Retinal signs and 20-year cognitive decline in the Atherosclerosis Risk in Communities Study

Abstract

Objective: To test the hypothesis that retinal vascular signs are associated with greater cognitive decline over 20 years in 12,317 men and women 50 to 73 years of age at baseline.

Methods: A composite cognitive score was created with 3 neuropsychological tests measured at 3 time points (1990-1992 to 2011-2013). Retinal signs were measured with fundus photography (1993-1995). Differences in cognitive change by retinal signs status were estimated with linear mixed models. Cognitive scores were imputed for living participants with incomplete cognitive testing.

Results: In multivariable-adjusted analyses that controlled for attrition, loss of vascular integrity (retinopathy and its components) was associated with greater 20-year decline (difference in 20-year cognitive change for moderate/severe vs no retinopathy -0.53 SD, 95% confidence interval -0.74 to -0.33). Estimated differences were similar in participants with and without diabetes mellitus and in white and black participants.

Conclusions: Retinopathy was associated with accelerated rates of 20-year cognitive decline. These findings support the exploration of more sensitive measures in the eye such as optical coherence tomography angiography, which may provide surrogate indexes of microvascular lesions relevant to cognitive decline in older adults.

Figure 1. Multivariable-adjusted differences in estimated rates of 20-year change in cognitive function by retinal signs and diabetes status, ARIC Neurocognitive Study, 1990 to 1992 to 2011 to 2013, n = 12317

(A) Participants with diabetes mellitus (n = 1723). (B) Participants without diabetes mellitus (n = 10604). p Values for interaction between diabetes mellitus and retinal sign: mild retinopathy p = 0.862, moderate/severe retinopathy p = 0.316, microaneurysms p = 0.083, retinal hemorrhages p = 0.016, soft exudates p = 0.134, arteriovenous nicking p = 0.890, focal narrowing p = 0.588, and CRAE p = 0.709. ARIC = Atherosclerosis Risk in Communities; CRAE = central retinal arteriolar equivalent.

Figure 2. Multivariable-adjusted differences in estimated rates of 20-year change in cognitive function by retinal signs and race, ARIC Neurocognitive Study, 1990 to 1992 to 2011 to 2013, n = 12317

(A) Black race (n = 2689). (B) White race (n = 9628). p Values for interaction between race and retinal sign: mild retinopathy p = 0.470, moderate/severe retinopathy p = 0.645, microaneurysms p = 0.681, retinal hemorrhages p = 0.595, soft exudates p = 0.821, arteriovenous nicking p = 0.637, focal narrowing p = 0.073, and CRAE p = 0.642. ARIC = Atherosclerosis Risk in Communities; CRAE = central retinal arteriolar equivalent.