Background: The simple, convenient and well-validated biomarkers are imperative for detection of cognitive decline (CD). The powerful evidence is lacked for verifying the reliability and clinical utility of retinal biomarkers for detection of CD with repeated assessments. To investigate the association of retinal thickness with CD using repeated assessments. Methods: This study included 446 older adults with three-time repeated assessments of cognitive function during 5-years follow-up. Retinal thickness measured on spectral-domain optical coherence tomography. Logistic regression models were conducted to analyze the association of retinal thickness with cognitive function. Results: According to cognitive status in three assessments, individuals were categorized into consistently normal cognition groups (N = 159), persistently CD groups (N = 134), progressed to CD groups (N = 70), and reverting or fluctuating CD groups (N = 83). Thinner ganglion cell-inner plexiform layer (GC-IPL) was associated with persistently CD (odds ratio [OR] per 1-μm decrease: 1.09, 95% confidence interval [CI], 1.02-1.18; per standard deviation [SD] decrease: 1.78, 95%CI, 1.04-3.19) rather than progressed to CD, reverting or fluctuating CD. No significant relationship was found between retinal nerve fiber layer and any CD subgroups (p > 0.05). Conclusions: Thinner GC-IPL was associated with persistently CD, suggesting retinal neurodegeneration may be a promising biomarker for persistently CD. Further studies, including both longitudinal and repeated measurements of retinal layer thickness and cognitive function, are needed to assess the possibility of retinal thickness as a biomarker for persistent CD.