Cognitive Impairment in Alzheimer’s Disease Is Modified by APOE Genotype

Aim: We examined whether impairment in specific cognitive domains in Alzheimer’s disease (AD) differed according to APOE genotype and age at onset. Methods: Cognitive functions of 229 consecutive AD patients were assessed using Visual Association Test (VAT), Memory Impairment Screen+ (MIS+), VAT object naming, fluency test and Trail Making Test (TMT). Dementia severity was assessed using MMSE. ANOVAs were performed with APOE genotype and age at onset as independent variables and sex, education and MMSE as covariates. Results: 28% of patients were APOE Ε4-negative, 58% heterozygous and 14% homozygous. A significant association between APOE genotype and VAT and MIS+ was found when correcting for sex and education. An interaction effect between APOE genotype and age at onset on VAT and VAT object naming was found, with young carriers performing worse than young noncarriers. By contrast, when additionally correcting for MMSE, a significant association between APOE genotype and VAT object naming, TMT-A and TMT-B was found, with noncarriers performing worse than carriers. Conclusion: Memory was more impaired among APOE Ε4 carriers than among noncarriers. By contrast, naming, executive functions and mental speed were more impaired among APOE Ε4 noncarriers. This suggests that the APOE genotype modifies the clinical phenotype in terms of cognitive impairment in AD.

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