Alterações cognitivas e polimorfismo da apolipoproteína E (APOE) em pacientes com neurocovid longo

Abstract

Neurological manifestations associated with COVID-19 have been described since the beginning of the pandemic. In addition to the general neurological manifestations, cognitive complaints and cognitive impairment associated with COVID-19 have been described in the acute/subacute phases of the disease (<12 weeks of infection) and after these phases, in a condition that has been named Long-Covid. Apolipoprotein E (apoE) is important in cholesterol transport, is related to the risk of sporadic Alzheimer's disease, is encoded by the APOE gene on the long arm of chromosome 19, and comprises three allelic variants (E2, E3, and E4). Regarding the investigation of the APOE gene polymorphism in patients with COVID-19, more severe COVID-19 conditions were related to the presence of the E4 allele. To the best of our knowledge, only one publication from our group evaluated cognitive manifestations after COVID-19 and correlated them with polymorphisms of the APOE gene. The aim of our study was to investigate whether the APOE gene polymorphism is related to cognitive manifestations in patients with long-term Covid. This cross-sectional study was carried out with patients with COVID-19, treated as outpatients in Fortaleza, between July 2020 and April 2022. In addition to a standardized clinical record, tests for cognitive, psychiatric and functional assessment were applied. Patients were classified cognitively as normal, subjective cognitive decline (SCD), mild cognitive impairment (MCI) or dementia. These last three groups were brought together under the term cognitive decline (CD). Peripheral blood tubes were collected to investigate the polymorphism of the APOE gene. The final number of patients included in this study was 219, evaluated, on average, 4.5 months after COVID-19. There was a predominance of females (64.7%). Mean age was 46 ± 15 years, with most patients having more than 8 years of schooling (N = 176; 80.4%). Most patients were not hospitalized in the acute phase of the disease (74.7%). Most patients (N = 143; 64.7%) had symptoms of memory impairment as their main complaint, and cognitive changes were the main complaint in our study, even in mild cases of COVID-19 in a mostly outpatient population. The cognitive decline group had a higher frequency of the E4 allele compared to the normal group (30.6 vs 16.4%, respectively, p=0.038). The CD group also showed a higher frequency of sleep disorders compared to the normal group (35.7 vs 17.1%, respectively, p=0.004) and a higher frequency of anxiety symptoms compared to the normal group (30.8 vs 17. 1%, respectively, p=0.028). In this study, memory complaints were common after the acute and subacute phases of the disease. Our study also found a higher frequency of sleep complaints and anxiety symptoms in the CD group. In our study, individuals 10 with cognitive decline did not have a higher frequency of depression. Regarding the subtype of cognitive decline found, most patients had subjective cognitive decline. The scores of the cognitive assessment batteries did not show differences between the groups with and without cognitive decline, preventing us from drawing a cognitive profile with the most affected cognitive domains in the present study. Longitudinal follow-up of these patients is essential to determine the duration of this cognitive impairment. Also, the neuropsychological evaluation of these patients can contribute to a better characterization of DCS or MCI and determination of the most affected cognitive domains. Future studies evaluating biomarkers of neurodegenerative diseases in cerebrospinal fluid or plasma may bring a link between COVID-19 and the onset or worsening of neurodegenerative diseases.