1 NeuroQAM Research Centre, Université du Québec à Montréal (UQAM), Canada; McConnell Brain Imaging Centre, Montreal Neurological Institute, Canada.
2 McConnell Brain Imaging Centre, Montreal Neurological Institute, Canada; PERFORM Research Centre, Concordia University, Canada.
3 McConnell Brain Imaging Centre, Montreal Neurological Institute, Canada; McGill Centre for Studies in Aging, Douglas Mental Health University Institute, Canada.
4 McConnell Brain Imaging Centre, Montreal Neurological Institute, Canada.
5 NeuroQAM Research Centre, Université du Québec à Montréal (UQAM), Canada; McConnell Brain Imaging Centre, Montreal Neurological Institute, Canada; McGill Centre for Studies in Aging, Douglas Mental Health University Institute, Canada. Electronic address: bedard.marc-andre@uqam.ca.

Background: Severe cholinergic degeneration is known to occur in Parkinson's disease (PD) and is thought to play a primary role in the cognitive decline associated with this disease. Although cholinergic losses occur in all patients with PD, cognitive performance remains normal for many of them, suggesting compensatory mechanisms in those.

Objectives: This exploratory study aimed at verifying if normal cognition in PD may involve distinctive features of the brain cholinergic systems.

Methods: Following extensive neuropsychological screening in 25 patients with PD, 12 were selected and evenly distributed between a cognitively normal (PD-CN) group, and a mild cognitive impairment (PD-MCI) group. Each group was compared with matched healthy volunteers (HV) on standardized cognitive scales (MoCA, PDCRS), and PET imaging with [¹⁸F]-FEOBV, a sensitive measurement of brain cholinergic innervation density.

Results: [¹⁸F]-FEOBV uptake reductions were observed in PD-CN as well as in PD-MCI, with the lowest values located in the posterior cortical areas. However, in PD-CN but not in PD-MCI, there was a significant and bilateral increase of [¹⁸F]-FEOBV uptake, exclusively located in the hippocampus. Significant correlations were observed between cognitive performance and hippocampal [¹⁸F]-FEOBV uptake.

Conclusion: These findings suggest a compensatory upregulation of the hippocampal cholinergic innervation in PD-CN, which might underly normal cognitive performances in spite of cortical cholinergic denervation in other regions.