ICS 2022: The Impact Of Prevalent Overactive Bladder Anticholinergic Use On Cognitive Change In Adults With Normal Cognition, Mild Cognitive Impairment, Or Dementia

(UroToday.com) Research suggests that OAB anticholinergic medications may lead to cognitive dysfunction and an increased risk of dementia, but few studies have evaluated the effect of these medications in those with pre-existing cognitive dysfunction and few have followed patients long term.  APOE-e4 allele is a genetic risk factor for Alzheimer's, and may lead to increased sensitivity to anticholinergic-mediated cognitive decline, but has not been evaluated in the context of OAB anticholinergics.

This was a retrospective, propensity-score matched cohort study using prospective collected data (enrollees from 9/2005 to 1/2020) from the voluntary National Alzheimer’s Coordinating Centers (NACC), 40 specialized Alzheimer’s research centers in the United States, to see if the use of OAB anticholinergics was associated with an increased risk of cognitive decline, and to examine if APOE-e4 carrier status interacts with any observed cognitive decline with OAB anticholinergic use.

The primary exposure was defined as new reported use of an OAB anticholinergic medication (oxybutynin, tolterodine, solifenacin, trospium, darifenacin, or fesoterodine) at a subsequent NACC visit. Patients brought all medication bottles to the appointment for review by study staff. APOE-e3/e4 or APOE-e4/e4 status was determined as being positive for the APOE-e4 allele.

Exclusions were those individuals:

  • who did not have at least one follow-up visit
  • medication list was not available, already on an OAB anticholinergic medication at enrollment
  • had a cognitive condition other than normal cognition, mild cognitive impairment, or dementia
  • missing genetic testing results for APOE-e4 allele status
  • if there were >4 years between their first and second visit.

Co-primary outcomes were the clinical dementia rating (CDR, 0=no dementia, 4=severe cognitive impairment) and the mini-mental state examination (MMSE). Secondary outcomes included the Boston naming test, Wechsler Adult Intelligence Scale-revised (WAIS-R), and the Trail Making test part B. Outcomes were compared between the baseline visit and the next follow-up visit.

The analysis was of 38 variables available in the NACC dataset relevant to cognition such as age, gender, language, years of education, marital status, vision and hearing impairment, and the prevalent use of several medications. Patients who were newly taking an OAB anticholinergic medication were matched 1:1 with participants who were not newly taking an OAB anticholinergic medication using the propensity score, data era (pre/post 2015), total number of NACC visits, and based on their cognitive status (normal, mild cognitive impairment, or dementia).

Of 18,835 people identified, 782 were matched who newly started an OAB anticholinergic to 782 who did not start an OAB anticholinergic. Among the new OAB anticholinergic users, the most common OAB anticholinergic medications were oxybutynin (299/782, 38%), tolterodine (178/782, 23%), and solifenacin (163/782, 21%). The mean time between the primary visit and follow-up visit was 445 days. There was no significant increased risk of important cognitive decline among OAB anticholinergic users, no significant interaction between APOE-e4 carriers, and clinically important cognitive decline measured with either the CDR or MMSE. Results were similar within each cognitive group (normal, mild cognitive impairment, dementia). There was an increased risk of a clinically important change in CDR among users of oxybutynin or tolterodine that was close to statistical significance (p=0.06); this was not seen in users of the other anticholinergics.

The prevalent use of OAB anticholinergic medications was not associated with a clinically important change in overall cognitive status, or with a change in three tests of cognitive function. APOE-e4 allele carrier status did not have a significant interaction with OAB anticholinergic medication and cognitive decline. The conclusion was that in a population with mixed normal and cognitive impairment, the researchers did not find a significant difference in the proportion of people that developed cognitive impairment when comparing new anticholinergic OAB medication users to propensity score-matched nonusers.

Presented by: Blayne Welk MD, MSc, FRCSC, Western University, Ontario, Canada

Written by: Written by: Diane Newman, DNP, CRNP, FAAN, BCB-PMD, Urologic Nurse Practitioner, Adjunct Professor of Urology in Surgery, Senior Research Investigator, Perelman School of Medicine, University of Pennsylvania during the International Continence Society Annual Meeting, September 7-10, 2022, Vienna, Austria.


  1. Araklitis G, Robinson D, Cardozo L. Cognitive effects of anticholinergic load in women with overactive bladder. Clin Interv Aging. 2020 Aug 25;15:1493-1503. doi: 10.2147/CIA.S252852.
  2. Malcher MF, Droupy S, Berr C, Ziad A, Huguet H, Faillie JL, Serrand C, Mura T. Dementia Associated with Anticholinergic Drugs Used for Overactive Bladder: A Nested Case-Control Study Using the French National Medical-Administrative Database. J Urol. 2022 Oct;208(4):863-871. doi: 10.1097/JU.0000000000002804
  3. Welk B, Richardson K, Panicker JN. The cognitive effect of anticholinergics for patients with overactive bladder. Nat Rev Urol. 2021 Nov;18(11):686-700. doi: 10.1038/s41585-021-00504-x
  4. Zillioux J, Welk B, Suskind AM, Gormley EA, Goldman HB. SUFU white paper on overactive bladder anticholinergic medications and dementia risk. Neurourol Urodyn. 2022 Sep 6. doi: 10.1002/nau.25037