The metabolic, cerebral haemodynamic, and cognitive effects of trans-resveratrol in healthy, young and older humans

Eschle, Timothy (2017) The metabolic, cerebral haemodynamic, and cognitive effects of trans-resveratrol in healthy, young and older humans. Doctoral thesis, Northumbria University.

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Abstract

The stilbene polyphenol trans-resveratrol has shown to interact with several mechanisms that may serve to preserve or even enhance cognitive function, either directly or indirectly. A small, but growing body of research has found resveratrol is capable of nitric oxide (NO)-mediated increases to cerebral blood flow (CBF), which, in turn, serve to increase access to the neural metabolic substrates (oxygen & glucose). To date, research has found increases in CBF and oxygen extraction resulting from oral resveratrol administration, yet these have not been found in conjunction with improved cognitive performance in young, healthy samples; questioning the CBF mechanism of resveratrol as an appropriate means to enhance cognitive performance.

Additionally, it was hypothesized that the CBF effects of resveratrol may provide increased utility in naturally ageing populations, as such cohorts are noted to experience reductions to CBF and neural oxygen metabolism; which, in turn, is an acknowledged contributor of age-related cognition. To link the reduced neural oxygen availability suffered during ageing and subsequent poorer cognitive performance, the current thesis also aimed to test the use of hypoxia as a representative, experimental model for the cognitive ageing process. The purpose of this model was to provide clear and direct evidence that the CBF effects of resveratrol can function to attenuate reductions to cognition imposed via a compromised neural fuel supply. Therefore, the four acute, placebo-controlled, double-blind, crossover investigations of this thesis aimed to assess the efficacy of the resveratrol-mediated CBF effects to engender cognitive enhancement; in both young and older adults.

The key findings from this thesis show that there is merit to a hypoxia model of cognitive ageing, evidenced by clear cognitive deficits that are also commonly observed with ageing cohorts. Furthermore, a single dose of resveratrol showed to increase fuel oxidation during cognitive performance when measured via indirect calorimetry. However, resveratrol was unable to provide increases to CBF (when measured by Near-Infrared Spectroscopy) or cognitive performance in hypoxia or in ageing populations. In fact, resveratrol was found to impair cognitive performance in the latter. The results of this thesis therefore do not support the argument that resveratrol can provide CBF-mediated cognitive enhancement in healthy, young or naturally ageing samples.

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