Distinct brain susceptibility alteration pattern in Parkinson's disease with drooling: evidence from quantitative susceptibility mapping.

Parkinson’s disease (PD) is a common progressive neurodegenerative disorder, pathologically characterized by the progressive loss of dopaminergic neurons in the nigrostriatal pathway. Clinically, it manifests with a variety of motor and non-motor symptoms. Drooling (sialorrhea), defined as the involuntary leakage of saliva due to its excessive accumulation, is one of the relatively frequent non-motor symptoms in PD patients (). Drooling not only leads to inconveniences such as frequent wiping of saliva, damp clothing, and oral odor, significantly impairing personal image and life comfort (), but may also cause embarrassment, diminished self-esteem, and social avoidance behaviors, contributing to social isolation and mood disorders (). In severe cases, it may also increase the risk of aspiration pneumonia and perioral skin infections, thereby further adding to the healthcare burden (). The pathophysiology of drooling in PD is not yet completely clarified. Thus, elucidating its underlying mechanisms is crucial for developing effective interventions, bearing significant clinical and societal implications. Drooling in PD involves multi-system, multi-level neural dysfunction, and its mechanisms can be parsed from peripheral to central levels. At the local level, salivary gland secretion function may be affected by dysregulation of autonomic control (). For instance, some studies have reported accelerated parotid excretion rates in PD patients (), suggesting alterations in saliva production and clearance processes. However, the core issue of drooling is not an absolute increase in saliva secretion, but rather impaired swallowing function. The latter stems from degenerative changes in the nigrostriatal dopaminergic pathway, leading to bradykinesia and incoordination of the oropharyngeal muscles, thereby substantially reducing the efficiency of saliva clearance and causing saliva retention in the oral cavity (,). Beyond peripheral mechanisms, the dysregulation of central regulatory networks plays a more critical role in PD-related drooling. Neuroimaging studies suggest that drooling is closely associated with abnormal brain network connectivity, involving functional integration disturbances in cortico-limbic-striatal-cerebellar circuits and cortico-cortical networks (), indicating the presence of neural compensatory or decompensatory mechanisms at the systems level. Furthermore, the degree of nigral dopaminergic neuron degeneration () and co-morbid cognitive dysfunction (,) have also been demonstrated to be important factors exacerbating drooling.