In vivo cholinergic basal forebrain degeneration and cognition in Parkinson's disease: Imaging results from the COPPADIS study

• Published in: Parkinsonism & related disorders Vol. 88; pp. 68 - 75
• Main Authors: Grothe, Michel J., Labrador-Espinosa, Miguel A., Jesús, Silvia, Macías-García, Daniel, Adarmes-Gómez, Astrid, Carrillo, Fátima, Camacho, Elena Iglesias, Franco-Rosado, Pablo, Lora, Florinda Roldán, Martín-Rodríguez, Juan Francisco, Barberá, Miquel Aguilar, Pastor, Pau, Arroyo, Sonia Escalante, Vila, Berta Solano, Foraster, Anna Cots, Martínez, Javier Ruiz, Padilla, Francisco Carrillo, Morlans, Mercedes Pueyo, Aramburu, Isabel González, Ceberio, Jon Infante, Vara, Jorge Hernández, de Fábregues-Boixar, Oriol, de Deus Fonticoba, Teresa, Pascual-Sedano, Berta, Kulisevsky, Jaime, Martínez-Martín, Pablo, Santos-García, Diego, Mir, Pablo
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.07.2021
• Subjects: Aged; Basal Forebrain - diagnostic imaging; Basal Forebrain - pathology; Cognitive Dysfunction - etiology; Cognitive Dysfunction - physiopathology; Cohort Studies; Diffusion; Diffusion Tensor Imaging; DTI; Female; Hippocampus - diagnostic imaging; Hippocampus - pathology; Humans; Magnetic Resonance Imaging; Male; Middle Aged; MRI; Multimodal Imaging; Neuroimaging; Neuropsychological Tests; Nucleus basalis Meynert; Parkinson Disease - complications; Parkinson Disease - diagnostic imaging; Parkinson Disease - pathology; Parkinson Disease - physiopathology; Parkinson's disease; Substantia innominata; DTI; Nucleus basalis Meynert; Parkinson's disease; Substantia innominata; Diffusion; MRI
• ISSN: 1353-8020; 1873-5126
• DOI: 10.1016/j.parkreldis.2021.05.027

We aimed to assess associations between multimodal neuroimaging measures of cholinergic basal forebrain (CBF) integrity and cognition in Parkinson's disease (PD) without dementia. 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. Compared to controls, CBF volume was not significantly reduced in PD patients as a group. However, across PD patients lower CBF volume was significantly associated with lower global cognition (PD-CRStotal: 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). 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. •Multimodal MRI study of cognitive deficits in nondemented Parkinson's disease (PD).•Cognitive deficits in PD relate to lower cholinergic basal forebrain (CBF) volume.•Hippocampal volume not associated with cognitive deficits.•DTI diffusion measures more sensitive than volume in hippocampus but not in CBF.•Implications for the development of imaging biomarkers of cognitive decline in PD.