Background and ObjectivesUse 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.MethodsThis 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.ResultsAmong 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.DiscussionRegular use of laxatives was associated with a higher risk of all-cause dementia, particularly in those who used multiple laxative types or osmotic laxative.