Quantitative EEG changes in Alzheimer patients during long-term donepezil therapy

Twenty patients affected with probable mild-to-moderate Alzheimer's disease (AD; NINCDS-ADRDA criteria; 14 women and 6 men, mean age 75.2 ± 7.1 years) who regularly received an oral acetylcholinesterase inhibitor (AChEI; donepezil 5 mg/day; Dz group) were compared with a control group of 11 AD patients (6 women and 5 men, mean age 73.5 ± 6.0 years) diagnosed and followed up in the pre-AChEIs era (C group). At basal evaluation (t0), the 2 groups were comparable for age, education, and severity of disease (Global Deterioration Scale). All patients underwent quantitative EEG (qEEG, average reference, 10-20 International System), and were reexamined about 1 year later (t1; i.e., after 12.3 ± 3.6 months the Dz group, and after 13.7 ± 3.9 months the C group). Log-transformed values of two qEEG bands, i.e. 2-6 and 6.5-12 Hz, were averaged between adjacent channels (frontal F3 and F7, F4 and F8; parietotemporal P3 and T7, P4 and T8) to obtain a qEEG ratio (6.5-12/2-6 Hz.) from one frontal and one temporoparietal region in each hemisphere. Neuropsychological impairment was summarized by the Mini-Mental Status Examination (MMSE). At t0, both the MMSE score and the qEEG ratio values were somewhat higher in the C than in the Dz group, although nonsignificantly. Between t0 and t1, the MMSE score decreased significantly (p < 0.01) more in the C group (-4.36 ± 2.25) than in the Dz group (-1.45 ± 2.16), as did the qEEG ratio in the right frontal region (p < 0.01), whereas in the left frontal region the significance level was not reached (p =0.02). Between t0 and t1, the qEEG ratio difference in both frontal regions and in the right temporoparietal region significantly correlated with the MMSE difference (p < 0.01), but neither with time between examinations nor with the difference on the Visual Search Test score. Long-term treatment with Dz led to a lesser deterioration of qEEG, paralleling a milder neuropsychological decline. The effect was significant in frontal regions, possibly because they are relatively spared during the mild-to-moderate phases of the disease.