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.

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.

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.

Effect of the STRIDE fall injury prevention intervention on falls, fall injuries, and health-related quality of life.

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.

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.

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.

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.

Effect of a Multifactorial Fall Injury Prevention Intervention on Patient Well-Being: The STRIDE Study.

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.

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.).

Early changes in bone turnover predict longer-term changes in bone mineral density but not trabecular bone score in frail older women.

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.

Nocturnal Excretion in Healthy Older Women and Rationale for a Safer Approach to Sleep Disruption.

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.

Exonic Variants in Aging-Related Genes Are Predictive of Phenotypic Aging Status.

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.

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.

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.

The Nursing Home Physical Performance Test: A Secondary Data Analysis of Women in Long-Term Care Using Item Response Theory.

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.

Identifying Sarcopenia in Female Long-Term Care Residents: A Comparison of Current Guidelines.

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.

Inflammatory Markers and Frailty in Long-Term Care Residents.

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.

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.