Effects of long-term Donepezil therapy on rCBF of Alzheimer's patients

Background: The recent introduction of acetylcholinesterase inhibitors (AChEIs) therapy for Alzheimer's Disease (AD) has led to the need to assess the brain's response to the therapy on an objective, neurophysiological basis. Brain perfusion single photon emission computed tomography (SPECT) was used in an open-label study to evaluate the effect of chronic Donepezil administration to a group of patients affected by mild to moderate AD, compared to a group of AD patients not receiving AChEIs and kept under observation for a similar period. Methods: Twenty-five consecutive patients with probable AD (National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria) (19 women, 6 men; mean age: 74.2 +/- 7.2; mean Mini-Mental State Examination score, MMSE: 19.8 +/- 3.5) underwent (t(0)) brain SPECT with Tc-99m-hexamethylpropylene-amine-oxime by a brain-dedicated, high-resolution camera and were re-evaluated (t(1)) after I L 2.6 months of chronic Donepezil administration (5 mg/day) (treated group). Thirteen AD patients (9 women, 4 men, mean age: 71.4 +/- 5.7. MMSE score: 20.6 +/- 3.5) were not treated with AChEIs and served as controls (untreated group). They were subjected to the same evaluation after 13 1.4 months as the treated group. Statistical parametric mapping (SPM) was employed to analyse SPECT findings. Results: The MMSE score declined significantly (P < 0.01) from t(0) to t(1) both in untreated (from 20.6 +/- 3.5 to 17.8 +/- 4.4) and in treated (from 19.8 +/- 3.5 to 17.8 +/- 4.1) group. At t(0) the untreated group showed higher regional cerebral blood flow (rCBF) than the treated group in a frontal and a frontal-parietal region of the left hemisphere. Between t(0) and t(1), significant rCBF reduction was observed in the temporal lobe and occipital-temporal cortex of the left hemisphere in the untreated group, whereas no significant change was observed in the treated group. The rCBF of the two groups did not significantly differ at t(1). By covariate SPM analysis between t(0) and t(1) in treated patients, MMSE score changes correlated significantly with rCBF changes in a large left frontal-temporal region. Conclusions: Brain perfusion is preserved in AD patients undergoing chronic Donepezil therapy while it is reduced in untreated patients. SPECT is a promising tool with which to assess the impact of AChEI therapy on brain functioning of AD patients. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.