ArticleJournal of advanced research2024
Slow gut transit increases the risk of Alzheimer's disease: An integrated study of the bi-national cohort in South Korea and Japan and Alzheimer's disease model mice.
Article in Journal of advanced research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- Biomarkers for Alzheimer's disease across diverse biological domains: an umbrella review and evidence map.Journal of advanced research · 2026Pooled it
- Review
- Comparative Analysis of Live and Heat-KilledNutrients · 2026Article
- Article
- The short-chain fatty acid butyrate prevents gut-brain amyloid-β pathology and neuroinflammation in an Alzheimer mouse model.Molecular psychiatry · 2026Article
- Neuropsychiatric Disorders and Constipation: Unraveling Causal Links Through Genetic Analysis.Brain and behavior · 2026Article
- More than Dysbiosis: Imbalance in Humoral and Neuronal Bidirectional Crosstalk Between Gut and Brain in Alzheimer's Disease.International journal of molecular sciences · 2025Review
- Investigation of the Determinants of Disease Severity in Patients with Idiopathic Normal Pressure Hydrocephalus.Movement disorders clinical practice · 2025Article
- Modulation of Intestinal Smooth Muscle Cell Function by BL-99 Postbiotics in Functional Constipation.Foods (Basel, Switzerland) · 2025Article
- Gut-brain nexus: Mapping multimodal links to neurodegeneration at biobank scale.Science advances · 2025Article
- Targeting Fyn Kinase for Alleviation of Cognitive Impairment in Streptozocin-Induced Alzheimer's Disease in Mice by Loperamide; An Experimental and in Silico Analysis.Neurochemical research · 2025Article
- Gastrointestinal Dysfunction and Low-Grade Inflammation Associate With Enteric Neuronal Amyloid-β in a Model for Amyloid Pathology.Neurogastroenterology and motility · 2025Article
- Early detection of Alzheimer's disease using the MEMORIES mnemonic.Chronic diseases and translational medicine · 2025Review
- Intermittent supplementation withFrontiers in aging neuroscience · 2025Article
- Article
- Causal associations and shared genetic etiology between neurodegenerative diseases and constipation.Journal of Alzheimer's disease reportsArticle
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionAlthough the association between Alzheimer's disease (AD) and constipation is controversial, its causality and underlying mechanisms remain unknown.
objectivesTo investigate the potential association between slow gut transit and AD using epidemiological data and a murine model.
methodsWe conducted a bi-national cohort study in South Korea (discovery cohort, N=3,130,193) and Japan (validation cohort, N=4,379,285) during the pre-observation period to determine the previous diagnostic history (2009-2010) and the follow-up period (2011-2021). To evaluate the causality, we induced slow gut transit using loperamide in 5xFAD transgenic mice. Changes in amyloid-beta (Aβ) and other markers were examined using ELISA, qRT-PCR, RNA-seq, and behavioral tests.
resultsConstipation was associated with an increased risk of AD in the discovery cohort (hazard ratio, 2.04; 95% confidence interval [CI], 2.01-2.07) and the validation cohort (hazard ratio; 2.82; 95% CI, 2.61-3.05). We found that loperamide induced slower gut transit in 5xFAD mice, increased Aβ and microglia levels in the brain, increased transcription of genes related to norepinephrine secretion and immune responses, and decreased the transcription of defense against bacteria in the colonic tissue.
conclusionImpaired gut transit may contribute to AD pathogenesis via the gut-brain axis, thus suggesting a cyclical relationship between intestinal barrier disruption and Aβ accumulation in the brain. We propose that gut transit or motility may be a modifiable lifestyle factor in the prevention of AD, and further clinical investigations are warranted.
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