Neuropsychological profiles and cerebral glucose metabolism in neurocognitive Long COVID-syndrome

Abstract

During the Corona Virus Disease 2019 (COVID-19) pandemic, Long COVID-syndrome, which impairs patients through cognitive deficits, fatigue, and exhaustion, has become increasingly relevant. Its underlying pathophysiology, however, is unknown. In this study, we assessed cognitive profiles and regional cerebral glucose metabolism as a biomarker of neuronal function in outpatients suffering from long-term neurocognitive symptoms after COVID-19. Methods: Outpatients seeking neurological counseling with neurocognitive symptoms persisting for more than three months after polymerase chain reaction (PCR)-confirmed COVID-19 were included prospectively between June 16, 2020, and January 29, 2021. Patients (n = 31, 54±2.0 years) in the long-term phase after COVID-19 (202±58 days after positive PCR) were assessed with a neuropsychological test battery. Cerebral ¹⁸F-FDG PET imaging was performed in 14/31 patients. Results: Patients self-reported impaired attention, memory, and multitasking abilities (31/31), word-finding difficulties (27/31), and fatigue (24/31). Twelve of 31 patients could not return to the previous level of independence/employment. For all cognitive domains, average group results of the neuropsychological test-battery showed no impairment, but deficits (z-score<-1.5) were present on single-patient level mainly in the domain of visual memory (in 7/31; other domains ≤2/31). Mean MoCA performance (27/30 points) was above the cutoff-value for detection of cognitive impairment (< 26 points), although 9/31 patients performed slightly below this level (23-25 points). In the subgroup of patients who underwent ¹⁸F-FDG PET, we found no significant changes of regional cerebral glucose metabolism. Conclusion: Long COVID patients self-report uniform symptoms hampering their ability to work in a relevant fraction. However, cognitive testing showed minor impairments only on single-patient level approximately six months after the infection, whereas functional imaging revealed no distinct pathological changes. This clearly deviates from previous findings in subacute COVID-19 patients, suggesting that underlying neuronal causes are different and possibly related to the high prevalence of fatigue.