1. Geriatric Urinary Incontinence & Overactive Bladder Joseph G. Ouslander, M.D. Professor of Medicine and Nursing Director, Division of Geriatric Medicine and Gerontology Chief Medical Officer, Wesley Woods Center of Emory University Director, Emory Center for Health in Aging Research Scientist, Birmingham/Atlanta VA GRECC

2. Geriatric Urinary Incontinence & Overactive Bladder (OAB)  Prevalence & impacts  Pathophysiology  Diagnostic evaluation  Management  Prevalence & impacts  Pathophysiology  Diagnostic evaluation  Management An Update

3. Geriatric Urinary Incontinence Prevalence Community (General) Community (Frail)/ Acute Hospital N H Women Men

4. Overactive Bladder (OAB)  Urinary Frequency >8 voids/24 hrs  Nocturia awakening at night to void  Urgency, with or without urge incontinence

5. Overactive Bladder Prevalence 17% 16% Women Men Milsom et al: BJU International, 87:760, 2001 Telephone survey of 16,776 adults age 40+

6. Overactive Bladder Prevalence Women Men

7. 0 5 10 15 20 25 30 35 40 Chronic sinusitis Allergic rhinitis High cholesterol Chronic bronchitis Diabetes Arthritis Heart disease Asthma Incontinence Ulcer Top Chronic Conditions in the U.S. Millions OAB

8. OAB: “Dry” vs “Wet” (Urge Incontinence) Wet (37%) Dry (63%) OAB Adapted from Stewart W et al. ICI 2001

9. Spectrum of OAB and Urinary Incontinence z Urgency Frequency Nocturia Stress UI Mixed Urge UI OAB Incontinence

10. Impact of UI & OAB on Quality of Life Quality of Life Occupational  Decreased productivity  Absence from work Social  Limited travel and activity around toilet availability  Social isolation Psychological  Fear and anxiety  Loss of self-esteem  Depression Sexual  Avoidance of sexual contact and intimacy Physical  Discomfort, odor  Falls and injuries

11. Adverse Consequences of UI & OAB  87 Y.O. woman living at home, with minimal assistance from family  Incontinent rushing to the toilet at 2 a.m., slipped and fell in urine  Sustained a hip fracture  Now confined to a wheelchair and required admission to a nursing home

12. Urge Incontinence, Falls, and Fractures 6,049 women, mean age 78.5 25% reported urge UI (at least weekly) Followed for 3 yrs 55% reported falls, 8.5% fractures Odds ratios for urge UI and Falls:1.26 Non-spine fracture:1.34 Brown et al: JAGS 48: 721 – 725, 2000

13. Predispose Gender Racial Neurologic Anatomic Collagen Muscular Cultural Environmental Incite Childbirth Nerve damage Muscle damage Radiation Tissue disruption Radical surgery Intervene Behavioral Pharmacologic Devices Surgical Decompensate Aging Dementia Debility Disease Environment Medications Constipation Occupation Recreation Obesity Surgery Lung disease Smoking Menstrual cycle Infection Medications Fluid intake Diet Toilet habits Menopause Promote Abrams P, Wein A. Urology. 1997:50(suppl 6A):16. Geriatric Urinary Incontinence and OAB Multi-factorial Pathophysiology

14. Drugs/Other Conditions Urinary Tract Neurological Functional/ Behavioral Geriatric Urinary Incontinence & OAB

15. Lower urinary tract  Bladder pathology ( infection, tumor, etc)  Detrusor overactivity  Women – atrophic urethritis, sphincter weakness  Men – prostate enlargement  Urinary retention Obstruction Impaired bladder contractility Lower urinary tract  Bladder pathology ( infection, tumor, etc)  Detrusor overactivity  Women – atrophic urethritis, sphincter weakness  Men – prostate enlargement  Urinary retention Obstruction Impaired bladder contractility Pathophysiology

16. 100 Volume Bladder pressure 2004003000 0 100 Involuntary bladder contractions Normal voluntary void Geriatric Urinary Incontinence & OAB Detrusor Overactivity

17. DHIC % bladder emptying DH 0 20 40 60 80 100 Resnick, Yalla JAMA 1987;148:3076 Geriatric Urinary Incontinence & OAB DHIC

18. Pathophysiology of Detrusor Overactivity  Neurogenic  Myogenic  Combination  Unknown

19. Sphincter Weakness Geriatric Urinary Incontinence & OAB

20. Neurological  Brain Stroke, dementia, Parkinson’s  Spinal cord Injury, compression, multiple sclerosis  Peripheral innervation Diabetic neuropathy Neurological  Brain Stroke, dementia, Parkinson’s  Spinal cord Injury, compression, multiple sclerosis  Peripheral innervation Diabetic neuropathy Pathophysiology Geriatric Urinary Incontinence & OAB

21. Functional/Behavioral  Mobility impairment  Dementia  Fluid intake Amount and timing Caffeine, alcohol  Bowel habits/constipation  Psychological (anxiety) Functional/Behavioral  Mobility impairment  Dementia  Fluid intake Amount and timing Caffeine, alcohol  Bowel habits/constipation  Psychological (anxiety) Pathophysiology Geriatric Urinary Incontinence & OAB

22. Other Conditions  Diabetes (polyuria)  Volume overload (polyuria, nocturia) Congestive heart failure Venous insufficiency with edema  Sleep disorders (nocturia) Sleep apnea Periodic leg movements Other Conditions  Diabetes (polyuria)  Volume overload (polyuria, nocturia) Congestive heart failure Venous insufficiency with edema  Sleep disorders (nocturia) Sleep apnea Periodic leg movements Pathophysiology Geriatric Urinary Incontinence & OAB

23. Requirements for Continence Adequate: Lower urinary tract function Mental function Mobility, Dexterity Environment Motivation (patients, caregivers)

24. Reversible Causes (“DRIP”) D elirium R estricted mobility, R etention I nfection, I nflammation, I mpaction P olyuria, P harmaceuticals

25. Geriatric Urinary Incontinence & OAB Drugs  Diuretics  Narcotics  Anticholinergics  Psychotropics  Cholinesterase inhibitors  Alpha adrenergic drugs Drugs  Diuretics  Narcotics  Anticholinergics  Psychotropics  Cholinesterase inhibitors  Alpha adrenergic drugs

26. Overflow Urge Stress Functional Persistent Incontinence

27.  History (Bladder Diary in selected patients)  Physical exam  Cough test for stress incontinence  Non-invasive flow rate (helpful in men)  Measurement of voided and post-void residual volumes  Urinalysis Diagnostic Assessment Geriatric Urinary Incontinence & OAB

28. History  Most bothersome symptom (s)  Treatment preferences and goals  Medical history for relevant conditions and medications  Onset and duration of symptoms  Prior treatment and response  Characterization of symptoms Overactive bladder Stress incontinence Voiding difficulty Other (pain, hematuria)  Bowel habits  Fluid intake

29. Physical Exam  Cardiovascular  Abdominal  Neurological  Perineal skin condition  External genitalia  Pelvic exam Atrophic vaginitis Pelvic prolapse  Rectal exam  Sphincter control  Prostate

30. Post-Void Residual Determination  Diabetics  Neurological conditions (e.g. post acute stroke, multiple sclerosis, spinal cord injury)  Men (especially those who have not had a TUR)  Anticholinergics and narcotics  History of urinary retention or elevated PVR

31. Urinalysis  Infection  Sterile hematuria  Glucosuria

32. Examples of criteria for further evaluation Recurrent UTI Recent pelvic surgery Severe pelvic prolapse Sterile hematuria Urinary retention Failure to respond to initial therapy, and desire for further improvement Geriatric Urinary Incontinence and OAB

33. Management of Geriatric Incontinence and OAB  Reversible causes  Supportive measures Education Environmental Toilet substitutes Catheters Garments/pads  Behavioral interventions  Pharmacologic therapy  Surgical interventions  Devices

34.  Modify fluid intake  Modify drug regimens (if feasible)  Reduce volume overload (for nocturia) e.g. take furosemide in late afternoon in patients with nocturia and edema  Treat: Infection (new onset or worsening symptoms) Constipation Atrophic vaginitis (topical estrogen) Treat Reversible Causes Management of Geriatric Incontinence and OAB

35.  Education  Environmental Clear well-lit path to toilet Bedside commodes, urinals  Catheters For skin problems, retention, palliative care/patient preference  Garments/pads Supportive Measures Management of Geriatric Incontinence and OAB

36. Chronic Indwelling Catheters Significant, irreversible retention Skin lesions/surgical wounds Patient comfort/preference Appropriate indications

37. Management of Geriatric Incontinence and OAB Undergarments and Pads  Nonspecific  Foster dependency  Expensive

38. Management of Geriatric Incontinence and OAB  Stress incontinence Periurethral injections Bladder neck suspension Sling procedure Artificial sphincter  Urge incontinence Implantable stimulators Augmentation cystoplasty  Stress incontinence Periurethral injections Bladder neck suspension Sling procedure Artificial sphincter  Urge incontinence Implantable stimulators Augmentation cystoplasty Surgical Interventions

39. Management of Geriatric Incontinence and OAB Behavioral Interventions  “Bladder Training” Education Urge suppression techniques Pelvic muscle rehabilitation With and without biofeedback  Toileting programs Prompted voiding (and others)

40. Pelvic Muscle Exercises Locate pelvic muscles Repeat in sets of up to 10 3-4 times/day, and use in everyday life Relax completely for at least 10 seconds Squeeze muscles tightly for up to 10 seconds

41. Burgio et al: JAMA 280: 1995, 1998 Management of Geriatric Incontinence and OAB Behavioral vs. Drug Treatment

42. Much better Better Able to wear fewer pads Completely satisfied Continue treatment Wants another treatment Management of Geriatric Incontinence and OAB Behavior 74 26 76 78 97 14 51 31 56 49 58 76 27 39 34 28 43 76 DrugControlPatient Perceptions Burgio et al: JAMA 280: 1995, 1998 Behavioral vs. Drug Treatment

43. Prompted Voiding Protocol Opportunity (prompt) to toilet every 2 hours Toileting assistance if requested Social interaction and verbal feedback Encourage fluid intake

44. Prompted Voiding  Reduces severity by half  25%-40% of frail nursing home patients respond well UI episodes decrease from 3 or 4 per day to 1 or fewer  Responsive patients can be identified during a 3-day trial Efficacy in Research Studies Ouslander JG et al. JAMA 273:1366-70

45. Management of Geriatric Incontinence and OAB Drug Therapy

46. Lower Urinary Tract Cholinergic and Adrenergic Receptors Detrusor muscle (M) Trigone () Bladder neck () Urethra () Μ=muscarinic = 1 -adrenergic

47. Motor Innervation of the Bladder Neurotransmitter: Acetylcholine Receptors: Muscarinic Pelvic Nerve Contraction

48. Ouslander J. N Engl J Med. 2004;350:786-799 Motor Innervation of the Bladder

49. Ouslander J. N Engl J Med. 2004;350:786-799 Sensory Innervation of the Bladder

50. Drug Therapy for Stress Incontinence  Limited efficacy  Two basic approaches: Estrogen to strengthen periurethral tissues (not effective by itself) Alpha adrenergic drugs to increase urethral smooth muscle tone (no drugs are FDA approved for this indication)  Pseudoephedrine (“Sudafed”)  Duloxitene (“Cymbalta”)

51. Drug Therapy for Urge UI and OAB  Antimuscarinic/Anticholinergics   -Blockers Men with concomitant benign prostatic enlargement  Estrogen (topical) May be a helpful adjunct for women with severe vaginal atrophy and atrophic vaginitis  DDAVP (Off label in the U.S.) Carefully selected patients with primary complaint of nocturia

52. Drug Therapy for Urge UI and OAB  Darifenacin (“Enablex”)  Oxybutynin (“Ditropan”) IR ER (“ XL”) Patch (“Oxytrol”)  Solifenacin (“Vesicare”)  Tolterodine (“Detrol”) IR Long-acting (“LA”)  Trospium (“Sanctura”)

53. Drug Therapy for UI and OAB  Several factors influence the decision to use pharmacologic therapy: Degree and bother of symptoms Patient/family preference Risk for side effects/co-morbidity Responsiveness to behavioral interventions Cost

54. Drug Therapy for Urge UI and OAB  Anticholinergics: meta-analysis 32 trials; most double-blind; 6,800 subjects Significant effects on: Incontinence and voiding frequency Cure/improvement Bladder capacity Modest clinical efficacy vs. placebo Measured over short time periods Herbison P, et al. BMJ. 2003;326:841-844

55. Drug Therapy for Urge UI and OAB  Efficacy  ~ 60 - 70% reduction in urge UI  ~ 30 - 50% placebo effect  Efficacy is similar in elderly vs. younger  Adverse events  Dry mouth ~ 20-25% (~ 5% “severe”)  Others – less common

56. Iris/Ciliary Body = Blurred Vision Lacrimal Gland = Dry Eyes Salivary Glands = Dry Mouth Heart = Tachycardia Stomach = GERD Colon = Constipation Bladder = Retention CNS Potential Side Effects of Antimuscarinic Drugs Somnolence Impaired Cognition

57. Antimuscarinics and Cognition Antimuscarinic drugs used for the bladder can theoretically cause cognitive impairment ACh is a pivotal mediator of short- term memory and cognition Cholinergic system involvement in Alzheimer’s disease has been clearly established Of the 5 muscarinic receptors M 1 appears most involved in memory and learning

58. Antimuscarinic Drugs and Cognition Tolterodine Oxybutynin, Solifenacin Trospium Low lipophilicity Charged Relatively “bulky” High lipophilicity, Neutral Relatively “small ” Relatively “bulky” Highly polar + Vasculature CNS BBB + + + + + + + + ++ + Darifenacin Lipophilic, small “M3 selective”

59. Summary 1.UI and OAB are common conditions in the geriatric population, and are associated with considerable morbidity and cost 2.The pathophysiology is multifactorial, and many potentially reversible factors can contribute 3.All patients should have a basic diagnostic assessment, and selected patients should be referred for further evaluation 4.A variety of treatment options are available; behavioral interventions and drug therapy for urge UI and OAB are most commonly prescribed 5.Treatment should be guided by patient preference, their most bothersome symptoms, and the pathophysiology felt to underlie these symptoms