Cognitive and Cholinergic Systems Trajectories in Parkinson Disease

Area of Science:

• Neuroscience
• Neurology
• Radiochemistry

Background:

• Cognitive decline is a significant non-motor symptom in Parkinson disease (PD).
• Cholinergic system degeneration is implicated in PD-related cognitive impairment.
• Previous studies primarily used cross-sectional designs to examine this association.

Purpose of the Study:

• To investigate whether baseline vesicular acetylcholine transporter (VAChT) binding predicts longitudinal cognitive changes in non-demented PD patients.
• To explore the relationship between [18F]-FEOBV binding patterns and cognitive trajectories over two years.
• To elucidate the role of the cholinergic system in cognitive variability in PD.

Main Methods:

• Seventy-five mild to moderate, non-demented PD subjects underwent baseline cognitive assessments and [18F]-FEOBV PET imaging.
• Cognitive function was reassessed after two years, classifying participants into four cognitive groups.
• Whole-brain voxel comparisons and correlation analyses were performed between [18F]-FEOBV binding and cognitive changes.

Main Results:

• Distinct baseline [18F]-FEOBV binding patterns were observed across cognitive classes.
• Increased binding in anterior regions was noted in persistent normal cognition and MCI reversion groups.
• Reduced posterior cortical, limbic, and paralimbic [18F]-FEOBV binding predicted global and domain-specific cognitive decline over two years.

Conclusions:

• Cholinergic system integrity, as measured by [18F]-FEOBV binding, correlates with cognitive trajectories in PD.
• Upregulation of cholinergic neurotransmission may represent a compensatory mechanism in mild to moderate PD.
• Baseline VAChT binding is a significant predictor of future cognitive decline in PD.