From imaging to modulating the human locus coeruleus along healthy aging and the Alzheimer’s disease continuum

This thesis explores the aging population’s challenges, particularly the rise in Alzheimer’s disease (AD), and investigates potential early interventions targeting the locus coeruleus (LC). The LC, vulnerable to early AD processes, plays a key role in maintaining cognitive functions and brain health in aging. The research focuses on two areas: understanding LC structure in aging and AD, and assessing non-invasive stimulation techniques to modulate LC function for boosting cognition. Part I examined LC structure using advanced imaging and autopsy data. Findings revealed that LC health impacts brain microstructure and that asymmetry in LC neuronal density may signal advanced AD progression. Part II explored non-invasive stimulation techniques: blue light exposure and transcutaneous vagus nerve stimulation (tVNS). Results showed that blue light enhances LC-related cognitive responses, while tVNS benefits attention in individuals with healthier LC integrity, highlighting variability in response.
Together, these findings underscore the LC as a key nucleus and a potential target for early AD interventions and cognitive aging strategies.