Urge urinary incontinence (Ul) is the most common form of geriatric Ul, with significant impact on patients'lives and on society as a whole. It is manifested by urgency to void and urine leakage, associated with involuntary bladder contraction (detrusor overactivity), implying failure of the brain to fulfill its role in controlling the bladder. Rapidly emerging neuroimaging data support this role, at least in healthy young volunteers. The candidate has been working with a team that has pioneered the study of brain control of bladder (functional brain imaging with simultaneous urodynamics). Together they have shown, in older women with urge Ul, a different response to bladder filling in 2 key brain regions involved in mapping and monitoring bladder afferent signals, combined with impaired response in frontal cortex (responsible for executive control of voiding) and recruitment of compensatory pathways to suppress urgency and prevent urine leakage. The present proposal is designed to provide the candidate with the additional skills needed to become an independent investigator capable of continuing to address the complex syndrome of geriatric Ul in an innovative, cross-disciplinary manner. Activities are structured in two major components: 1) academic, with further development of theoretical and practical expertise in neuroimaging, urodynamics and urinary incontinence, obtained by performing the relevant procedures and clinical consults under the direct supervision of designated mentors, and supported by coursework in neuroscience, statistics and imaging techniques;and 2) scientific, by carrying out a research plan based on hypotheses derived from previous observations. The proposed Research Plan is strongly oriented toward aging, as it aims: 1) to test existing preliminary observations in a larger sample of older urge incontinent subjects;and 2) to investigate the role of age-associated white matter hyperintensities (WMHI) in urge Ul, because of their known association with urge incontinence and detrusor overactivity and their negative effect on frontal cortex (executive) function. Relevance: geriatric urinary incontinence affects 15% of US elderly and thus represents an important public health issue for which therapeutic efficacy has advanced little in the past half century. The proposed training ill provide the candidate with academic development and a novel set of skills to use in investigating the potential causes of geriatric Ul and in developing new treatment strategies.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Mentored Patient-Oriented Research Career Development Award (K23)
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National Institute on Aging Initial Review Group (NIA)
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Salive, Marcel
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University of Pittsburgh
Internal Medicine/Medicine
Schools of Medicine
United States
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Tyagi, Shachi; Perera, Subashan; Clarkson, Becky D et al. (2017) Nocturnal Polyuria in Older Women with Urge Urinary Incontinence: Role of Sleep Quality, Time in Bed and Medications Used. J Urol 197:753-758
Tadic, Stasa D; Tannenbaum, Cara; Resnick, Neil M et al. (2013) Brain responses to bladder filling in older women without urgency incontinence. Neurourol Urodyn 32:435-40
Tadic, Stasa D; Griffiths, Derek; Schaefer, Werner et al. (2012) Brain activity underlying impaired continence control in older women with overactive bladder. Neurourol Urodyn 31:652-8
Tadic, Stasa D; Griffiths, Derek; Schaefer, Werner et al. (2010) Brain activity measured by functional magnetic resonance imaging is related to patient reported urgency urinary incontinence severity. J Urol 183:221-8
Tadic, Stasa D; Griffiths, Derek; Murrin, Andrew et al. (2010) Brain activity during bladder filling is related to white matter structural changes in older women with urinary incontinence. Neuroimage 51:1294-302