Association Between Regular Laxative Use and Incident Dementia in UK Biobank Participants

doi:10.1212/WNL.0000000000207081

. 2023 Apr 18;100(16):e1702-e1711.

doi: 10.1212/WNL.0000000000207081. Epub 2023 Feb 22.

Association Between Regular Laxative Use and Incident Dementia in UK Biobank Participants

Zhirong Yang¹, Chang Wei², Xiaojuan Li², Jinqiu Yuan², Xuefeng Gao², Bingyu Li², Ziyi Zhao², Sengwee Toh², Xin Yu², Carol Brayne², Zuyao Yang¹, Feng Sha¹, Jinling Tang²

Affiliations

¹ From the Shenzhen Institute of Advanced Technology (Zhirong Yang, C.W., Z.Z., F.S., J.T.), Chinese Academy of Sciences, Guangdong, China; Primary Care Unit (Zhirong Yang), School of Clinical Medicine, University of Cambridge, United Kingdom; Department of Population Medicine (X.L., S.T.), Harvard Medical School & Harvard Pilgrim Health Care Institute, Boston, MA; Center for Digestive Disease (J.Y.), The Seventh Affiliated Hospital, Sun Yat-sen University; Central Laboratory (X.G.), Shenzhen Key Laboratory of Precision Medicine for Hematological Malignancies, Shenzhen University General Hospital; School of Government (B.L.), Shenzhen University, Guangdong; Peking University Sixth Hospital (X.Y.), Peking University Institute of Mental Health, Beijing, China; Cambridge Public Health (C.B.), School of Clinical Medicine, University of Cambridge, United Kingdom; Division of Epidemiology (Zuyao Yang, J.T.), The JC School of Public Health & Primary Care, The Chinese University of Hong Kong; and Clinical Data Center (J.T.), Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong, China. feng.sha@siat.ac.cn zyang@cuhk.edu.hk.
² From the Shenzhen Institute of Advanced Technology (Zhirong Yang, C.W., Z.Z., F.S., J.T.), Chinese Academy of Sciences, Guangdong, China; Primary Care Unit (Zhirong Yang), School of Clinical Medicine, University of Cambridge, United Kingdom; Department of Population Medicine (X.L., S.T.), Harvard Medical School & Harvard Pilgrim Health Care Institute, Boston, MA; Center for Digestive Disease (J.Y.), The Seventh Affiliated Hospital, Sun Yat-sen University; Central Laboratory (X.G.), Shenzhen Key Laboratory of Precision Medicine for Hematological Malignancies, Shenzhen University General Hospital; School of Government (B.L.), Shenzhen University, Guangdong; Peking University Sixth Hospital (X.Y.), Peking University Institute of Mental Health, Beijing, China; Cambridge Public Health (C.B.), School of Clinical Medicine, University of Cambridge, United Kingdom; Division of Epidemiology (Zuyao Yang, J.T.), The JC School of Public Health & Primary Care, The Chinese University of Hong Kong; and Clinical Data Center (J.T.), Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong, China.

PMID: 36813729
PMCID: PMC10115504
DOI: 10.1212/WNL.0000000000207081

Association Between Regular Laxative Use and Incident Dementia in UK Biobank Participants

Zhirong Yang et al. Neurology. 2023.

. 2023 Apr 18;100(16):e1702-e1711.

doi: 10.1212/WNL.0000000000207081. Epub 2023 Feb 22.

Authors

Zhirong Yang¹, Chang Wei², Xiaojuan Li², Jinqiu Yuan², Xuefeng Gao², Bingyu Li², Ziyi Zhao², Sengwee Toh², Xin Yu², Carol Brayne², Zuyao Yang¹, Feng Sha¹, Jinling Tang²

Affiliations

¹ From the Shenzhen Institute of Advanced Technology (Zhirong Yang, C.W., Z.Z., F.S., J.T.), Chinese Academy of Sciences, Guangdong, China; Primary Care Unit (Zhirong Yang), School of Clinical Medicine, University of Cambridge, United Kingdom; Department of Population Medicine (X.L., S.T.), Harvard Medical School & Harvard Pilgrim Health Care Institute, Boston, MA; Center for Digestive Disease (J.Y.), The Seventh Affiliated Hospital, Sun Yat-sen University; Central Laboratory (X.G.), Shenzhen Key Laboratory of Precision Medicine for Hematological Malignancies, Shenzhen University General Hospital; School of Government (B.L.), Shenzhen University, Guangdong; Peking University Sixth Hospital (X.Y.), Peking University Institute of Mental Health, Beijing, China; Cambridge Public Health (C.B.), School of Clinical Medicine, University of Cambridge, United Kingdom; Division of Epidemiology (Zuyao Yang, J.T.), The JC School of Public Health & Primary Care, The Chinese University of Hong Kong; and Clinical Data Center (J.T.), Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong, China. feng.sha@siat.ac.cn zyang@cuhk.edu.hk.
² From the Shenzhen Institute of Advanced Technology (Zhirong Yang, C.W., Z.Z., F.S., J.T.), Chinese Academy of Sciences, Guangdong, China; Primary Care Unit (Zhirong Yang), School of Clinical Medicine, University of Cambridge, United Kingdom; Department of Population Medicine (X.L., S.T.), Harvard Medical School & Harvard Pilgrim Health Care Institute, Boston, MA; Center for Digestive Disease (J.Y.), The Seventh Affiliated Hospital, Sun Yat-sen University; Central Laboratory (X.G.), Shenzhen Key Laboratory of Precision Medicine for Hematological Malignancies, Shenzhen University General Hospital; School of Government (B.L.), Shenzhen University, Guangdong; Peking University Sixth Hospital (X.Y.), Peking University Institute of Mental Health, Beijing, China; Cambridge Public Health (C.B.), School of Clinical Medicine, University of Cambridge, United Kingdom; Division of Epidemiology (Zuyao Yang, J.T.), The JC School of Public Health & Primary Care, The Chinese University of Hong Kong; and Clinical Data Center (J.T.), Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong, China.

PMID: 36813729
PMCID: PMC10115504
DOI: 10.1212/WNL.0000000000207081

Abstract

Background and objectives: The use of over-the-counter laxatives is common in the general population. The microbiome-gut-brain axis hypothesis suggests that the use of laxatives could be associated with dementia. We aimed to examine the association between the regular use of laxatives and the incidence of dementia in UK Biobank participants.

Methods: This prospective cohort study was based on UK Biobank participants aged 40-69 years without a history of dementia. Regular use of laxatives was defined as self-reported use in most days of the week for the last 4 weeks at baseline (2006-2010). The outcomes were all-cause dementia, Alzheimer disease (AD), and vascular dementia (VD), identified from linked hospital admissions or death registers (up to 2019). Sociodemographic characteristics, lifestyle factors, medical conditions, family history, and regular medication use were adjusted for in the multivariable Cox regression analyses.

Results: Among the 502,229 participants with a mean age of 56.5 (SD 8.1) years at baseline, 273,251 (54.4%) were female, and 18,235 (3.6%) reported regular use of laxatives. Over a mean follow-up of 9.8 years, 218 (1.3%) participants with regular use of laxatives and 1,969 (0.4%) with no regular use developed all-cause dementia. Multivariable analyses showed that regular use of laxatives was associated with increased risk of all-cause dementia (hazard ratio [HR] 1.51; 95% CI 1.30-1.75) and VD (HR 1.65; 95% CI 1.21-2.27), with no significant association observed for AD (HR 1.05; 95% CI 0.79-1.40). The risk of both all-cause dementia and VD increased with the number of regularly used laxative types (p trend 0.001 and 0.04, respectively). Among the participants who clearly reported that they were using just 1 type of laxative (n = 5,800), only those using osmotic laxatives showed a statistically significantly higher risk of all-cause dementia (HR 1.64; 95% CI 1.20-2.24) and VD (HR 1.97; 95% CI 1.04-3.75). These results remained robust in various subgroup and sensitivity analyses.

Discussion: Regular use of laxatives was associated with a higher risk of all-cause dementia, particularly in those who used multiple laxative types or osmotic laxative.

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Conflict of interest statement

The authors report no disclosures relevant to the manuscript. Go to Neurology.org/N for full disclosures.

Figures

**Figure 1. Flowchart of the Study**
BMI = body mass index; SES = socioeconomic status.

See this image and copyright information in PMC

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References

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1. Higgins PD, Johanson JF. Epidemiology of constipation in North America: a systematic review. Am J Gastroenterol. 2004;99(4):750-759. doi:10.1111/j.1572-0241.2004.04114.x. - DOI - PubMed
1. Koloski NA, Jones M, Wai R, et al. . Impact of persistent constipation on health-related quality of life and mortality in older community-dwelling women. Am J Gastroenterol. 2013;108(7):1152-1158. doi:10.1038/ajg.2013.137. - DOI - PubMed
1. Fosnes GS, Lydersen S, Farup PG. Drugs and constipation in elderly in nursing homes: what is the relation? Gastroenterol Res Pract. 2012;2012:290231. doi:10.1155/2012/290231. - DOI - PMC - PubMed

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[1] WHO. Risk Reduction of Cognitive Decline and Dementia: WHO Guidelines. WHO; 2019. - PubMed

[2] WHO. Risk Reduction of Cognitive Decline and Dementia: WHO Guidelines. WHO; 2019. - PubMed

[3] WHO. Dementia: A Public Health Priority. WHO; 2012. Accessed August 1, 2021. who.int/publications/i/item/dementia-a-public-health-priority.

[4] WHO. Dementia: A Public Health Priority. WHO; 2012. Accessed August 1, 2021. who.int/publications/i/item/dementia-a-public-health-priority.

[5] Higgins PD, Johanson JF. Epidemiology of constipation in North America: a systematic review. Am J Gastroenterol. 2004;99(4):750-759. doi:10.1111/j.1572-0241.2004.04114.x. - DOI - PubMed

[6] Higgins PD, Johanson JF. Epidemiology of constipation in North America: a systematic review. Am J Gastroenterol. 2004;99(4):750-759. doi:10.1111/j.1572-0241.2004.04114.x. - DOI - PubMed

[7] Koloski NA, Jones M, Wai R, et al. . Impact of persistent constipation on health-related quality of life and mortality in older community-dwelling women. Am J Gastroenterol. 2013;108(7):1152-1158. doi:10.1038/ajg.2013.137. - DOI - PubMed

[8] Koloski NA, Jones M, Wai R, et al. . Impact of persistent constipation on health-related quality of life and mortality in older community-dwelling women. Am J Gastroenterol. 2013;108(7):1152-1158. doi:10.1038/ajg.2013.137. - DOI - PubMed

[9] Fosnes GS, Lydersen S, Farup PG. Drugs and constipation in elderly in nursing homes: what is the relation? Gastroenterol Res Pract. 2012;2012:290231. doi:10.1155/2012/290231. - DOI - PMC - PubMed

[10] Fosnes GS, Lydersen S, Farup PG. Drugs and constipation in elderly in nursing homes: what is the relation? Gastroenterol Res Pract. 2012;2012:290231. doi:10.1155/2012/290231. - DOI - PMC - PubMed

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Association Between Regular Laxative Use and Incident Dementia in UK Biobank Participants

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Association Between Regular Laxative Use and Incident Dementia in UK Biobank Participants

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