2026 Volume 63 Issue 3 Pages 75-78
Parkinson’s disease (PD) is increasingly recognized not merely as a central nervous system disorder but as a systemic disease characterized by widespread α-synuclein pathology. Gastrointestinal (GI) symptoms, particularly constipation, frequently precede the onset of classic motor symptoms and significantly impair patients’ quality of life. This review outlines the pathophysiology of GI dysfunction in PD, focusing on the autonomic nervous system, neurotransmitter alterations, and the gut-brain axis. According to Braak’s hypothesis, α-synuclein pathology may originate in the enteric nervous system and propagate to the brainstem via the vagus nerve. The early involvement of lower brainstem structures, including the defecation center, provides a neuroanatomical basis for prodromal GI symptoms. Furthermore, beyond dopaminergic depletion, the early impairment of the acetylcholine (ACh) system causes peripheral parasympathetic dysfunction, which directly contributes to impaired GI motility. Clinical interventions targeting this cholinergic deficit have shown clinical promise. Our long-term randomized controlled trial demonstrated that donepezil, a cholinesterase inhibitor, safely improved not only cognitive function but also non-motor symptoms such as constipation in PD patients with severe hyposmia. Although the precise mechanisms of the gut-brain axis―whether propagation is bottom-up, top-down, or bidirectional―remain a subject of active debate, appropriate evaluation and management of early GI symptoms are crucial. Further elucidation of these pathways holds significant potential for the development of novel, gut-targeted disease-modifying therapies for PD.
