The Cognitive and Structural Brain Impacts Following COVID-19 Recovery

Abstract

The hippocampus appears to be a vulnerable region to structural and functional damage from COVID-19. The severe respiratory symptoms may be one mechanism that leads to long-term cognitive difficulties related to the hippocampus following infection. However, studies that directly evaluate respiratory symptom severity during the acute infection using sensitive cognitive tests in conjunction with neuroimaging are limited. This dissertation included 79 participants ranging in respiratory symptom severity during COVID-19 infection, from no reported respiratory symptoms, reported respiratory symptoms, and respiratory symptoms resulting in hospitalization. Control participants without reported COVID-19 diagnosis were used for comparison. Study 1 used sensitive cognitive tests that rely on the hippocampus, in addition to tests of executive functioning. Pronounced difficulty on pattern separation, associative memory, and switching was observed among the hospitalized participants. Neurofilament light (NfL) a biomarker for axonal damage was specifically related to aspects of executive function. Study 2 analyzed global and regional perfusion using arterial spin labelling (ASL) and indicated lower perfusion also among the hospitalized group compared to controls and those with less severe respiratory symptoms. Global perfusion was specifically correlated with pattern separation performance, and not with other measures of cognitive performance. Study 3 evaluated white matter integrity in the medial temporal lobe (MTL) using diffusion tensor imaging (DTI), including the fornix and posterior cingulum. Group differences in multiple measures of diffusion did not emerge, and most diffusion measures were not correlated with cognitive performance. Taken together, cognitive difficulties were present even over a year from infection among the most severe cases, and it appears that disruption to cortical perfusion might be one mechanism that underlies these long-COVID cognitive sequalae.