Monoaminergic degeneration, cognition, and autonomic symptom trajectory in early Parkinson's ' s disease

Introduction: Parkinson's disease (PD) encompasses a range of non-motor symptoms attributed to deficits in various neurotransmitter systems. This study aimed to investigate the associations between cognitive and autonomic symptoms and the degeneration of brainstem monoaminergic nuclei, particularly the serotonergic and noradrenergic nuclei, in a prospective cohort of early PD patients. Methods: Twenty-eight early PD patients (with an average disease duration of approximately three years) underwent baseline [18F]FP-CIT 18 F]FP-CIT positron emission tomography (PET) scans, Montreal Cognitive Assessment (MoCA), and Composite Autonomic Symptom Scale-31 (COMPASS-31) evaluations, followed by repeat MoCA and COMPASS-31 assessments three years later. Regression models were utilized to analyze both cross-sectional and longitudinal changes in non-motor symptoms relative to baseline degeneration of the noradrenergic locus coeruleus (LC) and serotonergic raphe, normalized by striatal dopaminergic terminal loss. Results: Baseline LC and raphe degeneration in early PD was cross-sectionally associated with poorer MoCA performances. Over the three-year follow-up, gastrointestinal symptoms exhibited progression, while cognitive scores remained stable. Profound baseline degeneration of the LC and raphe, relative to nigrostriatal terminal loss, were predictive of subsequent accelerated deterioration in gastrointestinal symptoms. Conclusion: Brainstem non-dopaminergic dysfunction in early PD is linked to cognitive dysfunction and predicts progression in gastrointestinal symptoms, offering potential indicators for worsening non-motor trajectories.