P3-029: Pattern of cognitive impairment in AD is modified by APOE genotype

Abstract

The Apolipoprotein E (APOE) gene is known to influence susceptibility to development of AD. It is conceivable that the APOE–gene also modifies clinical presentation. We examined if clinical phenotype of AD in terms of pattern of cognitive impairment differs according to APOE genotype. Cognitive functions of 198 consecutive AD patients were assessed using the Visual Association Test part A (VAT–A) and Memory Impairment Screening test+ (MIS+) for memory, VAT picture naming for language, fluency test and Trail Making Test (TMT) for executive functions (fluency and TMT–B) and mental speed (TMT–A). Dementia severity was assessed using the MMSE. APOE genotype was determined. Analysis of variance (ANOVA) was used with age, sex, education and MMSE as covariates. There were 58 (29%) APOE e4 negative patients, 114 (58%) heterozygous patients and 26 (13%) homozygous patients. There was no association between APOE status and sex, age, level of education or MMSE. There was a significant association between APOE genotype and VAT–A–score (p = 0.039), MIS+delayed recall score (p = 0.006), and fluency–score (p = 0.043), when corrected for sex, age, level of education and MMSE. Post–hoc analysis revealed that VAT–A score was lower in the APOE e4 homozygous group than in the e4 negative group (p = 0.014) and the e4 heterozygous group (p = 0.040). The same direction was found for the MIS+delayed recall score, with p–levels of 0.002 for the APOE e4 negative group and 0.004 for the heterozygous group. By contrast, fluency score was lower in the APOE e4 negative group than in the heterozygous group (p = 0.031) and the homozygous group (p = 0.041). In this study different patterns of cognitive impairment were found among AD patients according to their APOE e4 genotype. Memory function was more impaired among homozygous APOE e4 carriers than among heterozygous carriers and APOE e4 negative patients. However, executive functions were more impaired among APOE e4 negative patients than among heterozygous APOE e4 carriers and homozygous carriers. This suggests that the APOE e4 genotype modifies the clinical phenotype in terms of cognitive impairment in AD.