Objective: In this study, we aimed to investigate the association between brainstem monoaminergic nuclear degeneration, particularly the serotonergic raphe and noradrenergic locus coeruleus, and cognitive and autonomic dysfunction in a prospective, longitudinal cohort of patients with early Parkinson’s disease (PD).

Background: Parkinson’s disease (PD), primarily characterized by dopaminergic loss and motor symptoms, is increasingly recognized for its involvement of multiple neurotransmitter systems, including acetylcholine, serotonin, and noradrenaline. These deficits contribute to various non-motor manifestations, significantly impacting the patient’s quality of life from the early stages of the disease.

Method: Twenty-eight individuals with early PD (disease duration shorter than or equal to three years) received baseline 18F-FP-CIT positron emission tomography (PET) scans and clinical evaluation including the Montreal Cognitive Assessment (MoCA) and Composite Autonomic Symptom Scale-31 (COMPASS-31). Three years later, the patients were re-assessed with MoCA and COMPASS-31. Regression analyses were employed to investigate the severity and progression of non-motor symptoms in correlation with the degeneration of the locus coeruleus (LC) and raphe nuclei at baseline, which were normalized based on the nigrostriatal dopaminergic degeneration.

Results: Severe degeneration of the locus coeruleus (LC) and raphe nuclei, relative to the loss of dopamiergic nigrostriatal terminals, was associated with lower baseline MoCA scores. Over the span of three years, gastrointestinal symptoms advanced, while cognitive scores remained stable. Reduced baseline ratios of LC and raphe-to-posterior-putamen were predictive of a faster decline in gastrointestinal symptoms.

Conclusion: Dysfunction in brainstem non-dopaminergic systems correlates with cognitive performance in early PD, and forecasts the faster progression of gastrointestinal symptoms, suggesting promising indicators for deteriorating non-motor conditions.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/brainstem-monoaminergic-degeneration-cognition-and-autonomic-symptom-progression-in-early-parkinsons-disease/