034-23 – Investigating novel microscopic and metabolic brain abnormalities in newly diagnosed Parkinson’s disease: A future pilot study

Parkinson’s disease (PD) is a heterogenous disease that typically presents with disturbances to motor and non-motor functioning. Four subtypes have previously been identified, the two most common being tremor dominant PD (TD-PD) and non-tremor dominant PD (nTD-PD), differentiated by motor symptomology. Prior research has also identified a higher prevalence of cognitive decline in nTD-PD compared to TD-PD. Therefore, abnormalities in non-motor networks should also be taken into consideration when investigating imaging correlates. There is a considerable amount of imaging research to distinguish abnormalities between controls and people with PD; however, numbers are markedly reduced when only patients with a new diagnosis of PD are investigated, and even more so when phenotypes are differentiated. Advanced MRI sequences represent a promising tool to further demarcate the imaging abnormalities between early PD phenotypes.
The proposed research will pilot Fiber Ball Imaging (FBI) and Proton-Echo-Planar-Spectroscopic-Imaging (PEPSI) in the early stages of PD. FBI models the white matter microstructure allowing separate calculations of intra and extra axonal diffusivity. PEPSI compares the chemical composition of brain tissue and quantifies metabolic function. Patients will be recruited by a neurologist at The Walton Centre NHS Foundation Trust, with a target of 45 participants: 15 with TD-PD, 15 with nTD-PD, and 15 controls. Participants will undergo a neuropsychological battery to measure motor dysfunction, cognitive dysfunction, and mood abnormalities. The main research objective is to determine if patients with newly diagnosed PD have measurable abnormalities in local brain microstructure and metabolism, and if these abnormalities systematically differ based on primary disease phenotype. The secondary objective is to determine if phenotypical abnormalities are related to cognitive performance. These approaches have yet to be utilised in phenotype-sensitive PD research