Age‐related Changes in Systemic Circulation Promote Vascular Maladaptation and Impair Vascular Reactivity in Retinal and Brain Circulation in Older Adults

Abstract

IntroductionNormal brain function requires appropriate provision of oxygen, glucose, and other nutrients. This requirement is fulfilled through continuous adjustment of cerebral blood flow (CBF), the process also known as neurovascular coupling (NVC). Therefore, impairment of the resting CBF or impairment of NVC in the brain may be responsible for the development of vascular cognitive deficits in aging. A novel method, Dynamic Retinal Vessel Analysis (DVA) allows evaluation of NVC responses in the retinal circulation in response to photoreceptor stimulation. Considering that human retina shares similar embryologic origins with the central nervous system, this approach may provide a novel and non‐invasive tool to screen subjects at risk for development of vascular cognitive impairment. In this study, we hypothesize that examination of retinal vessels may provide a proxy measure of the microcirculatory health of the brain. We test whether the arterio‐venous ratio (AVR) and NVC measured in the retina correlate with age, cognitive function, central and cerebrovascular hemodynamics.MethodsFor our study, we enrolled 44 healthy adults 23–86 years of age. DVA and static vessel analysis was performed using a mydriatic retinal camera to determine retinal NVC and AVR. Transcranial Doppler Sonography (TCD) was used to assess resting CBF velocity and pulsatility in the middle cerebral artery (MCA). Pulse Waveform Analysis was used to measure central hemodynamic pressures. and stiffness (augmentation index, AIx) was calculated from these results. Cognitive performance was assessed using Cambridge Neuropsychological Cognitive Test Automated Battery (CANTAB), specifically, Paired Associates Learning (PAL) and Delayed Matching to Sample (DMS) tests. Spearman’s correlation between variables was used for statistical analysis.ResultsRetinal NVC showed negative (rho=−0.48, p=0.02), and MCA pulsatility showed positive (rho=0.69, p<0.01) correlation with aortic pulse pressure. Neither of these vascular parameters correlated with central arterial stiffness (AIx). Older age was associated with decreased cognitive performance: total errors on PAL test (PALTEA28, rho=0.49, p<0.01),mean latency to the correct response during DMS (DMSMLAD, rho=0.46, p<0.01), and correct responses in DMS (DMSPC rho=−0.43, p<0.01). AVR correlated negatively with PALTEA28 (rho=−0.48, p<0.01) and positively with DMSPC (rho=0.64, p<0.01), retinal arteriolar dilation correlated negatively with DMSMLAD (rho=−0.32, p=0.04).ConclusionsOur results demonstrate that age‐related changes in the macrocirculation lead to the maladaptation and decreased reactivity of retinal microcirculation. The association between retinal‐, and brain hemodynamics, together with cognitive performance suggests that the retinal microcirculation may reflect the health of the cerebral microcirculation.