Association Between Regular Laxative Use and Incident Dementia in UK Biobank Participants
Zhirong Yang, Chang Wei, Xiaojuan Li, Jin-Qiu Yuan, Xuefeng Gao, Bingyu Li, Zi-Yi Zhao, Sengwee Toh, Xin Yu, Carol Brayne, Zu‐Yao Yang, Feng Sha, Jin-Ling Tang
Abstract
<h3>Background and Objectives</h3> Use of OTC laxatives is common in the general population. The microbiome-gut-brain axis hypothesis suggests use of laxatives is associated with dementia. We aimed to examine the association between regular use of laxatives and incidence of dementia in UK Biobank participants. <h3>Methods</h3> This prospective cohort study was based on UK Biobank participants aged 40 to 69 years without 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’s disease and vascular dementia, identified from linked hospital admissions or death register (up to 2020). Socio-demographic characteristics, lifestyle factors, medical conditions, family history and regular medication use were adjusted for in the multivariable Cox regression analyses. <h3>Results</h3> Among the 502,229 participants with a mean age of 56.5 (SD=8.1) 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% confidence interval 1.30-1.75) and vascular dementia (HR 1.65; 1.21-2.27), with no significant association observed for Alzheimer’s disease (HR 1.05; 0.79-1.40). The risk of both all-cause dementia and vascular dementia 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 one type of laxative (n=5800), only those using osmotic laxatives showed a statistically significantly higher risk of all-cause dementia (HR 1.64 [1.20-2.24]) and vascular dementia (HR 1.97 [1.04-3.75]). These results remained robust in various subgroup and sensitivity analyses. <h3>Discussion</h3> 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.