← Back to all signals
RESEARCH PAPER ANALYSIS

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

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.

PMID41948786
JournalJournal of gastroenterology and hepatology
Publication Date2026-04-08
Ingested2026-04-28 08:58 PM
EXECUTIVE SUMMARY

What the AI sees

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.

WHY IT MATTERS

Research significance

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.

ABSTRACT

Source 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 (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.

SUPPORTING PAPER SET

32 more papers to review

Ranked by current scoring engine
1 The cGAS-STING-Glymphatic-gut Axis in Parkinson's disease: A proposed self-amplifying triad of Neuroinflammation and therapeutic opportunity. International immunopharmacology 91.0 2 Immunosenescence and Inflammaging as Drivers of Neurodegeneration: Cellular Mechanisms, Neuroimmune Crosstalk, and Therapeutic Implications. Cells 91.0 3 Flavonoids improve neurotransmitters for Parkinson's treatment: mechanism and therapeutic potential. Frontiers in pharmacology 88.0 4 Alpha-Lipoic Acid and Biotin in Neurodegenerative Diseases: Convergent Mechanistic Insights from Preclinical Models to Clinical Perspectives. Neurology international 78.0 5 The Gut Microbiota in Parkinson's Disease: Mechanistic Insights into Microbial-Host Interactions. Microorganisms 85.0 6 Linking inflammation, metabolic dysfunction, and neurodegeneration: a comprehensive review of TLR2 pathways in type 2 diabetes. Frontiers in clinical diabetes and healthcare 80.0 7 Neuroprotective effects of GLP-2 and a GLP-2/GIP dual receptor agonist in an MPTP-induced mouse model of Parkinson's disease. Peptides 86.0 8 TNF alpha unmasks enteric malate aspartate shuttle dysfunction bridging Parkinson disease and intestinal inflammation. Nature communications 91.5 9 Lipid Metabolism and Neurodegeneration: Mechanistic Insights and Therapeutic Targets. Ageing research reviews 82.0 10 Shared functional microbiome signatures in Parkinson's disease and constipation predominate irritable bowel syndrome despite taxonomic divergence. Brain, behavior, & immunity - health 80.0 11 Benzimidazole as a Versatile Scaffold for Developing Neurotherapeutics Against Neurodegenerative Diseases. ChemMedChem 74.0 12 Biomimicking neuromelanin reverses the gait deficits and dopaminergic neuronal loss in the Parkinson's disease. Colloids and surfaces. B, Biointerfaces 86.0 13 Neuroprotective roles of klotho: Molecular pathways and therapeutic implications for cognitive health in neurological and psychiatric diseases. Experimental physiology 84.0 14 Flavonoid Rutin Reduces Intestinal Inflammation in an Experimental Model of Parkinson's Disease. Neurotoxicity research 70.0 15 Nanostructured Lipid Carriers Enhance Brain Delivery and Antioxidant Efficacy of a Small-Molecule MAO B Inhibitor for Neurodegenerative Disease Therapy. Molecular pharmaceutics 78.0 16 Pathophysiological Role of the Gut Brain Axis in Parkinson's Disease: From Microbial Metabolites and Intestinal Permeability to Central Neuroinflammation. Current neurovascular research 86.0 17 Parkinson's Disease: From Metabolism to Genetics-A Comprehensive Review. Current issues in molecular biology 86.0 18 Navigating the cholesterol maze: Key insights on use of statins in neurodegenerative disorders. Neuroprotection (Chichester, England) 76.0 19 Integrative network pharmacology delineates dual GPCR and non-GPCR mechanisms of blended and individual Taikong Blue lavender and Pingyin rose essential oils in neurodegenerative and psychiatric disorders. Computers in biology and medicine 65.0 20 Models of neuroprotection in Parkinson's disease: Exploring cellular, molecular, and microenvironmental targets. Experimental neurology 78.0 21 Hyaluronic acid: emerging roles and biomaterial innovations in Alzheimer's and Parkinson's disease therapy. Frontiers in pharmacology 75.2 22 Molecular mechanisms underlying Parkinson's disease and role of phytochemicals, α-synuclein, sirtuins, and incretin mimetics in potential therapy. Frontiers in pharmacology 75.0 23 Lipid droplets in neurodegenerative diseases: pathological drivers and therapeutic vulnerabilities. Cell death discovery 82.0 24 Brain-gut-microbiota axis: a review on the bidirectional regulatory mechanisms between gut microbiota and brain and their disease interactions. Frontiers in microbiology 74.0 25 Long non-coding RNAs in neurodegenerative diseases - Molecular mechanisms, liquid biopsy biomarkers, and therapeutic targets: A review. Biomolecules & biomedicine 84.0 26 Neurosyphilis and Parkinsonism: Overlapping Pathophysiology and Emerging Therapeutic Insights. Current neurovascular research 76.0 27 Molecular biochemistry of soluble epoxide hydrolase in lipid mediator pathways and neuroinflammatory responses. The Journal of steroid biochemistry and molecular biology 82.0 28 Multifaceted role of CNPY2 beyond ER stress: Disease implications and therapeutic potential. Cell stress 83.3 29 Neuroprotective Role of Exercise-based Physiotherapy Combined with Pharmacological Agents in Parkinson's Disease. Central nervous system agents in medicinal chemistry 64.0 30 Distinct metabolomic and proteomic signatures in Parkinson's disease patients with REM sleep behavior disorder. Signal transduction and targeted therapy 84.0 31 HMGB1-mediated neuroinflammation: molecular mechanisms and emerging therapeutic approaches. Inflammopharmacology 78.0 32 Beyond acid-base dyshomeostasis: Dynamic instability of neuronal lysosomal pH as a pathogenic mechanism and therapeutic target in neurological diseases. Biochemical pharmacology 88.0
Neurocompute Parkinson’s Narrative Velocity Infographic
NEUROCOMPUTE VISUAL SYSTEM

Open the Narrative Velocity Map

Explore the full Parkinson’s research intelligence diagram.

Expand Intelligence View →
Full Neurocompute Infographic