Age‐related neurovascular coupling impairment is associated with cognitive decline in healthy individuals
Authors: Lipecz Agnes , Csipo Tamas , Tarantini Stefano , Hand Rachel A. , Ngo Bich‐Thy N. , Balasubramanian Priya , Kiss Tamas , Csiszar Anna , Ungvari Zoltan , Yabluchanskiy Andriy 
Published: June 2021

BackgroundIt is predicted that by the year 2030 every 5th American will be >65 years of age. There is growing importance to understand age‐associated changes that lead to vascular cognitive impairment (CI) and dementia. Normal brain function is critically dependent on moment‐to‐moment adjustment of cerebral blood flow (CBF) to neuronal activity, the process also known as neurovascular coupling (NVC). It is now well established that diminished NVC, specifically in cerebral microvasculature, plays a causal role in CI in animal models of aging, however, little is known about the effects of aging on NVC responses and their role in cognitive decline in human subjects. Transcranial Doppler (TCD) ultrasound is currently employed as an important tool to measure NVC responses in larger cerebral vessels in response to cognitive stimulation in humans, however, TCD does not provide direct information about the diameter of measured cerebral vessels and it is not clear whether same changes are applicable to cerebral microcirculation. Since human retina shares similar embryologic origins with central nervous system, studying NVC responses in the retinal vessels using Dynamic Vessel Analysis (DVA) may provide another important tool to study changes in cerebral microcirculation with aging. In this study, our goal was to investigate age‐related changes of NVC responses in macro‐ and microcirculation and their association with cognitive decline.MethodsFor our study, we enrolled 23 healthy adult volunteers of 26–80 years of age (Y: n=10, <40 y.o.; and A: n=12, >65 y.o.). NVC responses in cerebral macrocirculation were measured using TCD in the middle cerebral artery (MCA) during cognitive stimulation with N‐back task. CBF velocity was evaluated as a percent change of the flow during 2‐back test relative to 0‐back test. DVA was performed on the right eye of each subject using a mydriatic retinal camera and change of diameter relative to baseline in the pair of retinal artery and vein was measured during and after three consecutive 20s flicker/80s recovery intervals. NVC measurements were adjusted to mean arterial pressure.ResultsIn agreement with current knowledge, we observed age‐dependent decline in cognitive performance during N‐back test (98.8±0.4% correct answers in Y vs 91.1±2.1% in A, p<0.002), and our data showed that these changes were accompanied by a decrease in CBFv in large cerebral vessels such as MCA (0.84±0.11‰/mmHg in Y vs 0.41±0.13‰/mmHg in A, p= 0.02). We have also observed that aging impaired NVC responses in retinal vessels evidenced by near‐significant decrease in maximal arterial dilation (0.37±0.06‰/mmHg in Y vs 0.18±0.06‰/mmHg in A, p=0.055) and pronounced arterial constriction (0.43±0.07‰/mmHg in Y vs 0.11±0.03‰/mmHg in A, p=0.0005).SummaryOur results indicate that cognitive performance in healthy aged individuals is associated with impairment of NVC responses in cerebral macro‐ and microcirculation. DVA may be a useful tool for detailed assessment of vascular function and for early detection of individuals at risk for VCID.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.