Comparative neurocognitive effects of commonly used sedative agents in aged mice

Sedative agents are widely used in older patients, but their comparative neurocognitive effects remain incompletely understood. Aging-related vulnerability of the brain may contribute to differential neurocognitive responses following sedative exposure. This study investigated the effects of commonly used sedative agents on cognitive function in aged mice. Male mice aged 24 months were assigned to control, remimazolam, dexmedetomidine, midazolam, or propofol groups. Sedation, defined as loss of the righting reflex, was maintained for 1h with each agent. Cognitive function was assessed using the novel object recognition test for recognition memory and the Y-maze for spatial working memory at 1, 7, and 30 days after sedation. Recognition memory showed no significant group effect or group-time interaction, although a significant effect of time was observed (P = 0.009). In contrast, significant effects of group, time, and group-time interaction were observed in Y-maze spontaneous alternation performance (all P < 0.05). At days 1 and 7, propofol showed significantly lower alternation performance compared with control (OR = 0.537 and 0.576, respectively; both P < 0.001), whereas no significant differences were observed between the other sedative groups and the control group. At day 30, no between-group differences were observed. These findings suggest that commonly used sedative agents demonstrated largely comparable neurocognitive profiles in aged mice. Recognition memory showed no significant group differences at all time points, whereas propofol was associated with transient reductions in spatial working memory at days 1 and 7, suggesting that sedative-related neurocognitive effects may be domain-specific and time-dependent in the aged brain.