Visual impairment and
retinal neurodegeneration are intrinsically connected and both have been associated with
cognitive impairment and brain
atrophy, but the underlying mechanisms remain unclear. To investigate whether transneuronal degeneration is implicated, we systematically assessed the relation between visual function and
retinal, visual pathway, hippocampal and brain degeneration. We analyzed baseline data from 3316 eligible Rhineland Study participants with visual acuity (VA), optical coherence tomography (OCT), and magnetic resonance imaging (MRI) data available. Regional volumes, cortical volume, and fractional anisotropy (FA) were derived from T1-weighted and diffusion-weighted 3 T MRI scans. Statistical analyses were performed using multivariable linear regression and structural equation modeling. VA and
ganglion cell layer (GCL) thinning were both associated with global brain
atrophy (SD effect size [95% CI] -0.090 [-0.118 to -0.062] and 0.066 [0.053-0.080], respectively), and hippocampal
atrophy (-0.029 [-0.055 to -0.003] and 0.114 [0.087-0.141], respectively). The effect of VA on whole brain and hippocampal volume was partly mediated by
retinal neurodegeneration. Similarly, the effect of
retinal neurodegeneration on brain and hippocampal
atrophy was mediated through intermediate visual tracts, accounting for 5.2%-23.9% of the effect.
Visual impairment and
retinal neurodegeneration were robustly associated with worse brain
atrophy, FA, and hippocampal
atrophy, partly mediated through disintegration of intermediate visual tracts. Our findings support the use of OCT-derived
retinal measures as markers of neurodegeneration, and indicate that both general and transneuronal neurodegeneration along the visual pathway, partly reflecting
visual impairment, account for the association between
retinal neurodegeneration and brain
atrophy.