Is Early Age-related Maculopathy Related to Cognitive Function? The Atherosclerosis Risk in Communities Study TIEN YIN WONG, MD, PHD, RONALD KLEIN, MD, MPH, F. JAVIER NIETO, MD, PHD, SUZANA A. D. MORAES, MD, PHD, THOMAS H. MOSLEY, PHD, DAVID J. COUPER, PHD, BARBARA E. K. KLEIN, MD, MPH, LORI L. BOLAND, MPH, LARRY D. HUBBARD, MAT, AND A. RICHEY SHARRETT, MD, DRPH ● PURPOSE: Age-related maculopathy (ARM) and cog- nitive impairment are both neurodegenerative disorders associated with aging and have been hypothesized to share common pathogenic pathways. We describe the association between cognitive function and ARM in middle-aged persons. ● DESIGN: Population-based, cross-sectional study in- volving participants of the Atherosclerosis Risk in Com- munities Study, an ongoing cardiovascular investigation of persons 51 to 70 years of age, examined every 3 years between 1987 to 1998. ● METHODS: At visit three (1993–1995), retinal photo- graphs were obtained and evaluated for ARM using a modification of the Wisconsin ARM Grading System. Cognitive function was assessed using standardized tests (Delayed Word Recall, Digit Symbol, and Word Fluency) at visits two (1990 –1992) and four (1996 –1998) and averaged for analysis. Severe cognitive impairment was defined as scores falling in the lowest 10th percentile of the population. ● RESULTS: Data were available in 9286 persons after exclusion of persons with stroke or using antipsychotic medication. After adjusting for age, gender, race, educa- tion, diabetes, hypertension, cigarette smoking, and alco- hol consumption, persons with severe cognitive impairment based on Word Fluency Test scores were more likely to have early ARM (odds ratio [OR]: 1.6, 95% confidence interval [CI]: 1.1–2.2) and its compo- nents, soft drusen (OR: 1.6; 95% CI: 1.1–2.3) and pigmentary abnormality (OR: 1.5; 95% CI: 0.9 –2.5) than those without severe impairment. However, severe cognitive impairment in scores of the other two cognitive function tests was not associated with ARM. ● CONCLUSION: These population-based data suggest a weak association between cognitive function and early ARM in middle-aged persons. (Am J Ophthalmol 2002;134:828 – 835. © 2002 by Elsevier Science Inc. All rights reserved.) A GE-RELATED MACULOPATHY (ARM) IS A LEADING cause of visual impairment in the elderly. 1,2 The pathogenesis of ARM remains poorly under- stood. 3–5 Cognitive decline, with or without Alzheimer’s disease, reflects an age-related chronic neurodegenerative process in the brain. 6,7 Age-related maculopathy and Alzheimer’s disease have been hypothesized to share a common pathogenesis, based on similar histopathological alterations related to neuronal cell loss, 3,8 –11 analogous vascular risk factors (for example, hypertension, cigarette smoking), 12–17 and, possibly, shared genetic susceptibility (for example, apolipoprotein E polymorphism). 18 –20 However, few clinical data exist regarding a possible association between cognitive function and ARM. In the Rotterdam Study, among white persons aged 75 years or older, late ARM was associated with 2-year incident Accepted for publication June 11, 2002. From the Singapore Eye Research Institute & Department of Ophthal- mology, National University of Singapore, Singapore (T.Y.W.); Depart- ment of Ophthalmology, University of Wisconsin, Madison, Wisconsin (T.Y.W., R.K., B.E.K.K., L.D.H.); Department of Epidemiology, Johns Hopkins University School of Public Health, Baltimore, Maryland (F.J.N., S.A.D.M.); Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi (T.H.M.); Department of Biostatis- tics, University of North Carolina, Chapel Hill, North Carolina (D.J.C.); Division of Epidemiology, University of Minnesota, Minneapolis, Min- nesota (L.L.B.); National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland (A.R.S.). This study was supported by contracts N01-HC-35125, N01-HC- 35126, N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC- 55019, N01-HC-55020, N01-HC-55021, and N01-HC-55022 from the National Heart, Lung, and Blood Institute, Bethesda, MD. The authors thank the staff and participants in the ARIC study for their important contributions. Reprint requests to Tien Yin Wong, MD, PhD, Department of Ophthalmology, National University of Singapore, 10 Lower Kent Ridge Road, Singapore 119074; fax: (+65)6777 7161; e-mail: ophwty@ nus.edu.sg © 2002 BY ELSEVIER SCIENCE INC.ALL RIGHTS RESERVED. 828 0002-9394/02/$22.00 PII S0002-9394(02)01672-0