Treating Hyperexcitability in AD With Levetiracetam

This is a randomized, placebo-controlled crossover study. Participants with early Alzheimer's Disease (AD) will be tested in a double-blind crossover design with placebo, low-dose levetiracetam (LEV) 125 mg twice daily or high-dose LEV 500mg twice daily. These results will be contrasted with results from a demographically similar control group who will undergo baseline testing only, without any intervention, to establish a comparison norm for the AD group.

Each subject will undergo four screening and baseline visits consisting of a baseline neurological, medical, and cognitive evaluation. If amyloid status is unknown in AD patients, the participant will have an amyloid PET scan. Additional baseline measures include: a high density electroencephalogram (EEG); a 24 hour ambulatory EEG; functional magnetic resonance imaging (fMRI); neuropsychological testing; and transcranial magnetic stimulation with electromyogram (EMG) and EEG measures to assess cortical excitability. AD participants will be randomized to one of six possible groups that consists of a varying order of 3 treatment periods (LEV 125 mg, LEV 500 mg and placebo). The group assignments will be counterbalanced across subjects. Each treatment period will last for 4 weeks with a 4 week washout between treatments. All participants will be assessed prior to initiation of a treatment period (with the initial assessment occurring as part of the baseline assessment) and at the end of each treatment period. The following measures will be repeated as done at baseline at these time points: fMRI; neuropsychological testing; and TMS-EMG-EEG. AD participants will be enrolled for approximately 5 months.