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Cognitive Function and Urologic Medications for Lower Urinary Tract Symptoms

배재현|태범식|김연주
대한배뇨장애요실금학회 (Korean Continence Society)|2020.09|International Neurourology Journal|제24권 제3호|pp. 231-240|DOI 10.5213/inj.2040082.041

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키워드

DementiaCognitive dysfunctionAdrenergic alpha-antagonists5-Alpha reductase inhibitorsCholinergic antagonistsAdrenergic beta-3 agonists

초록

Special considerations should be made when selecting medications for the treatment of lower urinary tract symptoms (LUTS) in older patients especially those over 65 years old. This review summarizes the relationship between current treatments for LUTS and cognitive impairment. Although the recently reported association between dementia and tamsulosin is debatable, the effects of α-blockers and pharmacokinetics are not reported in this context. Five-alpha reductase inhibitors appear to affect mood. However, the association between the development of dementia and cognitive impairment is unlikely. Anticholinergic agents, other than trospium, fesoterodine, and imdafenacin have a relatively high distribution in the central nervous system. In particular, oxybutynin is reported to cause cognitive impairment. Several animal studies on the blood-brain barrier permeability of oxybutynin support this. Therefore, care must be taken when they are used in older patients (65 years and older). Beta-3 agonists are an alternative to, or may be used in combination with, anticholinergic drugs for patients with an overactive bladder (OAB). Several phase 2 and 3 clinical studies report high tolerability and efficacy, making them relatively safe for OAB treatment. However, there is a possibility that cognitive function may be affected; thus, long-term study data are required. We have reviewed studies investigating the correlation of urologic medications with cognitive dysfunction and have provided an overview of drug selection, as well as other considerations in older patients (65 years and older) with LUTS. This narrative review has focused primarily on articles indexed in PubMed, Google Scholar, Scopus, and Embase databases. No formal search strategy was used, and no meta-analysis of data was performed.

Abstract

Special considerations should be made when selecting medications for the treatment of lower urinary tract symptoms (LUTS) in older patients especially those over 65 years old. This review summarizes the relationship between current treatments for LUTS and cognitive impairment. Although the recently reported association between dementia and tamsulosin is debatable, the effects of α-blockers and pharmacokinetics are not reported in this context. Five-alpha reductase inhibitors appear to affect mood. However, the association between the development of dementia and cognitive impairment is unlikely. Anticholinergic agents, other than trospium, fesoterodine, and imdafenacin have a relatively high distribution in the central nervous system. In particular, oxybutynin is reported to cause cognitive impairment. Several animal studies on the blood-brain barrier permeability of oxybutynin support this. Therefore, care must be taken when they are used in older patients (65 years and older). Beta-3 agonists are an alternative to, or may be used in combination with, anticholinergic drugs for patients with an overactive bladder (OAB). Several phase 2 and 3 clinical studies report high tolerability and efficacy, making them relatively safe for OAB treatment. However, there is a possibility that cognitive function may be affected; thus, long-term study data are required. We have reviewed studies investigating the correlation of urologic medications with cognitive dysfunction and have provided an overview of drug selection, as well as other considerations in older patients (65 years and older) with LUTS. This narrative review has focused primarily on articles indexed in PubMed, Google Scholar, Scopus, and Embase databases. No formal search strategy was used, and no meta-analysis of data was performed.

참고문헌 (85)

  1. "Prospective Population Estimates of Korea" (2019)[URL]
  2. Bum Sik Tae, "Seasonal Variation of Overactive Bladder Symptoms in Female Patients", International Neurourology Journal, 23(4), pp.334~340 (2019), 대한배뇨장애요실금학회[DOI]
  3. Irwin DE, "Population-based survey of urinary incontinence, overactive bladder, and other lower urinary tract symptoms in five countries: results of the EPIC study", Eur Urol, 50, pp.1306~1314 (2006)
  4. 김규식, "Do Lifestyle Factors Affect Lower Urinary Tract Symptoms? Results from the Korean Community Health Survey", International Neurourology Journal, 23(2), pp.125~135 (2019), 대한배뇨장애요실금학회[DOI]
  5. Irwin DE, "Prevalence, severity, and symptom bother of lower urinary tract symptoms among men in the EPIC study: impact of overactive bladder", Eur Urol, 56, pp.14~20 (2009)
  6. Stewart WF, "Prevalence and burden of overactive bladder in the United States", World J Urol, 20, pp.327~336 (2003)
  7. Kim HA, "Prevalence and predictors of polypharmacy among Korean elderly", PLoS one, 9, pp.e98043~ (2014)
  8. 조영삼, "Treatment of Prostate Disease and Cognitive Problems", International Neurourology Journal, 23(2), pp.89~90 (2019), 대한배뇨장애요실금학회[DOI]
  9. Clegg A, "Improving recruitment of older people to clinical trials : use of the cohort multiple randomised controlled trial design", Age Ageing, 44, pp.547~550 (2015)
  10. Shenoy P, "Elderly patients’ participation in clinical trials", Perspect Clin Res, 6, pp.184~189 (2015)
  11. Leelakanok N, "Association between polypharmacy and death: a systematic review and meta-analysis", J Am Pharm Assoc, 57, pp.729~738.e10 (2017)
  12. Zia A, "Polypharmacy and falls in older people : balancing evidence-based medicine against falls risk", Postgrad Med, 127, pp.330~337 (2015)
  13. Park HY, "The association between polypharmacy and dementia : a nested case-control study based on a 12-year longitudinal cohort database in South Korea", PLoS One, 12, pp.e0169463~ (2017)
  14. Oelke M, "Appropriateness of oral drugs for long-term treatment of lower urinary tract symptoms in older persons : results of a systematic literature review and international consensus validation process(LUTS-FORTA 2014)", Age Ageing, 44, pp.745~755 (2015)
  15. van den Akker M, "Multimorbidity in general practice: prevalence, incidence, and determinants of co-occurring chronic and recurrent diseases", J Clin Epidemiol, 51, pp.367~375 (1998)
  16. Wehling M, "Multimorbidity and polypharmacy : how to reduce the harmful drug load and yet add needed drugs in the elderly? Proposal of a new drug classification : fit for the aged", J Am Geriatr Soc, 57, pp.560~561 (2009)
  17. Muderrisoglu AE, "Cognitive and mood side effects of lower urinary tract medication", Expert Opin Drug Saf, 18, pp.915~923 (2019)
  18. Oelke M, "Cardiovascular and ocular safety of alpha1-adrenoceptor antagonists in the treatment of male lower urinary tract symptoms", Expert Opin Drug Saf, 13, pp.1187~1197 (2014)
  19. Duan Y, "Tamsulosin and the risk of dementia in older men with benign prostatic hyperplasia", Pharmacoepidemiol Drug Saf, 27, pp.340~348 (2018)
  20. Giuliano F, "Impact of medical treatments for benign prostatic hyperplasia on sexual function", BJU Int, 97(Suppl 2), pp.34~38 (2006)
  21. Szot P, "Changes in adrenoreceptors in the prefrontal cortex of subjects with dementia : evidence of compensatory changes", Neuroscience, 146, pp.471~480 (2007)
  22. Andrade C, "How to read a research paper : an exercise in critical thinking in the context of an epidemiologic study on tamsulosin and the risk of dementia", J Clin Psychiatry, 79, pp.18f12660~ (2018)
  23. Rouquier L, "Alpha 1-adrenoceptor antagonists differentially control serotonin release in the hippocampus and striatum : a microdialysis study", Eur J Pharmacol, 261, pp.59~64 (1994)
  24. Tsuyoshi Hattori, "Emotional Stress Facilitates Micturition Reflex: Possible Inhibition by an α1-Adrenoceptor Blocker in the Conscious and Anesthetized State", International Neurourology Journal, 23(2), pp.100~108 (2019), 대한배뇨장애요실금학회[DOI]
  25. Yamada S, "In vivo demonstration of alpha(1A)-adrenoceptor subtype selectivity of KMD-3213 in rat tissues", J Pharmacol Exp Ther, 296, pp.160~167 (2001)
  26. Tamsulosin of alpha1 adrenoceptors in rat tissues in relation to the pharmacokinetics, "J Pharmacol Exp Ther", 1999, 1575~1583
  27. Okura T, "Selective and sustained occupancy of prostatic α1-adrenoceptors by oral administration of KMD-3213 and its plasma concentration in rats", J Pharm Pharmacol, 54, pp.975~982 (2002)
  28. 김창희, "Alpha1-Adrenoceptor Antagonists Improve Memory by Activating N-Methyl-D-Aspartate-Induced Ion Currents in the Rat Hippocampus", International Neurourology Journal, 19(4), pp.228~236 (2015), 대한배뇨장애요실금학회
  29. Grimes DA, "Bias and causal associations in observational research", Lancet, 359, pp.248~252 (2002)
  30. Madersbacher S, "Re : Tamsulosin and the risk of dementia in older men with benign prostatic hyperplasia", Eur Urol, 74, pp.522~523 (2018)
  31. Tae BS, "α-Blocker and risk of dementia in patients with benign prostatic hyperplasia : a nationwide population based study using the national health insurance service database", J Urol, 202, pp.362~368 (2019)
  32. Coelho BP, "Dual effect of doxazosin : anticancer activity on SH-SY5Y neuroblastoma cells and neuroprotection on an in vitro model of Alzheimer’s disease", Neuroscience, 404, pp.314~325 (2019)
  33. Nickel JC, "Comparison of dutasteride and finasteride for treating benign prostatic hyperplasia : the Enlarged Prostate International Comparator Study(EPICS)", BJU Int, 108, pp.388~394 (2011)
  34. Traish AM, "5alpha-reductases in human physiology : an unfolding story", Endocr Pract, 18, pp.965~975 (2012)
  35. 신말순, "Long-term Surgical and Chemical Castration Deteriorates Memory Function Through Downregulation of PKA", CREB, MEK, pp.ERK Pathways in Hippocampus, International Neurourology Journal[DOI]
  36. Mendell AL, "Inhibition of 5α reductase impairs cognitive performance, alters dendritic morphology and increases tau phosphorylation in the hippocampus of male 3xTg-AD mice", Neuroscience, 429, pp.185~202 (2020)
  37. Welk B, "Association of suicidality and depression with 5alpha-reductase inhibitors", JAMA Intern Med, 177, pp.683~691 (2017)
  38. Resnick SM, "Testosterone treatment and cognitive function in older men with low testosterone and age-associated memory impairment", JAMA, 317, pp.717~727 (2017)
  39. Welk B, "The risk of dementia with the use of 5 alpha reductase inhibitors", J Neurol Sci, 379, pp.109~111 (2017)
  40. Corkin S, "Acetylcholine, aging and Alzheimer’s disease: implications for treatment", Trends Neurosci, 4, pp.287~290 (1981)
  41. Pavia J, "Alzheimer’s disease: relationship between muscarinic cholinergic receptors, β‐amyloid and tau proteins", Fundam Clin Pharmacol, 12, pp.473~481 (1998)
  42. Quirion R, "Muscarinic receptor subtypes in human neurodegenerative disorders : focus on Alzheimer’s disease", Trends Pharmacol Sci, (Suppl), pp.80~84 (1989)
  43. Avery EE, "Potential role of muscarinic agonists in Alzheimer’s disease", Drugs Aging, 11, pp.450~459 (1997)
  44. (+)3-MPB, "Neuroimage", 2011, 1~9
  45. Risacher SL, "Association between anticholinergic medication use and cognition, brain metabolism, and brain atrophy in cognitively normal older adults", JAMA Neurol, 73, pp.721~732 (2016)
  46. Ferreira-Vieira TH, "Alzheimer’s disease : targeting the cholinergic system", Curr Neuropharmacol, 14, pp.101~115 (2016)
  47. Jirschele K, "Oxybutynin: past, present, and future", Int Urogynecol J, 24, pp.595~604 (2013)
  48. Katz IR, "Identification of medications that cause cognitive impairment in older people : the case of oxybutynin chloride", J Am Geriatr Soc, 46, pp.8~13 (1998)
  49. Pietzko A, "Influences of trospium chloride and oxybutynin on quantitative eeg in healthyvolunteers", Eur J Clin Pharmacol, 47, pp.337~343 (1994)
  50. Wagg A, "Randomised, multicentre, placebo-controlled, double-blind crossover study investigating the effect of solifenacin and oxybutynin in elderly people with mild cognitive impairment: the SENIOR study", Eur Urol, 64, pp.74~81 (2013)
  51. van de Waterbeemd H, "Estimation of blood-brain barrier crossing of drugs using molecular size and shape, and H-bonding descriptors", J Drug Target, 6, pp.151~165 (1998)
  52. Ertl P, "Fast calculation of molecular polar surface area as a sum of fragment-based contributions and its application to the prediction of drug transport properties", J Med Chem, 43, pp.3714~3717 (2000)
  53. Eyal S, "Drug interactions at the blood-brain barrier: fact or fantasy?", Pharmacol Ther, 123, pp.80~104 (2009)
  54. Liu X, "Progress in brain penetration evaluation in drug discovery and development", J Pharmacol Exp Ther, 325, pp.349~356 (2008)
  55. Callegari E, "A comprehensive non-clinical evaluation of the CNS penetration potential of antimuscarinic agents for the treatment of overactive bladder", Br J Clin Pharmacol, 72, pp.235~246 (2011)
  56. Maruyama S, "In vivo quantitative autoradiographic analysis of brain muscarinic receptor occupancy by antimuscarinic agents for overactive bladder treatment", J Pharmacol Exp Ther, 325, pp.774~781 (2008)
  57. Yoshida A, "Noninvasive evaluation of brain muscarinic receptor occupancy of oxybutynin, darifenacin and imidafenacin in rats by positron emission tomography", Life Sci, 87, pp.175~180 (2010)
  58. Fetscher C, "M3muscarinic receptors mediate contraction of human urinary bladder", Br J Pharmacol, 136, pp.641~644 (2002)
  59. Miyamae K, "Pharmacological effects of darifenacin on human isolated urinary bladder", Pharmacology, 69, pp.205~211 (2003)
  60. Lipton RB, "Assessment of cognitive function of the elderly population : effects of darifenacin", J Urol, 173, pp.493~498 (2005)
  61. Ikeda M, "Prevalence of overactive bladder and its related factors in Japanese patients with diabetes mellitus", Endocrine J, 62, pp.847~854 (2015)
  62. Wesnes KA, "Exploratory pilot study assessing the risk of cognitive impairment or sedation in the elderly following single doses of solifenacin 10 mg", Expert Opin Drug Saf, 8, pp.615~626 (2009)
  63. Chase TN, "Donepezil plus solifenacin(CPC-201)treatment for Alzheimer’s disease", Neurotherapeutics, 14, pp.405~416 (2017)
  64. Schwantes U, "Importance of pharmacological and physicochemical properties for tolerance of antimuscarinic drugs in the treatment of detrusor instability and detrusor hyperreflexia--chances for improvement of therapy", Int J Clin Pharmacol Ther, 37, pp.209~218 (1999)
  65. Esin E, "Influence of antimuscarinic therapy on cognitive functions and quality of life in geriatric patients treated for overactive bladder", Aging Mental Health, 19, pp.217~223 (2015)
  66. "Prog Urol", 2013, 227~236
  67. "Prog Urol", 2014, 672~681
  68. Dubeau CE, "Effect of fesoterodine in vulnerable elderly subjects with urgency incontinence: a double-blind, placebo controlled trial", J Urol, 191, pp.395~404 (2014)
  69. Sakakibara R, "Cognitive safety and overall tolerability of imidafenacin in clinical use: a long-term, open-label, post-marketing surveillance study", Low Urin Tract Symptoms, 6, pp.138~144 (2014)
  70. Emorine LJ, "Molecular characterization of the human beta 3-adrenergic receptor", Science, 245, pp.1118~1121 (1989)
  71. Berkowitz DE, "Distribution of β3-adrenoceptor mRNA in human tissues", Eur J Pharmacol, 289, pp.223~228 (1995)
  72. Fujimura T, "Expression and possible functional role of the beta 3-adrenoceptor in human and rat detrusor muscle", J Urol, 161, pp.680~685 (1999)
  73. Dehvari N, "Mirabegron : potential off target effects and uses beyond the bladder", Br J Pharmacol, 175, pp.4072~4082 (2018)
  74. Kaidoh K, "Effects of selective beta2 and beta3-adrenoceptor agonists on detrusor hyperreflexia in conscious cerebral infarcted rats", J Urol, 168, pp.1247~1252 (2002)
  75. Woods M, "Efficacy of the beta3-adrenergic receptor agonist CL-316243 on experimental bladder hyperreflexia and detrusor instability in the rat", J Urol, 166, pp.1142~1147 (2001)
  76. acetanilide (YM178), a novel selective beta3-adrenoceptor agonist, on bladder function, "J Pharmacol Exp Ther", 2007, 642~647
  77. Chapple CR, "Mirabegron for the treatment of overactive bladder: a review of efficacy, safety and tolerability with a focus on male, elderly and antimuscarinic poor-responder populations, and patients with OAB in Asia", Expert Rev Clin Pharmacol, 10, pp.131~151 (2017)
  78. Chapple CR, "Mirabegron in overactive bladder: a review of efficacy, safety, and tolerability", Neurourol Urodynam, 33, pp.17~30 (2014)
  79. Chapple CR, "A phase II dose-ranging study of mirabegron in patients with overactive bladder", Int Urogynecol J, 24, pp.1447~1458 (2013)
  80. Herschorn S, "A phase III, randomized, double-blind, parallelgroup, placebo-controlled, multicentre study to assess the efficacy and safety of the β3 adrenoceptor agonist, mirabegron, in patients with symptoms of overactive bladder", Urology, 82, pp.313~320 (2013)
  81. Chapple CR, "A proof‐of‐concept study: mirabegron, a new therapy for overactive bladder", Neurourol Urodynam, 32, pp.1116~1122 (2013)
  82. Nitti VW, "Results of a randomized phase III trial of mirabegron in patients with overactive bladder", J Urol, 189, pp.1388~1395 (2013)
  83. Griebling TL, "Effect of mirabegron on cognitive function in elderly patients with overactive bladder: MoCA results from a phase 4randomized, placebo-controlled study (PILLAR)", BMC Geriatr, 20, pp.109~ (2020)
  84. Wagg A, "Efficacy, safety, and tolerability of mirabegron in patients aged >", =65yr with overactive bladder wet: a phase IV, double-blind, randomised, placebo-controlled study (PILLAR), 2020, pp.77, 211~220
  85. Nasreddine ZS, "The Montreal Cognitive Assessment, MoCA:a brief screening tool for mild cognitive impairment", J Am Geriatr Soc, 53, pp.695~699 (2005)

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