Scale) were conducted in 240 patients who voluntarily to our outpatient memory-clinic, due to persisting subjective cognitive impairment after COVID-19. Blood samples were collected to assess peripheral immune markers (IL-6, CRP) and ApoE-ε4 genotype.

Results Objective cognitive impairment in at least one domain was present in 40% of the patients and 47% showed signs of moderate or severe depression. ApoE-ε34/44 was present in 30% of the patients. Higher rates of depressive symptoms (OR=1.39, 95%-CI=1.02-1.92) and ApoE-ε34/44 allele (OR=3.19, 95%-CI=1.43-7.31) predicted objective cognitive impairment, regardless of age, sex, years of formal education, time since infection, and medication for diabetes or hypertension. Fatigue severity, acute COVID-19 severity or inflammation markers had no impact. Moreover, subgroup analyses showed no evidence of an association between peripheral inflammation and cognitive performance, dependent on depressive symptoms or history of mental illness.

Conclusions Subjective cognitive impairment after COVID-19 infection was more likely associated with high rates of depression rather than objective cognitive performance. Further, we found no evidence that infection-associated parameters such as peripheral inflammation or acute infection severity has an impact on cognitive performance. Thus, the study emphasizes the necessity of extensive neuropsychological testing and evaluation of depression when examining Post-COVID patients in clinical practice. Moreover, the link between cognitive impairment, depression and ApoE-ε34/44 genotype does not appear to be specific to Post-COVID populations. Therefore, depression- and ApoE-ε34/44-mediated neurodegenerative pathomechanisms might be a promising therapeutical target.

Publication History

Article published online:
30 April 2025