Overactive bladder syndrome (OAB) is one of the most common medical conditions that refers to Urologists. It is defined as urgency with or without urgency incontinence, usually with frequency and nocturia. Usually, anticholinergic agents are the best therapeutic medications for these patients. The relationship between cognitive impairment or dementia and anticholinergic medications remain uncertain. There has been an ongoing debate considering the relationship of the adverse event of these drugs and Central Nervous system (CNS) impairment in these patients. The aim of our study is to evaluate the reported relationship between using anticholinergic drugs for patients with OAB and the risk of having cognitive impairment or dementia as an adverse event.

A literature search was conducted using PubMed, Scopus, Web of science, and Science Direct to identify relevant studies published until December 2018. Studies included were randomized controlled trials (RCTs) and cohort studies in patients with OAB, comparing anticholinergic agents with placebo or any active treatment and reported CNS adverse events. Data were pooled as risk ratio (RR) or mean difference (MD) between the two compared groups in a random effects meta-analysis model. Subgroup and sensitivity analysis were conducted. We included only the studies which use the mean change of Mini-Mental State Examination (MMSE) as a scale for assessment the cognitive status among (OAB) Patients.

Three cohort studies and six RCTs with a total of 2,594 participants (mean age 70.7 ± 9.4 years) were included.. The RCTs consisted of a total 1,626 participant with OAB of which 949 participants were using anticholinergic drugs. This included Fesoterodine (41.4%), Darifenacin (3.0%), Trospium (2.0%), Oxybutynin (7.5%) or Placebo (46.1%). The cohort studies consisted of 968 participants with OAB using Solifenacin (82.5%), Darifenacin (5.2%), Oxybutynin (4.4%), Trospium (2.7%), Tolterodine (2.2%) or other drugs including Placebo (3.0%).  The longest period of follow up duration was 6 months. Meta-analysis of the primary outcome showed that Darifenacin was slightly significant to lowering MMSE Score compared to Trospium (MD= -1.60, 95% CI [-3.10, -010], p=0.04). This is the only study that showed dementia as side effect (11.9%). There was no significant difference in MMSE between Oxybutynin Extended and Immediate Release. The pooled estimate of two studies did not favor either Fesoterodine or Placebo to reducing MMSE Score (MD= -0.01, 95% CI [-0.25, 0.27], p=0.94). No significant differences were observed between other anticholinergic drugs when compared to each other or to Placebo. With regards to the secondary outcomes, Fesoteridine had higher risk of Dizziness than Placebo (RR= 2.82, 95% CI [1.12,7.09], p=0.03). No significant difference was observed in term of Serious Side Effects between Fesoteridine and Placebo (RR= 1.45, 95% CI [0.76, 2.78], p=0.26).

From our review study, we can see that there were a few studies that discussed the effect of anticholinergic medication on cognitive impairment and using the Mini-mental State Examination as a standard scale for cognition and dementia. The average follow up duration in all relevant studies was 12 weeks, with only one study reporting follow up at 6 months. However, no previous RCT discussed the effect on dementia except for one cohort study that showed dementia as side effect but was not significant. Also, few studies talked about Immediate and Extended release of anticholinergic agents. No significant difference was observed in term of serious adverse events or other CNS side effects that were analysed from the included studies. In fact, longer follow up for these medications are required in order to assess their effects of cognition.

The present meta-analysis of RCTs and cohort studies with short term follow up duration of up to 6 months has demonstrated that anticholinergic medications does not impair cognitive functions according to the Mini Mental State Examination scores in patients with OAB. Further RCTs with larger number of patients and longer follow up period with MMSE assessment are needed to confirm our findings.