Meta-analysis of 7,042 PD patients found GI symptoms—particularly constipation—were associated with higher prevalence of PD dementia (RR 1.37) and, in a subgroup of prospective studies, with a mean MOCA decline of ~1.26 points over 5 years, though causation was not established.

Flags constipation as a potential biomarker and modifiable gut–brain axis target that justifies monitoring and prospective intervention trials (microbiome, motility, anti-inflammatory strategies) despite the current lack of mechanistic or therapeutic evidence.

OBJECTIVE: Gastrointestinal (GI) symptoms such as constipation are prevalent autonomic symptoms seen in prodromal and end-stage Parkinson's disease (PD). The aim of this systematic review and meta-analysis is to assess the association of GI symptoms and constipation alone with progression and severity of PD-associated cognitive impairment. METHODS: We searched MEDLINE, Cochrane, and Embase from database inception to 2023 for studies reporting outcomes related to cognitive decline. A random-effects meta-analysis was performed using change in the Montreal Cognitive Assessment (MOCA) as the primary cognitive outcome, and heterogeneity was evaluated (I2). RESULTS: Eleven prospective, nine cross-sectional, three retrospective, three case-control, and one randomized controlled studies were included, totaling 7042 PD patients. The presence of GI symptoms like constipation was significantly associated with PD dementia (RR 1.37; 95% CI 1.09, 1.71; p = 0.005). However, over 5 years, GI symptoms were not found to be associated with an increased prevalence of PD dementia. In subgroup analysis of three prospective studies, constipation was associated with worsened PD cognitive impairment over 5 years (decreased MOCA score by 1.259 points; 95% CI -2.059, -0.459; p = 0.002). CONCLUSIONS: GI symptoms, and constipation specifically, were commonly reported among patients with PD dementia. In a subgroup analysis of prospective studies, worsening constipation seemed to correlate with greater cognitive impairment over 5 years. Although this meta-analysis did not establish causation, these findings highlight the potential importance of monitoring constipation in PD individuals as ongoing research about the role of the gut-brain axis continues.