Quantitative EEG and perfusional single photon emission computed tomography correlation during long-term donepezil therapy in Alzheimer's disease

Objective: There is an increasing interest in the effects of the acetylcholinesterase inhibitors (AChEIs) in Alzheimer's disease (AD), as investigated by means of objective, neurophysiological tools. In an open-label study, we evaluated the neurophysiological effects of chronic administration of donepezil to AD patients, by means of a correlative approach between quantitative EEG (qEEG) and perfusional brain single photon emission computed tomography (SPECT). Methods: Sixteen patients (mean age: 74.8±7.9 years) with mild to moderate AD (MMSE score 13, mean: 20.7±4.6) underwent qEEG and SPECT examinations at the time of diagnosis (t0) and after approximately 1 year of donepezil therapy (t1). The brain SPECT (99mTc-hexamethylpropyleneamine oxime) was performed by means of a high-resolution SPECT camera; the qEEG was recorded from 19 scalp electrodes by average reference and digitized at 512 Hz. The mean frequency (MF) value of the mean power spectrum (fast Fourier transform) from 4 brain regions (one frontal and one temporal-parietal in each hemisphere) was chosen for statistical analysis. Changes in MMSE score and qEEG-MF values between t0 and t1 were assessed by analysis of variance. SPECT differences between t0 and t1, as well as the relationships between SPECT and qEEG changes, were assessed by statistical parametric mapping (SPM 99; height threshold: P=0.001 at cluster level). Results: Between t0 and t 1, the MMSE score significantly (P<0.05) decreased (from 20.7±4.64 to 19.1±5.09; 95% confidence interval: 1.14) and qEEG was unchanged. There was no regional perfusion decrease; a small area of relative perfusion increase was observed, including the right occipital cuneus and the left lingual gyrus. A positive correlation was found between the right frontal MF and brain perfusion in the left superior parietal lobule. A post hoc SPM analysis (height threshold: P=0.01) showed a positive correlation between brain perfusion and each of the 4 qEEG MF values in the left parietal lobe, including the precuneus, the superior parietal lobule, and the post-central gyrus. Conclusions: The posterior parietal region, which is involved in memory and attention, is often affected by hypoperfusion in AD, as a likely consequence of disconnection from the atrophic mesial temporal cortex. Metabolic activation induced by AChEIs may especially influence this disconnected but still not grossly impaired area, which could be one of the pathophysiological substrates of the cognitive effects of AChEIs. The modest topographical sensitivity of qEEG, reflecting the rather diffuse changes in AD, is further confirmed