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

J Alzheimers Dis. 2021;81(1):245-253. doi: 10.3233/JAD-201492.


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 APOEɛ4 genotype and adjusted for demographic and clinical factors.

Results: On review of 41,216 person-years (4,743 participants), 266 (5.6%) experienced RAVO. APOEɛ4 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-APOEɛ4 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 APOEɛ4 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Dementia, Vascular / etiology*
  • Female
  • Humans
  • Male
  • Prospective Studies
  • Retinal Artery Occlusion / complications*
  • Retinal Vein Occlusion / complications*
  • Risk Factors