Associations Between Retinal Artery/Vein Occlusions and Risk of Vascular Dementia

Article type: Research Article

Authors: Lee, Cecilia S.^{a; *} | Lee, Michael L.^b | Gibbons, Laura E.^b | Yanagihara, Ryan T.^a | Blazes, Marian^a | Kam, Jason P.^c | McCurry, Susan M.^d | Bowen, James D.^e | McCormick, Wayne C.^b | Lee, Aaron Y.^a | Larson, Eric B.^{f; 1} | Crane, Paul K.^{b; 1}

Affiliations: [a] Department of Ophthalmology, University of Washington, Seattle, WA, USA | [b] Department of Medicine, University of Washington, Seattle, WA, USA | [c] Kaiser Permanente Washington, Seattle, WA, USA | [d] Department of Child, Family, and Population Health Nursing, University of Washington, Seattle, WA, USA | [e] Department of Neurology, Swedish Medical Center, Seattle, WA, USA | [f] Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA

Correspondence: [*] Correspondence to: Cecilia S. Lee, MD MS, Associate Professor, Department of Ophthalmology, University of Washington, Box 359608, 325 Ninth Avenue, Seattle, WA 98104, USA. Tel.: +1 206 543 7250; E-mail: leecs2@uw.edu.

Note: [1] These authors contributed equally to this work and should be considered co-senior authors.

Abstract: Background:Vascular disease is a risk factor for Alzheimer’s disease (AD) and related dementia in older adults. Retinal artery/vein occlusion (RAVO) is an ophthalmic complication of systemic vascular pathology. Whether there are associations between RAVO and dementia risk is unknown. Objective:To determine whether RAVOs are associated with an increased risk of developing vascular dementia or AD. Methods:Data from Adult Changes in Thought (ACT) study participants were analyzed. This prospective, population-based cohort study followed older adults (age ≥65 years) who were dementia-free at enrollment for development of vascular dementia or AD based on research criteria. RAVO diagnoses were extracted from electronic medical records. Cox-regression survival analyses were stratified by APOE ɛ4 genotype and adjusted for demographic and clinical factors. Results:On review of 41,216 person-years (4,743 participants), 266 (5.6%) experienced RAVO. APOE ɛ4 carriers who developed RAVO had greater than four-fold higher risk for developing vascular dementia (Hazard Ratio [HR] 4.54, 95% Confidence Interval [CI] 1.86, 11.10, p = 0.001). When including other cerebrovascular disease (history of carotid endarterectomy or transient ischemic attack) in the model, the risk was three-fold higher (HR 3.06, 95% CI 1.23, 7.62). No other conditions evaluated in the secondary analyses were found to confound this relationship. There was no effect in non-APOE ɛ4 carriers (HR 1.03, 95% CI 0.37, 2.80). There were no significant associations between RAVO and AD in either APOE group. Conclusion:Older dementia-free patients who present with RAVO and carry the APOE ɛ4 allele appear to be at higher risk for vascular dementia.

Keywords: Alzheimer’s disease, cohort study, epidemiology, retinal artery occlusion, retinal vascular occlusion, retinal vein occlusion, vascular dementia

DOI: 10.3233/JAD-201492

Journal: Journal of Alzheimer's Disease, vol. 81, no. 1, pp. 245-253, 2021