Retinal thickness predicts the risk of cognitive decline over five years

Abstract

Background: Dementia poses a significant burden on healthcare systems. Early identification of individuals at risk for cognitive decline is crucial. The retina, an extension of the central nervous system, reflects neurodegenerative changes. Optical coherence tomography (OCT) is a non-invasive tool for assessing retinal health and has shown promise in predicting cognitive decline. However, prior studies produced mixed results.

Methods: This study investigated a large cohort (n = 490) of Asian individuals attending memory clinics. Participants underwent comprehensive neuropsychological testing annually for five years. Retinal thickness was measured by OCT at baseline. We assessed the association between baseline retinal thickness and subsequent cognitive decline.

Results: Participants with a significantly thinner macular ganglion cell-inner plexiform layer (GCIPL) at baseline (≤ 79 μm) had a 38% greater risk of cognitive decline compared to those who did not (≥ 88 μm; p = 0.037). In a multivariable model accounting for age, education, cerebrovascular disease status, hypertension, hyperlipidemia, diabetes and smoking, thinner GCIPL was associated with an increased risk of cognitive decline (hazard ratio = 1.14, 95% CI = 1.01-1.30, p = 0.035). Retinal nerve fiber layer (RNFL) thickness was not associated with cognitive decline.

Conclusions: This study suggests that OCT-derived macular GCIPL thickness may be a valuable biomarker for identifying individuals at risk of cognitive decline. Our findings highlight GCIPL as a potentially more sensitive marker compared to RNFL thickness for detecting early neurodegenerative changes.

Trial registration number and name of the trial registry: National Healthcare Group Domain-Specific Review Board (NHG DSRB) reference numbers DSRB Ref: 2018/01368. Name of the trial: Harmonisation project.

Keywords: Cognitive decline; Cognitive impairment; Dementia; Optical coherence tomography (OCT); Retinal ganglion cell-inner plexiform layer (GCIPL).

Fig. 1

Sample map of the ganglion cell layer - inner plexiform layer (GCIPL) and retinal nerve fiber layer (RNFL) thickness maps

Fig. 2

Adjusted hazard ratios for the three tertiles of ganglion cell layer - inner plexiform layer (GCIPL) thickness. Participants in the first tertile group with the thinnest baseline GCIPL thickness had a 38% higher risk of developing cognitive decline (p = 0.037) compared to the third group with the thickest GCIPL thickness

Fig. 3

Baseline ganglion cell layer - inner plexiform layer (GCIPL) thickness maps and cognitive decline. The participant who experienced cognitive decline demonstrated a thinner GCIPL thickness of 72 μm (left panel) compared to the participant who did not experience cognitive decline over the five-year period and exhibited a thicker baseline GCIPL thickness of 88 μm (right panel)