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

Abstract

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: 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-CRS total :

Cholinergic systems, attentional-motor integration, and cognitive control in Parkinson's disease

“…In both datasets, nBM-SI volume correlated with global measures of cognitive performance and some domain specific measures. Similarly, in an analysis of non-demented PD subjects enrolled in the COPPADIS study, Grothe et al (2021) found that nBM-SI volume correlated with a general measure of cognitive function.…”

Free-water imaging of the cholinergic basal forebrain and pedunculopontine nucleus in Parkinson’s disease

“… 14 In particular, mean diffusivity (MD) and axial diffusivity (AD) have been used to investigate the impact of degeneration in the cholinergic nuclei. 4 , 6 , 8 However, these traditional DTI indices assume a single-tissue compartment per voxel, thereby conflating the representation of free water (FW) and tissue. FW is present as CSF and also accumulates extracellularly due to neuroinflammation.…”

Imaging the Limbic System in Parkinson’s Disease—A Review of Limbic Pathology and Clinical Symptoms

“…The severity of volume loss has also been found to be predictive of conversion to dementia [ 53 , 98 , 99 ]. Additionally, PD-related alterations in iron content [ 61 , 100 , 101 ], texture [ 34 ], microstructural integrity [ 102 , 103 , 104 ], arteriolar-cerebral-blood-volume [ 105 ], connectivity [ 106 , 107 , 108 ], but not synaptic density [ 109 ] have been reported in combination with reduced cognitive performance. Serotonergic binding in the hippocampus of PD patients was not associated with cognitive performance [ 110 ].…”

“…Using in vivo MR imaging, no volumetric difference is found for Ch1-2 and Ch4 between patients with PD and healthy controls in early PD [ 103 , 186 ]. However, lower volume is found in more advanced PD [ 187 , 188 ], correlating with cortical thinning in the bilateral posterior cingulate, parietal, and frontal and left insular regions in patients with PD-MCI [ 189 ].…”

“…Furthermore, free-water using diffusion-weighted imaging is consistently increased in the NbM in those with cognitive impairment at baseline and predicted future cognitive decline together with lower volume [ 97 , 199 , 200 , 201 , 202 ]. However, non-corrected DTI metrics were not related to cognitive impairment in the cholinergic forebrain but in the hippocampus [ 103 ]. Lower volume of the nbM also predicted cognitive decline in patients undergoing STN-DBS [ 203 ].…”