Retinal blood flow volume and pulsatility in aging and hypertension: relation with cognitive function and cardiovascular disease risk

Background: Aging increases risk of cardiovascular disease (CVD), cognitive decline, and vascular dementia, which are accelerated with hypertension and partially mediated by cerebrovascular dysfunction. Because retinal and cerebral vessels share embryologic origin and physiological properties, the retina may be a novel surrogate for the cerebral circulation. In these high-flow, low-resistance organs, excessive pulsatility can cause microvascular and target organ damage. Large artery pulse pressure, lower cerebral flow, and higher cerebral flow pulsatility are also associated with cognitive impairments with aging and hypertension. This study explored whether retinal blood flow dynamics could be used to provide insight into the effect of age and hypertension on cardiovascular disease risk and cognitive function. We hypothesized that decreased retinal flow volume (RFV) and increased flow pulsatility with aging would be associated with higher lifetime CVD risk and reduced cognitive function and would be exacerbated by hypertension. Methods: RFV and flow pulsatility index (PI) in the retina were assessed via Laser-Speckle Flowgraphy (LSFG) in middle-aged/older adults (age: 40-81 yrs) with (HTN; n=21; age=58±11 yrs) and without (NTN; n=9; age=52±6yrs) hypertension, and younger adults without HTN (n=23; age=30±4 yrs). LSFG non-invasively measures beat-by-beat ocular blood flow continuously during the cardiac cycle. Intraocular pressure and brachial blood pressure were measured from which ocular perfusion pressure (OPP) was calculated, which was included as a covariate in analysis. Lifetime atherosclerotic cardiovascular disease risk (ASCVD) and selected cognitive tests were performed in a subset of individuals with HTN. Results: RFV and PI did not differ between all three groups (p=0.16, p=0.76) and RFV was not correlated with age (r=-0.25, p=0.08). PI was correlated with age in the full cohort (r=0.45, p< 0.01) but was associated with age among middle-aged/older adults (r=0.50, p< 0.01) but not in the younger cohort (r=-0.08, p=0.72). The age-adjusted List Sorting test, for working memory, was negatively correlated with PI (r=-0.78, p=0.02), and positively correlated with RFV (r=0.92, p< 0.01). There was no correlation between ASCVD risk score and RFV (p=0.36) or PI (p=0.57). Conclusions: Higher retinal flow PI is associated with older age but exhibits a non-linear relation with age, with a positive relation present only after middle-age. The working memory domain of cognitive function was negatively correlated with PI and positively correlated with RFV. These data suggest that retinal flow pulsatility may be a novel surrogate for cerebral flow hemodynamics and related to cognitive aging. Funding: NIH grants R01 AG063790, P01 HL014388, T32 HL07121, and U54 TR001356. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.