Affiliations: [a] Berenson-Allen Center for Non-invasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| [b] Department of Neurology, Danish Dementia Research Centre (DDRC), Rigshospitalet, University of Copenhagen, Denmark
| [c] Department of Medicine, Surgery and Neuroscience, Neurology and Clinical Neurophysiology Section, Brain Investigation and Neuromodulation Lab, (Si-BIN Lab), University of Siena, Italy
| [d] Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
Correspondence:
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Correspondence to: Daniel Press, MD, Associate Professor in Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, KS-153, Boston, MA 02215, USA. Tel.: +1 617 667 0459; Fax: +1 617 667 7981; E-mail: dpress@bidmc.harvard.edu.
Note: [1] These authors contributed equally to this work.
Abstract: Seizures occur at a higher frequency in people with Alzheimer’s disease (AD) but overt, clinically obvious events are infrequent. Evidence from animal models and studies in mild cognitive impairment suggest that subclinical epileptic discharges may play a role in the clinical and pathophysiological manifestations of AD. In this feasibility study, the neurophysiological and cognitive effects of acute administration of levetiracetam (LEV) are measured in patients with mild AD to test whether it could have a therapeutic benefit. AD participants were administered low dose LEV (2.5 mg/kg), higher dose LEV (7.5 mg/kg), or placebo in a double-blind, within-subject repeated measures study with EEG recorded at rest before and after administration. After administration of higher dose of LEV, we found significant decreases in coherence in the delta band (1–3.99 Hz) and increases in the low beta (13–17.99 Hz) and the high beta band (24–29.99 Hz). Furthermore, we found trends toward increased power in the frontal and central regions in the high beta band (24–29.99 Hz). However, there were no significant changes in cognitive performance after this single dose administration. The pattern of decreased coherence in the lower frequency bands and increased coherence in the higher frequency bands suggests a beneficial effect of LEV for patients with AD. Larger longitudinal studies and studies with healthy age-matched controls are needed to determine whether this represents a relative normalization of EEG patterns, whether it is unique to AD as compared to normal aging, and whether longer term administration is associated with a beneficial clinical effect.
Keywords: Alzheimer’s disease, coherence, EEG, levetiracetam, power
