Age-related impairment of neurovascular coupling responses: a dynamic vessel analysis (DVA)-based approach to measure decreased flicker light stimulus-induced retinal arteriolar dilation in healthy older adults

摘要

Aging is a major risk factor for vascular cognitive impairment and dementia (VCID). Recent studies demonstrate that cerebromicrovascular dysfunction plays a causal role in the development of age-related cognitive impairment, in part via disruption of neurovascular coupling (NVC) responses. NVC (functional hyperemia) is responsible for adjusting cerebral blood flow to the increased energetic demands of activated neurons, and in preclinical animal models of aging, pharmacological restoration of NVC is associated with improved cognitive performance. To translate these findings, there is an increasing need to develop novel and sensitive tools to assess cerebromicrovascular function and NVC to assess risk for VCID and evaluate treatment efficacy. Due to shared developmental origins, anatomical features, and physiology, assessment of retinal vessel function may serve as an important surrogate outcome measure to study neurovascular dysfunction. The present study was designed to compare NVC responses in young (< 45 years of age; n = 18) and aged (> 65 years of age; n = 11) healthy human subjects by assessing flicker light-induced changes in the diameter of retinal arterioles using a dynamic vessel analyzer (DVA)-based approach. We found that NVC responses in retinal arterioles were significantly decreased in older adults as compared with younger subjects. We propose that the DVA-based approach can be used to assess NVC, as a surrogate cerebromicrovascular outcome measure, to evaluate the effects of therapeutic interventions in older individuals.