Association of Gastrointestinal Symptoms With Severity and Progression of Cognitive Impairment in Parkinson’s Disease: A Systematic Review and Meta‐Analysis

ABSTRACT 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 ( I 2 ). 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.