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ObjectivesThe impact of urinary incontinence (UI) on health-related quality of life (QoL) is significant yet variable, but little is known about patient-defined content areas regarding the influence of UI on QoL and whether patient-specific factors correlate with specific content areas of UI-related QoL. In order to identify the most valid content areas for a new UI-related QoL questionnaire, our primary goal was to determine the content areas of greatest concern regarding UI-related QoL among older persons with urge incontinence. The second goal was to examine the possible role of patients' explanatory style as a mediator of UI impact on health-related QoL. Data on the questionnaire will be presented elsewhere.DesignFocus groups comprising urge-incontinent persons were used to obtain verbatim descriptions of the impact of UI on QoL.SettingA university-affiliated tertiary hospital.ParticipantsCommunity-dwelling women (n = 25) and men (n = 5) more than 60 years of age, with urge incontinence, recruited from newspaper, newsletter, and radio advertisements.MeasurementsQualitative content analysis of focus group transcripts was used to determine QoL items. These were compared with previously described UI-related QoL items obtained from the literature. Subjects' statements regarding causes of UI were evaluated for predominant explanatory style.ResultsThirty-two UI-related QoL items were identified, more than half of which were not described previously. Compared with expert-defined UI-related QoL items from the literature, patient-defined items focused more on coping with embarrassment and interference from UI than on prevention of actual activity performance. Explanatory statements were made frequently by patients talking about their UI. Although positive style explanatory statements were most common, they did not correlate with any QoL items. By contrast, there was a significant correlation between negative explanatory style and six specific UI-related QoL items.ConclusionsFocus groups of older persons with urge incontinence suggest that experts and patients view the impact of urge UI on QoL differently. Whereas experts focus more on functional impact, patients more often cite the impact of UI on their emotional well-being and on the interruption of activities. In addition, the association between negative explanatory style and specific UI-related QoL items suggests that explanatory style may be an important mediator of patients' perceptions of UI-related QoL.

Background Although osteoporosis affects women of all ages, the impact is most pronounced in frail residents in long-term care. Nevertheless, few interventional trials have been performed in this population, and few data on therapeutic alternatives are available in this cohort.Purpose We describe the challenges and lessons learned in developing and carrying out a trial in frail long-term-care residents.Methods The Zoledronic acid in frail Elders to STrengthen bone (ZEST) study was designed to examine the safety and efficacy of a single-dose therapy for osteoporosis in frail residents in long-term care in the Pittsburgh area. Women with osteoporosis who were 65 years of age and older and currently not on therapy were randomized in a blinded fashion to intravenous zoledronic acid or placebo. Follow-up of each participant was planned for 2 years. All participants received appropriate calcium and vitamin D supplementation.Results Seven hundred and thirty-three contacts were made with long-term care residents of nine participating facilities. Of 252 women screened, 181 were eligible, enrolled, and randomized. Multiple barriers to research in long-term-care facilities were encountered but overcome with direct communication, information sessions, in-service trainings, and social events. Lessons learned included designing the study in a manner that avoided placing an additional burden on an already overcommitted facility staff, a two-stage consent process to separate screening from randomization, and a flexible examination schedule to accommodate residents while obtaining the necessary outcome measurements. Furthermore, a mobile unit accessible to participants containing state-of-the-art dual x-ray absorptiometry (DXA), assessment for vertebral fractures, and phlebotomy equipment allows all assessments to be performed on-site at each facility. Serious adverse events are collected from affiliated hospitals in real time with a novel electronic surveillance system.Limitations The major limitation is selection of outcomes that can be assessed at participating facilities and do not require transport of participants to hospitals or clinics.Conclusions Clinical research for osteoporosis can be successfully and safely performed with frail residents in long-term care facilities. Lessons learned from this study may inform future investigations among frail elderly residents of these facilities. [ABSTRACT FROM PUBLISHER]

Background: Androgen deprivation therapy (ADT) in men with prostate cancer is associated with bone loss and fractures.Objective: To determine whether once-weekly oral bisphosphonate can prevent bone loss and reduce bone turnover in men receiving ADT.Design: Randomized, double-blind, placebo-controlled, partial crossover trial. First-year, preplanned analysis of a 2-group, parallel-design phase.Setting: University medical center.Patients: 112 men with nonmetastatic prostate cancer receiving ADT.Intervention: Alendronate, 70 mg once weekly, or placebo. All patients received calcium and vitamin D supplementation.Measurements: Bone mineral density of the spine and hip and markers of bone resorption and formation.Results: At baseline, 39% of men had osteoporosis and 52% had low bone mass. In men treated with alendronate, bone mineral density increased over 1 year by 3.7% (95% CI, 2.8% to 4.6%; P < 0.001) at the spine and 1.6% (CI, 0.4% to 2.8%; P = 0.008) at the femoral neck. Men in the placebo group had losses of 1.4% (CI, -2.7% to - 0.03%; P = 0.045) at the spine and 0.7% (CI, -1.5% to 0.01%; P = 0.081) at the femoral neck. At 12 months, the difference between the 2 groups was 5.1 percentage points (CI, 3.5 to 6.7 percentage points; P < 0.001) at the spine and was 2.3 percentage points (CI, 1.0 to 3.7 percentage points; P < 0.001) at the femoral neck. Bone turnover statistically significantly decreased with active therapy compared with placebo. The groups did not differ in adverse events.Limitations: The study was short (1 year) and was not powered to detect differences in the frequency of fractures.Conclusions: Bone loss that occurred with ADT was prevented and improved with once-weekly oral alendronate. Because most men have low bone mass or osteoporosis, physicians should assess their patients' bone density and provide preventive and therapeutic measures as appropriate. ClinicalTrials.gov registration number: NCT00048841. [ABSTRACT FROM AUTHOR]

Ten million men and women in this country have urinary incontinence, but for many it remains a secret disease. Patients are embarrassed to report the problem, and physicians don't always know how to help. [ABSTRACT FROM AUTHOR]

Introduction : Independent Living residences for older adults can be divided into two categories and require better definitions for research purposes; the purpose of this manuscript is to provide those definitions and explore variation in provided services and resident characteristics: (a) Subsidized age-based housing (55+) (Department of Housing and Urban Development (HUD) housing units for low-income adults), and (b) non-subsidized age-based housing. Methods: Residents in the two settings were compared: 37 subsidized locations ( p  = 289 residents) and 19 non-subsidized ( p  = 208). Aging support services in each housing type were quantified. Results: Subsidized residents are more likely to be female (84.6% vs. 70.2%, p  = .0002) and have fair-poor health (36.5% vs. 12.5%, p  < .0001), frequent pain (28.4% vs. 12.8%, p  < .0001), and fair-poor mobility (37.5% vs. 23.5%, p  = .0298). Non-subsidized locations are more likely to offer support services; on average, residents are older (mean age 83vs. 75; p  < .0001) and white (97.6% vs. 69.2%, p  < .0001). Conclusion: Significant differences exist between populations living in subsidized and non-subsidized housing, suggesting the effect of cumulative disadvantage over the lifespan; populations in poorer health have access to fewer services. Research is needed to explore generalizability on a national level., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

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, β-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, β-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., (© 2024 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

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.

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., Competing Interests: T.F. is a founder and stockholder in Generian Pharmaceuticals and Coloma Therapeutics. S.J.S.R, S.L.G., N.M.R., and J.S.B. have no conflicts to report., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America.)

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 &lt; 0.005). Activity in the periaqueductal gray and prefrontal cortex was correlated with number of leakage episodes (p &lt; 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., (© 2022 Wiley Periodicals LLC.)

Background: Falls are common in older adults and can lead to severe injuries. The Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) trial cluster-randomized 86 primary care practices across 10 health systems to a multifactorial intervention to prevent fall injuries, delivered by registered nurses trained as falls care managers, or enhanced usual care. STRIDE enrolled 5451 community-dwelling older adults age ≥70 at increased fall injury risk., Methods: We assessed fall-related outcomes via telephone interviews of participants (or proxies) every 4 months. At baseline, 12 and 24 months, we assessed health-related quality of life (HRQOL) using the EQ-5D-5L and EQ-VAS. We used Poisson models to assess intervention effects on falls, fall-related fractures, fall injuries leading to hospital admission, and fall injuries leading to medical attention. We used hierarchical longitudinal linear models to assess HRQOL., Results: For recurrent event models, intervention versus control incidence rate ratios were 0.97 (95% confidence interval [CI], 0.93-1.00; p = 0.048) for falls, 0.93 (95% CI, 0.80-1.08; p = 0.337) for self-reported fractures, 0.89 (95% CI, 0.73-1.07; p = 0.205) for adjudicated fractures, 0.91 (95% CI, 0.77-1.07; p = 0.263) for falls leading to hospital admission, and 0.97 (95% CI, 0.89-1.06; p = 0.477) for falls leading to medical attention. Similar effect sizes (non-significant) were obtained for dichotomous outcomes (e.g., participants with ≥1 events). The difference in least square mean change over time in EQ-5D-5L (intervention minus control) was 0.009 (95% CI, -0.002 to 0.019; p = 0.106) at 12 months and 0.005 (95% CI, -0.006 to 0.015; p = 0.384) at 24 months., Conclusions: Across a standard set of outcomes typically reported in fall prevention studies, we observed modest improvements, one of which was statistically significant. Future work should focus on patient-, practice-, and organization-level operational strategies to increase the real-world effectiveness of interventions, and improving the ability to detect small but potentially meaningful clinical effects., Clinicaltrials: gov identifier: NCT02475850., (© 2022 Wiley Periodicals LLC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

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., (© 2021 Wiley Periodicals LLC.)

Fracture prevention in cognitively impaired individuals is lacking. This work highlights the benefits of zoledronic acid on bone health in cognitively impaired older adults. Demonstrating benefits of therapy may increase treatment uptake and reduce fracture risk in this group., Introduction: Osteoporosis has detrimental consequences for frail older adults. The effects on those with both osteoporosis and cognitive impairment are compounded due to increased risk of falls and changes in mobility, both of which can lead to fracture. However, there are limited data on treatment benefits for osteoporotic individuals with cognitive impairment., Methods: This post hoc, secondary analysis of data from a randomized, double-blind, placebo-controlled clinical trial of single-dose zoledronic acid included 179 women age ≥ 65 years residing in assisted living facilities or nursing homes, 43 of whom had mild to severe cognitive impairment. We assessed bone mineral density (BMD) of the total hip, femoral neck, and lumbar spine by dual-energy x-ray absorptiometry and serum bone turnover markers (C-terminal telopeptide of type I collagen and procollagen type I N propeptide) at 6 and 12 months., Results: In participants with cognitive impairment, those who received zoledronic acid had 4.3% greater BMD at the total hip (p=.005) and 5.3% greater BMD at the femoral neck (p<.001) after 12 months compared to those in the placebo group. Bone turnover markers demonstrated significant decreases at 6 months in those with cognitive impairment who received active treatment compared to the placebo group. Improvements in bone health measures with zoledronic acid were similar to those seen in participants without cognitive impairment., Conclusion: Zoledronic acid improves bone health in frail older women with cognitive impairment similar to those without impairment. Further studies are warranted to assess the benefit for fracture reduction in this undertreated population., (© 2021. International Osteoporosis Foundation and National Osteoporosis Foundation.)

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., (© 2020 Wiley Periodicals LLC.)

Background/objectives: In the Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) study, a multifactorial intervention was associated with a nonsignificant 8% reduction in time to first serious fall injury but a significant 10% reduction in time to first self-reported fall injury relative to enhanced usual care. The effect of the intervention on other outcomes important to patients has not yet been reported. We aimed to evaluate the effect of the intervention on patient well-being including concern about falling, anxiety, depression, physical function, and disability., Design: Pragmatic cluster-randomized trial of 5,451 community-living persons at high risk for serious fall injuries., Setting: A total of 86 primary care practices within 10 U.S. healthcare systems., Participants: A random subsample of 743 persons aged 75 and older., Measurements: The well-being measures, assessed at baseline, 12 months, and 24 months, included a modified version of the Fall Efficacy Scale, Patient-Reported Outcomes Measurement Information System (PROMIS) anxiety and depression scales, and Late-Life Function and Disability Instrument., Results: Participants in the intervention (n = 384) and control groups (n = 359) were comparable in age: mean (standard deviation) of 81.9 (4.7) versus 81.8 (5.0) years. Mean scores were similar between groups at 12 and 24 months for concern about falling, physical function, and disability, whereas the intervention group's mean scores on anxiety and depression were .7 points lower (i.e., better) at 12 months and .6 to .8 points lower at 24 months. For each of these outcomes, differences between the groups' adjusted least square mean changes from baseline to 12 and 24 months, respectively, were quantitatively small. The overall difference in means between groups over 2 years was statistically significant only for depression, favoring the intervention: -1.19 (99% confidence interval, -2.36 to -.02), with 3.5 points representing a minimally important difference., Conclusions: STRIDE's multifactorial intervention to reduce fall injuries was not associated with clinically meaningful improvements in patient well-being., (© 2020 The American Geriatrics Society.)

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.)., (Copyright © 2020 Massachusetts Medical Society.)

Clinicians and patients want to know if therapy is working early in their course of treatment. We found that early changes in bone turnover markers at 6 months were associated with long-term changes in bone mineral density but not trabecular bone score at 12 and 24 months., Purpose: We sought to examine the association between shorter-term changes in markers of bone turnover and longer-term changes in bone mineral density (BMD) and microstructure in a cohort of frail elderly women with multiple comorbid conditions including osteoporosis., Methods: We performed a secondary analysis of a 2-year zoledronic acid trial for osteoporosis in 155 women residents of long-term care communities (mean age 86.9 years). We examined the association of the 6-month change in serum C-terminal crosslinking telopeptide of type I collagen (CTX) and serum intact procollagen type I N propeptide (PINP) with the 12- and 24-month changes in BMD at the spine and hip and the trabecular bone score (TBS), an indirect measure of bone microstructure., Results: For every 0.2-ng/ml 6-month CTX decrease, the corresponding increase in spine BMD at 12 and 24 months was 0.2% (p = 0.7210) and 1.1% (p = 0.0396), respectively; total hip BMD 1.1% (p = 0.0279) and 0.9% (p = 0.0716); and femoral neck BMD 1.7% (p = 0.0079) and 0.9% (p = 0.1698). Similarly, for every 20-ng/ml 6-month PINP decrease, the corresponding increase in spine BMD at 12 and 24 months was 0.9% (p = 0.0286) and 1.4% (p = 0.0012), respectively; total hip BMD 1.4% (p = 0.0005) and 1.4% (p = 0.0006); and femoral neck BMD 2.3% (p < 0.0001) and 2.0% (p < 0.0001). Bone marker changes were not consistently associated with TBS changes., Conclusion: Shorter-term 6-month changes in bone turnover markers are associated with the long-term changes in BMD over 1-2 years in the spine and hip but not with TBS.

Background: Recent studies investigating longevity have revealed very few convincing genetic associations with increased lifespan. This is, in part, due to the complexity of biological aging, as well as the limited power of genome-wide association studies, which assay common single nucleotide polymorphisms (SNPs) and require several thousand subjects to achieve statistical significance. To overcome such barriers, we performed comprehensive DNA sequencing of a panel of 20 genes previously associated with phenotypic aging in a cohort of 200 individuals, half of whom were clinically defined by an "early aging" phenotype, and half of whom were clinically defined by a "late aging" phenotype based on age (65-75 years) and the ability to walk up a flight of stairs or walk for 15 min without resting. A validation cohort of 511 late agers was used to verify our results. Results: We found early agers were not enriched for more total variants in these 20 aging-related genes than late agers. Using machine learning methods, we identified the most predictive model of aging status, both in our discovery and validation cohorts, to be a random forest model incorporating damaging exon variants [Combined Annotation-Dependent Depletion (CADD) > 15]. The most heavily weighted variants in the model were within poly(ADP-ribose) polymerase 1 ( PARP1 ) and excision repair cross complementation group 5 ( ERCC5 ), both of which are involved in a canonical aging pathway, DNA damage repair. Conclusion: Overall, this study implemented a framework to apply machine learning to identify sequencing variants associated with complex phenotypes such as aging. While the small sample size making up our cohort inhibits our ability to make definitive conclusions about the ability of these genes to accurately predict aging, this study offers a unique method for exploring polygenic associations with complex phenotypes., (Copyright © 2019 Breitbach, Greenspan, Resnick, Perera, Gurkar, Absher and Levine.)

Objectives: Insomnia, especially difficulty maintaining sleep, is prevalent among older adults and increases the incidence of falls and fractures. Moreover, the drugs used to treat it exacerbate the risk. Yet current therapies fail to address one of its most common causes in older adults: nocturia and its primary contributor, nocturnal polyuria (NP), especially among the majority of individuals without lower urinary tract symptoms (LUTS). Therefore, we examined the factors associated with nocturia in two groups of such older women and the impact of nocturia on sleep., Design: Secondary analysis of two observational studies of bladder function in carefully evaluated healthy older women., Setting: Academic medical center., Participants: A total of 39 women without LUTS who had adequate fluid intake (ie, >1200 mL urine output/24 h recorded on their diary), normal videourodynamic testing, and normal daytime frequency (≤7 voids)., Measurements: Voided volumes and sleep duration obtained from subjects' 3-day voiding diary, and sleep quality from the Center for Epidemiologic Studies Depression Scale. Nighttime excretion of more than 33% of 24-hour urine volume was considered NP., Results: Overall, 21 of these healthy subjects (54%) awakened at least once nightly to void, and 19 (90%) of them had NP. Compared with those without nocturia, participants with nocturia had shorter duration of the first uninterrupted sleep period (182 ± 100 vs 250 ± 60 min; P = .03), and they reported worse sleep quality. Two factors contributed independently to nocturia: (1) a larger proportion of 24-hour urine output at night (43.4 ± 7.4% vs 25.4 ± 5.5%; P = <.001) and (2) smaller bladder capacity (484 ± 157 mL vs 608 ± 167 mL; P = .02)., Conclusions: Nocturia, NP, and reduced bladder capacity are very common even in healthy older women without LUTS and are associated with impaired sleep. Thus applying currently available modalities to address both NP and reduced bladder capacity may effectively treat sleep disruption without incurring the complications of sedative-hypnotics. J Am Geriatr Soc 67:2610-2614, 2019., (© 2019 The American Geriatrics Society.)

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., (© 2018 Wiley Periodicals, Inc.)

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., (© 2018 Wiley Periodicals, Inc.)

Background and Objectives: The Nursing Home Physical Performance Test (NHPPT) was developed to measure function among nursing home residents using sit-to-stand, scooping applesauce, face washing, dialing phone, putting on sweater, and ambulating tasks. Using item response theory, we explore its measurement characteristics at item level and opportunities for improvements., Research Design and Methods: We used data from long-term care women. We fitted a graded response model, estimated parameters, and constructed probability and information curves. We identified items to be targeted toward lower and higher functioning persons to increase the range of abilities to which the instrument is applicable. We revised the scoring by making sit-to-stand and sweater items harder and dialing phone easier. We examined changes to concurrent validity with activities of daily living (ADL), frailty, and cognitive function., Results: Participants were 86 years old, had more than three comorbidities, and a NHPPT of 19.4. All items had high discrimination and were targeted toward the lower middle range of performance continuum. After revision, sit-to-stand and sweater items demonstrated greater discrimination among the higher functioning and/or greater spread of thresholds for response categories. The overall test showed discrimination over a wider range of individuals. Concurrent validity correlation improved from 0.60 to 0.68 for instrumental ADL and explained variability (R2) from 22% to 36% for frailty., Discussion and Implications: NHPPT has good measurement characteristics at the item level. NHPPT can be improved, implemented in computerized adaptive testing, and combined with self-report for greater utility, but a definitive study is needed.

Objectives: To establish the prevalence of sarcopenia in a long-term care population, assess agreement among different consensus sarcopenia diagnostic criteria, and examine agreement of a self-reported questionnaire with consensus guidelines., Design: Cross-sectional secondary analysis., Setting: Long-term care communities in the greater Pittsburgh, Pennsylvania, area., Participants: Women aged 65 and older (mean 83.6) undergoing eligibility screening for a fracture reduction trial (N = 141)., Measurements: We measured appendicular lean muscle mass using dual-energy X-ray absorptiometry. Hand grip strength and usual gait speed were also evaluated. Sarcopenia status was determined according to European Working Group on Sarcopenia in Older People (EWGSOP) and the Foundation for the National Institutes of Health (FNIH) Sarcopenia Project criteria and the SARC-F questionnaire., Results: Eleven participants were sarcopenic (7.8%) according to the EWGSOP criteria, six (4.3%) according to FNIH conservative cut-point guidelines, and 32.6% (n = 46) according to FNIH intermediate cut-points. Only 2 of 141 participants met criteria for sarcopenia according to all three guidelines. Sarcopenia was identified in 30 (21.3%) participants according to the SARC-F questionnaire. Sensitivity of the SARC-F with consensus panel definitions ranged from 18.2% to 33.3%. Specificity ranged from 78.7% to 81.1%., Conclusion: Current consensus criteria from the EWGSOP and FNIH Sarcopenia Project do not agree and have little overlap in older female long-term care residents. The SARC-F questionnaire is a simple tool that could be implemented in long-term care, but it has low sensitivity compared with current consensus guidelines in the identification of sarcopenic individuals., (© 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.)

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., (© 2016 Wiley Periodicals, Inc.)

Objectives: To determine whether proinflammatory biomarkers are associated with frailty assessed according to functional status, mobility, mental health, and falls over 24 months., Design: Secondary analysis of a 2-year double-blind clinical trial for osteoporosis., Setting: Nursing homes and assisted living facilities., Participants: Women aged 65 and older with osteoporosis in long-term care (LTC) (N = 178)., Measurements: Baseline serum concentrations of proinflammatory cytokines and soluble receptors (high sensitivity C-reactive protein (hs-CRP), tumor necrosis factor alpha (TNFα) and its two receptors (TNFα-R1 and TNFα-R2), interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), IL-10), functional status assessed according to activities of daily living, the Nursing Home Physical Performance Test, gait speed, cognitive status, mental health, and falls., Results: At baseline, older age was moderately associated with higher serum concentrations of hs-CRP (correlation coefficient (r) = 0.22), TNFα-R1 (r = 0.36), TNFα-R2 (r = 0.34), and IL-10 (r = 0.16) (all P < .05). Frail participants had significantly higher hs-CRP, TNFα-R1, TNFα-R2, IL-6, and IL-6-sR levels (all P < .05) than those nonfrail participants. Higher baseline hs-CRP and IL-6 levels were associated with worse physical performance and gait speed at 12 months independent of age, zoledronic acid use, and comorbidity (|r| = 0.25-0.30; all P < .05). Inflammatory markers were not significantly associated with incident falls., Conclusions: Higher proinflammatory biomarker levels are associated with frailty and poorer function and mobility in older women residing in LTC facilities., (© 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.)

We examined the impact of daily supplementation on vitamin D deficiency, function, and falls in female long-term care residents. Initial vitamin D deficiency was associated with greater functional decline and increased fall risk despite guideline-recommended supplementation, highlighting the importance of preventing vitamin D deficiency in frail elderly., Introduction: Institute of Medicine (IOM) guidelines recommend 800 IU vitamin D daily for older adults and maintaining serum 25-hydroxyvitamin D [25(OH) D] above 20 ng/ml for optimal skeletal health. The adequacy of IOM guidelines for sustaining function and reducing falls in frail elderly is unknown., Methods: Female long-term care residents aged ≥65 enrolled in an osteoporosis clinical trial were included in this analysis (n = 137). Participants were classified based on baseline 25(OH) D levels as deficient (<20 ng/ml, n = 26), insufficient (20-30 ng/ml, n = 40), or sufficient (>30 ng/ml, n = 71). Deficient women were provided initial vitamin D repletion (50,000 IU D 3 weekly for 8 weeks). All were supplemented with 800 IU vitamin D 3 daily for 24 months. Annual functional assessments included Activities of Daily Living (ADLs), Instrumental ADL (IADL), physical performance test (PPT), gait speed, cognition (SPMSQ), and mental health (PHQ-9). We used linear mixed models for analysis of functional measures and logistic regression for falls., Results: Daily supplementation maintained 25(OH) D levels above 20 ng/ml in 95% of participants. All groups demonstrated functional decline. Women initially deficient had a greater decline in physical function at 12 (IADL -2.0 ± 0.4, PPT -3.1 ± 0.7, both p < 0.01) and 24 months (IADL -2.5 ± 0.6, ADL -2.5 ± 0.6, both p < 0.01), a larger increase in cognitive deficits at 12 months (1.7 ± 0.4: p = 0.01) and more fallers (88.5%, p = 0.04) compared to those sufficient at baseline, despite supplementation to sufficient levels., Conclusions: IOM guidelines may not be adequate for frail elderly. Further study of optimal 25(OH) D levels for maintaining function and preventing falls is needed.

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., (Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Importance: Eighty-five percent of institutionalized elderly people have osteoporosis and bone fracture rates 8 to 9 times higher than rates observed among community-dwelling elderly people. Nevertheless, most of these persons are left untreated and are excluded from pivotal osteoporosis trials., Objective: To determine the efficacy and safety of zoledronic acid to treat osteoporosis in frail elderly women in long-term care facilities., Design, Setting, and Participants: We conducted a 2-year, randomized, placebo-controlled, double-blinded study from December 2007 through March 2012. Included were 181 women 65 or older with osteoporosis, including those with cognitive impairment, immobility, and multimorbidity, who were living in nursing homes and assisted-living facilities., Interventions: One 5-mg dose of zoledronic acid or placebo intravenously and daily calcium and vitamin D supplementation., Main Outcomes and Measures: Hip and spine bone mineral density (BMD) at 12 and 24 months and adverse events., Results: There were no baseline differences in mean (SE) age (85.4 [0.6] years), BMD, or functional or cognitive status, but the treatment group included more participants with frailty, falls history, diabetes, and anticonvulsant medication use. Values for BMD were available for 87% of participants at 12 months and 73% at 24 months. Mean (SE) BMD changes were greater in the treatment group: 3.2 (0.7) and 3.9 (0.7) percentage-point differences in the total hip at 12 and 24 months, respectively (P < .01 for both comparisons), and 1.8 (0.7) and 3.6 (0.7) percentage-point differences at the spine (P < .01); adjusted analyses were similar. The treatment and placebo groups' fracture rates were 20% and 16%, respectively (OR, 1.30; 95% CI, 0.61-2.78); mortality rates were 16% and 13% (OR, 1.24; 95% CI, 0.54-2.86). Groups did not differ in the proportion of single fallers (28% vs 24%; OR, 1.24; 95% CI, 0.64-2.42; P = .52), but more participants in the treatment group had multiple falls (49% vs 35%; OR, 1.83; 95% CI, 1.01-3.33; P = .047); however, this difference was no longer significant when adjusted for baseline frailty., Conclusions and Relevance: In this group of frail elderly women with osteoporosis, 1 dose of zoledronic acid improved BMD over 2 years. The clinical importance of nonsignificant increases in fracture and mortality rates in the treatment group needs further study. Since it is not known whether such therapy reduces the risk of fracture in this cohort, any change in nursing home practice must await results of larger trials powered to assess fracture rates., Trial Registration: clinicaltrials.gov Identifier: NCT00558012.

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.

Objective: To evaluate the impact of nocturia on the therapeutic response of chronic insomnia to behavioral treatment in older adults., Methods: Secondary analysis of a randomized clinical trial designed to assess the efficacy of brief behavioral treatment of insomnia (BBTI) vs. an information-only control (IC) in 79 community-dwelling older adults with chronic insomnia. For the current analysis, participants were stratified into 2 groups: those with self-reported nocturia at baseline i.e., ≥ 1 void/night (N = 30; 16 IC, 14 BBTI) and those without nocturia (N = 49; 24 IC, 25 BBTI). We then determined the impact of BBTI on sleep, sleep quality, and nocturia as assessed by self-report, actigraphy, and polysomnography., Results: Individuals without baseline nocturia responded well to BBTI with significant decrease in sleep latency, wake after sleep onset, and total sleep time assessed by sleep diary and actigraphy; these changes were significantly greater than those in the IC group. In comparison, changes in the same sleep parameters among participants with nocturia were not significantly different from the IC control. Although BBTI showed significant improvement in sleep quality in groups with and without nocturia (as assessed by PSQI and sleep diary), the effect size of these improvements was larger in those without nocturia than in those with nocturia (PSQI d = 0.82 vs. 0.53, diary sleep quality d = 0.83 vs. 0.51)., Conclusions: These secondary analyses suggest that brief behavioral treatment of insomnia may be more efficacious in improving insomnia in participants without nocturia. Addressing nocturia may improve the efficacy of behavioral insomnia treatment.

Although the number of older adults is rapidly expanding, the number of healthcare professionals trained in geriatrics is small and declining. The reasons are multifaceted, but because responsibility for training such professionals resides largely in academic health centers (AHCs), their support for geriatrics is critical. As AHCs face increasing financial pressure, many are seeking metrics to measure productivity and the Relative Value Unit (RVU) may be the one most commonly selected. Yet little is known about the RVU's effect on geriatric programs. Review of the literature and a survey of the leaders of the Association of Directors of Geriatric Academic Programs suggest that the advantages of an RVU-based metric are likely eclipsed by its negative impact on the care of older adults, the ability of academic geriatrics to accomplish its mission, and even the survival of geriatrics. If the RVU is to continue to be used as the index of productivity, it should be modified--by reweighting its codes (or by adding new ones)--and complemented by interventions to ensure patient access, care quality, and efficiency. Because an alternative metric, such as a Patient-based Value Unit may be preferable, this article describes the principles on which one might be based. Regardless, urgent action is required by all stakeholders to address this issue. Without it, the future of academic geriatrics--and with it the innovative care models, research, and training the nation needs to improve care and bend the cost curve--will be difficult if not impossible to sustain., (© 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.)

Objectives: To evaluate changes in self-reported nocturia in community-dwelling adults aged 60 and older who received behavioral treatment for chronic insomnia., Design: Secondary analysis of a randomized controlled trial of a behavioral intervention for sleep., Setting: Academic medical center., Participants: Of the 79 enrollees, this analysis focused on 30 who, in addition to insomnia, also reported at least one nightly episode of waking up to void., Intervention: The brief behavioral treatment of insomnia (BBTI) group (n = 14) received instructions on reducing time in bed and setting a regular sleep schedule. The information control (IC) group (n = 16) received printed materials. A nurse clinician delivered both interventions., Measurements: Self-reported nocturnal awakenings to void assessed daily for 14 days at baseline and 4 weeks after the intervention. Participants who reported at least one episode of nocturia per night at baseline were included in this analysis., Results: In individuals with nocturia at baseline, the total number of nocturnal voids over the 14-day assessment period decreased by 6.5 ± 4.8 in the BBTI group and increased by 1.3 ± 7.3 in the IC group (P = .04, effect size 0.82). After adjusting for baseline nocturia episodes, the difference remained significant (P = .05)., Conclusion: In older adults with concurrent insomnia and nocturia, behavioral treatment directed solely at insomnia may also improve self-reported nocturia. Behavioral treatment of insomnia should be further investigated for its effect on nocturia in individuals with concurrent insomnia and nocturia., (© 2013, Copyright the Authors Journal compilation © 2013, The American Geriatrics Society.)

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., (Copyright © 2012 Wiley Periodicals, Inc.)

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., (Copyright © 2013 Wiley Periodicals, Inc.)

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.

Androgen deprivation therapy (ADT), a treatment for prostate cancer, is associated with bone loss and fractures. Dual-energy X-ray absorptiometry (DXA)-measured bone mineral density does not assess vertebral fractures (VF). High-resolution micro-magnetic resonance imaging (HR-MRI) assesses bone microarchitecture and provides structural information. To determine if VF identification increased the diagnosis of osteoporosis beyond DXA and if HR-MRI demonstrated skeletal deterioration in men with VF, we cross-sectionally studied 137 men aged ≥ 60 years with nonmetastatic prostate cancer on ADT for ≥ 6 months. Vertebral fracture assessment (VFA) by DXA was confirmed with X-rays. HR-MRI of the wrist included bone volume to total volume (BV/TV), surface density (trabecular plates), surface/curve ratio (plates/rods), and erosion index (higher depicts deterioration). VF were found in 37% of men; the majority were unknown. Seven percent of participants were classified as osteoporotic by hip or spine DXA. Thirty-seven percent of men without osteoporosis by DXA had VF identified, suggesting that 90% of patients with clinical osteoporosis would have been misclassified by DXA alone. By ANOVA comparison across VF grades, the BV/TV, surface density, and spine, hip, and wrist DXA were lower, and erosion index was higher in men with moderate-severe VF compared with lesser grades (all p < 0.05). By unadjusted ROC analysis, the addition of HR-MRI to DXA at the spine, hip, and femoral neck added substantially (AUC increased 0.831 to 0.902, p < 0.05) to prediction of moderate-severe vertebral fracture. HR-MRI indices were associated with spine, hip, and wrist DXA measures (p < 0.01). Longer duration of ADT was associated with lower BV/TV, surface density, and surface/curve ratio (p < 0.05). ADT for men with prostate cancer is associated with silent VF. DXA alone leads to misclassifications of osteoporosis, which can be avoided by VF assessment. HR-MRI provides a novel technique to assess deterioration of structural integrity in men with VF and adds micro-structural information., (Copyright © 2013 American Society for Bone and Mineral Research.)

Background: Medication use is a potentially reversible cause of urinary incontinence (UI). The objective of this longitudinal cohort study was to evaluate whether self-reported UI in community-dwelling older women is associated with the use of different classes of antihypertensive agents., Methods: The sample consisted of 959 black and white women aged 72-81 years without baseline (Year 1) UI from the Health, Aging, and Body Composition Study. Use of any antihypertensive from 10 drug classes (ie, alpha blockers [central], alpha blockers [peripheral], angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, beta blockers, calcium channel blockers, diuretics [loop], diuretics [potassium-sparing], diuretics [thiazide], and vasodilators) was determined during Year 3 in-person interviews. The number of unique antihypertensive agents used and the standardized daily dosage were also examined. Self-reported UI, operationally defined as leaking urine at least weekly during the previous 12 months, was assessed at Year 4 visits., Results: A total of 197 women (20.5%) reported UI at Year 4. Although any antihypertensive use, number of agents used, and standardized daily dosage at Year 3 were not associated with UI at Year 4, use of one particular drug class-peripheral alpha blockers (ie, doxazosin, prazosin, and terazosin)-was associated with fourfold greater odds of UI (adjusted odds ratio = 4.47; 95% confidence interval = 1.79-11.21; p = .0014). Further, in post hoc analyses, these odds nearly doubled in those also taking loop diuretics (adjusted odds ratio = 8.81; 95% confidence interval = 1.78-43.53; p = .0076)., Conclusion: In community-dwelling older women, peripheral alpha blocker use was associated with UI, and the odds nearly doubled when used with loop diuretics.