Cognitive Impairment and Brain Metabolic Changes in Post-Acute Sequelae of COVID-19: Insights From an [ 18 F]FDG PET/CT Cohort Study

Abstract

Purpose: Neurological symptoms often prominent in post-acute sequelae of COVID-19 (PASC) necessitate deeper understanding. Our objective was to investigate brain metabolism in PASC and examine correlations with neurological symptoms during both the acute and chronic stages.

Methods: Eighty-seven adults experiencing PASC with neurocognitive symptoms were recruited in the PERSICOR prospective study and examined using brain [ 18 F]FDG PET/CT. Comprehensive clinical variables including neurocognitive symptoms were evaluated. PET images were compared voxel-wise with SPM12 software ( P < 0.05, false discovery rate corrected) and volume-of-interest basis (BrainVisa software) with those of 55 healthy controls recruited before COVID-19 pandemic. We also investigated differences in brain metabolism according to the time interval after acute COVID-19. The correlation between brain metabolism and neurocognitive symptoms was assessed.

Results: Frequently reported neurological symptoms included concentration difficulties (79%) and immediate/working memory impairments (66%). Significant hypometabolism was identified in regions previously identified in PASC: left fusiform gyrus (33% of patients), amygdala (23% on left, 28% on right), parahippocampal area (25% left, 24% right), and vermis (22%). The most substantial metabolism decreases were observed in the pons (5.5% decrease in the whole patient group vs controls) and right amygdala (-4.2%). Concentration and memory impairments correlated with decreased metabolism in prefrontal and mesial/inferior temporal areas, respectively ( P < 0.01 for both). A shorter interval between PET imaging and the acute phase of COVID-19 correlated with reduced glucose metabolism in the brainstem, thalamus, mesiotemporal lobe, frontobasal cortex, and olfactory bulb ( P < 10 -3 ).

Conclusions: This study underscores the links between neurological symptoms and cerebral hypometabolism in specific regions in PASC. These findings illuminate the complex neuropathophysiological mechanisms of PASC and pave the way for potential therapeutic interventions.