Constipation Is Linked to Neuroinflammation in Early Parkinson's Disease

Abstract Background Constipation is a risk factor for the onset and accelerated progression of Parkinson's disease (PD), but the mechanisms underlying this association are unknown. Neuroinflammation in PD has been demonstrated in postmortem and neuroimaging studies; however, its relationship with constipation has not been investigated. Methods We used 11 C‐PK11195 positron emission tomography (PET) to index neuroinflammation in a cohort of 27 people with early‐stage PD. The Gastrointestinal Dysfunction Scale for PD (GIDS‐PD) was used to assess gut symptom severity. Matched blood and cerebrospinal fluid (CSF) samples were collected. Results Higher GIDS‐PD constipation scores were associated with 11 C‐PK11195 binding in whole‐brain gray matter, frontal, parietal, temporal, and occipital lobes, and multiple subcortical and cortical regions. GIDS‐PD Constipation scores were also significantly associated with higher CSF lymphocyte count and blood T helper 1 (Th1) cell and Th17‐like Th1 cells. Conclusions Constipation in early PD is associated with widespread neuroinflammation, suggesting a possible mechanism underlying the association between constipation and faster PD progression. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.