MODERATE VOLUME REDUCTION BUT REDUCED CONNECTIVITY AND ARTERIAL PERFUSION IN THE HIPPOCAMPUS IN LONG COVID

While research into Long COVID has consistently highlighted episodic memory deficits, evidence regarding structural hippocampal damage has remained contradictory. This study addressed this gap by investigating hippocampal volume, white matter integrity, and arterial brain perfusion in 93 patients with persistent cognitive symptoms compared to 36 healthy controls who recovered fully from COVID-19. Utilizing a comprehensive multimodal imaging approach, including manual and automated 3D T1 MRI volumetry, Tract-Based Spatial Statistics (TBSS), and non-invasive Arterial Spin Labeling (ASL), we mapped physiological changes alongside standardized neuropsychological assessments. Although patients exhibited a statistically significant but moderate 11% reduction in hippocampal volume, the more striking findings involved microstructural and hemodynamic alterations. Specifically, the Long COVID cohort demonstrated significantly lower Fractional Anisotropy (FA), higher Radial Diffusivity (RD), and reduced Cerebral Blood Flow (CBF) within the posterior hippocampus and parahippocampal cortex. These results suggest that even when gross hippocampal volume appears relatively spared, underlying neurovascular dysfunction and compromised white matter integrity in the hippocampal formation might be the driver of cognitive impairment. This evidence supports the hypothesis that altered microcirculation and subsequent disruptions in oxygen and nutrient supply represent a primary pathophysiological mechanism for the neurological symptoms of acute COVID-19. Furthermore, such cortical vascular and microstructural vulnerability of the white likely underlie the prolonged neurological sequelae, offering a clearer mechanisms framework for the persistent memory deficits reported by millions of Long COVID survivors worldwide. Funded by Spanish Instituto de Salud Carlos III Ref. PI21/00010.