The Ageing Lower Urinary Tract

Dr. Adrian Wagg Division of Geriatric Medicine Department of Medicine

Expressions of interest

Funding from Astellas, Pfizer and GSK for research, sponsorship to meetings, lectures Funding from CIHR, BUPA, HQIP, DH for research

The Brain lavatory axis

Cognition, co-morbidities white matter lesions brakes off , habit, adaptation

Medication

Physiology, pathophysiology,

Mobility, dexterity, co-morbidity, habit, adaptation

UI as a Geriatric Syndrome
Multiple risk factors, across multiple organ systems and domains

Young

Elderly

RF 1

RF 2

UI

UI

Modulating factor Tinetti et al11995; Inouye et al, 2007

Symptom prevalence and age

35 30

Men
Nocturia ( 2 times/night) Urgency Frequency UUI

% (95%CI)

25 20 15 10 5 0 0 1 <39 Age group 2 40-59 3 >60

MUI SUI

European Urology Volume 50, Issue 6, December 2006, Pages 1306-1315

Symptom prevalence and age

40 35 30

Women
Nocturia (2 times/night) Urgency Frequency UUI MUI SUI

% (95%CI)

25 20 15 10 5 0 0 1 <39 age group 2 40-59

>603

European Urology Volume 50, Issue 6, December 2006, Pages 1306-1315

Prevalence and Severity of Urinary Incontinence by Sex and Age Group

35 30 Prevalence % 25 20 15 10 5 0 40-49
Monthly and slight Monthly and damp Monthly and wet Monthly and soaked

Females

50-59

60-69 Age group (years)

70-79

80+

Perry S et al. J Public Health Med 2000; 22(3):427-34.

Prevalence and Severity of Urinary Incontinence by Sex and Age Group

35 30

Males

Prevalence %

25 20 15 10 5 0 40-49

50-59

60-69

70-79

80+

Age group (years)

Monthly and slight Monthly and damp Monthly and wet Monthly and soaked Perry S et al. J Public Health Med 2000; 22(3):427-34.

What makes incontinence more likely in older people?

Changes in LUT physiology Increased prevalence of LUT disease Impact of co-existent disease Impact of treatments

.ability to compensate

Ageing and the lower urinary tract - whats normal?

56 elderly subjects - comprehensive urodynamic assessment and CT /MRI (26) Normal UDS in 18% (PVR < 250mL) Detrusor Instability commonest diagnosis DI seen as commonly in unobstructed as obstructed men Obstruction with and without symptoms equally common in the men

Normal bladder architecture

Collagen

Susset JG, Servot-Viguier D, Lamy F, Madernas P, Black R. Collagen in 155 human bladders. Invest Urol 1978;16:204-206

Changes in matrix

Increase in collagen in association with greater age collagen: muscle >53% and infiltration of smooth muscle bundles

Similar increase in response to ischaemia

Similar changes in addition to detrusor hypertrophy in detrusor smooth muscle in response to outflow tract obstruction

Normal innervation

Changes in innervation
Linear loss of acetylcholinesterase containing nerves in association with greater age
p<0.05

Mean nerve/mm2 muscle measured by light microscopy related to subject age

Mean nerve profiles/mm2 of detrusor measured by e.m

Yoshida M, Miyamae K, Iwashita H, Otani M, Inadome A. Management of detrusor dysfunction in the elderly: changes in acetylcholine and adenosine triphosphate release during aging. Urology. 2004;63:17-23.

Contractile function as measured by Q* in association with age

Age-related fall in women p<0.001, men p=0.17 n women = 844, men = 157

Bladder capacity

Maximum bladder capacity falls in association with greater age Functional capacity also falls There is a greater urinary frequency
Saito M, Kondo A, Kato T, Yamada Y. Frequency-volume charts: Comparison of frequency between elderly and adult patients. Br J Urol 1993; 72: 38-41

Maximum bladder capacity by decade of life (median and 95% CI)

600 500 400 300 200 100 0

Volume (mL)

n=78

n=185

n=332

n=262

n=184

n=199 n=130 n=11

2030

3040

4050

5060

6070

7080

8090

90+

Age group

Collas DM, Int Urogynecol J 1996; 7: 24-29.

Voiding Function

Both sexes void less successfully in later life Larger residual volumes (50-150mL) Increased incidence of incomplete emptying (men > women)

Median (95%CI) maximum flow rate for men and women in relation to greater age

Women and men, p<0.001

Residual volumes

Malone-Lee JG. Br J Urol 1993; 72: 873-880.

Bladder Sensation
There is a decreased sensation of bladder filling in association with ageing. Studies of sensation in association with studies of cerebral perfusion have demonstrated decreased perfusion of right insula
Griffiths 2007

Sensation

 The decreased sensation and decreased bladder capacity may conspire to give an elderly person less time to reach the lavatory.

Urge in older v younger men

200

150

100

50

The interval was (median and 95%CI) 5 (4 5) and 3 (3 5) minutes in older men. The intervals were statistically significantly different (W=31294.5, p<0.0001)

-50 R1 Young R2 Old

Young and old, n=30

Urethral Function
Lower urethral pressures found in both sexes in association with increased age The urethra becomes less compliant and able to resist pressure Increased stiffness of urethra and bladder in association with increased age - observed clinically as reduced compliance. Women with USI show reduced stiffness of the urethra

Urethral Function
Loss of striated muscle cells in association with greater age

Strasser H, Tiefenthaler M, Steinlechner M, Bartsch G, Konwalinka G. Urinary incontinence in the elderly and age-dependent apoptosis of rhabdosphincter cells. Lancet 1999;354:918-9

Maximum urethral closure pressure is lower in association with greater age No incontinence stress urinary incontinence

r= -0.4, p=0.03

Resting urethral pressure with age and sex, measured by UPP

100 90
Urethral pressure (mmHg)

80 70 60 50 40 30 20 10 0 0 1 2 3 4 5 6 7 8 Decade of life males females

From Haubensak 1975

Detrusor overactivity
In both sexes, detrusor overactivity is associated with lower bladder capacities with advancing age. Sensation of filling in older people with DO is increased Contraction strength is decreased compared to younger people with DO Urethral resistance is increased

Median and interquartile ranges for Q star in women with and without detrusor overactivity

120 100
Q star (mL/s)

non- DO DO

80 60 40 20 0 10 20 30 40 50 60 70 80
Age (by decade)

In women with pure stress incontinence, these pressures are lower

Detrusor pressures at urethral opening and closure in women with detrusor overactivity or stress incontinence
(medians and 95% CI)

Detrusor pressure (cmH

40 30 20 10 0
0

pdet.clos pdet.open

DO

In women with detrusor overactivity, there is an increase in urethral resistance

Pdet.open for stable and overactive bladders in women under and over the age of 70. Median and 95%CI
45 40
Detrusor pressure (cmH2

35 30 25 20 15 10 5 0 <70 Stable 70+ <70 Unstable 70+

Nocturnal frequency / polyuria - mechanisms

Loss of renal concentrating ability
Kirkland JL, Lye M, Banerjee AK. Patterns of urine flow and electrolyte excretion in healthy elderly people. Brit Med J 1983; 287:1665-1667

loss of diurnal ADH / ANP secretion

Asplund R, Aberg H. Diurnal variation in the levels of antidiuretic hormone in the elderly J Intern Med 1993; 229: 131

increase in GFR when supine

Nocturnal frequency / polyuria - mechanisms

dependent oedema reduced bladder capacity in late life co-existent disease other reasons for waking

Physiological changes which predispose to increased nocturnal urinary frequency

Increased 24h urine volume output Increased urinary frequency Reduction in the ability of the kidney to concentrate urine Delayed diuresis in response to a fluid load Alteration in the circadian rhythm of ADH secretion Increased level of Na secretion by night

Other factors

the elderly with nocturia have a higher 24-hour urine production than age matched controls with no nocturia. Nocturics also produce a higher proportion of their daily urine output at night

Protect the brain

Studies in the community-dwelling elderly link structural white matter changes in the brain with
mobility impairment cognitive impairment urinary urgency urinary incontinence

Elderly individuals with greater white matter hyperintensity burden also show increased prevalence of detrusor overactivity and difficulty maintaining continence on urodynamic studies
J Gerontol A Biol Sci Med Sci 2009;64A; 8:902-909 J. Neurol. Neurosurg. Psychiatry 1999; 67, 658660.

Central control of the bladder

Pre frontal insula

Kavia, DasGupta, Fowler 2005

Anterior cingulate gyrus

thalamus hypothalamus

PAG cerebellum Pons Sacral afferent input Sacral efferent output

Protect the brain

Right frontal and inferior frontal WMH associated with UI severity OR: 1.05 (1.00-1.77) UI associated with WMH in:
Cingulate gyrus OR 1.52 (1.01-2.3)

UI severity associated with WMH in

Anterior corona radiata

UI bother associated with WMH in:

Anterior corona radiata

J Gerontol A Biol Sci Med Sci 2009;64A; 8:902-909

The Brain

Blue: Areas where the response to bladder filling diminished with increased age

Brain response to bladder filling during self-reported urgency showed significant activations in a cluster of frontal regions, including medial and superior frontal gyri as well as right inferior frontal gyrus adjacent to right insula, dorsolateral prefrontal cortex and cerebellum