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Expressions of interest
Funding from Astellas, Pfizer and GSK for research, sponsorship to meetings, lectures Funding from CIHR, BUPA, HQIP, DH for research
Medication
Physiology, pathophysiology,
UI as a Geriatric Syndrome
Multiple risk factors, across multiple organ systems and domains
Young
Elderly
RF 1
RF 2
UI
UI
35 30
Men
Nocturia ( 2 times/night) Urgency Frequency UUI
% (95%CI)
MUI SUI
40 35 30
Women
Nocturia (2 times/night) Urgency Frequency UUI MUI SUI
% (95%CI)
>603
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
70-79
80+
35 30
Males
Prevalence %
25 20 15 10 5 0 40-49
50-59
60-69
70-79
80+
Changes in LUT physiology Increased prevalence of LUT disease Impact of co-existent disease Impact of treatments
.ability to compensate
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
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 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
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.
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
Volume (mL)
n=78
n=185
n=332
n=262
n=184
2030
3040
4050
5060
6070
7080
8090
90+
Age group
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
Residual volumes
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.
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)
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
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)
Detrusor pressures at urethral opening and closure in women with detrusor overactivity or stress incontinence
(medians and 95% CI)
40 30 20 10 0
0
pdet.clos pdet.open
DO
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
dependent oedema reduced bladder capacity in late life co-existent disease other reasons for waking
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
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.
thalamus hypothalamus
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)
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