Prevalence of Retinal Signs and Association With Cognitive Status

The ARIC Neurocognitive Study

Moon Jeong Lee, BS; Jennifer A. Deal, MHS, PhD; Pradeep Y. Ramulu, MD, MHS, PhD; A. Richey Sharrett, MD, DrPH; Alison G. Abraham, MHS, MS, PhD


J Am Geriatr Soc. 2019;67(6):1197-1203. 

In This Article

Abstract and Introduction


Objective: To determine the prevalence of retinal microvascular signs and associations between retinal signs and cognitive status.

Design: Cross-sectional analysis of visit 5 (2011–2013) of the Atherosclerosis Risk in Communities (ARIC) cohort. Data analysis took place November 30, 2017, to May 1, 2018.

Setting: Biracial population-based cohort from four US communities.

Participants: A total of 2624 participants with a mean age of 76 years (SD = 5 years) (19% African American) with data on cognitive status and complete retinal examination.

Measurements: Retinal signs measured with fundus photography. Cognitive status: normal cognition, mild cognitive impairment (MCI)/dementia with a primary diagnosis of Alzheimer disease (AD) without cerebrovascular disease (CVD), and MCI/dementia with a primary or secondary diagnosis of CVD (irrespective of AD).

Results: Overall, 6% of the cohort had mild retinopathy and 2% had moderate/severe retinopathy. Of the cohort, 7% had microaneurysms, 6% had retinal hemorrhages, and 8% had arteriovenous (AV) nicking. There was a low prevalence of soft exudates (1%) and focal narrowing (1%). In weighted fully adjusted models, individuals with retinal hemorrhages had a two-fold higher odds of all-cause MCI/dementia (95% confidence interval [CI] = 1.3-3.0; P = .001) and a 2.5-fold higher odds (95% CI = 1.6-3.9; P < .001) of MCI/dementia with CVD compared to individuals with no retinal hemorrhages. Individuals with AV nicking had a 1.6-fold higher odds of MCI/dementia with CVD (95% CI = 1.0-2.4) compared to individuals with no AV nicking (P < .05). There were no associations between retinal signs and MCI/dementia without CVD.

Conclusion: Our findings are confirmatory of recent research, and suggest that retinal microvascular signs may reflect microvascular pathology in the brain, potentially contributing to dementia and earlier MCI. The low prevalence of retinal signs and modest associations with cognitive status, however, limit the current clinical utility of these findings. Further work is needed to determine whether more sophisticated imaging may detect more subtle retinal signs with higher sensitivity to identify individuals at risk of dementia.


Cognitive impairment remains frequently underdiagnosed in older adults.[1] Current neurologic guidelines suggest that individuals with mild cognitive impairment (MCI) are evaluated using cognitive tests, such as the Mini-Mental State Examination (MMSE), and neuropsychologic batteries to monitor for progression to dementia.[2] However, cognitive batteries are not routinely used in nonneurologic specialty settings, and the sensitivity of such tests is limited, suggesting a role for biomarkers in the identification of individuals at risk of cognitive impairment.[3] Previous research suggests that the eye may serve as a window to the brain, and that retinal microvasculature may reflect small-vessel disease in the brain as well.[4,5] If this is the case, examination of retinal microvasculature, as a biomarker of small-vessel disease in the brain, may potentially contribute additional information on the etiology of cognitive impairment. With new emerging imaging technologies, it may also contribute to a noninvasive screening tool in the future for assessing cognitive impairment risk due to microvascular disease.[4,5]

Several previous studies have demonstrated an association between retinal microvascular abnormalities (ie, retinopathy, arteriovenous [AV] nicking) and the prevalence and progression of brain microvascular disease associated with risk of dementia.[4,6,7] Retinal signs have also been associated with both cognitive status and cognitive decline. Signs such as retinopathy, microaneurysms, retinal hemorrhages, and soft exudates have all been associated with lower cognitive test scores.[8,9] Retinopathy was also associated with declines in cognitive function over 14 years, as measured by the Word Fluency Test and Digit Symbol Substitution Test.[10] However, in investigations using the Atherosclerosis Risk in Communities (ARIC) data when the cohort was middle aged, many signs of retinopathy were rare. In addition, this cross-sectional study of older participants is clinically applicable to older individuals with unidentified cognitive impairment, who may present with retinal signs and may or may not require further cognitive evaluation.

In this study, we evaluated the: (1) prevalence of retinopathy by cognitive status (normal, MCI, dementia) and (2) cross-sectional associations at visit 5/Neurocognitive Study (NCS) in 2011 to 2013 of the ARIC cohort. We assessed two etiologies of MCI and dementia (MCI/dementia with a primary diagnosis of Alzheimer disease [AD] without cerebrovascular disease [CVD] and MCI/dementia with a primary or secondary diagnosis of CVD [irrespective of AD]) and hypothesized that retinal microvasculature signs would demonstrate associations more specifically with MCI/dementia due to CVD.