The cognitive effect of anticholinergics for patients with overactive bladder

Abstract

Overactive bladder (OAB) is often treated with medications that block the cholinergic receptors in the bladder (known as anticholinergics). The effect of this medication class on cognition and risk of dementia has been increasingly studied over the past 40 years after initial studies suggested that the anticholinergic medication class could affect memory. Short-term randomized clinical trials demonstrated that the administration of the anticholinergic oxybutynin leads to impaired memory and attention, and large, population-based studies showed associations between several different anticholinergic medications and dementia. However, trials involving anticholinergics other than oxybutynin have not shown such substantial effects on short-term cognitive function. This discordance in results between short-term cognitive safety of OAB anticholinergics and the long-term increased dementia risk could be explained by the high proportion of patients using oxybutynin in the OAB subgroups of the dementia studies, or a study duration that was too short in the prospective clinical trials on cognition with other OAB anticholinergics. Notably, all studies must be interpreted in the context of potential confounding factors, such as when prodromal urinary symptoms associated with the early stages of dementia lead to an increase in OAB medication use, rather than the use of OAB medication causing dementia. In patients with potential risk factors for cognitive impairment, the cautious use of selected OAB anticholinergic agents with favourable physicochemical and pharmacokinetic properties and clinical trial evidence of cognitive safety might be appropriate. Anticholinergics are a common class of medication used in the treatment of overactive bladder. However, concerns have been raised over the potential association of anticholinergics and cognitive impairment or dementia. This Review discusses the clinical evidence and provides guidance for prescribing anticholinergics in at-risk populations. Short-term randomized clinical trials (most <4 weeks) have not shown substantial cognitive impairment with overactive bladder (OAB) anticholinergics other than oxybutynin. Very few long-term clinical studies (>3 months) on OAB anticholinergics exist, and those studies that are available have conflicting results and are limited by methodological issues. Large, observational studies of OAB anticholinergic use have shown that these medications are associated with an ~20% increased relative risk of dementia, but residual confounding and reverse causality cannot be ruled out. Alternative OAB treatments might be more appropriate for patients >65 years of age and those patients with underlying mild cognitive impairment (or conditions that put them at risk of it); if necessary, careful use of anticholinergics with favourable physicochemical, pharmacokinetic and pharmacodynamic properties and cognitive safety data could be considered. Short-term randomized clinical trials (most <4 weeks) have not shown substantial cognitive impairment with overactive bladder (OAB) anticholinergics other than oxybutynin. Very few long-term clinical studies (>3 months) on OAB anticholinergics exist, and those studies that are available have conflicting results and are limited by methodological issues. Large, observational studies of OAB anticholinergic use have shown that these medications are associated with an ~20% increased relative risk of dementia, but residual confounding and reverse causality cannot be ruled out. Alternative OAB treatments might be more appropriate for patients >65 years of age and those patients with underlying mild cognitive impairment (or conditions that put them at risk of it); if necessary, careful use of anticholinergics with favourable physicochemical, pharmacokinetic and pharmacodynamic properties and cognitive safety data could be considered.