REDUCED BASAL FOREBRAIN ATROPHY PROGRESSION IN DONEPEZIL-TREATED PRODROMAL ALZHEIMER'S DISEASE PATIENTS

Abstract

Acetylcholinesterase inhibitors remain the most effective drugs used for Alzheimer's Disease (AD). Recent evidence showed that basal forebrain pathology precedes both entorhinal pathology and memory impairment, moving forward the current model on the temporal sequence of pathological topographical events underlying AD. This study investigates the effect of one year Donepezil treatment on the rate of basal forebrain cholinergic system (BFCS) atrophy in prodromal AD patients. Prodromal AD patients participated in a double-blind, randomized, placebo-controlled parallel group design using Donepezil (10 mg/day) (N=88 Placebo, N=75 Donepezil). A recently developed technique for in-vivo assessment of BFCS atrophy rates on serial MRI scans has been used to identify Annualized Percentage Change (APC) of BFCS and global Grey Matter (GM) volumes. The Donepezil treated group showed a significantly reduced BFCS rate of atrophy (APC= -0.31) compared to the Placebo group (APC= -0.78, p=0.008). GM rate of atrophy was also significantly reduced in the Donepezil group compared to the Placebo group (p=0.047). Exploratory analyses conducted on specific BFCS subregions revealed greatest effects of Donepezil treatment on reducing rate of atrophy in the Nucleus Basalis of Meynert (NbM, p=0.013) and the medial septum/diagonal band (Ch1/2; p < 0.001). A trend towards significance was found for the posterior subdivision of the Nucleus basalis of Meynert (Ch4p; p =0.06).