JUOP August 2025 Editorial: Anticholinergics—Does Treating the Bladder Harm the Brain?

This month, we feature the annual meeting of the Urological Association of Asia which met in Taipei this month. A featured state-of-the art lecture was from our consulting editorial board member Howard Goldman on the interesting topic of dementia risk with anticholinergic medications. We include a lecture summary below with his former fellow as co-author. Anticholinergics (AC) remain an important treatment option for patients with overactive bladder (OAB). The 2024 AUA/SUFU guidelines recommend treatment with either an anticholinergic or a beta-3 agonist, but caution that prescribers should counsel patients that the use of OAB AC medications may put them at risk for dementia.1 If this is factual, it represents a serious issue given the frequency of OAB in the US population and the significant impact of dementia. In fact, when older patients with OAB are asked which potential side effect of AC concerns them the most, loss of cognitive function is their number one concern.2 In 2019, Coupland et al3 published a large observational study indicating that patients who had taken certain types of AC, including those for OAB, had a significantly elevated risk of developing dementia. While there were several studies in the years prior with similar findings, this study in particular received a lot of coverage in the lay press. Other studies followed which seemed to confirm the Coupland findings.4-8 There is a plausible biologic mechanism as the AC drugs not only block M2 and M3 receptors (most common in the bladder) but also have effects on the other types of muscarinic receptors.9 In the central nervous system (CNS), acetylcholine is a ubiquitous neurotransmitter involved in memory, learning and attention, and blocking any of its receptors could potentially cause harm. Unique characteristics of different AC drugs including polarity, charge, and molecular weight may influence their ability to penetrate the CNS and cause such effects. Previous studies looking at various AC found that the use of oxybutynin immediate release clearly affected memory, attention, and other higher order functions.9 A 2020 population-based cohort study from Canada by Welk and McArthur demonstrated that while there was no increased risk of dementia in those patients with OAB taking a beta-3 agonist, there was an increased risk in those who took an AC.10 There are contradictory studies that report no association of dementia and AC intake, but the preponderance of the evidence is contrary to that.9 The published data do support an association between AC use and dementia, and the overall increased risk seems to be about 1% to 5% above baseline.11,12 However, some caution must be exercised before assuming a definite cause and effect because all evidence is observational, there may be protopathic bias (reverse causality), and oxybutynin is overrepresented in many of the studies. Furthermore, several more recent studies also suggest that risks may be lower or not present for those AC with low/no CNS penetration/accumulation, such as trospium.4-6,8 Nevertheless, as strong evidence seems to suggest AC uniquely increase the risk of developing dementia, what is the clinician to do? A team from SUFU reviewed the data and made a number of recommendations which include—avoid immediate release oxybutynin, preferentially use beta-3 agonists when possible, consider cognitive risks before prescribing and rapidly move to minimally invasive treatments if medical therapy is not working.12 As noted earlier the AUA/SUFU OAB 2024 updated guideline recommends discussing the risk of dementia when prescribing AC. In addition, the American Board of Internal Medicine Choosing Wisely program recommends not prescribing highly AC medications (including OAB AC) without considering safer alternatives or non-drug alternatives.13 Despite the potential risks, cost remains an issue and the potential benefit of AC treatment vs the risks must be evaluated on an individual basis. If a patient's only practical option is oxybutynin and they respond to it, one has to consider the potential improvements in their quality of life vs the potential increased risk of dementia. So, does treating the bladder with an AC potentially harm the brain? In a minority of patients, this may be the case and thus appropriate consideration of treatment options, counseling, and shared decision-making should rule the day. AUGUST 2025 JUOP NEW ARTICLES Reviews McGill et al14 performed a systematic review of different open vs minimally invasive techniques across several urology procedures with the goal of showing real world outcomes. Their search led to 45 final studies from cystectomy, prostatectomy, and nephrectomy that were analyzed and looked at outcomes in the clinical effectiveness and safety categories. This leads to a lot of data and conclusions to summarize, and significant opportunity to mark the paper for future reference as needed. Clinical effectiveness is similar for robotic cystectomy, whereas better robotic clinical outcomes for prostatectomy. For nephrectomy, an interesting improvement for robotic vs open but similar vs laparoscopy. Owing to the volume of comparisons, there is not a typical forest plot but rather several tables summarizing the findings and sources. An editorial from Arca and Fernández15 provides additional comment and brings up the cost-effective data needs because the outcomes provided might help prioritize resources. Crawford et al16 provide another review in the RADAR series (Radiographic Assessments for Detection of Advanced Recurrence) for prostate cancer. This review focuses on prostate specific membrane antigen positron emission tomography imaging for metastatic castration sensitive prostate cancer. For classification of disease, they discussed lesion counts, similar to those proposed from the CHAARTED study with conventional imaging, and proposed cutoffs of < 5, 5 to 19, and 20 or more (or any visceral location). The group then discusses how to translate the classification into treatment directions such as metastasis directed therapy and doublet/triple systemic. Lin and Woo17 discuss this paper in more detail and outline future needs in this era where most patients in this category will only have. Prostate specific membrane antigen positron emission tomography imaging instead of conventional. Clinical Trials Li et al18 conducted an in-depth study of the adverse event reporting metrics surrounding benign vs malignant disease of the lower urinary tract. Of course, in malignant trials, disease-related death is a more realistic concern and alters the risk tolerance reasonable for a novel study. As expected, malignant trials will have a higher serious adverse event rate than benign trials; however, benign trials do have adverse (nonserious) events to report as well. The authors demonstrate how key information on adverse events can be reviewed from public reporting requirements of clinical trials and gives great assistance to future authors in the benign space on how to make likewise comparisons rather than rely on malignant trial data, even if some of the endpoints overlap. Our new editorial board member Danny Darlington Carbin provides additional insight.19 Retrospective Study MacDonald et al20 addressed the emerging question of whether or not a confirmatory biopsy is necessary for active surveillance if the initial was done with MRI guidance. The rates of upgrading were high, approximately half, and not a lot of difference between the initial being same center (academic) vs outside. There remains a lot of variability on the amount of up-front diagnostic effort on an active surveillance case with differences in 1 vs 2 pathology reads, MRI reads, fusion or not, and even fusion software vs cognitive. In this series, systematic biopsies on the repeat were still contributing to upgraded cases. Epstein and Jacobs21 offer additional analysis and recommendations. MacDonald et al22 in a second publication in this issue examined another prostate biopsy data topic of MRI vs ultrasound prostate volume measurements. Overall, the measurement discrepancies in over 2000 cases were only 3%. However, in multivariate analyses, they found that larger volume measurements were also a predictor of biopsy grade discrepancy between targeted and systematic. The authors discuss the many causes of measurement variation and the importance of minimizing it to properly coregister a fusion biopsy procedure. Stratton23 provides additional editorial comment. Kobayashi et al24 looked at racial disparities after surgery for nonmetastatic renal cell carcinoma. In this multiregional study, Asian patients had lower rates of cancer-specific mortality, despite similar recurrence rates. They proposed a finding of racial heterogeneity in the biology of nonmetastatic renal cell carcinoma. Rare Conditions Vishwanath et al25 present an unusual case report of priapism. The senior editors discussed this paper at triage and several commented that they had heard of this. In this case, a patient did not have enough response from oral tadalafil and decided to mix several tablets into a liquid and inject it intracavernosal. This resulted in a 36-hour erection requirement intervention with a shunt. This report should improve awareness on patient counselling. PEOPLE, PLACES, AND THINGS The Urological Association of Asia is a relatively newer association at just over 20 years of age and incorporates a massive regional area of traditional Asia, Middle East, Australia, and Pacific Islands. This group met in conjunction with the Taiwanese Urological Association and had a diverse agenda covering all of urology, and AUA educational course for residents, and many international guests. From my perspective, it was interesting in that the Intuitive Single Port robot was just approved for clinical use and several of us taught an introductory course with a lot of engagement from surgeons about to start their practice learning (Figures 1-5). The meeting was a great state-of-the art event in our field and well conducted. This was my first trip to Taiwan and found it to be a really nice, well organized city with a lot to offer in the city center as well as the surrounded areas for sight-seeing post meeting. Next year, this group visits The Philippines.Figure 1.: People. A large gathering of surgeons met to start their journey into single port robotics. We went well over an hour past time to discuss the many areas of patient selection, technique, and outcomes. No picture in Taiwan is complete without a gestured pose.Figure 2.: People. Consulting editor Howard Goldman reviews the data and controversies around anticholinergics and dementia risk.Figure 3.: People. Jacob Tang was one of the conference organizers and meeting President. In addition to a fantastic meeting, he performed some karaoke songs for the crowd at the president's dinner.Figure 4.: Places. The Taipei 101 building (A) highlights the Taipei skyline at 85 stories and far ranging pictures of the city and surrounding mountains (B).Figure 5.: Things. A tour outside of Taipei includes many unique attractions such as the Shifen Waterfall (A) and the Yehliu Geopark, (B) which includes many natural rock formations that bear various resemblances such as the Queen's Head. The Queen's Head is so popular for tourist photographs I had to use artifical intellegence to delete people from the shot.

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