Emotion Reactivity and Cerebrovascular Burden in Late-Life GAD: A Neuroimaging Study

Abstract

Generalized anxiety disorder (GAD) in older adults is associated with persistent deficits in emotion reactivity (ER) and regulation, yet the neural basis of these deficits has not been explored. This study focuses on the neural basis of ER deficits in late-life GAD and the association with cerebrovascular burden. Twenty elderly nonanxious participants and 17 late-life GAD participants were included. The faces-shapes functional magnetic resonance imaging task was used to assess ER; the Hamilton Anxiety Rating Scale and the Penn State Worry Questionnaire to measure global anxiety and worry, respectively; linear regression models to examine the association between ER and global anxiety severity and between ER and worry severity; and mediation analysis to explore the effect of ER on the relationship between global anxiety/worry severity and cerebrovascular burden. A positive association was found between ER and global anxiety in the left parahippocampus, left and right precuneus, and right superior occipital gyrus. A negative association was found between ER and worry severity in the left and right precuneus. The association between cerebrovascular burden and anxiety/worry severity was indirectly mediated by increased ER in limbic and paralimbic areas and by decreased ER in prefrontal regulatory regions. These results indicate that ER is associated with different neural activation patterns for worry and global anxiety and that ER-related functional connectivity indirectly mediates the relationship between cerebrovascular burden and late-life GAD. This latter result supports a yet-unexplored cerebrovascular pathway involved in the pathophysiology of late-life anxiety.