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

Claudio Babiloni, Emanuele Cassetta, Gloria Dal Forno, Claudio Del Percio, Florinda Ferreri, Raffaele Ferri, Bartolo Lanuzza, Carlo Miniussi, Davide V. Moretti, Flavio Nobili, Roberto D. Pascual-Marqui, Guido Rodriguez, Gian Luca Romani, Serenella Salinari, Orazio Zanetti, Paolo M. Rossini

Research output: Contribution to journalArticlepeer-review


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 eyes-closed 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.

Original languageEnglish
Pages (from-to)1650-1665
Number of pages16
Issue number4
Publication statusPublished - Jul 15 2006


  • Alpha rhythm
  • Donepezil
  • Electroencephalography (EEG)
  • Low resolution brain electromagnetic tomography (LORETA)
  • Mild Alzheimer's disease (mild AD)

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Neurology


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