Acetylcholinesterase inhibitor (donepezil hydrochloride) reduces heart rate variability

An acetylcholinesterase inhibitor (donepezil hydrochloride) has recently been used for the treatment of senile dementia of Alzheimer type. The effect of this acetylcholinesterase inhibitor on the autonomic nervous control of the heart was investigated in 17 patients with senile dementia of Alzheimer type. Donepezil administration did not change the plasma concentration of norepinephrine or epinephrine. Twenty-four hour electrocardiogram monitoring was performed, and heart rate variability before and 6 weeks after treatment with donepezil (5 mg per orally) was determined. The heart rate averaged over 24 h was reduced slightly from 74.1 +/- 2.7 beats/min before treatment to 71.1 +/- 2.3 beats/min after treatment. Low (0.04-0.15 Hz) and high (0.15-0.40 Hz) frequency components were reduced significantly with treatment. Ultralow (0.0001-0.003 Hz) and very low (0.003-0.04 Hz) frequency components were not affected. The reduction in the high frequency (41.9 +/- 7.4%) component was greater (p < 0.03) than the reduction in the low frequency (18.6 +/- 10.7%) component. It therefore appears that acetylcholinesterase inhibitor reduces the 1-30 s modulation of heart rate variability but that it has no influence on the much longer 1 min-1 h fluctuation.