Abstract
Purpose :
Early detection of neurodegenerative disease could provide opportunities to prevent irreversible damage. Optical coherence tomography (OCT) allows for noninvasive retina visualization, serving as a potential window for assessment of neurological conditions. For complex multifactorial disease, polygenic risk scores (PRS) involving genetic variants of individual small effects, are associated with disease outcomes. Here we investigate the correlation between retinal layer thickness and neurodegenerative disease, polygenic risk of disease, as well as current and future cognitive performance.
Methods :
We utilized OCT images from 50,342 UK Biobank participants to calculate retinal layer thicknesses. We associated these thicknesses with ICD-based diagnosis of Alzheimer’s disease (AD) or Parkinson’s disease (PD) as well as a Lassosum-derived PRS for each disease. Multivariate Cox proportional hazard models were developed to predict future cognitive decline. All models were adjusted for age, sex, and glaucoma.
Results :
AD diagnosis was associated with a thinner outer plexiform layer (OPL) (adjusted OR (aOR)=1.69, p=0.027). AD PRS was associated with thicker inner nuclear layer (INL), choroid-sclera interface (CSI), inner plexiform layer (IPL), and photoreceptor inner segment/outer segment junction layer (ISOS) and thinner retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) (p<0.05 for all) (Figure 1). PD diagnosis was associated with a thinner ISOS (aOR=2.38, p=0.005) and PD PRS was associated with thinner OPL and CSI (p<0.05 for both) (Figure 2).
Worse baseline cognitive performance was associated with thinner RNFL (aOR=1.067, p<0.001), OPL (aOR=1.017, p<0.001) and ISOS (aOR=1.071, p<0.001), and thicker INL (aOR=0.948, p< 0.001), retinal pigment epithelium (RPE) (aOR=0.977, p=0.033), and GCL (aOR=0.982, p=0.012). In a stepwise Cox model, thinner RNFL (aHR=0.99, p=0.007) and OPL (aHR=0.99, p=0.02) and thicker IPL (aHR=1.04, p=0.002), as well as higher AD PRS predicted future cognitive decline. The model containing retinal thicknesses and PRS improved prediction of future cognitive decline compared to demographic factors alone.
Conclusions :
OCT measurements are associated with diagnosis and genetic risk of neurodegenerative disease, as well as cognitive function suggesting that retinal layers may be used as biomarkers for future cognitive disease and decline.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.