Time of Day Effects on Inhibitory Functioning: Cognitive and Neural Evidence of Sundowning in Amnestic Mild Cognitive Impairment

Abstract

Background: Amnestic mild cognitive impairment (aMCI), a prodromal phase of Alzheimer’s disease (AD), is characterized by episodic memory dysfunction, but inhibitory deficits have also been commonly reported. Time of day (TOD) effects have been confirmed in 1) healthy aging on cognitive processes such as inhibitory control, and 2) on behavior in AD (termed the sundowning effect), but no such research has addressed aMCI. Objective: The present study examined the impact of TOD on the behavioral and electrophysiological correlates of inhibition in 54 individuals with aMCI and 52 healthy controls (HCs), all of morning chronotype. Methods: Participants were randomly assigned to complete two inhibition tasks (Go-NoGo and Flanker) during their optimal (morning) or non-optimal (evening) TOD, while electroencephalography was recorded. Results: Both tasks elicited changes in N2 and P3 event-related potential (ERP) components, which commonly index inhibitory functioning. Analyses showed that the Go-NoGo difference in P3 amplitude was reduced in individuals with aMCI relative to HCs. Compared to HCs, the Flanker difference in P3 amplitude was also reduced and coincided with more errors in the aMCI group. Notably, these behavioral and ERP differences were exaggerated in the non-optimal TOD relative to the optimal TOD. Conclusion: Findings confirm the presence of inhibition deficits in aMCI and provide novel evidence of sundowning effects on inhibitory control in aMCI. Results reinforce the need to consider the influences of TOD in clinical assessments involving individuals with aMCI.