Brivaracetam, but not ethosuximide, reverses impairments in spatial memory in APP/PS1 mice. Aged APP/PS1 mice were administered brivaracetam by osmotic minipump or continuous delivery of ethosuximide (ETX) via drinking water. Four-week administration of brivaracetam (Briva) fully reversed memory impairments in APP/PS1 mice in the Morris water maze (A) and Probe Trial (B). Chronic (7-week) administration of ethosuximide did not improve performance in the Morris water maze or probe trial in APP/PS1 mice (C, D). For the Briva cohort, wild-type (WT) + vehicle: n = 11; WT + Briva: n = 11, APP/PS1 + vehicle: n = 15, APP/PS1 + Briva: n = 16. For chronic ETX therapy, WT + vehicle: n = 7, WT + ETX: n = 7, APP + vehicle: n = 6, APP + ETX: n = 7. *P < 0.05, ***P < 0.001, repeated-measures analysis of variance with post hoc comparisons. V1 through V4 indicate visible platform swim trials. + Indicates drug therapy; - indicates vehicle.