By Chiara Ghetti, MD

Associate Professor, Obstetrics and Gynecology, Division of Female Pelvic Medicine and Reconstructive Surgery, Washington University School of Medicine, St. Louis

Dr. Ghetti reports no financial relationships relevant to this field of study.

SYNOPSIS: Available evidence has shown significant associations between anticholinergic medication use and increased risk of cognitive impairment. Behavioral therapies for overactive bladder should be first-line treatment. If these treatments fail and pharmacologic treatment is considered, providers should counsel patients on associated risks, prescribe the lowest effective dose, and consider alternative treatments in patients at risk.

SOURCE: This document was developed by the American Urogynecologic Society (AUGS) Guidelines Committee with the assistance of Tonya N. Thomas, MD, and Mark D. Walters, MD. AUGS Consensus Statement: Association of Anticholinergic Medication Use and Cognition in Women With Overactive Bladder. Female Pelvic Med Reconstr Surg 2017;23:177-178.

The purpose of this consensus statement was to highlight recent evidence regarding anticholinergic medications and their association with cognitive impairment, dementia, and Alzheimer’s disease. Anticholinergic medications are the mainstay of pharmacologic treatment of overactive bladder (OAB). OAB affects a large proportion of women and has a significant effect on quality of life. In light of evidence of strong associations between anticholinergic medications and cognitive impairments, if providers consider pharmacologic treatment of OAB/detrusor overactivity (DO), they should counsel patients about the associated risks, prescribe the lowest effective dose, and consider alternative therapies in patients at increased risk.

COMMENTARY

Recent analyses estimate that 27 to 36 million people live with Alzheimer’s disease or dementia worldwide. Alzheimer’s disease is the most common form of dementia. Dementia is very uncommon at younger ages, but its prevalence doubles with every five years of age after age 65 years. In a report by the Organization for Economic Cooperation and Development, dementia was found to affect < 3% of people aged 65 to 69 years, but almost 30% of those aged 85 to 89 years.1 As the world’s population ages, there will be a growing number of people affected by dementia. Risk factors for dementia include age, genetics, alcohol use, atherosclerosis, diabetes, hypertension, smoking, and mental illness.2

The published consensus statement reviews several recent studies reporting strong associations between anticholinergic medications and cognitive impairment and dementia. Gray et al published a population-based prospective cohort study of 3,434 participants examining the association between cumulative anticholinergic use and the risk for dementia.3 In this study, bladder antimuscarinics accounted for 10.5% of anticholinergic use. Subjects in the highest exposure category (corresponding to oxybutynin chloride 5 mg taken daily for more than three years) had a statistically significant increased risk for dementia or Alzheimer’s disease compared to nonusers of anticholinergics. These subjects were one and a half times more at risk of having dementia or Alzheimer’s disease. A second large cohort study found significant differences in cognitive performance between anticholinergic users and nonusers. Anticholinergic users also had significantly reduced brain glucose metabolism and significant brain atrophy on neuroimaging when compared to nonusers.4

Anticholinergic medications include some antidepressants, bladder antimuscarinics, antihistamines, and other medications. Antimuscarinic medications and beta-3 agonists are the mainstay of pharmacologic treatment for OAB. Urinary urgency and frequency and nocturia, with or without urgency incontinence, comprise a spectrum of symptoms included in the clinical diagnosis of overactive bladder (OAB). The diagnosis of OAB overlaps with DO, which is a urodynamic diagnosis defined as involuntary detrusor contraction during filling cystogram. OAB is thought to affect 12-17% of the general population, and OAB symptoms have a significant effect on quality of life.5

In the December 2015 issue of OB/GYN Clinical Alert, we reviewed findings that pelvic floor physical therapy improves urinary symptoms.6 Behavioral therapies are the first-line therapies described in the American Urological Association and Society for Urodynamics, Female Pelvic Medicine, and Urogenital Reconstruction Guidelines on OAB.7 Behavioral therapies include the use of bladder training, pelvic floor muscle exercises (PME), biofeedback, lifestyle modification, and dietary changes, as well as approaches that combine bladder training with PME and/or biofeedback.8

The new guidelines recommend trials of pharmacologic treatment if behavioral therapies do not control symptoms. Antimuscarinics are an anticholinergic medication that blocks acetylcholine activity at muscarinic receptors. Because muscarinic receptors are ubiquitous through the body, antimuscarinic medications can cause systemic side effects including dry mouth, constipation, and blurred vision. Recent studies clearly indicate a strong relationship between anticholinergic use and cognitive impairment.

These studies and this consensus statement emphasize the gravity of prescribing anticholinergics for OAB/DO treatment. A large number of patients presenting and being treated for OAB/DO in our practices are older and may have multiple preexisting risk factors for dementia. When considering pharmacologic treatment of OAB/DO, we should assess each patient’s risks for dementia and whether the patient is taking other types of anticholinergic medications. If prescribing antimuscarinics, it is best to use the lowest effective dose possible and consider use of beta-3 agonists. When prescribing antimuscarinics, we must educate our patients about the specific risks of cognitive impairment, dementia, and Alzheimer’s disease while reviewing potential benefits of medication use and discussing alternative therapies, including intradetrusor onabotulinum toxin A9 or neuromodulation.

REFERENCES

  1. National Institute on Aging. Global Health and Aging. The Burden of Dementia. Available at: https://www.nia.nih.gov/research/publication/longer-lives-and-disability/burden-dementia. Accessed June 13, 2017.
  2. National Institute on Aging. Risk Factors for Dementia. Available at: https://www.nia.nih.gov/alzheimers/publication/dementias/risk-factors-dementia. Accessed June 13, 2017.
  3. Gray SL, Anderson ML, Dublin S, et al. Cumulative use of strong anticholinergics and incident dementia: A prospective cohort study. JAMA Intern Med 2015;175:401-407.
  4. Risacher SL, McDonald BC, Tallman EF, et al. Association between anticholinergic medication use and cognition, brain metabolism, and brain atrophy in cognitively normal older adults. JAMA Neurol 2016;73:721-732.
  5. Stewart WF, Van Rooyen JB, Cundiff GW, et al. Prevalence and burden of overactive bladder in the United States. World J Urol 2003;20:327-336.
  6. Ghetti C. Urinary urge incontinence and pelvic floor physical therapy. OB/GYN Clin Alert 2015;32:60-61.
  7. Gormley EA, Lightner DJ, Faraday M, et al. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline amendment. J Urol 2015;193:1572-1580.
  8. Hartmann KE, McPheeters ML, Biller DH et al. Treatment of overactive bladder in women. Evid Rep Technol Assess (Full Rep) 2009;1-120.
  9. Ghetti C. OnabotulinumtoxinA and the bladder. OB/GYN Clin Alert 2015;32:1-2.