Objective: To study the associations of retinal microvascular changes, which are associated with systemic conditions and cognitive decline, with disability in performing activities of daily living (ADL). Design: Prospective cohort study of 1487 communitydwelling participants in the Cardiovascular Health Study (mean age, 78 years) who were free of ADL disability and had available data on retinal signs and carotid intimamedia thickness at the 1998-1999 visit. Main outcome measures were incident ADL disability, defined as selfreported difficulty in performing any ADL, by the presence of retinal signs and advanced carotid atherosclerosis, defined by carotid intima-media thickness in the 80th percentile or more or 25% or more stenosis, and potential mediation by cerebral microvascular disease on brain imaging or by executive dysfunction, slow gait, and depressive mood, which are symptoms of frontal subcortical dysfunction. Results: During the median follow-up of 3.1 years (maximum, 7.8 years), participants with 2 or more retinal signs had a higher rate of disability than those with fewer than 2 retinal signs (10.1% vs 7.1%; adjusted hazard ratio, 1.45; 95% confidence interval, 1.24-1.69; P<.001). There was no evidence of interaction by advanced carotid atherosclerosis (P>.10). The association seemed to be partially mediated by executive dysfunction, slow gait, and depressive symptoms but not by cerebral microvascular disease on brain imaging. Conclusions: These results provide further support for the pathophysiologic and prognostic significance of microvascular disease in age-related disability. However, it remains to be determined how to best use retinal photography in clinical risk prediction.
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