The correlation between cognitive performance and retinal nerve fibre layer thickness is largely explained by genetic factors

Abstract

Retinal nerve fibre layer (RNFL) thickness has been associated with cognitive function but it is unclear whether RNFL thinning is secondary to cortical loss, or if the same disease process affects both. We explored whether there is phenotypic sharing between RNFL thickness and cognitive traits, and whether such sharing is due to genetic factors. Detailed eye and cognitive examination were performed on 1602 twins (mean age: 56.4 years; range: 18–89) from the TwinsUK cohort. Associations between RNFL thickness and ophthalmic, cognitive and other predictors were assessed using linear regression or analysis of variance models. Heritability analyses were performed using uni- and bivariate Cholesky decomposition models. RNFL was thinner with increase in myopia and with decrease in disc area (p < 0.001). A thicker RNFL was associated with better performance on mini mental state examination (MMSE, F(5,883) = 5.8, p < 0.001), and with faster reaction time (RT, β = −0.01; p = 0.01); independent of the effects of age, refractive error and disc area (p < 0.05). RNFL thickness was highly heritable (82%) but there was low phenotypic sharing between RNFL thickness and MMSE (5%, 95% CI: 0–10%) or RT (7%, 95% CI: 1–12%). This sharing, however, was mostly due to additive genetic effects (67% and 92% of the shared variance respectively).

The relationship between age, axial length and retinal nerve fiber layer thickness in the normal elderly population in Taiwan: The Chiayi eye study in Taiwan

“…It is known that the retina forms as a functional extension of the central nervous system, developing as a result of diencephalic evagination of pluripotent cells during embryogenesis [ 15 ]. In many cross-sectional studies, the RNFL has been shown to be thinner in people with memory loss and cognitive decline due to certain neurodegenerative disorders, such as AD and MS [ 6 – 9 ]. There is also some controversy regarding the effect of lens opacity on signal detection in OCT.…”

“…The average RNFL thickness loss in patients with AD is 11 μm; in patients with MS, it is 7 μm. However, it is unclear whether the main ocular biomarker of RNFL thinning investigated for AD and MS is secondary to cortical loss (retrograde damage), or if the same disease process affects both the brain and the retina [ 8 , 9 ].…”

Optic Nerve Parameters and Cognitive Function in the Northern Finland Birth Cohort Eye Study

“…There is extensive variation in testing for cognitive function even in different studies regarding the correlation to ophthalmological neuro-anatomy. 6,7,14,16,17 By exploring the data of the NFBC Eye Study we were able to find statistically significant correlations between the ONH parameters and surrogates for cognition: A higher education level and a faster HFA were associated with larger disc areas. These same correlations have been reported in the Beijing Eye Study.…”

Retinal Morphometric Markers of Crystallized and Fluid Intelligence Among Adults With Overweight and Obesity

“…Finally, we did not account for genetic factors that may contribute to retinal morphometric measures. For example, Jones-Odeh et al (2016) examined a large cohort of twins in the United Kingdom and learned that RNFL thickness was highly heritable (82%). Markers of vascular health in the retina have also been previously linked to neuropsychological functioning at midlife should be accounted for in future research (Shalev et al, 2013).…”

“…Although emerging evidence points to the utility of OCT as a neuroimaging technique, only a limited number of studies have examined retinal morphometric measures and cognitive function. RNFL thickness has been positively associated with performance on the mini mental state examination among a large cohort of twins between 18 and 89 years (Jones-Odeh et al, 2016). Total macular volume and RNFL have also been associated with verbal intelligence and IQ among persons with MS (Ashtari et al, 2015).…”