The potential link between certain medications and cognitive decline, including dementia, is a serious concern for patients and healthcare providers. Fesoterodine (brand name Toviaz) belongs to a class of drugs known as anticholinergics, commonly prescribed for overactive bladder (OAB). While the broader class has been associated with cognitive side effects, the specific risk for fesoterodine is under scrutiny.
Understanding Anticholinergic Medications and Dementia Risk
Anticholinergic drugs work by blocking the action of acetylcholine, a neurotransmitter that plays a crucial role in the brain's functions, including learning, memory, and attention. In the periphery, this action can help reduce the symptoms of OAB by relaxing the bladder muscle. However, if the medication crosses the blood-brain barrier (BBB) and acts on the central nervous system (CNS), it can interfere with cognitive processes, leading to side effects like confusion, memory impairment, and delirium.
The Role of Anticholinergic Burden
An individual's anticholinergic burden (ACB) refers to the cumulative effect of taking one or more medications with anticholinergic properties. Numerous studies have established a dose-dependent relationship between ACB and the risk of cognitive decline and dementia. The risk is generally higher with longer duration and higher cumulative doses. Older adults are particularly susceptible because their bodies metabolize and clear drugs less efficiently, and age-related changes in the brain's cholinergic system can magnify the drug's effects.
The Evidence: Fesoterodine and Dementia
Research on the specific relationship between fesoterodine and long-term cognitive outcomes presents a mixed and evolving picture. It is important to distinguish between older, less precise studies that group all anticholinergics together and newer, more specific research focused on individual agents.
Studies Suggesting a Potential Link (General Anticholinergic Class)
Early studies and meta-analyses often associated the broad class of anticholinergics used for OAB with an increased risk of dementia. For example, a 2021 Canadian cohort study found that patients taking fesoterodine, among other antimuscarinics, had increased odds of incident dementia compared to those on mirabegron. Similarly, a 2021 study in Urology Times cited research showing that anticholinergic use for three or more months increases dementia risk, without differentiating specific agents. These findings were instrumental in raising awareness about the class-wide risks.
Studies Showing Lower or No Risk (Fesoterodine-Specific)
More targeted research provides a more favorable view of fesoterodine's cognitive safety profile, especially when compared to certain other anticholinergics. Key findings include:
- April 2025 Cohort Study: A recent retrospective cohort study using the TriNetX Research Collaborative Network specifically examined dementia risk associated with various OAB drugs. It found that while most anticholinergics and even mirabegron showed an association with increased dementia risk compared to untreated controls, fesoterodine was not associated with an increased risk in any group studied.
- February 2024 Study in MCI Patients: A four-way randomized crossover study involving older adults with mild cognitive impairment (MCI) found that exposure to fesoterodine (at 4 mg and 8 mg doses) had no detectable effect on cognitive function when compared to a placebo. This suggests that even in a vulnerable population, the drug's cognitive impact is minimal.
- 2022 French Case-Control Study: This study found a dose-response relationship between OAB anticholinergic use and dementia risk but highlighted that the risk was most marked for oxybutynin and solifenacin. No significant association was found for fesoterodine.
- 2024 Animal Study on CNS Penetration: Research using brain microdialysis in rats indicated that 5-hydroxymethyl tolterodine (5-HMT), the active metabolite of fesoterodine, has a much lower brain distribution compared to other anticholinergics like oxybutynin. This suggests a lower likelihood of CNS-related side effects.
The Importance of Context and Patient Factors
Despite the reassuring recent data, several factors can influence a patient's risk of cognitive side effects from fesoterodine:
- Acute vs. Chronic Effects: While studies suggest the long-term dementia risk may be lower, acute CNS effects like delirium can still occur, especially in frail or renally impaired elderly patients.
- Drug Interactions: Other medications, particularly potent CYP3A4 inhibitors, can increase the blood concentration of fesoterodine's active metabolite, raising the risk of adverse effects. Additive anticholinergic effects with other anticholinergic drugs must also be considered.
- Anticholinergic Load: As mentioned, the total anticholinergic burden from all medications a patient takes is a critical consideration. Fesoterodine may contribute less to this burden than some other drugs, but it is not zero.
Comparison of Overactive Bladder (OAB) Medications
When treating OAB, healthcare providers weigh the risks and benefits of various medications. Below is a comparison focusing on cognitive risk and mechanism of action.
| Medication (Class) | Mechanism | Cognitive Risk Profile | Notes |
|---|---|---|---|
| Fesoterodine (Anticholinergic) | Blocks acetylcholine receptors in the bladder | More favorable profile than older anticholinergics due to lower CNS penetration; recent studies suggest minimal long-term dementia risk. | Extended-release formulation is preferred. Acute delirium possible in vulnerable patients. |
| Oxybutynin (Anticholinergic) | Blocks acetylcholine receptors in the bladder | Higher CNS penetration, consistently linked with higher cognitive side effect risk, including dementia. | Immediate-release formulation has the highest cognitive risk and should generally be avoided in older adults. |
| Tolterodine (Anticholinergic) | Blocks acetylcholine receptors in the bladder | Some studies show an increased risk of dementia, particularly with higher doses. | Use with caution, especially long-term. |
| Solifenacin (Anticholinergic) | Blocks acetylcholine receptors in the bladder | Linked with an increased risk of dementia in several studies, particularly at higher cumulative doses. | A higher-risk anticholinergic in terms of cognitive effects. |
| Mirabegron (Beta-3 Agonist) | Activates beta-3 adrenergic receptors in the bladder | Initially considered cognitively safer due to different mechanism, but a 2024 study showed a significant association with new-onset dementia compared to untreated controls, though less than some anticholinergics. | Generally considered a first-line alternative to anticholinergics, but long-term cognitive effects still under investigation. |
| Trospium (Anticholinergic) | Blocks acetylcholine receptors in the bladder | Lower cognitive risk due to minimal CNS penetration; less likely to cause cognitive impairment. | A cognitively safer anticholinergic option. |
Expert Recommendations and Patient Guidance
Given the complexity, experts provide guidance to minimize risk, especially for older patients.
- Consider Alternatives First: Where appropriate, beta-3 agonists like mirabegron are often recommended as a first-line pharmacological treatment for OAB, especially in older adults, due to their different mechanism and historically lower perceived cognitive risk compared to anticholinergics. However, recent research associating mirabegron with dementia compared to untreated controls suggests further investigation is needed into its long-term cognitive effects.
- Prioritize Favorable Profiles: If an anticholinergic is deemed necessary, guidelines recommend considering those with more favorable neuropharmacological profiles, like extended-release fesoterodine or trospium, over higher-risk options like immediate-release oxybutynin.
- Monitor for Symptoms: Patients, especially older adults, should be monitored for any signs of cognitive decline or CNS side effects, such as confusion or delirium, particularly when initiating or increasing the dose.
- Engage in Shared Decision-Making: The decision to use any anticholinergic, including fesoterodine, should involve a thorough discussion between the patient and physician about the potential benefits for OAB symptoms versus the possible risks, especially with long-term use.
- Minimize Anticholinergic Burden: Healthcare providers should review a patient's entire medication list to calculate the total anticholinergic burden and minimize it by deprescribing or substituting medications with lower anticholinergic activity whenever possible.
For more detailed guidance and a comprehensive review of anticholinergic burden and dementia, refer to authoritative clinical guidelines and resources like those published in professional journals. For example, the American Geriatrics Society has published criteria (Beers Criteria) addressing potentially inappropriate medications in older adults.
Conclusion
The question of whether fesoterodine causes dementia does not have a simple yes or no answer. The relationship between anticholinergic medications and cognitive health is complex, with varying levels of risk across different drugs. While the body of evidence, including recent 2025 research, suggests that fesoterodine poses a lower long-term dementia risk than many other anticholinergics due to its low brain penetration, it is not entirely without risk, particularly for acute cognitive effects in vulnerable populations. The cumulative effect of multiple anticholinergic medications is a significant factor. Optimal management requires a careful, personalized assessment of the drug's benefits for OAB symptoms against the potential cognitive risks, informed by the latest research and expert guidelines.
