Lower urinary tract symptoms (LUTS) disproportionately affect older adults and are associated with significant impairment in health-related quality of life in this population.
The relationship between LUTS and older age is likely mediated, in large part, by bladder aging, as several alterations in bladder function are known to be highly common with advancing age. Detrusor overactivity (DO) with detrusor underactivity (DU) (DO-DU) was first described in older women and, like both DO and DU, is known to predominate in older adults [1]. While combined DO-DU has been described as typical urodynamics pattern of bladder aging, the pathogenesis of DO-DU is highly multifactorial and often thought to involve medical conditions beyond the urinary tract. 
The etiology of DO-DU remains poorly understood, and likely involves multiple complex factors, with growing evidence implicating diabetes mellitus and other systemic disease states beyond the lower urinary tract in the pathogenesis of DO-DU [2]. Given that older age has been linked separately to both DO-DU and comorbidity burden, it remains unclear whether comorbidity burden, in and of itself, is associated with this unique form of bladder dysfunction. Accordingly, we aimed to explore potential associations between idiopathic combined DO-DU and comorbidities among older women with urodynamically confirmed bladder dysfunction after accounting for their age.

The present study is a clinical single center cross-sectional analysis of consecutive female patients who underwent urodynamic evaluation from 2015 to 2019 in a outpatient urodynamic unit specializing in geriatrics. All women aged ≥65 years who underwent urodynamic evaluation and a comprehensive geriatric assessment, were screened for inclusion in the present study. Patients with a history of neurological disorders were excluded. Additional exclusion criteria were an inability to urinate >100 ml, expulsion of the urethral catheter during pressure flow study, and bladder outlet obstruction on urodynamic assessment. The clinical assessment consisted of a comprehensive medical history and physical examination, as well as and an assessment of mood, cognition, functional performance, nutrition status, mobility, and urinary symptoms. Urodynamic studies were conducted in accordance with International Continence Society Good Urodynamic Practices. Participants were categorized as having DO, DU, combined DO-DU after a urodynamic assessment. Patients who did not have one of these diagnoses were deemed to have a negative urodynamic study. The association between the primary indices of contractility (Bladder Contractility Index [BCI], modified projected isovolumetric pressure [PIP-1] and k parameter from Valentini-Besson-Nelson [VBN] model; derived from detrusor pressure at maximum flow [Pdet-Qmax], maximum urine flow rate [Qmax] and initial volume when urination is triggered [Vini] values) and the urodynamic diagnoses was verified. Mann-Whitney U and Kruskal Wallis tests were used to compare variables between groups. Multinomial logistic regression analysis was used to assess the relationship between urodynamic outcomes and comorbidity burden as quantified using the Geriatric Cumulative Illness Rating Scale (CIRS-G). A p-value <0.05 was deemed statistically significant and the Benjamini-Hochberg procedure was applied for repeated tests.

Eighty-nine patients were included (median age 77 [IQR 71-83] years), among whom 28% had combined DO-DU followed by DU (25.8%), negative urodynamic study (23.6%), and DO (22.5%). Contractility indices were all significantly associated with different urodynamic diagnoses (Table 1). On univariate analysis, patient age was highest in patients with DU (median age 82 [IQR 76-85] years) and DO-DU (median age 81 [IQR 71-84] years) and significantly differed between groups, although significance did not persist on pairwise analysis following correction for multiple comparisons (p=0.03). Comorbidity burden, who was represented by CIRS-G score, have a median score at 8 [IQR 5-12]. It was highest in patients with DO-DU (11[IQR 8-14]) and likewise significantly differed between groups (p=0.001). The association between urodynamic findings and comorbidity burden was then further examined using a multinomial logistic regression model adjusting for age (Table 2). When subjects with a negative urodynamic evaluation were employed as the reference group, a higher comorbidity burden was associated with significantly greater age-adjusted odds (odds ratio [OR] 1.24, [95% confidence interval (CI) 1.06-1.43]) of DO-DU. A similar result was also observed using DU as the reference group (OR 1.20 [95% CI 1.05-1.38]). Conversely, age was not significantly associated with DO-DU across all analyses.

The present study findings are, to our knowledge, the first to demonstrate a higher cumulative comorbidity burden to be associated with an increased likelihood of DO-DU. Further, this observation could not be attributed to the effects of age alone, which failed to persist as a predictor of DO-DU on multivariable analysis. These results are consistent with and extend upon growing evidence implicating medical conditions beyond the genitourinary tract as pertinent risk markers of this unique urodynamic entity. The present study findings, particularly in view of the failure of age to persist as a predictor of DO-DU on multivariate analysis, underscore the fact that DO-DU may not be simply understood as a phenomenon of chronological aging. However, the findings of the present study results must also be interpreted in view of several limitations. The cross-sectional study design precludes assessment of causality in the observed association between DO-DU and comorbidities. While neurological disorders and bladder outlet obstruction are highly pertinent confounders, exclusion of these variables also constitutes an additional barrier in generalizing the present study findings

A higher comorbidity burden was associated with an increased likelihood of DO-DU, which could not be attributed to the effect of age alone. The pathogenesis of DO-DU is likely more complex than chronological aging in and of itself and merits further study.

Resnick NM, Yalla SV. Detrusor hyperactivity with impaired contractile function. An unrecognized but common cause of incontinence in elderly patients. JAMA. 1987;257(22):3076-3081. doi:10.1001/jama.257.22.3076
Stav Kobi, Shilo Yaniv, Zisman Amnon, Lindner Arie, Leibovici Dan. Comparison of Lower Urinary Tract Symptoms Between Women with Detrusor Overactivity and Impaired Contractility, and Detrusor Overactivity and Preserved Contractility. Journal of Urology. 2013;189(6):2175-2178. doi:10.1016/j.juro.2012.11.178