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 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.
Babiloni
Claudio
C
Dip. Fisiologia Umana e Farmacologia, Univ. La Sapienza, Rome, Italy. claudio.babiloni@uniroma1.it
Cassetta
Emanuele
E
Dal Forno
Gloria
G
Del Percio
Claudio
C
Ferreri
Florinda
F
Ferri
Raffaele
R
Lanuzza
Bartolo
B
Miniussi
Carlo
C
Moretti
Davide V
DV
Nobili
Flavio
F
Pascual-Marqui
Roberto D
RD
Rodriguez
Guido
G
Luca Romani
Gian
G
Salinari
Serenella
S
Zanetti
Orazio
O
Rossini
Paolo M
PM
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
D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D000077265:Donepezil