title: Donepezil effects on sources of cortical rhythms in mild Alzheimer's disease: Responders vs. Non-Responders.
abstract: 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 >or=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.
authors.affiliation: Dip. Fisiologia Umana e Farmacologia, Univ. La Sapienza, Rome, Italy. claudio.babiloni@uniroma1.it
authors.forename: Claudio
authors.initials: C
authors.lastname: Babiloni
authors.forename: Emanuele
authors.initials: E
authors.lastname: Cassetta
authors.forename: Gloria
authors.initials: G
authors.lastname: Dal Forno
authors.forename: Claudio
authors.initials: C
authors.lastname: Del Percio
authors.forename: Florinda
authors.initials: F
authors.lastname: Ferreri
authors.forename: Raffaele
authors.initials: R
authors.lastname: Ferri
authors.forename: Bartolo
authors.initials: B
authors.lastname: Lanuzza
authors.forename: Carlo
authors.initials: C
authors.lastname: Miniussi
authors.forename: Davide V
authors.initials: DV
authors.lastname: Moretti
authors.forename: Flavio
authors.initials: F
authors.lastname: Nobili
authors.forename: Roberto D
authors.initials: RD
authors.lastname: Pascual-Marqui
authors.forename: Guido
authors.initials: G
authors.lastname: Rodriguez
authors.forename: Gian
authors.initials: G
authors.lastname: Luca Romani
authors.forename: Serenella
authors.initials: S
authors.lastname: Salinari
authors.forename: Orazio
authors.initials: O
authors.lastname: Zanetti
authors.forename: Paolo M
authors.initials: PM
authors.lastname: Rossini
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology*; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000503:physiopathology*; D003627:Data Interpretation, Statistical; D000077265:Donepezil; D004569:Electroencephalography / Q000187:drug effects*; D005260:Female; D006801:Humans; D007189:Indans / Q000627:therapeutic use*; D015225:Magnetoencephalography / Q000187:drug effects*; D008297:Male; D009483:Neuropsychological Tests; D018697:Nootropic Agents / Q000627:therapeutic use*; D010880:Piperidines / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales
chemical_list: D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D000077265:Donepezil