Donepezil for cognitive decline following coronary artery bypass surgery: a pilot randomized controlled trial.
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.


CONCLUSIONS
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.
Doraiswamy
P Murali
PM
Department of Psychiatry, Center for the Study of Aging, and Duke Heart Center, Duke University Medical Center, Durham, North Carolina, USA. dorai001@mc.duke.edu
Babyak
Michael A
MA
Hennig
Therese
T
Trivedi
Ranak
R
White
William D
WD
Mathew
Joseph P
JP
Newman
Mark F
MF
Blumenthal
James A
JA
D000368:Aged; D002315:Cardiopulmonary Bypass / Q000009:adverse effects / Q000523:psychology; D003072:Cognition Disorders / Q000175:diagnosis / Q000188:drug therapy*; D001026:Coronary Artery Bypass / Q000009:adverse effects* / Q000523:psychology; D000077265:Donepezil; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007189:Indans / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects; D011939:Mental Recall / Q000187:drug effects; D008875:Middle Aged; D009483:Neuropsychological Tests; D018697:Nootropic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D011183:Postoperative Complications / Q000175:diagnosis / Q000188:drug therapy*; D014888:Wechsler Scales
D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D000077265:Donepezil