Effect of <i>ApoE</i> Genotype on Response to Donepezil in Patients with Alzheimer’s Disease

<i>Background/Aims: </i>The possible influence of apolipoprotein E <i>(ApoE)</i> genotype on the response to acetylcholinesterase inhibitor therapy in patients with Alzheimer’s disease (AD) remains a matter of controversy. In order to address this issue, we investigated the effects of <i>ApoE</i> genotype on the clinical response to donepezil in patients with mild to moderate AD. <i>Methods: </i>An open study was carried out in 51 patients with probable AD who were treated with 5–10 mg of donepezil per day for 48 weeks.<i> Results: </i> Eighteen (35.3%) of the 51 patients had 1 or 2 <i>ApoE </i>Ε<i>4</i> alleles. <i>ApoE </i>Ε<i>4</i> carriers with AD showed a mean 1.1-point increase from the baseline score of 23.9 on the 70-point Alzheimer’s Disease Assessment Scale-Cognitive Component at 48 weeks, while the <i>ApoE </i>Ε<i>4</i> noncarrier group showed a 3.1-point increase from the baseline score of 22.5 (p = 0.03). The <i>ApoE </i>Ε<i>4</i> carrier group exhibited a mean 0.13-point worsening from the baseline score of 0.97 on the Korean Instrumental Activities of Daily Living at 48 weeks, while the <i>ApoE </i>Ε<i>4</i> noncarrier group exhibited a 0.17-point worsening from the baseline score of 0.64 (p = 0.05). <i>Conclusion: </i>AD patients who carry the <i>ApoE </i>Ε<i>4</i> allele may respond more favorably to donepezil than Ε<i>4</i> noncarriers.