APOE-ε4 is not associated with pure-tone hearing thresholds, visual acuity or cognition, cross-sectionally or over 3 years of follow up in the Canadian Longitudinal Study on Aging

Abstract

Introduction: Hearing loss and diminished visual acuity are associated with poorer cognition, but the underlying mechanisms are not understood. The apolipoprotein (APOE) ε4 allelic variant may drive the associations. We tested whether APOE-ε4 allele count (0, 1, or 2) was associated with declines in memory, executive function, pure-tone hearing threshold averages, and pinhole-corrected visual acuity among participants in the Canadian Longitudinal Study on Aging (CLSA).

Methods: Multivariable linear mixed regression models were utilized to assess associations between APOE-ε4 allele count and each of the outcome variables. For each main effects model, interactions between APOE-ε4 and sex and age group (45-54-, 55-64-, 65-74-, and 75-85 years) respectively, were analyzed.

Results: Significant associations were not observed in main effects models. Models including APOE-ε4 * age (but not APOE-ε4 * sex) interaction terms better fit the data compared to main effects models. In age group-stratified models, however, there were minimal differences in effect estimates according to allele count.

Conclusion: APOE-ε4 allele count does not appear to be a common cause of sensory-cognitive associations in this large cohort.

Plain Language Summary

Apolipoprotein E is a gene that produces a protein molecule called APOE that is important for proper functioning of the brain and the body. There are three variants of the gene that each produce a different form of the protein. Each person can have up to two types. The three different proteins are called APOE2, APOE3, and APOE4. Having APOE4 is associated with a higher risk of Alzheimer’s disease and other age-related diseases, such as atherosclerosis (hardening of the blood vessels). Our study was performed to determine if having APOE4 is associated with poorer cognition, hearing loss and vision loss in the general population. Many studies have shown that hearing loss and vision loss each predict faster declines in cognition, but the reasons are unknown. One possibility is that there is an underlying genetic risk factor driving all of the declines. Our study was performed to see if APOE4 is such a risk factor. The participants in our study were healthy people recruited from across Canada, who were aged 45-85 years at the beginning of the study. They were part of a large study called the Canadian Longitudinal Study on Aging. We determined if participants who had APOE4 were more likely to have lower cognition, poorer hearing and poorer visual acuity to begin with, and/or if their cognition, hearing or vision declined faster than others over 3 years of follow up. We controlled for other factors that might influence the results (e.g., age, education, and health). The analysis showed that that having APOE4 was not associated with poorer cognition, hearing or vision to begin with, or faster declines in each condition. We thus concluded that APOE4 is unlikely to be a common cause explaining associations between sensory loss and cognitive aging.