Abstract
Background: Microvascular retinal abnormalities may be markers of cerebrovascular and renal microvascular disease and are associated with cognitive impairment. Hypothesis: Stroke and albuminuria mediate the association of retinal abnormalities with cognitive performance. Methods: In a racially diverse longitudinal MESA cohort, we used retinal imaging from MESA exams 2 (2002-2004) and 5 (2010-2012) to determine the association of retinal microvascular changes with global cognitive function (Cognitive Abilities Screening Instrument; CASI version 2), processing speed (Digit Symbol Coding; DSC) and working memory (Digit Span; DS) scores at MESA Exam 5 after adjusting for vascular risk factors and interactions with albuminuria at Exam 2 and incident stroke (ischemic or hemorrhagic). Results: A total of 4,392 participants were included. At Exam 5, the mean (±SD) age of participants was 69.5 (9.3), 46.6% were women, 41.3% were non-Hispanic White. Albuminuria was present in 373 and stroke occurred in 77 participants. Over the 8-year period, the mean change in central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) was -2.9 (11.4) μm and -7.6 (14.8) μm, respectively. The CRAE at Exam 5, change in CRAE between Exam 2 and 5, and CRVE at Exam 2 were associated with a poorer CASI score (Table). Greater CRVE at Exam 2 and 5 was associated with a poorer DSC (Table) and no associations were found with DS scores (all p>0.05). Stroke and albuminuria were associated with CASI and DSC. The interaction of stroke with the change in CRAE and with CRVE at exam 5 in predicting DSC was significant. However, albuminuria and incident stroke did not mediate or significantly interact with microvascular retinal changes to predict CASI (all p>0.05). Conclusions: Stroke and albuminuria do not explain the association between retinal microvascular caliber and global cognitive performance but the interaction with stroke in predicting processing speed is significant.
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