Alzheimer's Imaging Consortium

Area of Science:

• Neuroscience
• Neurology

Background:

• Cognitive impairment is common in Parkinson's disease (PD).
• The brain's cholinergic system, particularly projections from the nucleus basalis of Meynert (NBM), supports normal cognition.
• Previous research linked NBM integrity and PET measures of cholinergic function to cognition in PD.

Purpose of the Study:

• To investigate if the structural integrity of cortical cholinergic pathways at baseline is associated with longitudinal cognitive function in PD patients.
• To determine if baseline cholinergic projection integrity predicts the rate of cognitive decline in Parkinson's disease.

Main Methods:

• Bayesian linear mixed-effects models were used to analyze data from 101 PD participants at baseline and 59 at follow-up (average 3.2 years).
• Cognitive function was assessed across four domains using neuropsychological testing.
• Cortical cholinergic integrity was quantified using a composite score from diffusion-weighted MRI (DWI) measures (mean diffusivity, free water fraction, fibre density, and cross-section).

Main Results:

• Baseline cortical cholinergic projection integrity showed a modest, independent association with cognitive performance (p=0.98%).
• No significant association was found between cognitive performance and time, indicating no overall cognitive decline in this sample.
• There was no evidence of an interaction between baseline integrity and time, meaning baseline integrity did not predict the rate of cognitive change.

Conclusions:

• A modest association exists between baseline cortical cholinergic integrity and cognitive performance in PD.
• The findings suggest that the measured cholinergic integrity is consistently related to cognition but does not predict cognitive decline rates.
• Future research could explore combining measures from other brain neurotransmitter systems to better understand cognitive trajectories in PD.