- Email: [email protected]
The Aging Lower Urinary Tract
The Aging Lower Urinary Tract Catherine E. DuBeau*,† From the University of Chicago, Chicago, Illinois
Purpose: Age related changes in continence and the GU system, and how they affect the management of LUT dysfunction are discussed. Guidelines are offered regarding the diagnosis and management of incontinence in the elderly population. Materials and Methods: Published literature and current treatment practice specific to elderly patients with LUT dysfunction were reviewed. Results: LUT symptoms in the elderly population are affected by the high prevalence of comorbidity and polypharmacy. In addition, the GU system undergoes age related changes that increase the risk of LUT dysfunction. Conclusions: Incontinence in older persons is almost always caused by multiple factors, of which not all are directly related to the GU system. Issues such as polypharmacy, comorbidity, and the increased risk of medication side effects must be considered in planning treatment. The primary care physician and urologist or gynecologist should establish a partnership to co-manage the broad spectrum of factors affecting continence in elderly patients. Key Words: bladder, urinary incontinence, aged, urination disorders, polypharmacy
LUT dysfunction in the elderly population is almost always a multifactorial condition, with broad determinants of continence. These domains include mobility, manual dexterity, environment and access to toilets, mentation, and medical conditions and medications. Mobility affects the ability to get to the bathroom in time to void. It is important to realize that mobility problems are not immutable and often are treatable. Manual dexterity affects the ability to undress in time to void, as may occur in persons with conditions such as severe arthritis. The environment in which the patient is situated also becomes important. If bathrooms are not easily accessible, either inside or outside of the home, the patient may not be able to find a toilet in time to prevent urinary leakage. In patients with cognitive impairment, delirium, or severe psychiatric disease, mentation and motivation may impair voiding and toileting. For example, patients with Alzheimer’s disease may not recognize the urge to void as a cue to head toward the bathroom.
ging is a true growth industry, not only in the United States, but also globally. By 2020 half of the United States adult population will be older than 45 years; approximately 20% of the labor force will be 65 years or older.1 Even in this subgroup, the most rapidly growing population is persons older than 85 years. Therefore, there is a growing need for clinicians who are skilled in treating illnesses and conditions particular to the elderly population. The variability in older patient mobility, cognitive skills, comorbidity, and activity levels should be considered when evaluating these patients. With the aging of the population, clinicians are likely to see an “epidemic” of older persons with LUTS.
A
AGE AND GENITOURINARY FUNCTION LUTS increase with age, especially those of overactive bladder syndrome (fig. 1).2 Age associated changes occur continually in this population, and age associated comorbidity has an increasingly important role in LUTS. In discussing LUTS in older persons, it is necessary to consider a broader definition of continence and the domains that determine it. A precise characterization of the effects of the aging process on LUT function is difficult to quantify, partly because of the challenges of performing long-term studies in this population with a high mortality rate. In addition, the confounding effects of multiple comorbidities make it difficult to determine which changes are related to aging alone and which are related to disease. The heterogeneity of the elderly population adds to the challenge of determining the definition of what is “normal” in older persons.
NonGU factors. Many nonGU factors common in elderly persons may cause or exacerbate UI (see Appendix). For example, diabetes is prevalent in up to 20% of this population. The associated osmotic diuresis can lead to polyuria, while neuropathic changes may cause detrusor overactivity and, in more advanced stages, diabetic cystopathy. CHF, arthritis, sleep apnea, and severe constipation may also lead to UI. Many clinicians believe that persons with dementia are doomed to UI because of cortical dysfunction, but multivariate studies in this population have shown that impaired mobility is a stronger determinant of UI than cognitive impairment. Many patients with dementia can still walk or be assisted in walking to the bathroom and, therefore, they have a good chance of remaining continent. Medications have a major role in causing or exacerbating UI. For example, angiotensin-converting enzyme inhibitors may cause a cough and, therefore, precipitate stress incontinence. Potent diuretics can overwhelm the ability to fore-
* Correspondence: 5841 South Maryland Ave., MC6098, Chicago, Illinois 60637 (telephone: 773-834-5988; FAX: 773-702-3538; e-mail: [email protected]). † Financial interest and/or other relationship with Pfizer, Yamanouchi, Novartis, Odyssey/Indevus and Watson.
0022-5347/06/1753-0011/0 THE JOURNAL OF UROLOGY® Copyright © 2006 by AMERICAN UROLOGICAL ASSOCIATION
S11
Vol. 175, S11-S15, March 2006 Printed in U.S.A. DOI:10.1016/S0022-5347(05)00311-3
S12
AGING LOWER URINARY TRACT
FIG. 1. Prevalence of OAB symptoms by age2
stall voiding. Calcium blockers, opiates, and anticholinergics can impair bladder emptying. Lack of caregiver support may be an important factor, particularly among elderly women who live alone and lack the appropriate assistance to help them remain continent. All of these factors are important to consider when evaluating elderly patients, because LUT dysfunction is almost always a multifactorial condition. UI in older persons is frequently related to nonGU comorbidities, in addition to impaired mobility. This presents an opportunity for the PCP and urologist/gynecologist to work together for optimal management of these symptoms. LUT function itself is one of the domains to consider when evaluating an elderly patient. In the aging detrusor, there is a slight widening of the spaces between the smooth muscle cells, and within the smooth muscle sarcolemma there is elongation of the dense band components and depletion of caveolae (small invaginations in the sarcolemma involved in transport and signaling processes).3 In older persons with involuntary detrusor contractions during urodynamics, there may be novel changes at the cell junctions.4 It should be noted that 42% of continent, healthy women older than 65 years will exhibit detrusor overactivity in urodynamic testing, and yet a third will be asymptomatic.5 While detrusor overactivity is a significant finding, it does not necessarily mean that the patient will be incontinent. Older persons also may experience impaired bladder contractility. It is not known whether this is related to a myogenic or neurogenic origin or to ischemia. The result is decreased urinary flow rates (even in women) and increased PVR, although it is generally 50 ml or less.6 In frail older persons, the bladder may be both overactive and have weak contractions, a condition called DHIC.7 Patients with DHIC have detrusor overactivity and increased PVR due to poor detrusor contractility (the diagnosis requires exclusion of outlet obstruction).7 DHIC is the second leading cause of UI in institutionalized elderly persons. The coexistence of urge UI and high PVR may affect the management strategy, particularly with regard to antimuscarinic treatment, which could potentially worsen the already high PVR, thereby, lowering functional bladder capacity and worsening UI. Age related changes related to the urethra are also seen in older patients. Most studies pertain to women, with the primary focus being decreased urethral closure pressure and urogenital atrophy. Related to lower levels of estrogen fol-
lowing menopause, these changes include thinning of the urethral epithelium, decreased volume and vascularity of the urethral submucosa, decreased proteoglycans, and possibly also decreased nerve density.8 –10 Change has also been noted in the morphology of the urethra. In comparing the urethras of a 15-year-old and a 69-year-old patient, Perucchini et al documented a pronounced change in the striated smooth muscle, particularly along the vaginal surface in the older patient (fig. 2).11 Although limited, these results suggest significant age related changes. It is not known whether these changes are related to the aging process itself or to other phenomena (eg childbirth, vascular changes, and other comorbidity), but they may predispose women to stress UI. Men also experience age related changes affecting the LUT, particularly related to prostate disease. BPH is seen in 80% of men 80 years or older.12 BPH is discussed in detail elsewhere in this supplement, but it is important to understand the potential for prostatic infarction and ischemia, which can lead to urinary retention in older male patients, particularly those with extensive cardiovascular disease. Nocturia. A very common LUT symptom in older persons is nocturia, defined as the need to void more than 1 time during sleeping hours.13 The prevalence of nocturia increases with age, such that up to 90% of individuals experience this condition by age 80 years. It is important to realize that nocturia is a multifactorial condition caused by nocturnal polyuria and primary sleep disorders, as well as by LUT dysfunction. Patients may not be awakened by the urge to void but may void when awakened by issues related to a primary sleep disorder. Primary sleep disorders are common in older persons and may be related to pain (eg from arthritis or spinal stenosis), depression, restless leg syndrome, and medications. Nocturnal polyuria has a major role in causing noctu-
FIG. 2. Age related change in urethra. Comparison of layer thicknesses in 15-year-old and 69-year-old urethras. Upper plots, layer thickness in median sagittal section, oriented with bladder neck end (BN) of urethra at left and external meatus (EM) at right. Lower plots, corresponding mid urethral cross sections show proximal loss (arrows) of thickness of striated muscle (sm) in dorsal wall and mid urethral cross-sections with age. Reprinted with permission from Elsevier.11
AGING LOWER URINARY TRACT ria in older persons. As with persons of all ages, life-style habits can increase the risk of nocturia, especially in regard to the timing and type of fluid intake. Unlike other age groups, however, older persons have a delay from time of fluid intake to urine excretion, with a shift toward greater excretion later in the day and into the evening. This may be caused by higher nocturnal atrial natriuretic peptide and/or altered secretion of vasopressin. Some older persons may excrete approximately 50% of the 24-hour urine output during the night. Thus, voiding once or twice during the night is considered normal in these patients. An important cause of nocturnal polyuria is pedal edema, which is associated with venous insufficiency, CHF, and medications (eg nonsteroidal anti-inflammatory drugs and the thiazolidinedione antidiabetic agents). Pedal edema causes nocturnal polyuria by mobilization of fluid when the patient is in the reclining position. Sleep apnea also causes nocturnal polyuria and should be considered in obese and/or hypertensive patients with nocturia. LUT causes of nocturia include detrusor overactivity, which may underlie the association between nocturia and symptomatic BPH, detrusor underactivity, and bladder outlet obstruction.
DIAGNOSIS AND TREATMENT The multifactorial nature of UI in older persons creates an important role for PCPs in the assessment and management of LUTS. When evaluating the elderly patient, it is important to consider not only available medical history, but also “circumstantial evidence” offered by caregivers. Caregivers may be family members or health care workers in the home or assisted living facility. Often, they can offer specific information about toileting habits and UI episodes if the patient cannot. Because older persons are likely to ingest multiple medications that are prescribed by multiple physicians, it is imperative to thoroughly review all medications by performing a “brown bag review.” This simply involves asking the patient or caregiver to bring all medications currently prescribed to the appointment with the physician. This offers crucial information not only about medications that possibly may be related to LUTS, but also about conditions for which the patient is being treated. For elderly patients with LUTS, a more comprehensive physical examination should be performed, especially with regard to cognition, pulmonary and heart disease, pedal edema, mobility, and neurological disease. Rapid screening tests of cognition and mobility may be helpful, including the Mini-Mental State Examination, which is a set of 11 questions and tasks designed to evaluate global cognitive performance.14 For frail elderly persons, including those in nursing homes, UI presents an important challenge. Although the approach to management of symptoms is generally similar to that in healthier patients, mobility should be a particular focus when determining management strategy. The 2005 International Consultation on Incontinence concluded that in frail elderly patients whose immobility and function cannot be improved, the chance of restoring continence is very low.15 This has important implications in terms of treating nursing home residents. Caregivers in these facilities generally are asked to treat all incontinent residents similarly,
S13
attempting to assist them in voiding in a toilet, regardless of whether they are likely to respond well. The MDS is a uniform set of data that is mandated to be collected on all nursing home residents in the United States at the time of admission and then quarterly, and also with any major change in clinical status. The MDS includes the Resident Assessment Instrument, which captures demographic, functional, and comorbidity information, including incontinence. If a resident has incontinence, the MDS mandates that nursing staff complete a UI Resident Assessment Protocol, which evaluates factors that may be contributing to UI, such as urinary tract infection, delirium, fecal impaction, and medications. This information is then used to devise a care plan for UI management, with the goal being a decrease in UI frequency. Although the MDS and UI Resident Assessment Protocol have been validated as diagnostic tools in the management of UI in nursing home residents,16 their implementation has been unsatisfactory. Realistic management goals should be set, recognizing that continence goals and preferences vary across patients, family members, and caregivers. Diagnostic tests. In patents with stress UI symptoms, a cough stress test should be performed, ensuring that the patient has a full bladder to avoid a false-negative result. Urinalysis is recommended for all older patients with LUTS. Approximately 20% of older women may be expected to have asymptomatic bacteriuria. If a woman has been incontinent for years, the bacteriuria is most likely unrelated, making antibiotic treatment unlikely to resolve UI, and possibly leading to antibiotic resistance. PVR determination (by catheterization or ultrasonography) is recommended, although it may be unwieldy in the primary care setting. As for younger persons, routine urodynamic testing is not recommended, since there is no evidence that it improves outcomes.15 Urodynamics may be useful when empirical treatment has failed, when the patient is an appropriate candidate for and wishes to undergo surgical treatment, or when the diagnosis is not clear following standard evaluation (eg in patients with complex neurological disease). Treatment for UI in older persons. Given the multifactorial nature of UI and the high prevalence of comorbidities in older patients, urologists/gynecologists and PCPs should work together in treating patients with LUTS. While the PCP may need to refer a patient for specialized evaluation and treatment of LUT dysfunction, the specialist also should refer the patient back to the PCP for appropriate management of conditions such as diabetes and CHF, and adjustment of medications potentially contributing to LUTS and UI. As with younger patients, treatment of OAB in older patients should begin with life-style changes (eg amount and type of fluid ingestion) and behavioral therapy, including bladder retraining for cognitive intact persons and prompted voiding for those who are cognitively impaired. In prescribing medication to treat LUTS, it is important to recognize how the aging process affects the pharmacokinetics and pharmacodynamics of certain agents. Increased fat mass in the elderly leads to an increased half-life of lipophilic drugs. Older patients also experience decreased hepatic glycosylation and renal clearance, and those with low
S14
AGING LOWER URINARY TRACT
albumin will have higher free plasma levels of protein bound drugs. Changes in receptor pharmacodynamics also occur (eg an increased binding affinity for benzodiazepines and a decrease for -blockers). In addition, elderly patients ingest an average of 5 medications, putting them at high risk for polypharmacy (both a greater number of medications with a greater chance of drug interactions and adverse effects, and the use of potentially inappropriate medications). This means they have a higher chance of ingesting a drug that could be affecting LUT function and continence. Polypharmacy also increases the risk of drug-drug interactions and AEs. Antimuscarinics, which are commonly prescribed for overactive bladder, are known to cause AEs, including dry mouth, constipation, blurred vision, and cognitive impairment.17–20 Because of the age related effects on pharmacokinetics and pharmacodynamics, and the high prevalence of polypharmacy, these AEs are more common, occur at lower doses, and often are more pronounced in elderly patients. These AEs can have significant detrimental effects. For example, long-standing dry mouth can lead to dental caries; this could lead to tooth loss with a negative impact on food intake, weight, and quality of life. Older persons are predisposed to constipation; ingesting antimuscarinics can exacerbate that condition and lead to increased episodes of UI. Impaired visual accommodation and other causes of poor vision are already common in older persons, making any drug induced blurred vision even more detrimental to patient function, safety, and independence. Increased cognitive impairment associated with antimuscarinics is currently a subject of debate. One study showed that oxybutynin caused greater decrements in cognitive function than diphenhydramine,21 and individual case reports of confusion and memory loss have been documented in patients on tolterodine, although it is difficult to determine the clinical significance of these findings.22,23 There has been 1 case report of an antimuscarinic agent precipitating delirium in a patient who was also on a cholinesterase inhibitor.24 This is a potentially significant finding, since prescription of cholinesterase inhibitors is being considered for the treatment of mild cognitive impairment, as well for as Alzheimer’s dementia. Persons with Alzheimer’s disease may be at increased risk for cognitive AEs with antimuscarinics for OAB, because of decreased central cholinergic transmission. However, this has yet to be systematically studied. Finally, there are the questions of whether antimuscarinics cross the blood-brain barrier and whether age related changes in the blood-brain barrier have significance for antimuscarinic drugs prescribed for UI.25 CONCLUSIONS The key to effective treatment of LUTS in older persons begins with recognition of the relationship between these symptoms and factors outside of the LUT, such as comorbid conditions, functional status, and cognition, and it may optimally involve partnership between the urologist/gynecologist and PCP. It is important to address factors outside of the LUT as potential causes of the symptoms. Elderly patients should be evaluated for polypharmacy prior to initiating treatment for LUTS; an attempt should be made to decrease or otherwise adjust the medication load. For elderly patients with cognitive impairment and severe mobil-
ity impairment, clinicians should attempt to manage incontinence in a manner that affords the patient the greatest level of dignity and quality of life. However, palliative treatment (incontinence pads and garments) should only be initiated as a last resort. APPENDIX Nongenitourinary factors related to urinary incontinence Comorbid Disease
Medications
Diabetes Congestive heart failure Degenerative joint disease Sleep apnea Severe constipation
␣-Adrenergics (blockers and agonists) Cholinergics (blockers and agonists) Angiotensin-converting enzyme inhibitors Calcium blockers Diuretics Opiates Anticholinergics (antidepressants, antipsychotics)
Neurological/Psychiatric
Function and Environment
Stroke Parkinson’s disease Normal pressure hydrocephalus Dementia Depression
Impaired cognition Impaired mobility Inaccessible toilets Lack of caregivers
Abbreviations and Acronyms AE BPH CHF DHIC
⫽ ⫽ ⫽ ⫽
GU LUT LUTS MDS PCP PVR UI
⫽ ⫽ ⫽ ⫽ ⫽ ⫽ ⫽
adverse effect benign prostatic hyperplasia congestive heart failure detrusor hyperactivity with impaired contractility genitourinary lower urinary tract LUT symptoms Minimum Data Set primary care physician post-void residual urine volume urinary incontinence
REFERENCES 1. Toossi, M.: A century of change: the U. S. labor force, 1950-2050. Mon Labor Rev, 2002 2. Milsom, I., Abrams, P., Cardozo, L., Roberts, R. G., Thuroff, J. and Wein, A. J.: How widespread are the symptoms of an overactive bladder and how are they managed? A populationbased prevalence study. BJU Int, 87: 760, 2001 3. Haferkamp, A. and Elbadawi, A.: Ultrastructural changes in the aging bladder. Urologe A, 43: 527, 2004 4. Elbadawi, A., Yalla, S. V. and Resnick, N. M.: Structural basis of geriatric voiding dysfunction. III. Detrusor overactivity. J Urol, 150: 1668, 1993 5. Resnick, N. M., Elbadawi, A. and Yalla, S. V.: Age and the lower urinary tract: what is normal? Neurourol Urodyn, 14: 577, 1995 6. Nordling, J.: The aging bladder—a significant but underestimated role in the development of lower urinary tract symptoms. Exp Gerontol, 37: 991, 2002 7. Resnick, N. M. and Yalla, S. V.: Detrusor hyperactivity with impaired contractile function. An unrecognized but common cause of incontinence in elderly patients. JAMA, 257: 3076, 1987
AGING LOWER URINARY TRACT 8. Forsberg, J. G.: A morphologist’s approach to the vagina—agerelated changes and estrogen sensitivity. Maturitas, suppl., 22: S7, 1995 9. Carlile, A., Davies, I., Rigby, A. and Brocklehurst, J. C.: Age changes in the human female urethra a morphometric study. J Urol, 139: 532, 1988 10. Verelst, M., Maltau, J. M. and Orbo, A.: Computerised morphometric study of the paraurethral tissue in young and elderly women. Neurourol Urodyn, 21: 529, 2002 11. Perucchini, D., DeLancey, J. O., Ashton-Miller, J. A., Galecki, A. and Schaer, G. N.: Age effects on urethral striated muscle. II. Anatomic location of muscle loss. Am J Obstet Gynecol, 186: 356, 2002 12. McConnell, J. D., Barry, M. J., and Bruskewitz, R. C.: Benign Prostatic Hyperplasia: Diagnosis and Treatment. Agency for Health Care Policy and Research Publication No. 94-0582. Rockville, Maryland: Agency for Health Care Policy and Research, 1994 13. Abrams, P., Cardozo, L., Fall, M., Griffiths, D., Rosier, P., Ulmsten, U. et al: The standardisation of terminology in lower urinary tract function: report from the standardisation subcommittee of the International Continence Society. Urology, 61: 37, 2003 14. Folstein, M. F., Folstein, S. E. and McHugh, P. R.: “Mini-mental state.” A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res, 12: 189, 1975 15. Abrams, P., Cardozo, L., Khoury, S. and Wein, A.: Incontinence: 3rd International Consultation on Incontinence. Plymouth, United Kingdom: Health Publication Ltd., 2005
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16. Resnick, N. M., Brandeis, G. H., Baumann, M. M. and Morris, J. N.: Evaluating a national assessment strategy for urinary incontinence in nursing home residents: reliability of the minimum data set and validity of the resident assessment protocol. Neurourol Urodyn, 15: 583, 1996 17. Detrol LA® package insert. Kalamazoo: Pharmacia and Upjohn Co., 2004 18. Ditropan XL® package insert. Raritan: Ortho-McNeil Pharmaceutical, 2004 19. Vesicare® package insert. Paramus: Yamanouchi Pharma America, 2004 20. Enablex® package insert. East Hanover, New Jersey: Novartis Pharmaceuticals Corp., 2004 21. Katz, I. R., Sands, L. P., Bilker, W., DiFilippo, S., Boyce, A. and D’Angelo, K: Identification of medications that cause cognitive impairment in older people: the case of oxybutynin chloride. J Am Geriatr Soc, 46: 8, 1998 22. Ouslander, J. G., Maloney, C., Grasela, T. H., Rogers, L. and Walawander, C. A.: Implementation of a nursing home urinary incontinence management program with and without tolterodine. J Am Med Dir Assoc, 2: 207, 2001 23. Womack, K. B. and Heilman, K. M.: Tolterodine and memory: dry but forgetful. Arch Neurol, 60: 771, 2003 24. Siegler, E. L. and Reidenberg, M.: Treatment of urinary incontinence with anticholinergics in patients taking cholinesterase inhibitors for dementia. Clin Pharmacol Ther, 75: 484, 2004 25. Todorova, A., Vonderheid-Guth, B. and Dimpfel, W.: Effects of tolterodine, trospium chloride, and oxybutynin on the central nervous system. J Clin Pharmacol, 41: 636, 2001
Purpose: Age related changes in continence and the GU system, and how they affect the management of LUT dysfunction are discussed. Guidelines are offered regarding the diagnosis and management of incontinence in the elderly population. Materials and Methods: Published literature and current treatment practice specific to elderly patients with LUT dysfunction were reviewed. Results: LUT symptoms in the elderly population are affected by the high prevalence of comorbidity and polypharmacy. In addition, the GU system undergoes age related changes that increase the risk of LUT dysfunction. Conclusions: Incontinence in older persons is almost always caused by multiple factors, of which not all are directly related to the GU system. Issues such as polypharmacy, comorbidity, and the increased risk of medication side effects must be considered in planning treatment. The primary care physician and urologist or gynecologist should establish a partnership to co-manage the broad spectrum of factors affecting continence in elderly patients. Key Words: bladder, urinary incontinence, aged, urination disorders, polypharmacy
LUT dysfunction in the elderly population is almost always a multifactorial condition, with broad determinants of continence. These domains include mobility, manual dexterity, environment and access to toilets, mentation, and medical conditions and medications. Mobility affects the ability to get to the bathroom in time to void. It is important to realize that mobility problems are not immutable and often are treatable. Manual dexterity affects the ability to undress in time to void, as may occur in persons with conditions such as severe arthritis. The environment in which the patient is situated also becomes important. If bathrooms are not easily accessible, either inside or outside of the home, the patient may not be able to find a toilet in time to prevent urinary leakage. In patients with cognitive impairment, delirium, or severe psychiatric disease, mentation and motivation may impair voiding and toileting. For example, patients with Alzheimer’s disease may not recognize the urge to void as a cue to head toward the bathroom.
ging is a true growth industry, not only in the United States, but also globally. By 2020 half of the United States adult population will be older than 45 years; approximately 20% of the labor force will be 65 years or older.1 Even in this subgroup, the most rapidly growing population is persons older than 85 years. Therefore, there is a growing need for clinicians who are skilled in treating illnesses and conditions particular to the elderly population. The variability in older patient mobility, cognitive skills, comorbidity, and activity levels should be considered when evaluating these patients. With the aging of the population, clinicians are likely to see an “epidemic” of older persons with LUTS.
A
AGE AND GENITOURINARY FUNCTION LUTS increase with age, especially those of overactive bladder syndrome (fig. 1).2 Age associated changes occur continually in this population, and age associated comorbidity has an increasingly important role in LUTS. In discussing LUTS in older persons, it is necessary to consider a broader definition of continence and the domains that determine it. A precise characterization of the effects of the aging process on LUT function is difficult to quantify, partly because of the challenges of performing long-term studies in this population with a high mortality rate. In addition, the confounding effects of multiple comorbidities make it difficult to determine which changes are related to aging alone and which are related to disease. The heterogeneity of the elderly population adds to the challenge of determining the definition of what is “normal” in older persons.
NonGU factors. Many nonGU factors common in elderly persons may cause or exacerbate UI (see Appendix). For example, diabetes is prevalent in up to 20% of this population. The associated osmotic diuresis can lead to polyuria, while neuropathic changes may cause detrusor overactivity and, in more advanced stages, diabetic cystopathy. CHF, arthritis, sleep apnea, and severe constipation may also lead to UI. Many clinicians believe that persons with dementia are doomed to UI because of cortical dysfunction, but multivariate studies in this population have shown that impaired mobility is a stronger determinant of UI than cognitive impairment. Many patients with dementia can still walk or be assisted in walking to the bathroom and, therefore, they have a good chance of remaining continent. Medications have a major role in causing or exacerbating UI. For example, angiotensin-converting enzyme inhibitors may cause a cough and, therefore, precipitate stress incontinence. Potent diuretics can overwhelm the ability to fore-
* Correspondence: 5841 South Maryland Ave., MC6098, Chicago, Illinois 60637 (telephone: 773-834-5988; FAX: 773-702-3538; e-mail: [email protected]). † Financial interest and/or other relationship with Pfizer, Yamanouchi, Novartis, Odyssey/Indevus and Watson.
0022-5347/06/1753-0011/0 THE JOURNAL OF UROLOGY® Copyright © 2006 by AMERICAN UROLOGICAL ASSOCIATION
S11
Vol. 175, S11-S15, March 2006 Printed in U.S.A. DOI:10.1016/S0022-5347(05)00311-3
S12
AGING LOWER URINARY TRACT
FIG. 1. Prevalence of OAB symptoms by age2
stall voiding. Calcium blockers, opiates, and anticholinergics can impair bladder emptying. Lack of caregiver support may be an important factor, particularly among elderly women who live alone and lack the appropriate assistance to help them remain continent. All of these factors are important to consider when evaluating elderly patients, because LUT dysfunction is almost always a multifactorial condition. UI in older persons is frequently related to nonGU comorbidities, in addition to impaired mobility. This presents an opportunity for the PCP and urologist/gynecologist to work together for optimal management of these symptoms. LUT function itself is one of the domains to consider when evaluating an elderly patient. In the aging detrusor, there is a slight widening of the spaces between the smooth muscle cells, and within the smooth muscle sarcolemma there is elongation of the dense band components and depletion of caveolae (small invaginations in the sarcolemma involved in transport and signaling processes).3 In older persons with involuntary detrusor contractions during urodynamics, there may be novel changes at the cell junctions.4 It should be noted that 42% of continent, healthy women older than 65 years will exhibit detrusor overactivity in urodynamic testing, and yet a third will be asymptomatic.5 While detrusor overactivity is a significant finding, it does not necessarily mean that the patient will be incontinent. Older persons also may experience impaired bladder contractility. It is not known whether this is related to a myogenic or neurogenic origin or to ischemia. The result is decreased urinary flow rates (even in women) and increased PVR, although it is generally 50 ml or less.6 In frail older persons, the bladder may be both overactive and have weak contractions, a condition called DHIC.7 Patients with DHIC have detrusor overactivity and increased PVR due to poor detrusor contractility (the diagnosis requires exclusion of outlet obstruction).7 DHIC is the second leading cause of UI in institutionalized elderly persons. The coexistence of urge UI and high PVR may affect the management strategy, particularly with regard to antimuscarinic treatment, which could potentially worsen the already high PVR, thereby, lowering functional bladder capacity and worsening UI. Age related changes related to the urethra are also seen in older patients. Most studies pertain to women, with the primary focus being decreased urethral closure pressure and urogenital atrophy. Related to lower levels of estrogen fol-
lowing menopause, these changes include thinning of the urethral epithelium, decreased volume and vascularity of the urethral submucosa, decreased proteoglycans, and possibly also decreased nerve density.8 –10 Change has also been noted in the morphology of the urethra. In comparing the urethras of a 15-year-old and a 69-year-old patient, Perucchini et al documented a pronounced change in the striated smooth muscle, particularly along the vaginal surface in the older patient (fig. 2).11 Although limited, these results suggest significant age related changes. It is not known whether these changes are related to the aging process itself or to other phenomena (eg childbirth, vascular changes, and other comorbidity), but they may predispose women to stress UI. Men also experience age related changes affecting the LUT, particularly related to prostate disease. BPH is seen in 80% of men 80 years or older.12 BPH is discussed in detail elsewhere in this supplement, but it is important to understand the potential for prostatic infarction and ischemia, which can lead to urinary retention in older male patients, particularly those with extensive cardiovascular disease. Nocturia. A very common LUT symptom in older persons is nocturia, defined as the need to void more than 1 time during sleeping hours.13 The prevalence of nocturia increases with age, such that up to 90% of individuals experience this condition by age 80 years. It is important to realize that nocturia is a multifactorial condition caused by nocturnal polyuria and primary sleep disorders, as well as by LUT dysfunction. Patients may not be awakened by the urge to void but may void when awakened by issues related to a primary sleep disorder. Primary sleep disorders are common in older persons and may be related to pain (eg from arthritis or spinal stenosis), depression, restless leg syndrome, and medications. Nocturnal polyuria has a major role in causing noctu-
FIG. 2. Age related change in urethra. Comparison of layer thicknesses in 15-year-old and 69-year-old urethras. Upper plots, layer thickness in median sagittal section, oriented with bladder neck end (BN) of urethra at left and external meatus (EM) at right. Lower plots, corresponding mid urethral cross sections show proximal loss (arrows) of thickness of striated muscle (sm) in dorsal wall and mid urethral cross-sections with age. Reprinted with permission from Elsevier.11
AGING LOWER URINARY TRACT ria in older persons. As with persons of all ages, life-style habits can increase the risk of nocturia, especially in regard to the timing and type of fluid intake. Unlike other age groups, however, older persons have a delay from time of fluid intake to urine excretion, with a shift toward greater excretion later in the day and into the evening. This may be caused by higher nocturnal atrial natriuretic peptide and/or altered secretion of vasopressin. Some older persons may excrete approximately 50% of the 24-hour urine output during the night. Thus, voiding once or twice during the night is considered normal in these patients. An important cause of nocturnal polyuria is pedal edema, which is associated with venous insufficiency, CHF, and medications (eg nonsteroidal anti-inflammatory drugs and the thiazolidinedione antidiabetic agents). Pedal edema causes nocturnal polyuria by mobilization of fluid when the patient is in the reclining position. Sleep apnea also causes nocturnal polyuria and should be considered in obese and/or hypertensive patients with nocturia. LUT causes of nocturia include detrusor overactivity, which may underlie the association between nocturia and symptomatic BPH, detrusor underactivity, and bladder outlet obstruction.
DIAGNOSIS AND TREATMENT The multifactorial nature of UI in older persons creates an important role for PCPs in the assessment and management of LUTS. When evaluating the elderly patient, it is important to consider not only available medical history, but also “circumstantial evidence” offered by caregivers. Caregivers may be family members or health care workers in the home or assisted living facility. Often, they can offer specific information about toileting habits and UI episodes if the patient cannot. Because older persons are likely to ingest multiple medications that are prescribed by multiple physicians, it is imperative to thoroughly review all medications by performing a “brown bag review.” This simply involves asking the patient or caregiver to bring all medications currently prescribed to the appointment with the physician. This offers crucial information not only about medications that possibly may be related to LUTS, but also about conditions for which the patient is being treated. For elderly patients with LUTS, a more comprehensive physical examination should be performed, especially with regard to cognition, pulmonary and heart disease, pedal edema, mobility, and neurological disease. Rapid screening tests of cognition and mobility may be helpful, including the Mini-Mental State Examination, which is a set of 11 questions and tasks designed to evaluate global cognitive performance.14 For frail elderly persons, including those in nursing homes, UI presents an important challenge. Although the approach to management of symptoms is generally similar to that in healthier patients, mobility should be a particular focus when determining management strategy. The 2005 International Consultation on Incontinence concluded that in frail elderly patients whose immobility and function cannot be improved, the chance of restoring continence is very low.15 This has important implications in terms of treating nursing home residents. Caregivers in these facilities generally are asked to treat all incontinent residents similarly,
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attempting to assist them in voiding in a toilet, regardless of whether they are likely to respond well. The MDS is a uniform set of data that is mandated to be collected on all nursing home residents in the United States at the time of admission and then quarterly, and also with any major change in clinical status. The MDS includes the Resident Assessment Instrument, which captures demographic, functional, and comorbidity information, including incontinence. If a resident has incontinence, the MDS mandates that nursing staff complete a UI Resident Assessment Protocol, which evaluates factors that may be contributing to UI, such as urinary tract infection, delirium, fecal impaction, and medications. This information is then used to devise a care plan for UI management, with the goal being a decrease in UI frequency. Although the MDS and UI Resident Assessment Protocol have been validated as diagnostic tools in the management of UI in nursing home residents,16 their implementation has been unsatisfactory. Realistic management goals should be set, recognizing that continence goals and preferences vary across patients, family members, and caregivers. Diagnostic tests. In patents with stress UI symptoms, a cough stress test should be performed, ensuring that the patient has a full bladder to avoid a false-negative result. Urinalysis is recommended for all older patients with LUTS. Approximately 20% of older women may be expected to have asymptomatic bacteriuria. If a woman has been incontinent for years, the bacteriuria is most likely unrelated, making antibiotic treatment unlikely to resolve UI, and possibly leading to antibiotic resistance. PVR determination (by catheterization or ultrasonography) is recommended, although it may be unwieldy in the primary care setting. As for younger persons, routine urodynamic testing is not recommended, since there is no evidence that it improves outcomes.15 Urodynamics may be useful when empirical treatment has failed, when the patient is an appropriate candidate for and wishes to undergo surgical treatment, or when the diagnosis is not clear following standard evaluation (eg in patients with complex neurological disease). Treatment for UI in older persons. Given the multifactorial nature of UI and the high prevalence of comorbidities in older patients, urologists/gynecologists and PCPs should work together in treating patients with LUTS. While the PCP may need to refer a patient for specialized evaluation and treatment of LUT dysfunction, the specialist also should refer the patient back to the PCP for appropriate management of conditions such as diabetes and CHF, and adjustment of medications potentially contributing to LUTS and UI. As with younger patients, treatment of OAB in older patients should begin with life-style changes (eg amount and type of fluid ingestion) and behavioral therapy, including bladder retraining for cognitive intact persons and prompted voiding for those who are cognitively impaired. In prescribing medication to treat LUTS, it is important to recognize how the aging process affects the pharmacokinetics and pharmacodynamics of certain agents. Increased fat mass in the elderly leads to an increased half-life of lipophilic drugs. Older patients also experience decreased hepatic glycosylation and renal clearance, and those with low
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albumin will have higher free plasma levels of protein bound drugs. Changes in receptor pharmacodynamics also occur (eg an increased binding affinity for benzodiazepines and a decrease for -blockers). In addition, elderly patients ingest an average of 5 medications, putting them at high risk for polypharmacy (both a greater number of medications with a greater chance of drug interactions and adverse effects, and the use of potentially inappropriate medications). This means they have a higher chance of ingesting a drug that could be affecting LUT function and continence. Polypharmacy also increases the risk of drug-drug interactions and AEs. Antimuscarinics, which are commonly prescribed for overactive bladder, are known to cause AEs, including dry mouth, constipation, blurred vision, and cognitive impairment.17–20 Because of the age related effects on pharmacokinetics and pharmacodynamics, and the high prevalence of polypharmacy, these AEs are more common, occur at lower doses, and often are more pronounced in elderly patients. These AEs can have significant detrimental effects. For example, long-standing dry mouth can lead to dental caries; this could lead to tooth loss with a negative impact on food intake, weight, and quality of life. Older persons are predisposed to constipation; ingesting antimuscarinics can exacerbate that condition and lead to increased episodes of UI. Impaired visual accommodation and other causes of poor vision are already common in older persons, making any drug induced blurred vision even more detrimental to patient function, safety, and independence. Increased cognitive impairment associated with antimuscarinics is currently a subject of debate. One study showed that oxybutynin caused greater decrements in cognitive function than diphenhydramine,21 and individual case reports of confusion and memory loss have been documented in patients on tolterodine, although it is difficult to determine the clinical significance of these findings.22,23 There has been 1 case report of an antimuscarinic agent precipitating delirium in a patient who was also on a cholinesterase inhibitor.24 This is a potentially significant finding, since prescription of cholinesterase inhibitors is being considered for the treatment of mild cognitive impairment, as well for as Alzheimer’s dementia. Persons with Alzheimer’s disease may be at increased risk for cognitive AEs with antimuscarinics for OAB, because of decreased central cholinergic transmission. However, this has yet to be systematically studied. Finally, there are the questions of whether antimuscarinics cross the blood-brain barrier and whether age related changes in the blood-brain barrier have significance for antimuscarinic drugs prescribed for UI.25 CONCLUSIONS The key to effective treatment of LUTS in older persons begins with recognition of the relationship between these symptoms and factors outside of the LUT, such as comorbid conditions, functional status, and cognition, and it may optimally involve partnership between the urologist/gynecologist and PCP. It is important to address factors outside of the LUT as potential causes of the symptoms. Elderly patients should be evaluated for polypharmacy prior to initiating treatment for LUTS; an attempt should be made to decrease or otherwise adjust the medication load. For elderly patients with cognitive impairment and severe mobil-
ity impairment, clinicians should attempt to manage incontinence in a manner that affords the patient the greatest level of dignity and quality of life. However, palliative treatment (incontinence pads and garments) should only be initiated as a last resort. APPENDIX Nongenitourinary factors related to urinary incontinence Comorbid Disease
Medications
Diabetes Congestive heart failure Degenerative joint disease Sleep apnea Severe constipation
␣-Adrenergics (blockers and agonists) Cholinergics (blockers and agonists) Angiotensin-converting enzyme inhibitors Calcium blockers Diuretics Opiates Anticholinergics (antidepressants, antipsychotics)
Neurological/Psychiatric
Function and Environment
Stroke Parkinson’s disease Normal pressure hydrocephalus Dementia Depression
Impaired cognition Impaired mobility Inaccessible toilets Lack of caregivers
Abbreviations and Acronyms AE BPH CHF DHIC
⫽ ⫽ ⫽ ⫽
GU LUT LUTS MDS PCP PVR UI
⫽ ⫽ ⫽ ⫽ ⫽ ⫽ ⫽
adverse effect benign prostatic hyperplasia congestive heart failure detrusor hyperactivity with impaired contractility genitourinary lower urinary tract LUT symptoms Minimum Data Set primary care physician post-void residual urine volume urinary incontinence
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16. Resnick, N. M., Brandeis, G. H., Baumann, M. M. and Morris, J. N.: Evaluating a national assessment strategy for urinary incontinence in nursing home residents: reliability of the minimum data set and validity of the resident assessment protocol. Neurourol Urodyn, 15: 583, 1996 17. Detrol LA® package insert. Kalamazoo: Pharmacia and Upjohn Co., 2004 18. Ditropan XL® package insert. Raritan: Ortho-McNeil Pharmaceutical, 2004 19. Vesicare® package insert. Paramus: Yamanouchi Pharma America, 2004 20. Enablex® package insert. East Hanover, New Jersey: Novartis Pharmaceuticals Corp., 2004 21. Katz, I. R., Sands, L. P., Bilker, W., DiFilippo, S., Boyce, A. and D’Angelo, K: Identification of medications that cause cognitive impairment in older people: the case of oxybutynin chloride. J Am Geriatr Soc, 46: 8, 1998 22. Ouslander, J. G., Maloney, C., Grasela, T. H., Rogers, L. and Walawander, C. A.: Implementation of a nursing home urinary incontinence management program with and without tolterodine. J Am Med Dir Assoc, 2: 207, 2001 23. Womack, K. B. and Heilman, K. M.: Tolterodine and memory: dry but forgetful. Arch Neurol, 60: 771, 2003 24. Siegler, E. L. and Reidenberg, M.: Treatment of urinary incontinence with anticholinergics in patients taking cholinesterase inhibitors for dementia. Clin Pharmacol Ther, 75: 484, 2004 25. Todorova, A., Vonderheid-Guth, B. and Dimpfel, W.: Effects of tolterodine, trospium chloride, and oxybutynin on the central nervous system. J Clin Pharmacol, 41: 636, 2001