Anticholinergic Medications May Increase Dementia Risk in Diabetes

Patients with diabetes who take anticholinergic medications for overactive bladder may have an increased risk for dementia.

Patients with diabetes mellitus (DM) taking oxybutynin, solifenacin, or tolterodine for treatment of overactive bladder (OAB) had a greater risk of developing dementia, with patients taking oxybutynin showing the greatest risk, according to recent research published in PLoS ONE.

Researchers at the China Medical University in Taichung, Taiwan evaluated 10,938 patients with DM who took oxybutynin, solifenacin, or tolterodine for OAB between January 2002 and December 2013 and 564,733 patients with DM who did not take the anticholinergic drugs.


“Typically, patients who respond well to a particular anticholinergic drug will continue to use that drug and not switch to another one,” the researchers wrote. “However, our research finds [show] that long-term use of a particular anticholinergic drug may increase subsequent risk of developing dementia.”

At 6-year follow-up, the researchers found patients taking oxybutynin had a 3.9% rate of dementia, while patients taking solifenacin had a 4.3% rate and patients taking tolterodine had a 2.2% rate compared with a 1.2% rate of dementia in the control group (P <.001).

After adjusting their multivariate adjusted competing-risk regression model for factors such as comorbidities, patient age, patient gender, socioeconomic status, geographical region, and urbanization, long-term use of oxybutynin carried the highest risk of dementia (hazard ratio [HR] 2.35; 95% CI, 1.96-2.81), while tolterodine (HR 2.24; 95% CI, 1.85-2.73) and solifenacin (HR 2.16; 95% CI, 1.81-2.58) also carried a high risk of developing dementia compared with the control group.

Limitations of the study included lack of data on the severity of OAB in the patient population, lack of a non-DM control group, lack of data on other drugs used to treat OAB such as trospium and darifenacin, and lack of data about physical activity and education in the database used for the study.

The researchers recommended that physicians and clinicians treating patients with DM who take long-term anticholinergic drugs for OAB should be mindful of the potential side effects of the treatment and closely monitor the cognitive function of their patients. 

“This is a key finding for clinicians who must keep this potentially increased risk in mind when prescribing long-term use of a specific anticholinergic drug to DM patients suffering from OAB,” the researchers concluded. “Even if the patient is responding well to the specific drug, once the patient’s OAB is under control, the physician should continue therapy while simultaneously undertaking dementia prevention measures such as regular exercise, participation in social activities, and controlling body mass index, high blood pressure, high blood sugar, and high blood fat.”

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