Association Between APOE Alleles and Change of Neuropsychological Tests in the Long Life Family Study

Background: The Long Life Family Study (LLFS) is a family based, prospective study of healthy aging and familial longevity. The study includes two assessments of cognitive function that were administered approximately 8 years apart. Objective: To test whether APOE genotype is associated with change of cognitive function in older adults. Methods: We used Bayesian hierarchical models to test the association between APOE alleles and change of cognitive function. Six longitudinally collected neuropsychological test scores were modelled as a function of age at enrollment, follow-up time, gender, education, field center, birth cohort indicator (<= 1935, or >1935), and the number of copies of epsilon 2 or epsilon 4 alleles. Results: Out of 4,587 eligible participants, 2,064 were male (45.0%), and age at enrollment ranged from 25 to 110 years, with mean of 70.85 years (SD: 15.75). We detected a significant cross-sectional effect of the APOE epsilon 4 allele on Logical Memory. Participants carrying at least one copy of the epsilon 4 allele had lower scores in both immediate (-0.31 points, 95%CI: -0.57, -0.05) and delayed (-0.37 points, 95%CI: -0.64, -0.10) recall comparing to non-epsilon 4 allele carriers. We did not detect any significant longitudinal effect of the epsilon 4 allele. There was no cross-sectional or longitudinal effect of the epsilon 2 allele. Conclusion: The APOE epsilon 4 allele was identified as a risk factor for poorer episodic memory in older adults, while the APOE epsilon 2 allele was not significantly associated with any of the cognitive test scores.

Automated summary

The study identified that the APOE epsilon 4 allele is a risk factor for poorer episodic memory in older adults, with participants carrying at least one copy showing lower scores in both immediate and delayed recall. However, there was no significant longitudinal effect of the epsilon 4 allele, and no significant association was found with the epsilon 2 allele on cognitive test scores.