Abstract

Objectives: The apolipoprotein E (apoE) ε4 allele is related to decline in multiple cognitive domains, especially episodic memory, but the effect of the ε2 allele on change in different forms of cognitive function has been difficult to establish.

Methods: Participants are from the Religious Orders Study. At baseline, they were at least 65 years old and free of clinical evidence of dementia. For up to eight years, they underwent annual clinical evaluations that included detailed cognitive function assessment from which previously established summary measures of episodic memory, semantic memory, working memory, perceptual speed, and visuospatial ability were derived. Growth curve models were used to assess change in each measure and its relation to apoE genotype, controlling for age, sex, education, and baseline level of cognition. Follow up data were available in 669 persons (98% of those eligible). We treated those with the ε3/3 genotype as the reference group (n=425), which was contrasted with ε2 (ε2/2, ε2/3; n=86), and ε4 (ε3/4, ε4/4; n=158) subgroups.

Results: Rate of episodic memory change in the three subgroups significantly differed, with an average annual increase of 0.016 units in the ε2 subgroup and annual decreases of 0.022 units in those with ε3/3 and of 0.073 units in the ε4 subgroup. The ε2 subgroup did not differ from those with ε3/3 in rate of decline in other cognitive systems. The ε4 subgroup declined more rapidly than those with ε3/3 in semantic memory and perceptual speed but not in working memory or visuospatial ability.

Conclusion: Possession of one or more apoE ε2 alleles is associated with reduced decline in episodic memory in older persons.