Retinal ganglion cell–inner plexiform layer thickness is nonlinearly associated with cognitive impairment in the community-dwelling elderly

Introduction: Thinning of optical coherence tomography–measured retinal nerve fiber layer thickness and ganglion cell–inner plexiform layer (GC-IPL) thickness has been found in patients with Alzheimer's disease. However, the association of these retinal markers and cognition in nondemented elders may not be linear. Methods: This cross-sectional study included 227 community-dwelling elders (age 65+ years). Multivariable regression analyses were performed to investigate the association between retinal nerve fiber layer/GC-IPL and global/domain-specific cognition. Results: The performance of global cognition decreased as mean GC-IPL of bilateral eyes deviated from the sample mean (77.5 μm) (quadratic GC-IPL: β = –0.49 × 10⁻²; 95% confidence interval: −0.74 × 10⁻² to −0.23 × 10⁻²). Similar associations were also found for logical memory. No significant association was observed between retinal nerve fiber layer and cognition. Discussion: Either thinning or thickening of GC-IPL was associated with poor cognition in nondemented elderly (a U-shaped association). GC-IPL may serve as a noninvasive preclinical predictor of Alzheimer's disease.