Retinal vascular caliber and risk of dementia: the Rotterdam study

Retinal vessels provide a unique opportunity to study both systemic and cerebrovascular disease. Smaller retinal arteriolar calibers are strongly related to hypertension, whereas larger retinal venular calibers are more related to inflammation, cerebral hypoperfusion, and cerebrovascular disease. Whether retinal vessel calibers are related to dementia remains unclear.

We investigated whether retinal arteriolar and venular calibers are associated with risk of dementia, and its subtypes Alzheimer disease (AD) and vascular dementia, in the prospective population-based Rotterdam Study. Digitized retinal images were available in 5,553 participants aged 55 years or over and dementia-free at baseline (1990-1993). Participants were re-examined in 1993-1994, 1997-1999, and 2002-2004 and were continuously monitored for development of dementia.

During a mean follow-up of 11.6 years, 655 participants developed dementia. AD was diagnosed in 519 and vascular dementia in 73 participants. Larger venular calibers were associated with an increased risk of dementia, in particular vascular dementia (age- and sex-adjusted hazard ratio per SD increase: 1.31; 95% confidence interval 1.06-1.64), but not AD. The association remained significant after adjustment for stroke and cardiovascular risk factors. Smaller arteriolar calibers were also associated with an increased risk of vascular dementia, yet only when adjusted for venular calibers.

Retinal venular widening is associated with an increased risk of vascular dementia. Our findings are in line with previous observations in stroke and cerebral small-vessel disease and suggest that the association between larger retinal venular calibers and dementia may reflect cerebral hypoperfusion and subsequent ischemia.