Greater physical fitness (VO2max) in healthy older adults associated with increased integrity of the locus coeruleus–noradrenergic system

Aim Physical activity (PA) is a key component for brain health and Reserve, and it is among the main dementia protective factors. However, the neurobiological mechanisms underpinning Reserve are not fully understood. In this regard, a noradrenergic (NA) theory of cognitive reserve (Robertson, 2013) has proposed that the upregulation of NA system might be a key factor for building reserve and resilience to neurodegeneration because of the neuroprotective role of NA across the brain. PA elicits an enhanced catecholamine response, in particular for NA. By increasing physical commitment, a greater amount of NA is synthetised in response to higher oxygen demand. More physically trained individuals show greater capabilities to carry oxygen resulting in greater Vo2max – a measure of oxygen uptake and physical fitness (PF). Methods We hypothesized that greater Vo2max would be related to greater Locus Coeruleus (LC) MRI signal intensity. In a sample of 41 healthy subjects, we performed Voxel‐Based Morphometry analyses, then repeated for the other neuromodulators as a control procedure (Serotonin, Dopamine and Acetylcholine). Results As hypothesized, greater Vo2max related to greater LC signal intensity, and weaker associations emerged for the other neuromodulators. Conclusion This newly established link between Vo2max and LC–NA system offers further understanding of the neurobiology underpinning Reserve in relationship to PA. While this study supports Robertson's theory proposing the upregulation of the NA system as a possible key factor building Reserve, it also provides ground for increasing LC–NA system resilience to neurodegeneration via Vo2max enhancement.