Caffeine is the most commonly used stimulant drug with well documented effects on cerebral vascula-ture. Caffeine is known to non-specifically bind to adenosine receptors in the brain and to reduce resting blood flow while improving attention and cognitive function, which suggests that it may allow a more efficient dynamic blood flow regulation through neurovascular coupling. This study will use standardized dose of caffeine to test its effect on NVC responses in cerebral and retinal arterioles.
Normal brain function is critically dependent on moment-to-moment adjustment of cerebral blood flow to match demands of activated neurons. This process is known as neurovascular coupling (NVC) and recent in vivo studies demonstrate that impairment of NVC responses is associated with worse cognitive performance. Several methods are available to measure NVC responses in human subjects, including transcranial Doppler (TCD), functional near infrared spectroscopy (fNIRS), and dynamic retinal vessel analysis (DVA). Although all these methodologies aim to measure hemodynamic changes in the brain vasculature in response to cognitive, motor, or visual stimulation, the responses are evaluated on the different levels of cerebral vasculature including microvasculature (fNIRS), large cerebral vessels such as middle cerebral artery (TCD), or in the arterioles and venules of the retina (DVA). Currently, there are limited data available on the simultaneous assessment of NVC responses using these methodologies. Caffeine is the most commonly used stimulant drug with well documented effects on cerebral vasculature. Caffeine is known to non-specifically bind to adenosine receptors in the brain and to reduce resting blood flow while improving attention and cognitive function, which suggests that it may allow a more efficient dynamic blood flow regulation through neurovascular coupling. This study will use standardized dose of caffeine to test its effect on NVC responses in cerebral and retinal arterioles. This study is designed to establish the direct link between reactivity in the cerebral and retinal micro- and macrovasculature. To achieve this goal, a prospective, single-blinded, placebo controlled, cross-over study will be employed to evaluate changes in the NVC responses measured simultaneously with DVA and TCD, or DVA and fNIRS before and after administration of 100mg of incapsulated caffeine or placebo pill.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
TRIPLE
Enrollment
10
Caffeine, also known as Trimethylxanthine, will be purchased through the University of Oklahoma Health Sciences Pharmacy and formulated into capsule pills containing 100mg of active ingredient
Placebo pill will be formulated with a non active ingredient such as rice flour powder
Translational GeroScience Laboratory
Oklahoma City, Oklahoma, United States
Modified Caffeine Research Visual Analogue Scales
Caffeine Research Visual Analogue Scales consists of seven visual analogue scales ("relaxed", "alert", "jittery", "tired", "tense", "headache", overall mood") are measured from 1 to 10 and have previously been used in research to evaluate the effects of caffeine. A single "mentally fatigued" visual analogue scale (scored from 1 to 10) will be included, as previous research has shown it to be sensitive to a caffeine-glucose drink.
Time frame: Change from baseline measurements 1 hour after treatment
Static retinal vessel assessment
Static analysis of retinal vasculature will be performed to evaluate averaged retinal arteriole and venule calibers. A ratio of these two measurements will be used to calculate arteriole-venule ratio.
Time frame: Change from baseline measurements 1 hour after treatment
Dynamic retinal vessel assessment
Flicker light-induced dilation of the retinal vessels (percentage increase over baseline diameter) will be measured in the right eye of each subject using the Dynamic Vessel Analyzer (DVA, IMEDOS Systems, Jena, Germany). The change in retinal vessel diameters is tracked and reported as a %change from baseline.
Time frame: Change from baseline measurements 1 hour after treatment
Cerebrovascular reactivity using transcranial Doppler
Transcranial Doppler sonography will be assessed simultaneously with the dynamic retinal vessel analysis and the blood flow velocity will be measured in the posterior cerebral artery. Change in the blood flow velocities from baseline will be measured.
Time frame: Change from baseline measurements 1 hour after treatment
Cerebrovascular reactivity using functional near infrared spectroscopy (fNIRS)
Functional near infrared spectroscopy (fNIRS) will be performed during the finger tapping task or go-no-go cognitive task. fNIRS approach generates data that represent a relative change in oxygenated and deoxygenated hemoglobin measured over the cortical brain tissues. Cerebrovascular reactivity will be evaluated as a change in oxy- and deoxy-hemoglobin between "during" and "before" task.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: Change from baseline measurements 1 hour after treatment