Associations between Large Optic Nerve Cupping, Related Genetic Risk Scores and Cognitive function

Abstract

Purpose : The optic nerve and the brain share anatomy and pathophysiology of the neurodegenerative process. This study investigates if genetic risk scores (GRS) for large optic nerve cupping (CDR) mediates the association between CDR and cognitive function.

Methods : We used data from the Women’s Health Initiative (WHI)-Sight Exam and WHI-Memory Study, excluding women with ocular hypertension (intraocular pressure > 23 mmHg) or glaucoma medication use. Large CDR was defined as > 0.6 in either eye. To form the GRS, we used the log odds ratio (OR) estimated from a previously identified single nucleotide polymorphisms (SNP) logistic regression model adjusted for age and two principle components. Cognitive function was measured by the Modified Mini-Mental State Examination (3MSE). We used multiple logistic regression to evaluate the association of the weighted GRS with large CDR, then a generalized linear model to assess the association between weighted GRS and 3MSE scores, and between weighted GRS, CDR, and 3MSE scores, adjusted for age, education, smoking, diabetes, body mass index, cardiovascular disease, diabetic retinopathy, and hormone therapy randomization. As 3MSE scores were non-normally distributed, a log-transformed function of scores, log (102-3MSE), was used.

Results : Final analyses included 1201 White women; mean age (± SD) was 69.59 ± 3.62 years. Of those, 7.24% had large CDR. The mean GRS in women with and without a large CDR was 1.51 ± 0.31 vs. 1.41 ± 0.36, p = 0.004, and the odds of large CDR for a one unit increase in GRS is 2.29 (95% CI: (1.21, 4.34), p = 0.011). There was no association between weighted GRS and 3MSE scores (p = 0.964). The final adjusted model showed that women without large CDR had significantly lower 3MSE scores than those with large CDR, yielding a predicted mean difference in 3MSE of 0.838 (p-value=0.0071). Adding GRS in the model, women with large CDR still had statistically significantly lower 3MSE scores than those without large CDR, yielding a predicted mean difference in 3MSE scores of 0.844 (p = 0.0069).

Conclusions : Prior work showed a mean difference of 0.21 3MSE units was associated with a 76% increased hazard for dementia. This analysis suggests independent of the GRS, women who had large CDR, without glaucoma or ocular hypertension had a lower cognitive function. Further investigation is warranted.

This is a 2021 ARVO Annual Meeting abstract.