Retinal microvascular signs and functional loss in older persons: the cardiovascular health study

Abstract

Background and purpose: We hypothesized that retinal microvascular signs are associated with executive dysfunction, slow gait, and depressive mood, which are characteristic features of microvascular disease affecting frontal subcortical regions of the brain.

Methods: In the Cardiovascular Health Study, 1744 participants (mean age, 78) free of stroke had retinal photographs and carotid ultrasound during the 1997 to 1998 visit. We examined the cross-sectional association of retinal signs with the digit-symbol substitution test (DSST) score, gait speed, the Center for Epidemiologic Studies-Depression score, and depressive mood, defined as Center for Epidemiologic Studies-Depression score >9 or antidepressant use.

Results: After adjusting for potential confounders, retinal signs were associated with lower DSST score (generalized arteriolar narrowing and arteriovenous nicking), slower gait (retinopathy), and depressive mood (generalized arteriolar narrowing). A higher number of retinal signs was associated with lower DSST score (-0.76 and -2.79 points for 1 sign and ≥2 signs versus none; P<0.001) and slower gait (-0.009 and -0.083 m/s; P=0.047), but not with the square root of Center for Epidemiologic Studies-Depression score (0.079 and -0.208; P=0.072). In addition, coexistence of retinal signs (generalized arteriolar narrowing and arteriovenous nicking) and carotid atherosclerosis was associated with lower DSST score compared with either process alone (P for interaction <0.01). Notably, further adjustment for ventricular size, white matter disease, and infarcts on MRI did not attenuate the association.

Conclusions: Retinal signs are associated with executive dysfunction and slow gait, and possibly with depressive mood, suggesting a common process involving small vessels.

Figure

Total Number of Retinal Signs and Functional Outcomes* Abbreviations: CES-D, the Center for Epidemiologic Studies – Depression scale; DSST, digit symbol substitution test. * Adjusted means (square) and 95% confidence intervals (vertical bars) were presented. Adjusted variables include age, gender, race, current smoking, heart disease systolic blood pressure, natural logarithm of carotid intima-media thickness, and C-reactive protein (for all three outcomes); additionally for years of education, diabetes status (for the DSST score and gait speed); blocks walked per week (for the DSST and CES-D scores); alcohol consumption (for the DSST score); and body mass index (for gait speed).