In vivo cholinergic basal forebrain degeneration and cognition in Parkinson's disease: Imaging results from the COPPADIS study
Michel J. Grothe, Miguel A. Labrador‐Espinosa, Silvia Jesús, Daniel Macías‐García, Astrid Adarmes‐Gómez, Fátima Carrillo, Elena Iglesias Camacho, Pablo Franco‐Rosado, Florinda Roldán Lora, Juan Francisco Martin‐Rodríguez, Miquel Aguilar Barberà, Pau Pástor, Sonia Escalante Arroyo, Berta Solano Vila, A. Cots Foraster, Javier Ruiz‐Martínez, Francisco Carrillo Padilla, Mercedes Pueyo Morlans, Isabel González Aramburu, Jon Infante Ceberio, Jorge Hernández‐Vara, Oriol de Fábregues-Boixar, Teresa de Deus Fonticoba, Berta Pascual‐Sedano, Jaime Kulisevsky, Pablo Martínez‐Martín, Diego Santos‐García, Pablo Mir
Abstract
INTRODUCTION: We aimed to assess associations between multimodal neuroimaging measures of cholinergic basal forebrain (CBF) integrity and cognition in Parkinson's disease (PD) without dementia. METHODS: The study included a total of 180 non-demented PD patients and 45 healthy controls, who underwent structural MRI acquisitions and standardized neurocognitive assessment through the PD-Cognitive Rating Scale (PD-CRS) within the multicentric COPPADIS-2015 study. A subset of 73 patients also had Diffusion Tensor Imaging (DTI) acquisitions. Volumetric and microstructural (mean diffusivity, MD) indices of CBF degeneration were automatically extracted using a stereotactic CBF atlas. For comparison, we also assessed multimodal indices of hippocampal degeneration. Associations between imaging measures and cognitive performance were assessed using linear models. RESULTS: : r = 0.37, p < 0.001), and this association remained significant after controlling for several potential confounding variables (p = 0.004). Analysis of individual item scores showed that this association spanned executive and memory domains. No analogue cognition associations were observed for CBF MD. In covariate-controlled models, hippocampal volume was not associated with cognition in PD, but there was a significant association for hippocampal MD (p = 0.02). CONCLUSIONS: Early cognitive deficits in PD without dementia are more closely related to structural MRI measures of CBF degeneration than hippocampal degeneration. In our multicentric imaging acquisitions, DTI-based diffusion measures in the CBF were inferior to standard volumetric assessments for capturing cognition-relevant changes in non-demented PD.