Abstract
PURPOSE: Age-related eye diseases are inconsistently associated with cognitive decline which could be due to effect modification. The purpose of this study was to investigate whether two genetic factors previously found to be associated with cognitive decline, the KIBRA (WWC1) and PDE7A/MTFR1 genes, modify the association between eye disease and cognitive function. METHODS: Data from a Montreal hospital-based cross-sectional study (n = 302) were used for the primary analysis. Candidate single-nucleotide polymorphisms (SNPs) rs17070145 (KIBRA gene) and rs10808746 (PDE7A/MTFR1 gene) were included in linear regression models to test for effect modification of the relationship between eye disease (glaucoma or age-related macular degeneration [AMD]) and cognitive function. Six oral cognitive tests were used. A replication analysis was done using the Quebec data from the Canadian Longitudinal Study on Aging (CLSA) (n = 4238). Effect modifications by expanded genomic regions around the candidate SNPs were tested. RESULTS: Three statistically significant interactions with two cognitive function measures -category verbal fluency and immediate story recall-were found in the Montreal study: glaucoma and AMD with rs17070145 and verbal fluency (P < 0.03) and glaucoma with rs10808746 with immediate story recall (P < 0.05). Similar interactions, although not with the same cognitive measure, were found in the CLSA: AMD with KIBRA and glaucoma with PDE7A/MTFR1. CONCLUSIONS: Our results suggest that the KIBRA and PDE7A/MTFR1 genes may modify the association between eye disease and cognitive function. This knowledge may help to better understand the mechanism by which glaucoma and AMD are related to cognitive function.