Odor identification and olfactory-system connectivity in the PPMI Parkinson's disease cohort - Preregistration

This record contains the preregistration and accompanying technical appendix for the study. Olfactory dysfunction can precede the manifestation of motor symptoms of Parkinson’s disease (PD) by several years (Ross et al., 2008). Understanding its neural correlates may help characterize how olfactory impairment relates to brain function in PD. A previous study using data from the Parkinson’s Precision Medicine Initiative (PPMI) examined entorhinal seed connectivity in relation to olfactory performance (Fan et al., 2022). This study will examine associations between odor-identification performance and resting-state connectivity using MRI and clinical data from PPMI. We will analyze one selected scan per participant, acquired between April 2021 and November 2024, with a temporally matched University of Pennsylvania Smell Identification Test (UPSIT). The primary analysis includes 267 participants and tests whether continuous UPSIT performance is associated with connectivity between the mean signal of an independently defined olfactory activation map and external brain voxels within the shared valid search territory. The secondary analysis includes 213 participants meeting regional signal criteria and tests whether UPSIT performance is associated with functional segregation, defined by the balance of connectivity within anatomical subdivisions of the olfactory map and their connectivity to fixed external cerebral reference parcels. Both analyses will adjust for prespecified demographic, motion and acquisition factors. The study will characterize cross-sectional neural correlates of odor-identification performance in PD.