Objectifying persistent subjective cognitive impairment following COVID-19 infection: cross-sectional data from an outpatient memory-clinic in Germany

OBJECTIVE: Subjective cognitive impairment is frequently reported by patients experiencing Post-COVID symptoms. 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 229 patients who voluntarily presented to our outpatient memory-clinic due to subjective cognitive impairment following 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 39% of the patients and 47% showed symptoms of moderate or severe depression. The APOE-ε4 allele was present in 32% of the patients. Higher rates of depressive symptoms (OR = 1.41, 95%-CI = 1.02-1.95) and higher burden of the APOE-ε4 allele (OR = 3.29, 95%-CI = 1.51-7.40) 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. CONCLUSIONS: In our study, subjective cognitive impairment following COVID-19 was more likely associated with high rates of depression rather than relatively low rates of objective cognitive performance. Thus, the study emphasizes the necessity for extensive neuropsychological testing and evaluation of depression when examining Post-COVID patients in clinical practice. Further, the link between objective cognitive impairment, depression and APOE-ε4 does not appear to be specific to Post-COVID symptoms. Therefore, depression- and APOE-ε4-mediated neurodegenerative pathomechanisms might be a promising therapeutical target.