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

Parkinson’s disease (PD) is the second most common type of neurodegeneration. Although prevailing for its diagnosis, motor symptoms are not the only type of alterations defining PD. Notably, non-motor alterations impact patients’ quality of life considerably and, interestingly, seem to predate the motor manifestations. In the context of PD-related non-motor abnormalities, the locus coeruleus (LC) is thought to be involved in cognitive decline and in sleep disturbances, including REM-sleep behavior disorder, known to be prodromal to parkinsonism. Therefore, the LC may be seen as a central brain site for preclinical manifestations of PD, although the impact of its altered structure and functioning on non-motor alterations remains to be determined. This study aims at determining how sleep and cognitive functioning relate with the LC structure and function in healthy participants with known genetic risk for the disease and if these variables exhibit different associations depending on the age-range considered.
100 healthy participants aged 20 to 70 years are being recruited. A genetic variable will be included to assess each participant’s genetic risk for PD through the computation of a polygenic risk score. It will then be related to REM sleep measures and cognition, especially memory, attention, and executive functions, along with the integrity and function of the LC. The use of the 7T MRI will be crucial to image such a small and deeply located brain structure. Specifically, both structural and functional measures will be included, aiming at monitoring LC neuromelanin contrast, its iron and myelin content, and its functional response to an oddball task.
This research may shed additional light on some of the core links among sleep, the LC and PD and may contribute to the isolation of novel intervention targets.