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HOW TO MANAGE OVERACTIVE BLADDER IN ELDERLY INDIVIDUALS WITH DEMENTIA? A COMBINED USE OF DONEPEZIL, A CENTRAL ACETYLCHOLINESTERASE INHIBITOR, AND PROPIVERINE, A PERIPHERAL MUSCARINE RECEPTOR ANTAGONIST

2009; Wiley; Volume: 57; Issue: 8 Linguagem: Inglês

10.1111/j.1532-5415.2009.02369.x

1532-5415

Ryuji Sakakibara, T. Ogata, Tomoyuki Uchiyama, Masahiko Kishi, Emina Ogawa, Shigeo Isaka, Jōji Yuasa, Tatsuya Yamamoto, Takashi Ito, Tomonori Yamanishi, Yusuke Awa, Chiharu Yamaguchi, Osamu Takahashi,

Dementia and Cognitive Impairment Research

Journal of the American Geriatrics SocietyVolume 57, Issue 8 p. 1515-1517 Free Access HOW TO MANAGE OVERACTIVE BLADDER IN ELDERLY INDIVIDUALS WITH DEMENTIA? A COMBINED USE OF DONEPEZIL, A CENTRAL ACETYLCHOLINESTERASE INHIBITOR, AND PROPIVERINE, A PERIPHERAL MUSCARINE RECEPTOR ANTAGONIST Ryuji Sakakibara MD, PhD, Ryuji Sakakibara MD, PhD Division of Neurology, Department of Internal Medicine, Sakura Medical Center, Toho University, Sakura, Japan Department of Neurology, Chiba University, Chiba, Japan Department of Neurology, Satte General Hospital, Saitama, JapanSearch for more papers by this authorTakeshi Ogata PhD, Takeshi Ogata PhD Division of Neurology, Department of Internal Medicine, Sakura Medical Center, Toho University, Sakura, Japan Department of Neurology, Satte General Hospital, Saitama, JapanSearch for more papers by this authorTomoyuki Uchiyama MD, PhD, Tomoyuki Uchiyama MD, PhD Department of Neurology, Chiba University, Chiba, JapanSearch for more papers by this authorMasahiko Kishi MD, PhD, Masahiko Kishi MD, PhD Division of Neurology, Department of Internal Medicine, Sakura Medical Center, Toho University, Sakura, JapanSearch for more papers by this authorEmina Ogawa MD, Emina Ogawa MD Division of Neurology, Department of Internal Medicine, Sakura Medical Center, Toho University, Sakura, JapanSearch for more papers by this authorShigeo Isaka MD, PhD, Shigeo Isaka MD, PhD Department of Urology, Satte General Hospital, Saitama, JapanSearch for more papers by this authorJoji Yuasa MD, PhD, Joji Yuasa MD, PhD Department of Urology, Satte General Hospital, Saitama, JapanSearch for more papers by this authorTatsuya Yamamoto MD, PhD, Tatsuya Yamamoto MD, PhD Department of Neurology, Chiba University, Chiba, JapanSearch for more papers by this authorTakashi Ito MD, PhD, Takashi Ito MD, PhD Department of Neurology, Chiba University, Chiba, JapanSearch for more papers by this authorTomonori Yamanishi MD, PhD, Tomonori Yamanishi MD, PhD Department of Urology, Dokkyo Medical College, Tochigi, JapanSearch for more papers by this authorYusuke Awa MD, PhD, Yusuke Awa MD, PhD Department of Urology, Chiba University, Chiba, JapanSearch for more papers by this authorChiharu Yamaguchi, Chiharu Yamaguchi Central Laboratory Unit, Chiba University Hospital Chiba, JapanSearch for more papers by this authorOsamu Takahashi, Osamu Takahashi Central Physiology Unit, Sakura Medical Center, Toho University, Sakura, JapanSearch for more papers by this author Ryuji Sakakibara MD, PhD, Ryuji Sakakibara MD, PhD Division of Neurology, Department of Internal Medicine, Sakura Medical Center, Toho University, Sakura, Japan Department of Neurology, Chiba University, Chiba, Japan Department of Neurology, Satte General Hospital, Saitama, JapanSearch for more papers by this authorTakeshi Ogata PhD, Takeshi Ogata PhD Division of Neurology, Department of Internal Medicine, Sakura Medical Center, Toho University, Sakura, Japan Department of Neurology, Satte General Hospital, Saitama, JapanSearch for more papers by this authorTomoyuki Uchiyama MD, PhD, Tomoyuki Uchiyama MD, PhD Department of Neurology, Chiba University, Chiba, JapanSearch for more papers by this authorMasahiko Kishi MD, PhD, Masahiko Kishi MD, PhD Division of Neurology, Department of Internal Medicine, Sakura Medical Center, Toho University, Sakura, JapanSearch for more papers by this authorEmina Ogawa MD, Emina Ogawa MD Division of Neurology, Department of Internal Medicine, Sakura Medical Center, Toho University, Sakura, JapanSearch for more papers by this authorShigeo Isaka MD, PhD, Shigeo Isaka MD, PhD Department of Urology, Satte General Hospital, Saitama, JapanSearch for more papers by this authorJoji Yuasa MD, PhD, Joji Yuasa MD, PhD Department of Urology, Satte General Hospital, Saitama, JapanSearch for more papers by this authorTatsuya Yamamoto MD, PhD, Tatsuya Yamamoto MD, PhD Department of Neurology, Chiba University, Chiba, JapanSearch for more papers by this authorTakashi Ito MD, PhD, Takashi Ito MD, PhD Department of Neurology, Chiba University, Chiba, JapanSearch for more papers by this authorTomonori Yamanishi MD, PhD, Tomonori Yamanishi MD, PhD Department of Urology, Dokkyo Medical College, Tochigi, JapanSearch for more papers by this authorYusuke Awa MD, PhD, Yusuke Awa MD, PhD Department of Urology, Chiba University, Chiba, JapanSearch for more papers by this authorChiharu Yamaguchi, Chiharu Yamaguchi Central Laboratory Unit, Chiba University Hospital Chiba, JapanSearch for more papers by this authorOsamu Takahashi, Osamu Takahashi Central Physiology Unit, Sakura Medical Center, Toho University, Sakura, JapanSearch for more papers by this author First published: 29 July 2009 https://doi.org/10.1111/j.1532-5415.2009.02369.xCitations: 40AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat To the Editor: Although urinary incontinence inevitably occurs in advanced stages of dementia of any etiology, urinary urgency or frequency (also called an overactive bladder, OAB) occurs more commonly in dementia with Lewy bodies (DLB)1 and vascular dementia (also called multiple cerebral infarction)2 (both >80%) than it does in Alzheimer's disease (AD) (40%).3 Comorbidity of AD and vascular etiologies is not uncommon. Acetylcholinesterase (AChE) inhibitors for dementia and anticholinergics for OAB have been widely used, although a combination of these medications is believed to be contradictory. Thus, there have been no established regimens to treat a patient who has dementia and OAB together. Twenty-six cognitively impaired older individuals were prospectively recruited (AD in 7, multiple cerebral infarction in 5, DLB in 5, frontotemporal dementia in 1, AD and multiple cerebral infarction in 8; of these, 5 with mild cognitive impairment, 19 with dementia, 17 with difficulty walking). They were seven men and 19 women, mean age 78 (range 62–88), already taking 5 mg per day (according to the drug formula in Japan) of donepezil hydrochloride, a central AChE inhibitor, for 7 months (range 3–20 months), but all still had OAB. The patients were started on 20 mg per day (according to the drug formula in Japan) of propiverine hydrochloride, a peripheral muscarinic receptor antagonist, for OAB. A urinary questionnaire (a part of the modified Functional Independence Measure,4 filled basically by the caregivers), Mini-Mental State Examination (MMSE; 0–30 scale), and the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog; 0–70 scale)5 were completed before and 3 months after the addition of propiverine. Statistical analysis was performed using the Student paired t-test and the chi-square test. At the first assessment, the patients showed a mean nighttime urinary frequency of 3.1 times and a daytime frequency of 5.9 times, and urinary incontinence was observed in 14 of 26 patients. Urinary incontinence occurred more than once a day in 11 patients, more than once a week in two, and more than once a month in one. Mean MMSE and ADAS-cog scores were 19.4 and 18.6, respectively (Figure 1). At the second assessment, none of the patients had discontinued the propiverine treatment because of dry mouth, constipation, delusion, or agitation. The patients showed a mean nighttime frequency of 2.5 times (P<.05) and a daytime frequency of 5.7 times (not significant), and urinary incontinence was observed in 12 of 26 patients (P<.01). Daily incontinence disappeared in 36% of patients with daily incontinence. Mean MMSE and ADAS-cog scores were 19.3 and 18.8, respectively (not significant) (Figure 1). There was no correlation between the changes in urinary symptoms and age, sex, underlying diseases, gait function, or MMSE or ADAS-cog scores. Figure 1Open in figure viewerPowerPoint Mini-Mental State Examination (MMSE; range 0–30, lower scores indicating worse cognition) and Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog; range 0–70, higher scores indicating worse cognition) scores before and after the addition of propiverine to donepezil. NS=not statistically significant. To the best of the authors' knowledge, this is the first report to show that addition of 20 mg per day propiverine to 5 mg per day donepezil improved OAB without any cognitive change. Although there were no larger such studies previously, two case reports are available, and the results suggested con and pro, respectively. One6 reported three cases taking 5 mg per day of donepezil, 6 mg per day of rivastigmine, and 10 mg per day donepezil, respectively. All patients developed delusion and agitation after starting 4 mg per day of tolterodine, a muscarinic receptor blocker, for OAB. Discontinuation of tolterodine reversed these events completely. Another study7 reported one case taking 10 mg per day of donepezil and 6 mg per day of tolterodine for OAB (details not known). After the dose of tolterodine was titrated to 4 mg per day, the subject came to have nocturia that might cause poor sleep and agitation. More recently, a retrospective study of 3,536 nursing home residents taking central AChE inhibitors, of whom 10.6% were prescribed anticholinergics together, found no differences in cognitive function between groups of AChE inhibitors alone and AChE inhibitors with anticholinergics, although the subjects scored only from 0 to 10 on the Minimum Data Set used for cognitive assessment.8 Propantheline and oxybutynin have been used to treat urinary incontinence in patients with dementia but without detailed cognitive assessments. Oxybutynin is known to produce cognitive problems9 because it is more lipophilic and more apt to penetrate the blood–brain barrier than other anticholinergic agents, including propiverine.10 Although the current study was a pilot study, it calls for an experimental study to determine whether the combined use of a "central" AChE inhibitor and a "peripheral" muscarine receptor antagonist would be pharmacologically sound as site-directed therapy, because many elderly patients and their caregivers seek medical care for dementia and OAB together. This combination therapy therefore could become an option in patients who suffer from dementia and OAB together. ACKNOWLEDGMENTS Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this letter. Author Contributions: R.S.: study concept and design, acquisition of subjects and data, analysis and interpretation of data, and preparation of manuscript. T.O.: acquisition of data. U.T., M.K., E.O., S.I., J.Y., T.Y., T.I., T.Y., Y.A., C.Y., and O.T.: analysis and interpretation of data. Sponsor's Role: None. REFERENCES 1 Sakakibara R, Ito T, Uchiyama T et al. Lower urinary tract function in dementia of Lewy body type (DLB). J Neurol Neurosurg Psychiatry 2005; 76: 729– 732. CrossrefCASPubMedWeb of Science®Google Scholar 2 Sakakibara R, Hattori T, Uchiyama T et al. Urinary function in the elderly with and without leukoaraiosis; in relation to cognitive and gait function. J Neurol Neurosurg Psychiatry 1999; 67: 658– 660. CrossrefCASPubMedWeb of Science®Google Scholar 3 Sugiyama T, Hashimoto K, Kiwamoto H. Urinary incontinence in senile dementia of the Alzheimer type (SDAT). Int J Urol 1994; 1: 337– 340. Wiley Online LibraryCASPubMedGoogle Scholar 4 Granger CV, Hamilton BB, Linacre JM et al. Performance profiles of the functional independence measure. Am J Phys Med Rehabil 1993; 72: 84– 89. CrossrefCASPubMedWeb of Science®Google Scholar 5 Rosen WG, Mohs RC, Davis KL. A new rating scale for Alzheimer's disease. Am J Psychiatr 1984; 141: 1356– 1364. CrossrefCASPubMedWeb of Science®Google Scholar 6 Edwards KR, O'Conner JT. Risk of delirium with concomitant use of tolterodine and acetylcholinesterase inhibitors. J Am Geriatr Soc 2002; 50: 1165– 1166. Wiley Online LibraryPubMedWeb of Science®Google Scholar 7 Siegler EL, Reidenberg M. Treatment of urinary incontinence with anticholinergics in patients taking cholinesterase inhibitors for dementia. Clin Pharmacol Ther 2004; 75: 484– 488. Wiley Online LibraryCASPubMedWeb of Science®Google Scholar 8 Sink KM, Thomas J III, Xu H et al. Dual use of bladder anticholinergics and cholinesterase inhibitors: Long-term functional and cognitive outcomes. J Am Geriatr Soc 2008; 56: 847– 853. PubMedWeb of Science®Google Scholar 9 Katz IR, Sands LP, Bilker W et al. Identification of medications that cause cognitive impairment in older people: The case of oxybutynin chloride. J Am Geriatr Soc 1998; 46: 8– 13. CASPubMedWeb of Science®Google Scholar 10 Uchida S, Kurosawa S, Fujino Oki T et al. Binding activities by propiverine and its N-oxide metabolites of L-type calcium channel antagonist receptors in the rat bladder and brain. Life Sci 2007; 80: 2454– 2460. CrossrefCASPubMedWeb of Science®Google Scholar Citing Literature Volume57, Issue8August 2009Pages 1515-1517 FiguresReferencesRelatedInformation