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Association of retinal optical coherence tomography metrics and polygenic risk scores with cognitive function and future cognitive decline
  1. Sayuri Sekimitsu1,
  2. Yusrah Shweikh2,3,
  3. Sarah Shareef2,
  4. Yan Zhao2,4,
  5. Tobias Elze5,
  6. Ayellet Segrè2,4,
  7. Janey Wiggs2,4,
  8. Nazlee Zebardast2
  1. 1 Tufts University School of Medicine, Boston, Massachusetts, USA
  2. 2 Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA
  3. 3 Sussex Eye Hospital, University Hospitals Sussex NHS Foundation Trust, Sussex, UK
  4. 4 Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA
  5. 5 Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts, USA
  1. Correspondence to Dr. Nazlee Zebardast, Harvard Medical School, Boston, MA 02115, USA; nazlee_zebardast{at}meei.harvard.edu

Abstract

Purpose To evaluate the potential of retinal optical coherence tomography (OCT) measurements and polygenic risk scores (PRS) to identify people at risk of cognitive impairment.

Methods Using OCT images from 50 342 UK Biobank participants, we examined associations between retinal layer thickness and genetic risk for neurodegenerative disease and combined these metrics with PRS to predict baseline cognitive function and future cognitive deterioration. Multivariate Cox proportional hazard models were used to predict cognitive performance. P values for retinal thickness analyses are false-discovery-rate-adjusted.

Results Higher Alzheimer’s disease PRS was associated with a thicker inner nuclear layer (INL), chorio-scleral interface (CSI) and inner plexiform layer (IPL) (all p<0.05). Higher Parkinson’s disease PRS was associated with thinner outer plexiform layer (p<0.001). Worse baseline cognitive performance was associated with thinner retinal nerve fibre layer (RNFL) (aOR=1.038, 95% CI (1.029 to 1.047), p<0.001) and photoreceptor (PR) segment (aOR=1.035, 95% CI (1.019 to 1.051), p<0.001), ganglion cell complex (aOR=1.007, 95% CI (1.002 to 1.013), p=0.004) and thicker ganglion cell layer (aOR=0.981, 95% CI (0.967 to 0.995), p=0.009), IPL (aOR=0.976, 95% CI (0.961 to 0.992), p=0.003), INL (aOR=0.923, 95% CI (0.905 to 0.941), p<0.001) and CSI (aOR=0.998, 95% CI (0.997 to 0.999), p<0.001). Worse future cognitive performance was associated with thicker IPL (aOR=0.945, 95% CI (0.915 to 0.999), p=0.045) and CSI (aOR=0.996, 95% CI (0.993 to 0.999) 95% CI, p=0.014). Prediction of cognitive decline was significantly improved with the addition of PRS and retinal measurements.

Conclusions and relevance Retinal OCT measurements are significantly associated with genetic risk of neurodegenerative disease and may serve as biomarkers predictive of future cognitive impairment.

  • Imaging
  • Genetics

Data availability statement

Data are available upon reasonable request. Data is available from the UK Biobank.

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Data availability statement

Data are available upon reasonable request. Data is available from the UK Biobank.

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Footnotes

  • SS, YS and SS contributed equally.

  • Contributors SSekimitsu, SShareef and YZ worked on data analysis. SSekimitsu and YS drafted the initial manuscript. TE, AS and JW worked on data acquisition and provided feedback. NZ led the project, assisted with study design and provided feedback on the final manuscript. NZ is the guarantor of this project.

  • Funding This work was supported in part by the NIH K23 Career Development Award (EY032634) (NZ), NIH R21 Exploratory/Developmental Research Grant Award (EY032953) (NZ), Research to Prevent Blindness Career Development Award (NZ), Fulbright Scholarship (YS), NIH R21 Exploratory/Developmental Research Grant Award (EY030631) (TE), NIH R01 Research Project Grant (EY030575) (TE), NIH P30 Center Core Grant (EY003790) (TE), NIH R01 Research Project Grant (EY032559) (JW, AS), NIH P30 Center Core Grant (EY014104) (JW) and NIH R01 Research Project Grant (EY031424-01) (AS). The funding organisation had no role in the design or conduct of this research.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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