Clinical Drug Investigation

, Volume 32, Issue 10, pp 697–705 | Cite as

Effect of Anticholinergic Use for the Treatment of Overactive Bladder on Cognitive Function in Postmenopausal Women

  • Elizabeth J. Geller
  • Andrea K. Crane
  • Ellen C. Wells
  • Barbara L. Robinson
  • Mary L. Jannelli
  • Christine M. Khandelwa
  • Anna Marie Connolly
  • Brent A. Parnell
  • Catherine A. Matthews
  • Julie B. Dumond
  • Jan Busby-Whitehead
Original Research Article


Background: Overactive bladder (OAB) is a common condition affecting the elderly. The mainstay of treatment for OAB is medical therapy with anti-cholinergics. However, adverse events have been reported with this class of drugs, including cognitive changes.

Objective: The objective of this study was to investigate the effect of an anticholinergic medication, trospium chloride, on cognitive function in post-menopausal women being treated for OAB.

Methods: This was a prospective cohort study conducted at a urogynaecology clinic at one academic medical centre from January to December 2010, with 12-week follow-up after medication initiation. Women aged 55 years or older seeking treatment for OAB and opting for anticholinergic therapy were recruited. Baseline cognitive function was assessed via the Hopkins Verbal Learning Test-Revised Form (HVLT-R) [and its five subscales], the Orientation, Memory & Concentration (OMC) short form, and the Mini-Cog evaluation. After initiation of trospium chloride extended release, cognitive function was reassessed at Day 1, Week 1, Week 4 and Week 12. Bladder function was assessed via three condition-specific quality-of-life questionnaires. Secondary outcomes included change in bladder symptoms, correlation between cognitive and bladder symptoms, and overall medication compliance. The main outcome measure was change in HVLT-R score at Week 4 after medication initiation, compared with baseline (pre-medication) score.

Results: Of 50 women enrolled, 35 completed the assessment. The average age was 70.4 years and 77.1% had previously taken anticholinergic medication for OAB. At enrollment 65.7% had severe overactive bladder and 71.4% had severe urge incontinence. Cognitive function showed an initial decline on Day 1 in HVLT-R total score (p = 0.037), HVLT-R Delayed Recognition subscale (p = 0.011) and HVLT-R Recognition Bias subscale (p = 0.01). At Week 1 the HVLT-R Learning subscale declined from baseline (p = 0.029). All HVLT-R scores normalized by Week 4. OMC remained stable throughout. The Mini-Cog nadired at a 90.9% pass rate at Week 4. OAB symptoms did not improve until Week 4, based on questionnaire scores (p < 0.05).

Conclusion: Cognitive function exhibited early changes after initiation of trospium chloride but normalized within 4 weeks. Cognitive changes occurred weeks prior to OAB symptom improvement. Surveillance for cognitive changes with anticholinergic use should be part of OAB management.


Cognitive Function Pelvic Floor Overactive Bladder Anticholinergic Medication Bladder Symptom 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This research was an oral presentation at the American Urogynecologic Society on 16 September 2011 and a poster presentation at the Society for Urodynamics in Female Urology from 28 February–2 March 2013.

This project was supported by the IBM Fund Award (Junior Faculty Development Grant, University of North Carolina). The content is solely the responsibility of the authors and does not necessarily represent the official views of the grant sponsors. There are no conflicts of interest to disclose.


  1. 1.
    Stewart WF, Van Rooyen JB, Cundiff GW, et al. Prevalence and burden of overactive bladder in the United States. World J Urol 2003; 20(6): 327–36PubMedGoogle Scholar
  2. 2.
    Haylen BT, de Ridder D, Freeman RM, et al. An International Urogynecological Association (IUGA)/International Continence Society (ICS) joint report on the terminology for female pelvic floor dysfunction. Int Urogynecol J 2010; 21(1): 5–26PubMedCrossRefGoogle Scholar
  3. 3.
    Scheife R, Takeda M. Central nervous system safety of anticholinergic drugs for the treatment of overactive bladder in the elderly. Clin Ther 2005; 27(2): 144–53PubMedCrossRefGoogle Scholar
  4. 4.
    Liberman JN, Hunt TL, Stewart WF, et al. Health-related quality of life among adults with symptoms of overactive bladder: results from a U.S. community-based survey. Urology 2001; 57(6): 1044–50PubMedCrossRefGoogle Scholar
  5. 5.
    Sexton CC, Coyne KS, Thompson C, et al. Prevalence and effect on health-related quality of life of overactive bladder in older americans: results from the epidemiology of lower urinary tract symptoms study. J Am Geriatr Soc 2011; 59(8): 1465–70PubMedCrossRefGoogle Scholar
  6. 6.
    Hu TW, Wagner TH. Health-related consequences of over-active bladder: an economic perspective. BJU Int 2005; 96 Suppl. 1: 43–5PubMedCrossRefGoogle Scholar
  7. 7.
    Hu TW, Wagner TH, Bentkover JD, et al. Costs of urinary incontinence and overactive bladder in the United States: a comparative study. Urology 2004; 63(3): 461–5PubMedCrossRefGoogle Scholar
  8. 8.
    Sexton CC, Coyne KS, Vats V, et al. Impact of overactive bladder on work productivity in the United States: results from EpiLUTS. Am J Manag Care 2009; 15(4 Suppl): S98–S107PubMedGoogle Scholar
  9. 9.
    Kay GG, Abou-Donia MB, Messer Jr WS, et al. Anti-muscarinic drugs for overactive bladder and their potential effects on cognitive function in older patients. J Am Geriatr Soc 2005; 53(12): 2195–201PubMedCrossRefGoogle Scholar
  10. 10.
    Abrams P, Andersson KE, Buccafusco JJ, et al. Muscarinic receptors: their distribution and function in body systems, and the implications for treating overactive bladder. Br J Pharmacol 2006; 148(5): 565–78PubMedCrossRefGoogle Scholar
  11. 11.
    Staskin DR, Harnett MD. Effect of trospium chloride on somnolence and sleepiness in patients with overactive bladder. Curr Urol Rep 2004; 5(6): 423–6PubMedCrossRefGoogle Scholar
  12. 12.
    Kaufer DI. Cholinesterase-inhibitor therapy for dementia: novel clinical substrates and mechanisms for treatment response. CNS Spectr 2002; 7(10): 742–50PubMedGoogle Scholar
  13. 13.
    Callegari E, Malhotra B, Bungay PJ, et al. A comprehensive non-clinical evaluation of the CNS penetration potential of antimuscarinic agents for the treatment of overactive bladder. Br J Clin Pharmacol 2011; 72(2): 235–46PubMedCrossRefGoogle Scholar
  14. 14.
    Lackner TE, Wyman JF, McCarthy TC, et al. Randomized, placebo-controlled trial of the cognitive effect, safety, and tolerability of oral extended-release oxybutynin in cognitively impaired nursing home residents with urge urinary incontinence. J Am Geriatr Soc 2008; 56(5): 862–70PubMedCrossRefGoogle Scholar
  15. 15.
    Pakulski C, Drobnik L, Millo B. Age and sex as factors modifying the function of the blood-cerebrospinal fluid barrier. Med Sci Monit 2000; 6(2): 314–8PubMedGoogle Scholar
  16. 16.
    Klotz U. Pharmacokinetics and drug metabolism in the elderly. Drug metabolism reviews 2009; 41(2): 67–76PubMedCrossRefGoogle Scholar
  17. 17.
    Pak RW, Petrou SP, Staskin DR. trospium chloride: a quaternary amine with unique pharmacologic properties. Current urology reports 2003; 4(6): 436–40PubMedCrossRefGoogle Scholar
  18. 18.
    Biastre K, Burnakis T. trospium chloride treatment of overactive bladder. Ann Pharmacother 2009; 43(2): 283–95PubMedGoogle Scholar
  19. 19.
    STROBE statement-checklist of items that should be included in reports of observational studies (STROBE initiative). Int J Public Health 2008; 53 (1): 3–4Google Scholar
  20. 20.
    Brandt J. The Hopkins Verbal Learning Test: development of a new memory test with six equivalent forms. Clin Neuropsychol 1991; 5: 125–42CrossRefGoogle Scholar
  21. 21.
    Borson S, Scanlan JM, Chen P, et al. The Mini-Cog as a screen for dementia: validation in a population-based sample. J Am Geriatr Soc 2003; 51(10): 1451–4PubMedCrossRefGoogle Scholar
  22. 22.
    Katzman R, Brown T, Fuld P, et al. Validation of a short Orientation-Memory-Concentration Test of cognitive impairment. Am J Psychiatry 1983; 140: 734–9PubMedGoogle Scholar
  23. 23.
    Barber MD, Walters MD, Bump RC. Short forms of two condition-specific quality-of-life questionnaires for women with pelvic floor disorders (PFDI-20 and PFIQ-7). Am J Obstet Gynecol 2005; 193(1): 103–13PubMedCrossRefGoogle Scholar
  24. 24.
    Rogers RG, Coates KW, Kammerer-Doak D, et al. A short form of the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12). Int Urogynecol J Pelvic Floor Dysfunct 2003; 14(3): 164–8; discussion 8PubMedCrossRefGoogle Scholar
  25. 25.
    Han L, Agostini JV, Allore HG. Cumulative anticholinergic exposure is associated with poor memory and executive function in older men. J Am Geriatr Soc 2008; 56(12): 2203–10PubMedCrossRefGoogle Scholar
  26. 26.
    Fox C, Richardson K, Maidment ID, et al. Anticholinergic medication use and cognitive impairment in the older population: the medical research council cognitive function and ageing study. J Am Geriatr Soc. 2011; 59(8): 1477–83PubMedCrossRefGoogle Scholar
  27. 27.
    Ancelin ML, Artero S, Portet F, et al. Non-degenerative mild cognitive impairment in elderly people and use of anticholinergic drugs: longitudinal cohort study. BMJ 2006; 332(7539): 455–9PubMedCrossRefGoogle Scholar
  28. 28.
    Lipton RB, Kolodner K, Wesnes K. Assessment of cognitive function of the elderly population: effects of darifenacin. J Urol 2005; 173(2): 493–8PubMedCrossRefGoogle Scholar
  29. 29.
    Staskin D, Kay G, Tannenbaum C, et al. Trospium chloride has no effect on memory testing and is assay undetectable in the central nervous system of older patients with over-active bladder. Int J Clin Pract 2010; 64(9): 1294–300PubMedCrossRefGoogle Scholar
  30. 30.
    Ieiri I, Takane H, Otsubo K. The MDR1 (ABCB1) gene polymorphism and its clinical implications. Clin Pharmacokinet 2004; 43(9): 553–76PubMedCrossRefGoogle Scholar
  31. 31.
    Van Kerrebroeck P, Kreder K, Jonas U, et al. Tolterodine once-daily: superior efficacy and tolerability in the treatment of the overactive bladder. Urology 2001; 57(3): 414–21PubMedCrossRefGoogle Scholar
  32. 32.
    FDA. Sanctura XR® (trospium chloride) Extended Release: full prescribing information [online]. 2011. Available from URL:, editor [Accessed 2012 Jul 1]

Copyright information

© Springer International Publishing AG 2012

Authors and Affiliations

  • Elizabeth J. Geller
    • 1
  • Andrea K. Crane
    • 1
  • Ellen C. Wells
    • 1
  • Barbara L. Robinson
    • 1
  • Mary L. Jannelli
    • 1
  • Christine M. Khandelwa
    • 1
    • 2
  • Anna Marie Connolly
    • 1
  • Brent A. Parnell
    • 1
  • Catherine A. Matthews
    • 1
  • Julie B. Dumond
    • 3
  • Jan Busby-Whitehead
    • 2
  1. 1.Division of Female Pelvic Medicine and Reconstructive Pelvic SurgeryUniversity of North Carolina at Chapel HillChapel HillUSA
  2. 2.Division of Geriatric MedicineUniversity of North Carolina at Chapel HillChapel HillUSA
  3. 3.Eshelman School of PharmacyUniversity of North Carolina at Chapel HillChapel HillUSA

Personalised recommendations