SUMMARY:

Overactive bladder (OAB) is clinically diagnosed by symptoms of urinary urgency/urge incontinence, frequency and usually nocturia. Several studies have raised concerns about the role of anticholinergic medications in cognitive decline, dementia and Alzheimer’s disease.  The risk was highest in patients taking the drugs with the most anticholinergic activity.

In response to these concerns AUGS recommends the following:

• When behavioral therapies have failed, counsel patients on risks of cognitive impairment/dementia/Alzheimer’s vs benefits of quality of life improvements prior to instituting anticholinergic medication
• Prescribe the lowest effective dose and consider a beta -3 agonist in patients at risk of cognitive decline
• Consider changing or decreasing the doses of other anticholinergics such as antidepressants/antihistimines
• Consider intradetrusor onabotulinum toxin A or neuromodulation for patients not desiring medication for OAB

KEY POINTS:

Behavioral therapy is the first line treatment for OAB and most effective if individualized to include multiple components

• Modify bladder function (e.g., changing voiding habits, such as delayed voiding)
• Pelvic floor muscle training and exercise (improve strength and control)
• Biofeedback
• Fluid management
• Dietary changes (avoid bladder irritants such as acidic drinks, caffeine)
• Weight Loss

If Behavioral therapy fails, the following medications may be offered:

• Antimuscarinics
  • Anticholinergic medication work by blocking acetylcholine at muscarinic receptors
  • Muscarinic receptors occur throughout the body giving rise to potential anticholinergic effects including dry mouth, blurred vision, constipation and impaired cognition
  • Brain penetration is greatest with oxybutynin, solifenacin and tolterodine
  • Brain penetration is lower with newer agents such as 5-hydroxylmethyl tolterodine, darifenacin and trospium
• Beta-3 agonists
  • Act on adrenergic receptors
  • Mirabegron is the first of a new class of drugs
  • Clinical effectiveness of mirabegron is similar to that of tolterodine
  • Dry mouth is similar to placebo and fewer arrhythmias than tolterodine

There are multiple recent studies, two of which specifically demonstrate an association between anticholinergics, dementia and Alzheimer’s disease, particularly in older individuals:

• Gray et al. (JAMA Internal Medicine, 2015): Those in the highest exposure category (oxybutynin 5 mg taken daily > than 3 years) had 1.5 times more risk of having dementia or Alzheimer’s disease (entry criteria 65 and older)
• Risacher et al. (JAMA Neurology, 2016): Reduced cognitive performance and brain glucose metabolism as well as increased brain atrophy was found in anticholinergic users compared to nonusers (average age of participants 73.3 years)

The American Geriatrics Society (AGS) Beers Criteria for Potentially Inappropriate Medication (PIM) Use in Older Adults

• Antimuscarinics are included in the Beers Criteria in Table 3 and Table 7 as PIMs to be avoided due to drug–disease or drug–syndrome interactions that may exacerbate the disease or syndrome
• Specifically, anticholinergics are to be avoided in the context of dementia or cognitive impairment
• Avoidance recommendation is rated as ‘strong’

Learn More – Primary Sources

AUGS Consensus Statement:  Association of Anticholinergic Medication Use and Cognition in Women with Overactive Bladder.  Female Pelvic Medicine and Reconstructive Surgery

Diagnosis and Treatment of Non-Neurogenic Overactive Bladder (OAB) in Adults: AUA/SUFU Guideline

American Geriatrics Society 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults

Overactive Bladder and the β3-Adrenoceptor Agonists: Current Strategy and Future Prospects

Anticholinergic medication use and dementia: latest evidence and clinical implications

Cumulative Use of Strong Anticholinergic Medications and Incident Dementia

Association between anticholinergic medication use and cognition, brain metabolism, and brain atrophy in cognitively normal older adults

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