Does Retinal Microvascular Structure Impact Neurocognitive Development in Children?

Retinal venular widening and a higher vessel tortuosity are associated with lower performance of short-term visual recognition memory in children aged 4 to 5 years, according to a study published in JAMA Network Open.

Because neurocognitive functions develop rapidly in early childhood, neurological development is at its most crucial phase during this point in a child’s life. These functions also depend on the intrinsic cooperation between cerebral structures and the circulatory system, the authors note.

“The microcirculation is a large part of the human vasculature that undergoes extensive, organ-specific perinatal maturation,” they write. “The retina is an outgrowth of the developing brain, and both tissues share morphological and functional characteristics…the retinal microvasculature can be considered as a proxy of the conditions of the blood vessels in the brain.”

Previous studies have shown poor cardiovascular health beginning at a young age results in suboptimal neurological outcomes later in life, such as lower psychomotor speed, executive function, and verbal memory.

To better understand the association between retinal vessel characteristics and neurological functioning, theninvestigators assessed data collected from 251 children by means of the Delayed Matching to Sample task of the Cambridge Neuropsychological Test Automated Battery (CANTAB).

From February 2010 to June 2014, mother-child pairs were recruited at birth, with follow-up between December 2014 and July 2018. All participants were followed up within the prospective Environmental Influence on Aging in Early Life birth cohort (ENVIRONAGE), while data for this study were analyzed from July to October 2019.

Specifically, the researchers investigated the association between retinal vasculatures and psychomotor speed, visuospatial short-term working memory, and visual short-term recognition memory. All children completed the following tasks: Motor Screening (MOT), Big/Little Circle (BLC), Spatial Span (SSP), and Delayed Matching to Sample (DMS).

Of the 251 participants, 135 (53.8%) were girls and the mean (SD) age was 4.5 (0.4) years. For the entire population, the researchers found mean measurement of the retinal arteriolar and venular diameter was 180.9 (14.4) mcm and 251.1 (19.6) mcm, respectively, while the mean vessel tortuosity value was 0.889 (0.012).

Data showed that for every 1-SD widening in central retinal venular equivalent (CRVE), children:

• Performed relatively 2.74% (95% CI, −0.12 to 5.49; P = .06) slower on the MOT test
• Had 1.76% (95% CI, −3.53% to −0.04%; P = .04) total fewer correct DMS assessments
• Made 2.94% (95% CI, 0.39-5.29; P = .02) more errors when given a previous correct answer in the DMS task on multiple linear regression modeling

In addition, “for every 1-SD widening in [central retinal arteriolar equivalent], the total percentage of errors and errors given previous correct answers in the DMS task increased 1.44% (95% CI, −3.25% to 0.29%; P = .09) and 2.30% (95% CI, −0.14% to 4.61%; P = .07), respectively.”

Higher (1-SD) vessel tortuosity was also associated with a 4.32% relative increase in latency in DMS task performance (95% CI, −0.48% to 9.12%; P = .07). However, data showed retinal vessel characteristics were not associated with BLC and SSP test outcomes.

“In this cohort study, a widening of the retinal venular diameter and increased information dimension and correlation dimension were associated with the outcome of established neurodevelopmental tests and can be regarded as potential biomarkers to evaluate neurobehavioral development in children as young as 4 years,” the authors conclude. “These noninvasive retinal measurements can support investigations into microvascular changes that accompany neurological development at a young age.”

Reference

Luyten LJ, Dockx Y, Madhloum N, et al. Association of retinal microvascular characteristics with short-term memory performance in children aged 4 to 5 years. JAMA Netw Open. 2020;3(7):e2011537. doi:10.1001/jamanetworkopen.2020.11537