Dissociable cognitive deficits associated with substantia nigra and locus coeruleus degeneration in Parkinson’s disease

Poster Session F - Tuesday, April 16, 2024, 8:00 – 10:00 am EDT, Sheraton Hall ABC

Sophie Sun¹ (sophie.sun@mail.mcgill.ca), Victoria Madge¹, Alain Dagher¹, D. Louis Collins¹, Madeleine Sharp¹; ¹McGill University

The dopaminergic substantia nigra (SN) and noradrenergic locus coeruleus (LC) play a critical role in modulating a wide range of cognitive processes. Though they have largely been studied in isolation, there is evidence that the dopaminergic and noradrenergic systems modulate overlapping cognitive functions. The question of if and how these two systems independently contribute to cognition is especially relevant to Parkinson’s disease (PD) where significant degeneration to the SN and LC occurs early in the disease. However, the shared and distinct contributions of SN and LC degeneration to the cognitive deficits of PD is unknown. To address this gap, we used neuromelanin-sensitive MRI to measure degeneration in the SN and LC in 70 Parkinson’s patients and 28 older adults. A reinforcement learning task was used to measure reward learning and standard neuropsychological tasks were used to measure attention/working memory, executive function, and memory. Visuospatial and language performance, not thought to be related to either dopamine or noradrenaline systems, were used as controls. We found that reduced SN neuromelanin signal was associated with worse reward learning in PD patients, but that LC was not. In contrast, reduced LC signal was associated with worse attention/working memory and executive function. We did not find similar relationships in controls, and SN and LC signals were not associated with memory, language, nor visuospatial function in either group. These results suggest that individual differences in the degree of degeneration in the SN and LC could explain differences in the cognitive profiles of PD patients.

Topic Area: OTHER