Study of the Impact of a Flavanol Containing Food Product and Exercise on Cognitive Function and Brain Structure

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.