The regular use of laxatives, particularly osmotic laxatives, is associated with an elevated risk for all-cause dementia, according to the findings of a prospective cohort study published in Neurology.
Laxative abuse is common among older adults, many of whom experience frequent constipation that is often associated with the use of multiple medications. These agents are readily accessible since laxatives are available over the counter. Multiple pathways seen in the microbiome-gut-brain axis support the theory that regular use of laxatives may be associated with the risk for dementia.
“[R]egular laxative use may change the microbiome of the gut, possibly affecting nerve signaling from the gut to the brain or increasing the production of intestinal toxins that may affect the brain,” according to researchers.
For the study, the researchers evaluated the link between regular laxative use and incidence of dementia among UK Biobank cohort participants. The study was conducted in UK Biobank participants who were between ages 40-69 with no history of dementia. The regular use of laxatives was defined as “self-reported use [on] most days of the week for the last 4 weeks at baseline” (from 2006 to 2010).
Algorithmically defined health-related outcomes were used, with all-cause dementia and subtypes of dementia established via linkage to data from primary care, hospitalizations, and death registers during follow-up.
All-cause dementia was the primary outcome. Secondary outcomes included Alzheimer disease (AD) and vascular dementia — both of which are subtypes of all-cause dementia.
The adjustment models utilized the following 4 groups of baseline covariates:
- Sociodemographics: age, sex, ethnicity, education level, socioeconomic status
- Lifestyle factors: smoking status; alcohol consumption; dietary consumption of vegetables, fruit, fish, processed/unprocessed meat; physical activity, body mass index
- Medical conditions or family history: diabetes, myocardial infarction, hypertension, stroke, Parkinson disease, depression, cognitive function, parental history of dementia
- Regular use of medication: opioids, statins, corticosteroids, anticholinergic drugs, calcium channel blockers, antidiarrheal agents.
Researchers based their findings on 502,229 eligible participants (mean age, 56.5 at baseline; 54.4% women). A total of 18,235 participants (3.6%) reported regular use of laxatives at the baseline visit.
Among 476,219 participants, a total of 2,187 cases of all-cause dementia (824 with AD and 450 with vascular dementia) were recorded over 9.8 years of follow-up. The mean age at diagnosis of all-cause dementia was 67.1, 68.8, and 67.0, among all participants, regular laxative users, and the other participants, respectively.
Per multivariable analysis, regular laxative use was associated with a significantly increased risk for all-cause dementia (hazard ratio [HR], 1.51; 95% CI, 1.30-1.75;
P <.001) and vascular dementia (HR, 1.65; 95% CI, 1.21-2.27; P <.001). No significant association was reported, however, between regular laxative use and AD (HR, 1.05; 95% CI, 0.79-1.40).
The risk for all-cause dementia increased with the number of laxative types used — an adjusted HR (aHR) of 1.28 (95% CI, 1.03-1.16) with the use of a single type of laxative and an aHR of 1.90 (95% CI, 1.20-3.01) with the combination use of ≥2 types of laxatives (P-trend =.001).
Regarding type of laxative, only osmotic laxatives were shown to be associated with a significantly higher risk for all-cause dementia (aHR, 1.64; 95% CI, 1.20-2.24;
P <.01) and for vascular dementia (aHR, 1.97; 95% CI, 10.4-3.75; P <.05).
Researchers cautioned their study has several limitations, including the lack of data on laxative dosage, which did not allow them to assess the relationship between laxative dosages and dementia risk.
“Further studies are needed to clarify whether the association between laxatives and dementia observed in our study is causal,” the researchers concluded.
Yang Z, Wei C, Li X, et al. Association between regular laxative use and incident dementia in UK Biobank participants. Neurology. Published online February 22, 2023. doi:10.1212/WNL.0000000000207081