Donepezil effects on sources of cortical rhythms in mild Alzheimer's disease: Responders vs. Non-Responders.

Acetylcholinesterase inhibitors (AChEI) such as donepezil act in
mild Alzheimer’s disease (AD) by increasing cholinergic tone.
Differences in the clinical response in patients who do or do not
benefit from therapy may be due to different functional features
of the central neural systems. We tested this hypothesis using
cortical electroencephalographic (EEG) rhythmicity. Resting eyesclosed
EEG data were recorded in 58 mild AD patients (Mini
Mental State Examination [MMSE] range 17– 24) before and
approximately 1 year after standard donepezil treatment. Based
on changes of MMSE scores between baseline and follow-up, 28
patients were classified as ‘‘Responders’’ (MMSEvar 0) and 30
patients as ‘‘Non-Responders’’ (MMSEvar <0). EEG rhythms of
interest were delta (2– 4 Hz), theta (4– 8 Hz), alpha 1 (8–10.5
Hz), alpha 2 (10.5–13 Hz), beta 1 (13– 20 Hz), and beta 2 (20– 30
Hz). Cortical EEG sources were studied with low-resolution brain
electromagnetic tomography (LORETA). Before treatment, posterior
sources of delta, alpha 1 and alpha 2 frequencies were greater
in amplitude in Non-Responders. After treatment, a lesser
magnitude reduction of occipital and temporal alpha 1 sources
characterized Responders. These results suggest that Responders
and Non-Responders had different EEG cortical rhythms. Donepezil
could act by reactivating existing yet functionally silent
cortical synapses in Responders, restoring temporal and occipital
alpha rhythms.