APOE e4 Causes Cognitive Changes During the Early Period of Alzheimer Disease

Abstract

It is generally accepted that the Apolipoprotein E（APOE）4 gene is associated with cognitive decline in patients with Alzheimer’s disease（AD）. However, contradictory results have been reported, which strongly suggest some confounding factors exist concerning the effects of APOE allele upon cognitive function. We assumed that the duration of AD is one of the main confounding factors. For example, the cognitive function of a subject with AD for half a year and that of a subject with AD for 4 years are estimated to be differently influenced by the APOE allele. In order to control this factor, the present study employed subjects that developed AD within 6 months. The results showed that in the subjects of more than or equal to 75 years old, APOE e3/e4 declined episodic memory more severe than the APOE e3/e3 at the 6 months before AD conversion（p ＜ 0.01）p ＜ 0.01 and at the onset of AD（p ＜ 0.05）. APOE e4 allele impaired episodic memory function in the subjects of more than or equal to 75 years old. They also revealed that in AD subjects below 75 years old, attention/executive function（Trails Making-A, Trails Making-B, and Digit Symbol Substitution）, and working memory （Digit Span backward）were better in the APOE e3/e4 group than the APOE e3/e3 group（p ＜ 0.05）. Only at AD conversion, constructive praxis（ADAS construction）was better in the APOE e3/e4 group than the APOE e3/e3 group（p ＜ 0.01）. APOE e3/e4 allele may restrain AD subject below 75 years old from decline of attention/executive function, working memory （Digit Span backward）and constructional praxia.