Objective: To study the effect of donepezil in treating patients with cognitive decline following coronary artery bypass graft (CABG) surgery.
Methods: Forty-four patients, with at least a 0.5 SD decline at 1 year post-CABG on at least one cognitive domain compared to their pre-CABG baseline score, were randomized to treatment with donepezil (titrated to 10 mg daily) or placebo in a 12-week double-blind, single center, randomized study. A composite cognitive change score served as the primary outcome. Secondary outcome measures included tests of memory, attention, psychomotor speed, and executive function.
Results: The composite cognitive outcome did not show significant treatment effects. Secondary measures varied in their sensitivity to donepezil effects with the largest effects seen on the Wechsler Visual Memory Scale-Delayed and Immediate recall tests. More than twice (52% vs. 22%) as many donepezil-treated patients showed a significant improvement compared with placebo patients on Delayed recall. Tests with weak effect sizes and minimal trends favoring donepezil were the Boston Naming and Digit Symbol. However, most of the other instruments (e.g., Digit Span, Trails B, and Controlled Word Association) showed no treatment benefits. More donepezil-treated than placebo-treated patients experienced diarrhea, but other adverse effects and safety measures did not differ between groups.
Conclusion: In the post-CABG mild cognitive decline setting, donepezil did not improve composite cognitive performance but improved some aspects of memory. Donepezil was well tolerated and had no significant effects on EKG parameters. Because of limitations such as small sample size and multiplicity of tests, these findings are preliminary but add to our knowledge of cholinergic effects in vascular mild cognitive decline.