Abstract
IntroductionThere are no published data on prospective clinical studies on drug treatment options for sleep‐related epileptiform spiking in Alzheimer's disease (AD).MethodsUsing video‐EEG with hippocampal electrodes in 17 APP/PS1 transgenic male mice we assessed the effects of donepezil and memantine, anti‐seizure drugs levetiracetam and lamotrigine, gamma‐secretase inhibitor semagacestat, anti‐inflammatory minocycline and adenosine receptor antagonist istradephylline on density of cortical and hippocampal spikes during sleep.ResultsLevetiracetam decreased the density of hippocampal giant spikes and cortical spikes. Lamotrigine reduced cortical single spikes and spike‐wave discharges but dramatically increased hippocampal giant spikes. Memantine increased cortical single spikes and spike‐wave discharges dose‐dependently. Memantine and istradephylline decreased total sleep time while levetiracetam increased it. Lamotrigine decreased REM sleep duration. Other drugs had no significant effects.DiscussionLevetiracetam appears promising for treating sleep‐related epileptiform spiking in AD while lamotrigine should be used with caution. Donepezil at low doses appeared neutral but the memantine effects warrant further studies.
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