AbstractBackgroundA common misconception about ageing is that a decline in brain health is solely observed in those who have dementia. In fact, decreases in cognitive function and reductions in brain volume are commonly observed in adults over the age of 65. Brain changes in older adulthood have been shown to be decreased in individuals who are more physically active, with alterations in lipid and lipoprotein metabolism emerging as a potential mechanism, however this is still not well understood. In light of this, our study aims to investigate the effects of moderate and high intensity aerobic exercise on lipid and lipoprotein metabolism to assess the efficacy of exercise in reducing brain atrophy in cognitively normal older adults.MethodSamples were collected from the Intense Physical Activity and Cognition (IPAC) study, during which a six‐month randomised controlled trial was performed to observe the impact of aerobic exercise on brain volume measurements in cognitively normal older adults (n = 99, aged 60‐80). Blood samples and neuroimaging measures were collected at baseline and following the completion of the intervention (6 months). Baseline and post‐intervention plasma samples were collected and analysed using 1H‐NMR spectroscopy to quantify 112 lipoproteins, followed by a comprehensive in‐house mass spectrometry (MS) lipids screen targeting >1200 individual lipid species.ResultPreliminary analyses suggest that lipid and lipoprotein metabolism is altered by aerobic exercise and that these alterations are associated with changes in brain volume. Further analyses will increase the sample size, and also evaluate other factors (i.e. sex, APOE status) as potential moderators of the link between aerobic exercise and the metabolism of lipids and lipoproteins.ConclusionTo our knowledge, this study is the first to establish the relationship between exercise and lipids and lipoprotein metabolism, and their association to brain volume in cognitively normal older adults. The significance of our findings will be evaluated further using an external validation cohort. The discovery of novel lipids or metabolic pathways will create avenues for future research into new therapeutic targets for future healthy ageing interventions.