Effects of long-term Donepezil therapy on rCBF of Alzheimerʹs patients

Background: The recent introduction of acetylcholinesterase inhibitors (AChEIs) therapy for Alzheimerʹs Disease (AD) has led to the need to assess the brainʹs 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 (t0) brain SPECT with 99mTc-hexamethylpropylene-amine-oxime by a brain-dedicated, high-resolution camera and were re-evaluated (t1) after 11±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 t0 to t1 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 t0, 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 t0 and t1, 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 t1. By covariate SPM analysis between t0 and t1 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.