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NEUROLOGY 2009;73:862-868
© 2009 American Academy of Neurology

Retinal microvascular abnormalities and cognitive decline

The ARIC 14-year follow-up study

S. R. Lesage, MD, T. H. Mosley, PhD, T. Y. Wong, MD, PhD, M. Szklo, MD, DrPH, D. Knopman, MD, D. J. Catellier, PhD, S. R. Cole, PhD, MPH, R. Klein, MD, MPH, J. Coresh, MD, PhD, L. H. Coker, PhD and A. R. Sharrett, MD, DrPH

From the Department of Neurology (S.R.L.), University of Maryland, Baltimore; Department of Medicine (T.H.M.), University of Mississippi Medical Center, Jackson; Centre for Eye Research Australia (T.Y.W.), University of Melbourne, Australia; Department of Epidemiology (M.S., J.C., A.R.S.), Johns Hopkins Bloomberg School of Public Health, Baltimore; Division of Behavioral Neurology (D.K.), Mayo Clinic College of Medicine, Rochester, MN; Departments of Biostatistics (D.J.C.) and Epidemiology (S.R.C.), University of North Carolina, Chapel Hill; Department of Ophthalmology and Visual Sciences (R.K.), University of Wisconsin School of Medicine and Public Health, Madison; and Department of Public Health Sciences (L.H.C.), Wake Forest University School of Medicine, Winston-Salem, NC.

Address correspondence and reprint requests to Dr. Suzanne Lesage, University of Maryland Medical Center, Department of Neurology, 22 S. Greene St., Baltimore, MD 21201 slesage{at}medicine.umaryland.edu

Background: Because retinal and cerebral arterioles share similar pathologic processes, retinal microvascular changes are expected to be markers of cerebral small vessel disease (SVD). To better understand the role of SVD in cognitive function, we investigated the relationship between retinal microvascular abnormalities and longitudinal changes in cognitive function in a community-based study.

Methods: A total of 803 participants underwent 4 cognitive assessments between 1990–1992 and 2004–2006, using the Word Fluency (WF) test, Digit Symbol Substitution (DSS), and Delayed Word Recall as well as retinal photography in 1993–1995. Covariate adjusted random effects linear models for repeated measures were used to determine the associations of cognitive change with specific retinal vascular abnormalities.

Results: Individuals with retinopathy showed declines in executive function and psychomotor speed, with 1) an average decline in WF of –1.64 words per decade (95% confidence interval [CI] –3.3, –0.02) compared to no decline in those without retinopathy +0.06 (95% CI –0.6, 0.8) and 2) a higher frequency of rapid decliners on the DSS test.

Conclusion: Signs of retinal vascular changes, as markers of the cerebral microvasculature, are associated with declines in executive function and psychomotor speed, adding to the growing evidence for the role of microvascular disease in cognitive decline in the elderly.

Abbreviations: ARIC = Atherosclerosis Risk in Communities; AV = arteriovenous; BP = blood pressure; CES-D = Center for Epidemiologic Studies–Depression scale; CI = confidence interval; CRAE = central retinal artery equivalent; CRVE = central retinal vein equivalent; DSS = digit symbol substitution; DWR = delayed word recall; MABP = mean arterial blood pressure; SVD = small vessel disease; WF = word fluency.


The ARIC Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, and N01-HC-55022. This work was also supported by grant R01-HL70825.

Disclosure: Author disclosures are provided at the end of the article.

Received January 9, 2009. Accepted in final form June 16, 2009.







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