Mars Flavanol Exercise and Cognitive Function Study
Condition: Cognitive Function
Study type: Interventional

Summary: 
      This is a randomized controlled trial to test the impact of a flavonol containing food
      product and aerobic exercise on cognitive function and brain structure.
    

Detailed description: 
      I. Background and Significance A. The epidemiology of cognitive aging. Encompassing multiple
      cognitive domains, higher order thinking includes memory, language, abstract reasoning, and
      visuospatial ability. A range of studies have established that memory is a cognitive domain
      differentially targeted by the normal aging process. With an increase in lifespan and a
      decrease in co-morbid diseases, aging individuals expect to lead cognitively-challenging
      lives. Even mild forgetfulness, therefore, is no longer considered 'benign'. Indeed, with the
      exponential growth of the aging population, and since memory decline will occur in all of us
      as we age, age-related memory decline has emerged as a major societal problem.

      B. The anatomy of cognitive aging. A range of studies in humans, non-human primates and
      rodents have established that the hippocampal formation, a brain circuit vital for memory, is
      targeted by the aging process. Age-related hippocampal dysfunction is therefore a major
      contributor to age-related memory decline.

      The hippocampal formation is organized as a circuit, made up of separate but interconnected
      regions, including the entorhinal cortex, the dentate gyrus, the CA subfields, and the
      subiculum. Because of hippocampal circuit properties, dysfunction in one subregion will
      affect the function of neighboring subregions and the hippocampal circuit as a whole. Thus,
      when confronted with any process that causes the hippocampal circuit to malfunction,
      pinpointing the subregion that is most effected becomes an important goal.

      In the case of age-related memory decline, a range of studies in humans, non-human primates,
      and rodents, have suggested that normal aging causes hippocampal dysfunction by
      differentially targeting the dentate gyrus.

      C. Imaging cognitive aging. The anatomical organization of the hippocampal circuit and the
      differential vulnerability of the dentate gyrus to cognitive aging imposes specific
      requirements on brain imaging techniques. Specifically, an imaging technique must be able to
      assess the functional integrity of the multiple hippocampal subregions, in particular the
      dentate gyrus. With this in mind, our lab has been dedicated to optimizing a functional brain
      imaging approach applicable to both the human and rodent hippocampal formation. We have
      recently achieved this goal, and have been applying our cross-species imaging capabilities to
      investigate a range of process that affect hippocampal function.

      D. Flavanols, exercise, and cognitive aging. Previous studies have established that physical
      exercise improved hippocampal function. We have recently exploited our cross-species imaging
      techniques to show, that within the hippocampal circuit, exercise has a selective effect on
      dentate gyrus function, in humans and in mice. Independently, a recent study has shown that
      the flavanol epichatechin improves hippocampal function, and importantly, within the
      hippocampal circuit, epichatechin was found to differentially target the dentate gyrus.
      Moreover, this study showed that epichatechin coupled with exercise had its greatest effect
      on dentate gyrus function.

      E. Summary. Starting at around 30 years of age, all of us will begin experiencing the
      insidious cognitive slide of age-related memory decline. With the expansion of aging,
      age-related memory decline is swelling to epidemic proportions, and ameliorating age-related
      memory decline has emerged as major societal goal.

      This proposal is designed to test the following hypothesis: That flavanols with or without
      physical exercise will ameliorate age-related memory decline. This hypothesis is informed by
      two sets of interleaving findings: First, a range of studies have pinpointed dysfunction in
      the dentate gyrus as a specific brain region contributing to age-related memory decline; and
      second, flavanol consumption with or without physical exercise enhances memory performance by
      improving dentate gyrus function.

      In order to experimentally test this hypothesis an imaging technique is required that can
      assess the functional integrity of the dentate gyrus, techniques that are now available.
      Importantly, these imaging techniques have been developed so that can they can be applied not
      only to humans but also to animal models, generating the same 'imaging readout'.
      Cross-species imaging is particularly important for translational studies.
    

Intervention name(s): Flavanol containing food product; Aerobic training; Food product lacking flavanol; Wait list control
Intervention type(s): Dietary Supplement; Behavioral; Dietary Supplement; Behavioral
Intervention description(s): 12 weeks, 2X/day, 20g serving; 4X/week, 1 hour/session at 75% maximum HR; 20 g serving, 2X/day, food additive lacking flavonol; 12 week wait list control condition during which participants abstain from aerobic exercise
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Single (Investigator)
Primary purpose: Basic Science
Keywords: flavonol; exercise; dentate gyrus; cerebral blood volume; dentate gyrus CBV