In its pioneering work, Ultimate Medicine, demonstrated the causative effect of the delta-valerobetaine pathway on cognitive impairment in aging mouse models. This project will extend these novel observations to man with the goal of developing a biomarker of early cognitive impairment. To do this, we will measure metabolites in serum samples stored from well-characterized Australian Alzheimer disease patients. If the results seen in mice are observed in man, then further studies will be required to prove that this pathway can be exploited as valuable biomarker in man. This first study will inform the design and size of future studies aimed at developing a useful, commercially available biomarker. The long-term benefit to mankind of this study could be an early biomarker of cognitive impairment allowing for earlier intervention than is possible now. In addition, new therapeutic targets and approaches for cognitive impairment could be identified.