Abstract
INTRODUCTION: The retinal nerve fiber layer (RNFL) or ganglion cell-inner plexiform layer (GC-IPL) is associated with cognitive impairment. However, the relationship between retinal asymmetry and cognitive frailty (CF) remains unknown. METHODS: Two hundred twenty-two community-dwelling older adults were assessed starting in 2015 and underwent biennial cognitive and frailty evaluations until 2022. Retinal asymmetry was defined as the absolute interocular retinal difference. Generalized linear mixed models estimated the risk of CF over time. RESULTS: Among the participants, 158 completed the 4-year follow-up. Greater baseline GC-IPL asymmetry was associated with worsening CF over time (adjusted odds ratio = 1.06; 95% confidence interval [CI] = 1.03, 1.10), with handgrip strength asymmetry significantly modifying this association (p(interaction )= 0.02). GC-IPL asymmetry was associated with cognitive impairment ( β̂ = -1.69 × 10(-2); 95% CI = -3.13 × 10(-2), -0.25 × 10(-2)) but not with physical frailty. RNFL showed no significant association with CF. DISCUSSION: Interocular GC-IPL asymmetry might be a new biomarker for CF in older adults. HIGHLIGHTS: Interocular ganglion cell-inner plexiform layer (GC-IPL) asymmetry was associated with impaired memory-frailty, with handgrip strength asymmetry significantly modifying this association. Interocular GC-IPL asymmetry was associated with cognitive impairment. Interocular retinal asymmetry might be a structural biomarker of cognitive frailty.