Pre-clinical manifestations of Parkinson's disease: Locus coeruleus, sleep, and cognition

Parkinson’s disease (PD) is the second most prevalent type of neurodegeneration, characterized by both motor and non-motor symptoms. Recent evidence highlights the relevance of the Locus Coeruleus (LC), located in the brainstem, as a key brain structure for this disease, exhibiting signs of neurodegeneration years prior to clinical manifestation of the symptoms. This brain site regulates sleep-wake cycles, and its structural and functional abnormalities most likely contribute to PD-related sleep disturbances. Additionally, the LC has proven critical for cognitive decline, which is another non-motor symptom of the disease. By further investigating the role of the LC in PD and its contribution to sleep disturbances and cognition, the main aims of my doctoral project are to determine how sleep and cognitive functioning relate with LC structure and function in healthy participants with known genetic risk for the disease and to explore if these variables exhibit different associations depending on the age-range considered. For this purpose, data will be collected on one-hundred healthy adults aged 20 to 70y using Ultra-High-Field (UHF) 7 Tesla Magnetic Resonance Imaging (MRI). The whole project comprises three complementary work packages. Here, we will present the first preliminary results that will relate LC structure to REM sleep quality and cognition in at least 75 healthy individuals aged 18 to 75y. These first results will determine some of the core link between sleep, cognition and the LC, and will pave the way for future investigations related to PD risk and PD prodromal stages.