Impact of sleep on chronobiology of micturition among healthy older adults.

Nocturia (waking to void) is prevalent among older adults. Disruption of the well-described circadian rhythm in urine production with higher nighttime urine output is its most common cause. In young adults, their circadian rhythm is modulated by the 24-h secretory pattern of hormones that regulate salt and water excretion, including antidiuretic hormone (ADH), renin, angiotensin, aldosterone, and atrial natriuretic peptide (ANP). The pattern of hormone secretion is less clear in older adults. We investigated the effect of sleep on the 24-h secretion of these hormones in healthy older adults. Thirteen participants aged ≥65 yr old underwent two 24-h protocols at a clinical research center 6 wk apart. The first used a habitual wake-sleep protocol, and the second used a constant routine protocol that removed the influence of sleep, posture, and diet. To assess hormonal rhythms, plasma was collected at 8:00 am, 12:00 pm, 4:00 pm, and every 30 min from 7:00 pm to 7:00 am. A mixed-effects regression model was used to compare subject-specific and mean trajectories of hormone secretion under the two conditions. ADH, aldosterone, and ANP showed a diurnal rhythm that peaked during sleep in the wake-sleep protocol. These nighttime elevations were significantly attenuated within subjects during the constant routine. We conclude that sleep has a masking effect on circadian rhythm amplitude of ADH, aldosterone, and ANP: the amplitude of each is increased in the presence of sleep and reduced in the absence of sleep. Disrupted sleep could potentially alter nighttime urine output in healthy older adults via this mechanism.NEW & NOTEWORTHY Nocturia (waking to void) is the most common cause of sleep interruption among older adults, and increased nighttime urine production is its primary etiology. We showed that in healthy older adults sleep affects the 24-h secretory rhythm of hormones that regulate salt-water balance, which potentially alters nighttime urine output. Further studies are needed to elucidate the impact of chronic insomnia on the secretory rhythms of these hormones.

A Randomized Trial of a Multifactorial Strategy to Prevent Serious Fall Injuries.

BACKGROUND: Injuries from falls are major contributors to complications and death in older adults. Despite evidence from efficacy trials that many falls can be prevented, rates of falls resulting in injury have not declined. METHODS: We conducted a pragmatic, cluster-randomized trial to evaluate the effectiveness of a multifactorial intervention that included risk assessment and individualized plans, administered by specially trained nurses, to prevent fall injuries. A total of 86 primary care practices across 10 health care systems were randomly assigned to the intervention or to enhanced usual care (the control) (43 practices each). The participants were community-dwelling adults, 70 years of age or older, who were at increased risk for fall injuries. The primary outcome, assessed in a time-to-event analysis, was the first serious fall injury, adjudicated with the use of participant report, electronic health records, and claims data. We hypothesized that the event rate would be lower by 20% in the intervention group than in the control group. RESULTS: The demographic and baseline characteristics of the participants were similar in the intervention group (2802 participants) and the control group (2649 participants); the mean age was 80 years, and 62.0% of the participants were women. The rate of a first adjudicated serious fall injury did not differ significantly between the groups, as assessed in a time-to-first-event analysis (events per 100 person-years of follow-up, 4.9 in the intervention group and 5.3 in the control group; hazard ratio, 0.92; 95% confidence interval [CI], 0.80 to 1.06; P = 0.25). The rate of a first participant-reported fall injury was 25.6 events per 100 person-years of follow-up in the intervention group and 28.6 events per 100 person-years of follow-up in the control group (hazard ratio, 0.90; 95% CI, 0.83 to 0.99; P = 0.004). The rates of hospitalization or death were similar in the two groups. CONCLUSIONS: A multifactorial intervention, administered by nurses, did not result in a significantly lower rate of a first adjudicated serious fall injury than enhanced usual care. (Funded by the Patient-Centered Outcomes Research Institute and others; STRIDE ClinicalTrials.gov number, NCT02475850.).

Neuroimaging of situational urgency and incontinence provoked by personal urgency cues.

INTRODUCTION: Situational triggers for urinary urgency and incontinence (UUI) such as "latchkey incontinence" and running water are often reported clinically, but no current clinical tools exist to directly address symptoms of UUI provoked by environmental stimuli. Previously we have shown that urgency and leakage can be reproduced during urodynamic studies with exposure to personal urgency-related images. Here we investigate the neural signatures associated with such situational triggers to inform potential therapies for reducing reactivity to these personal urgency-related cues among women with situational UUI. METHOD: We recruited 23 women with situational UUI who took photographs of their personal "urgency trigger" and "safe" situations and were exposed to them in a magnetic resonance imaging (MRI) scanner. We identified brain areas that were more active during urgency versus safe image exposure. RESULTS: We found that, during urgency image exposure, main components of the attention network and decision-related processes, the middle and medial frontal gyri, were more active (p < 0.01). In addition, areas well known to be involved in the continence mechanism, such as the cingulate and parahippocampal areas, were also more active during urgency image exposure. CONCLUSION: Exposure to personal situational urgency images activated different areas of the brain compared with safe environments, highlighting the complex brain mechanisms that provoke real-world urgency. Using brain and behavioral-based therapies which target the attentional areas identified here and extinguish cue reactivity might reduce symptom burden in this subset of UUI sufferers.

Changes in brain response to urgency before and after treatment of urgency urinary incontinence with onabotulinumtoxin A.

INTRODUCTION: To better understand the role of the brain in urgency urinary incontinence (UUI), we used onabotulinumtoxin A (BoNTA) as a probe to evaluate changes in the brain's response to urgency in successful and unsuccessful treatment. Because BoNTA acts peripherally, brain changes observed should represent a reaction to changes in bladder function caused by BoNTA, or changes in the brain's compensatory mechanisms, rather than a direct effect of BoNTA on the brain. METHODS: We recruited 20 women aged over 60 years with nonneurogenic UUI who were to undergo treatment with onabotulinum A toxin injected intravesically. We performed a baseline evaluation which included a 3-day bladder diary and functional magnetic resonance imaging with an urgency provocation task; we repeated this evaluation 6 weeks posttreatment. We performed an analysis of variance on a priori selected regions of interest and post hoc voxel-wise analysis on responders and nonresponders to treatment. RESULTS: We found a significant interaction in the right insula [F(1,18) = 5.5, p = 0.031]; activity was different during urgency provocation in responders and non-responders to therapy, before and after therapy. The supramarginal gyrus (SMG) and inferior frontal gyrus (IFG) also displayed significant interactions (p < 0.005). Activity in the periaqueductal gray and prefrontal cortex was correlated with number of leakage episodes (p < 0.05). CONCLUSION: The changes seen in the brain control mechanism after therapy likely reflect reduced bladder sensation caused by BoNTA's peripheral action. We ascribe the SMG and IFG changes to a coping mechanism for urgency which is reduced in those who respond well to treatment.

Testing a new, intensified infusion-withdrawal protocol for urinary urgency provocation in brain-bladder studies.

INTRODUCTION: The brain's role in bladder control has become an important area of study in the last 15 years. Typically, the brain's role in urinary urgency has been studied by repeated infusion and withdrawal of fluid, per catheter, to provoke urgency sensation during a whole brain magnetic resonance imaging (MRI) scan. Since this technique generally requires a large group size, we tested a more intense infusion-withdrawal protocol in an attempt to improve signal to noise ratio and repeatability of the signal which would, in turn, allow us to further probe subtypes of urgency urinary incontinence. METHODS: A total of 12 women over the age of 60 were recruited to test a new "intense" infusion withdrawal protocol. They underwent this new protocol during a functional brain MRI scan. The primary outcome was comparison of activity within the insula, medial pre-frontal cortex and dorsal anterior cingulate cortex/supplementary motor area (dACC/SMA). Immediate test-retest repeatability was measured using intraclass correlation. Secondary exploratory evaluation of differences in the whole brain between protocols was conducted. RESULTS: There was no significant difference in signal in any of the a priori regions of interest between protocols. Test-retest repeatability in the new protocol was poor compared to the original protocol, and variability was higher. Three participants were not able to tolerate the "intense" protocol. CONCLUSION: The small improvement in signal to noise ratio of the new protocol was not sufficient to overcome the poorly tolerated intense filling protocol.

Do brain structural abnormalities differentiate separate forms of urgency urinary incontinence?

AIMS: Urgency urinary incontinence (UUI) is a major problem for seniors. The underlying mechanisms of disease and therapy are unknown. We sought structural brain abnormalities that might underlie the functional differences previously observed by functional Magnetic Resonance Imaging in UUI patients versus controls, or among UUI responders versus non-responders to therapy-and thereby reveal potential disease mechanisms and therapeutic targets. METHODS: Secondary study of a trial of biofeedback-assisted pelvic floor muscle training (BFB) in 60 women (>60 yrs) with UUI, plus 11 age-matched continent controls. Brain structural abnormalities were investigated using: (1) white-matter hyperintensities (WMH); (2) diffusion tensor imaging (DTI) to reveal white-matter pathways with impaired integrity; and (3) voxel-based morphometry (VBM) to show regions of atrophy or hypertrophy. RESULTS: WMH burden was greater in UUI patients than controls (globally and in superior longitudinal fasciculus and cingulum), suggesting a possible causal connection. WMH burden was unexpectedly greater in responders than non-responders to BFB, and appeared to increase in non-responders but not in responders. DTI revealed even worse integrity of the cingulum than was apparent by WMH. VBM showed parahippocampal atrophy in UUI. CONCLUSIONS: Many women with UUI have white-matter damage that interferes with pathways critical to bladder control; they can be taught by techniques like BFB to exert stronger control over the bladder. For others, in whom abnormalities of key brain areas are less marked, UUI's cause may reside elsewhere, and therapy targeting these brain centers may be less effective than therapy targeting the bladder or other brain centers.

Functional connectivity of the brain in older women with urgency urinary incontinence.

BACKGROUND: The brain's role in continence is critical but poorly understood. Although regions activated during bladder stimulation have been identified, little is known about the interaction between regions. In this secondary analysis we evaluate resting state and effective connectivity in older women treated for urgency urinary incontinence (UUI). METHOD: 54 women ≥60 years old with UUI and 10 continent women underwent fMRI scanning during provocation of urinary urgency, both before and after therapy. Response was defined by >50% reduction in leaks on bladder diary. Regions of interest (RoIs) were selected a priori: right insula, medial prefrontal cortex, and dorsal anterior cingulate cortex. Generalized psycho-physiological interaction (gPPI) was used to calculate "effective connectivity" between RoIs during urgency. We performed a one-way ANOVA pre-treatment between groups (continent/responders/non-responders), as well as a two-way mixed ANOVA between group and time (responders/non-responders; pre-/post-therapy) using false discovery rate (FDR) correction. Principal component analysis was used to assess the variance within RoIs. Exploratory voxel-wise connectivity analyses were conducted between each RoI and the rest of the brain. RESULTS: RoI-RoI connectivity analysis showed connectivity differences between controls, responders, and non-responders, although statistical significance was lost after extensive correction. Principal component analysis confirmed appropriate RoI selection. Voxel-wise analyses showed that connectivity in responders became more like that of controls after therapy (cluster-wise correction P < 0.05). In non-responders, no consistent changes were seen. CONCLUSION: These data support the postulate that responders and non-responders to therapy may represent different subsets of UUI, one with more of a central etiology, and one without.

Nocturnal Polyuria in Older Women with Urge Urinary Incontinence: Role of Sleep Quality, Time in Bed and Medications Used.

PURPOSE: Nocturia is common and bothersome in older adults, especially those who are also incontinent. Since nocturnal polyuria is a major contributor, we examined factors associated with nocturnal polyuria in this population to identify those possibly amenable to intervention. MATERIALS AND METHODS: We analyzed baseline data from 2 previously completed studies of urge urinary incontinence. The studies involved 284 women (mean age ± SD 72.9 ± 7.9 years) who also completed 3-day voiding diaries. Participants with a nocturnal polyuria index greater than 33% were categorized as having nocturnal polyuria (nocturnal polyuria index = nocturnal urinary volume per 24-hour urine volume). Associations between nocturnal polyuria and various demographic, clinical and sleep related parameters were determined. RESULTS: Overall 55% of the participants had nocturnal polyuria. Multivariable regression analysis revealed that age, body mass index, use of angiotensin converting enzyme inhibitor/angiotensin receptor blocker, time spent in bed and duration of first uninterrupted sleep were independent correlates of nocturnal polyuria. Participants with a larger nocturnal excretion reported a shorter duration of uninterrupted sleep before first awakening to void and worse sleep quality despite spending similar time in bed. CONCLUSIONS: Body mass index, use of angiotensin converting enzyme inhibitor/angiotensin receptor blockers, time in bed and duration of uninterrupted sleep before first awakening to void are independently associated with nocturnal polyuria in older women with urge urinary incontinence, and are potentially modifiable. These findings also confirm the association between sleep and nocturnal polyuria. Further studies should explore whether interventions to reduce nocturnal polyuria and/or increase the duration of uninterrupted sleep before first awakening to void would help to improve sleep quality in this population and thereby reduce or eliminate the need for sedative hypnotics.

Test-retest repeatability of patterns of brain activation provoked by bladder filling.

OBJECTIVE: To assess short-term repeatability of an fMRI protocol widely used to assess brain control of the bladder. fMRI offers the potential to discern incontinence phenotypes as well as the mechanisms mediating therapeutic response. If so, this could enable more targeted efforts to enhance therapy. Such data, however, require excellent test-retest repeatability. METHODS: Fifty-nine older women (age ≥60 years) with urgency incontinence underwent two fMRI scans within 5-10 min with a concurrent bladder infusion/withdrawal protocol. Activity in three brain regions relevant to bladder control was compared using paired t tests and intra-class correlation. RESULTS: There were no statistically significant differences in brain activity between the two consecutive scans in the regions of interest. Intra-class correlation was 0.19 in the right insula, 0.32 in the dorsal anterior cingulate cortex/supplementary motor area, and 0.44 in the medial pre-frontal cortex. Such correlations are considered fair or poor, but are comparable to those from studies of other repeated fMRI tasks. CONCLUSIONS: This is the first evaluation of the repeatability of a bladder fMRI protocol. The technique used provides a framework for comparing different fMRI protocols applied to brain-bladder research. Despite universal patient response to the stimulus, brain response had limited repeatability within individuals. Improvement of the investigational protocol should magnify brain response and reduce variability. These results suggest that although analysis of fMRI data among groups of subjects yields valuable insight into bladder control, fMRI is not yet appropriate for evaluation of the brain's role in continence on an individual level.

Brain Mechanisms Underlying Urge Incontinence and its Response to Pelvic Floor Muscle Training.

PURPOSE: Urge urinary incontinence is a major problem, especially in the elderly, and to our knowledge the underlying mechanisms of disease and therapy are unknown. We used biofeedback assisted pelvic floor muscle training and functional brain imaging (functional magnetic resonance imaging) to investigate cerebral mechanisms, aiming to improve the understanding of brain-bladder control and therapy. MATERIALS AND METHODS: Before receiving biofeedback assisted pelvic floor muscle training functionally intact, older community dwelling women with urge urinary incontinence as well as normal controls underwent comprehensive clinical and bladder diary evaluation, urodynamic testing and brain functional magnetic resonance imaging. Evaluation was repeated after pelvic floor muscle training in those with urge urinary incontinence. Functional magnetic resonance imaging was done to determine the brain reaction to rapid bladder filling with urgency. RESULTS: Of 65 subjects with urge urinary incontinence 28 responded to biofeedback assisted pelvic floor muscle training with 50% or greater improvement of urge urinary incontinence frequency on diary. However, responders and nonresponders displayed 2 patterns of brain reaction. In pattern 1 in responders before pelvic floor muscle training the dorsal anterior cingulate cortex and the adjacent supplementary motor area were activated as well as the insula. After the training dorsal anterior cingulate cortex/supplementary motor area activation diminished and there was a trend toward medial prefrontal cortex deactivation. In pattern 2 in nonresponders before pelvic floor muscle training the medial prefrontal cortex was deactivated, which changed little after the training. CONCLUSIONS: In older women with urge urinary incontinence there appears to be 2 patterns of brain reaction to bladder filling and they seem to predict the response and nonresponse to biofeedback assisted pelvic floor muscle training. Moreover, decreased cingulate activation appears to be a consequence of the improvement in urge urinary incontinence induced by training while prefrontal deactivation may be a mechanism contributing to the success of training. In nonresponders the latter mechanism is unavailable, which may explain why another form of therapy is required.

Urinary incontinence and prevalence of high depressive symptoms in older black versus white women.

INTRODUCTION AND HYPOTHESIS: Previous studies report higher prevalence of depression among women with urgency (UUI) or mixed (MUI) urinary incontinence than those with stress UI (SUI). UUI is the dominant type among black women, whereas SUI is the predominant type among white women. Thus, UI-related mental health issues could be a key consideration among black women. We hypothesized that the association between UI and depression might be stronger in black versus white women. METHODS: These cross-sectional analyses assessed 934 black and 71,161 white women aged 58-83 in the Nurses' Health Study, which was established among women living in the USA. Depressive symptoms were assessed using the ten-item Center for Epidemiologic Studies Depression Scale (CESD-10). Multivariate adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) for high depressive symptoms (CESD-10 score ≥ 10) according to self-reported UI frequency, severity, and type were calculated using logistic regression models. RESULTS: Although point estimates for associations of UI frequency, severity, and type with high depressive symptoms were higher in black women, differences in ORs between black versus white women were not statistically significant. For example, the OR for at least weekly UI compared with no UI was 2.29 (95 % CI 1.30-4.01) in black women and 1.58 (95 % CI 1.49-1.68) in white women (p interaction = 0.4). CONCLUSIONS: We found no statistically significant differences in UI frequency, severity, and type with high depressive symptoms in black versus white women. However, the small number of black women in this study with high depressive symptoms limited statistical power to detect significant interactions. Thus, these results should be interpreted with caution.

A molecular index for biological age identified from the metabolome and senescence-associated secretome in humans.

Unlike chronological age, biological age is a strong indicator of health of an individual. However, the molecular fingerprint associated with biological age is ill-defined. To define a high-resolution signature of biological age, we analyzed metabolome, circulating senescence-associated secretome (SASP)/inflammation markers and the interaction between them, from a cohort of healthy and rapid agers. The balance between two fatty acid oxidation mechanisms, ß-oxidation and ω-oxidation, associated with the extent of functional aging. Furthermore, a panel of 25 metabolites, Healthy Aging Metabolic (HAM) index, predicted healthy agers regardless of gender and race. HAM index was also validated in an independent cohort. Causal inference with machine learning implied three metabolites, ß-cryptoxanthin, prolylhydroxyproline, and eicosenoylcarnitine as putative drivers of biological aging. Multiple SASP markers were also elevated in rapid agers. Together, our findings reveal that a network of metabolic pathways underlie biological aging, and the HAM index could serve as a predictor of phenotypic aging in humans.

Brain responses to bladder filling in older women without urgency incontinence.

AIMS: To investigate normal brain responses to bladder filling, especially when there is little or no sensation as in much of daily life. METHODS: We performed an functional magnetic resonance imaging (fMRI) study of brain responses to bladder filling in normal female subjects, evoked by infusion and withdrawal of fluid in and out of the bladder. Using the contrast (infusion-withdrawal), we imaged brain activity at small bladder volumes with weak filling sensation and also with full bladder and strong desire to void. RESULTS: Eleven women, average age 65 years (range: 60-71 years) were included. With full bladder and strong desire to void, filling provoked a well-known pattern of activation near the right insula and (as a trend) in the dorsal anterior cingulate cortex and supplementary motor area. There was no significant deactivation. With small bladder volume filling provoked widespread apparent deactivation and no significant activation. Apparent deactivation was associated with increased fMRI signal during withdrawal rather than decrease during infusion, suggesting artifact. A correction for global changes in cerebral blood flow eliminated it and revealed significant subcortical activation, although none in frontal or parietal cortex. CONCLUSIONS: In older women with normal bladder function, infusion into an already full bladder resulted in strong sensation and brain activation near the insula and in the dorsal anterior cingulate/supplementary motor complex. With near-empty bladder and little sensation, the situation during much of daily life, these cortical areas were not detectably activated, but activation in midbrain and parahippocampal regions presumably indicated unconscious monitoring of ascending bladder signals.

What predicts and what mediates the response of urge urinary incontinence to biofeedback?

AIMS: To better target a behavioral approach for urge urinary incontinence (UUI) and enhance its efficacy by (1) identifying predictors of response to biofeedback-assisted pelvic muscle training (BFB), and (2) determining factors that mediate response. METHODS: BFB (four biweekly visits) was administered to 183 women > 60 years (mean = 73.6). Before and after intervention, all underwent comprehensive evaluation and videourodynamic testing. Postulated predictors and mediators from four urodynamic domains, specified a priori, were correlated with reduction in UUI frequency. RESULTS: Median UUI frequency decreased from 3.2/day to 1/day (P =0.0001). UUI improved by ≥50% in 55% of subjects and by 100% in 13% of subjects. Frequent UUI predicted poor response (P < 0.01). Of the urodynamic parameters, only high amplitude and briskness of detrusor overactivity (DO) predicted decreased response (P < 0.05 and P < 0.01) and these could be measured only in the 43% of subjects with elicitable DO. Decreased DO elicitability was the only urodynamic variable that changed in concert with improvement and thus was a candidate mediator. Response was neither predicted nor mediated by proprioception/warning, cystometric capacity, detrusor contractility, sphincter strength, or baseline DO elicitability. CONCLUSIONS: Severe DO predicts poor response to BFB. Good response is mediated by reduction in DO elicitability. Other than baseline UUI frequency, there are no other clinically or urodynamically important predictors or mediators of BFB response in this population. BFB may be best for patients with less severe DO. Future research to enhance its efficacy might better focus on the brain than on the lower urinary tract.

Acidic fruit intake in relation to incidence and progression of urinary incontinence.

INTRODUCTION AND HYPOTHESIS: Acidic fruits are commonly cited in the lay press as potential bladder irritants that may promote urinary incontinence (UI), but no epidemiologic studies have examined this issue. We hypothesized that higher intake of acidic fruits might be related to greater risk of UI incidence and progression in women. METHODS: In one set of analyses, we included women without UI at study baseline in the Nurses' Health Studies (NHS), with 34,144 women aged 54-79 in NHS I and 31,024 women aged 37-54 in NHS II. These cohorts were established among women living in the USA. Incident UI was ascertained over 4 years of follow-up, and acidic fruit consumption was measured by food frequency questionnaire prior to UI onset. In a second set of analyses, we examined UI progression over 2 years of follow-up among 11,764 women in NHS I and 11,299 women in NHS II with existing UI. Multivariable-adjusted relative risks were calculated for the associations of acidic fruit intake and UI incidence and progression. RESULTS: We found no relation between acidic fruit intake and risk of developing UI, including urgency, mixed, and stress UI. In addition, there was no association between consumption of acidic fruits and UI progression, regardless of UI type. CONCLUSIONS: No associations were detected between acidic fruit intake and UI in this large, prospective study of women. These data have implications for the development of evidence-based dietary guidelines around acidic fruits and UI, particularly because acidic fruits likely have many health benefits.

Speaking the Same Language: Team Science Approaches in Aging Research for Integrating Basic and Translational Science With Clinical Practice.

Research on aging is at an important inflection point, where the insights accumulated over the last 2 decades in the basic biology of aging are poised to be translated into new interventions to promote health span and improve longevity. Progress in the basic science of aging is increasingly influencing medical practice, and the application and translation of geroscience require seamless integration of basic, translational, and clinical researchers. This includes the identification of new biomarkers, novel molecular targets as potential therapeutic agents, and translational in vivo studies to assess the potential efficacy of new interventions. To facilitate the required dialog between basic, translational, and clinical investigators, a multidisciplinary approach is essential and requires the collaborative expertise of investigators spanning molecular and cellular biology, neuroscience, physiology, animal models, physiologic and metabolic processes, pharmacology, genetics, and high-throughput drug screening approaches. In an effort to better enable the cross-talk of investigators across the broad spectrum of aging-related research disciplines, a goal of our University of Pittsburgh Claude D. Pepper Older Americans Independence Center has been to reduce the barriers to collaborative interactions by promoting a common language through team science. The culmination of these efforts will ultimately accelerate the ability to conduct first-in-human clinical trials of novel agents to extend health span and life span.

The epidemiology of urinary incontinence in women with type 2 diabetes.

PURPOSE: Little research has been conducted on the epidemiology of urinary incontinence in individuals with type 2 diabetes. We examined prevalence, incidence and risk factors for urinary incontinence among women with type 2 diabetes in the NHS (Nurses' Health Study) and NHS II. MATERIALS AND METHODS: We obtained urinary incontinence information at study baseline (2000 in NHS and 2001 in NHS II) and 2 followup periods (2002 and 2004 in the NHS, and 2003 and 2005 in the NHS II). Among women with type 2 diabetes we calculated the prevalence of urinary incontinence for 9,994 women with baseline urinary incontinence information, and urinary incontinence incidence rates for 4,331 women with no urinary incontinence at baseline and urinary incontinence information during followup. Multivariable adjusted odds ratios and relative risks were estimated for associations between possible risk factors and urinary incontinence. RESULTS: The prevalence of at least monthly urinary incontinence was 48% and at least weekly urinary incontinence was 29% among women with type 2 diabetes, and the corresponding incidence rates were 9.1 and 3.4 per 100 person-years, respectively. White race, higher body mass index, higher parity, lower physical activity, current postmenopausal hormone use and diuretic use were risk factors for prevalent and incident urinary incontinence in this study, and hysterectomy, vascular disease and longer duration of diabetes were associated with increased odds of prevalent urinary incontinence only. Increasing age and microvascular complications were associated with a greater risk of frequent urinary incontinence. CONCLUSIONS: Urinary incontinence was common in this study of women with type 2 diabetes. We identified multiple risk factors for urinary incontinence in these women, several of which suggest ways to reduce urinary incontinence.

Brain activity underlying impaired continence control in older women with overactive bladder.

AIMS: To identify, in subjects with overactive bladder (OAB), differences in brain activity between those who maintained and those who lost bladder control during functional magnetic resonance imaging (fMRI) of the brain with simultaneous urodynamics. METHODS: Secondary analysis of a cohort of older women (aged >60) with proven urgency urinary incontinence, who, in the scanner, either developed detrusor overactivity and incontinence (the "DO group") or did not (the "no DO" group). A priori hypothesis: during urgency provoked by bladder filling, without DO, activity in regions related to continence control is diminished in the DO group; specifically (1a) less activation in supplementary motor area (SMA) and (1b) less deactivation in prefrontal cortex (PFC) and parahippocampal complex (PH). We also explored phenotypic (clinical and urodynamic) differences between the groups. RESULTS: During urgency preceding DO, the DO group showed stronger activation in SMA and adjacent regions (hypothesis 1a rejected), and less deactivation in PH but no significant difference in PFC (hypothesis 1b partially accepted). These subjects were older, with more changes in brain's white matter, decreased tolerance of bladder filling and greater burden of incontinence. CONCLUSIONS: (1) In older women with OAB, brain activity in the SMA is greater among those with more easily elicitable DO, suggesting a compensatory response to failure of control elsewhere. (2) OAB is heterogeneous; one possible phenotype shows severe functional impairment attributable partly to age-related white matter changes. (3) Functional brain imaging coupled with urodynamics may provide CNS markers of impaired continence control in subjects with OAB.