Effect Of ApoE Genotype On Response To Donepezil In Elderly Patients With Mild Cognitive Impairment

Objective1. To analyze the ApoE allele distribution in in elderly patients with mild cognitive impairment(MCI).2. To evaluate the curative effect of donepezil in the whole elderly patients with mild cognitive impairment.3. To investigate the possible effect of ApoE genotype on the treatment of donepezil in elderly patients with mild cognitive impairment(MCI).Methods1. Detect Apolipoprotein E gene polymorphism in 92 elderly patients with MCI by the standardized procedures of Polymerase Chain Reaction–Restriction Fragment Length Polymorphism (PCR-RFLP). Preliminary estimates the Apolipoprotein E (ApoE) genotypes and its alleles frequencies distribution in elderly patients with MCI.2. ALL the patients with MCI in this study were treated with donepezil at a dose of 5 mg once a day. The overall effect of donepezil in elderly patients with MCI was assessed by clinical rating scale of cognitive function,including Mini-Mental State Examination (MMSE),Montreal Cognitive Assessment (MoCA),and Alzheimer's Disease Assessment Scale-Cognitive subscale(ADAS- cog).3. After the detection of ApoE genotype,the study group were divided into ApoEε4 carriers and ApoEε4 non-carriers according to whether they carry ApoEε4 allele or not. The two subgroups were treated with donepezil in a period of 12 months. Treatment differences between the two subgroups were assessed by the MMSE,MoCA,and ADAS-cog retests at 6 and 12 months.Results1. Of all the 92 elderly patients accepted Apolipoprotein E gene detection, the frequeneies of genotypes showed that ApoEε3/3 was highest(61.96%), ApoEε4/4 and ApoEε2/2 was lowest(1.09%). The frequencies of three common alleles were separatedly: ε3(78.80%),ε4(10.87%),ε2(10.33%).2. Within all the 85 patients who finished 6 months treatment with donepezil,though before and after self control study showed that scores of MMSE and MoCA increased from baseline for the first 6 months, and the difference was significant(P=0.003,P=0.004),but, by 12 months, the scores of MMSE and MoCA did not differ significantly in remaining 82 patients(P=-0.078,P=0.681). However, the scores of ADAS-cog increased from baseline throughout the 12 months course of treatment (P=0.001 at 6months and P<0.001 at 12months).3. A total of 85 subjects were retested at 6 months, including 18 ApoEε4 carriers with a mean 0.69-point increase from the baseline score of ADAS-cog and 67 ApoEε4 non-carriers with a mean 0.92-point increase from the baseline score of ADAS-cog. However,there were no significant differences between the two groups at 6 months(t=0.386, P=0.386).A total of 82 subjects were retested at 12 months,including 17 ApoEε4 carriers with a mean 2.20-point increase from the baseline score of ADAS-cog and 65 ApoEε4 non-carriers with a mean 4.27-point increase from the baseline score of ADAS-cog. ApoEε4 carriers showed a more favorable course at the end of this 12 months study(t=2.322 P=0.023). The two genotype-defined subgroups showed no significant differences on the score changing of MMSE and MoCA. There were no significant differences in age, sex, years of education and baseline score of MMSE,MoCA,ADAS-Cog between the subgroups(all P>0.05).Conclusions1. Among elderly patients with MCI in this study, theε3 allele frequency was lower though theε4 allele frequency was higher than the average level in Chinese.2. The treatment effect of donepezil in the whole population of elderly patients with MCI was not good.3. ApoEε4 carriers showed a more favorable response to donepezil in elderly patients with mild cognitive impairment.