Measure Of Reserve Research Articles

Predicting progression in subjective cognitive decline (SCD) using a machine learning (ML) approach: The role of the complaint’s severity

AbstractBackgroundPresence of significant subjective complaints about cognition (SCD) is considered the first behavioral manifestation of Alzheimer disease (AD). However, SCD has not yet overcome the challenge of becoming a reliable preclinical AD marker. Severity indices were proposed to improve the accuracy of complaints when predicting the risk of AD (Jessen et al., 2010).Our aim was to compare the predictive accuracy of ML algorithms using a more (95%ile) or less (5%ile) restrictive cut‐off point in severity of complaints for classification in Low (LSC) and High (HSC) subjective complaints groups.MethodOne hundred and ninety‐nine participants from the Compostela Aging Study (ComPAS) were identified at baseline as SCDs and completed three follow‐up measurements (54‐72 months). Considering their total scores in the Subjective Memory Questionnaire, participants were classified as LSC and HSC following using two distinct cut‐off points: complaint scores above or below than 5%ile vs 95%ile. Participants were labeled as ‘worsening’ or ‘stable’ based on their progression or not to MCI or AD. ML classifier algorithms (Random Forest, Support Vector Machine, Extra Tree) were applied to forty‐one measures (socio‐demographic, time, health, cognitive, behavioral, cognitive reserve) collected at baseline.ResultsThe best performing model was the Random Forest (95%ile: PPV =.87; Sensibility =.92; Specificity =.38; 5%ile: PPV =.66; Sensibility=.61; Specificity =.51). The confusion matrix (Figure 1) showed that: a) both, the more (95%ile) and the less (5%ile) restrictive criteria mostly classified the HSC‐stable participants as LSC‐stable; and b) criterion 5%ile, but not 95%ile, was able to differentially identify progressors based on their complaints. Episodic memory, executive functions, depression, cognitive reserve and progression timing measures assume the highest levels of importance in the ML algorithm that differentially predicts the progression of SCD to MCI and AD according to the level of complaints.ConclusionsFor both the criteria, algorithms failed to successfully identify stable SCD participants. The less restrictive criterion resulted in a better classification than the more lenient one to differentially identify LSC and HSC participants who get worse. Cognitive, affective, cognitive reserve and progression timing were the more prominent variables in conforming the predictive algorithm.

Abstract 17257: Stroke Volume Reserve Index in HFrEF: A Non-Invasive Predictor of Early Clinical Outcomes and Marker of Inotropic Reserve

Introduction: We investigated whether stroke volume reserve index (SVRI), a novel non-invasive measure of inotropic reserve at submaximal exercise, would predict 1-year mortality and need for advanced therapies in heart-failure with reduced ejection fraction (HFrEF) patients. Methods: We retrospectively studied a consecutive series of 245 ambulatory patients (57±11 years, 84% men) with HFrEF at a single center who underwent cardiopulmonary exercise testing (CPET) from January 2013 to December 2018. The primary outcome was defined as heart-transplantation, urgent left ventricular assist device (LVAD) implantation or death within 1 year of evaluation. SVRI was estimated at rest and at anaerobic threshold by VO 2 (oxygen consumption)/pulse and previously validated estimates of C[a-v]O 2 (arteriovenous difference in oxygen content). Multivariate regression selected the optimal predictors. Results: Among HFrEF patients studied, 82 (33.5%) deteriorated: 34 required heart-transplantation, 20 required LVADs and 28 died. SVRI of less than 130% was the best predictor of clinical deterioration (OR 3.98, p<0.005), followed by cardiac index of less than 2 L/min/m 2 (OR 3.74, p<0.005), and peak VO 2 below the International Society for Heart and Lung Transplantation (ISHLT) cut-off (OR 3.01, p=0.008). Kaplan-Meier curves showed that 1-year event-free survival was significantly better amongst patients with normal SVRI, compared to patients with impaired inotropic reserve. Notably, HFrEF patients with an abnormal SVRI had a poor 1-year prognosis regardless of their peak VO 2 . Conclusions: SVRI is a non-invasive measurement that provides a measure of inotropic reserve at submaximal exercise, provides valuable prognostic information independent of other known and validated CPET parameters, and may predict deterioration in HFrEF patients more accurately than currently recommended CPET predictors. SVRI and peak VO 2 provide complementary prognostic information.

Exercise cardiac MRI unmasks cardiac dysfunction in childhood and adolescent cancer survivors with reduced cardiopulmonary fitness

Abstract Background Young cancer survivors are at increased risk of impaired cardiopulmonary fitness (VO2peak) and heart failure. Assessment of exercise cardiac reserve may reveal sub-clinical abnormalities that better explain impairments in fitness and long term heart failure risk. Purpose To investigate the presence of impaired VO2peak in pediatric cancer survivors with increased risk of heart failure, and to assess its relationship with resting cardiac function and cardiac reserve Methods Twenty pediatric cancer survivors (aged 8–24 years) treated with anthracycline chemotherapy underwent cardiopulmonary exercise testing to quantify VO2peak, with a value <85% of predicted defined as impaired VO2peak. Resting cardiac function was assessed using 3-dimensional echocardiography, with cardiac reserve quantified from resting and peak exercise heart rate (HR), stroke volume index (SVi) and cardiac index (CI) using exercise cardiac magnetic resonance imaging. Results 12 of 20 survivors (60%) had impaired VO2peak (97±14% vs. 70±16% of age and gender predicted). There were no differences in echocardiographic or CMR measurements of resting cardiac function between survivors with normal or impaired VO2peak. However, those with reduced VO2peak had diminished cardiac reserve, with a lesser increase in CI (Fig. 1A) and SVi (Fig. 1B) during exercise (Interaction P=0.001 for both), whilst the HR response was similar (Fig. 1C; P=0.71). Conclusions Resting measures of cardiac function are insensitive to significant cardiac dysfunction amongst pediatric cancer survivors with reduced VO2peak. Measures of cardiopulmonary fitness and cardiac reserve may aid in early identification of survivors with heightened risk of long-term heart failure. Figure 1 Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): National Heart Foundation

Identifying the functional brain network of motor reserve in early Parkinson's disease

Objective: The severity of motor symptoms in Parkinson's disease (PD) does not always correlate with the degree of nigral dopaminergic neuronal loss. Individuals with greater motor reserve may have milder motor signs than their striatal dopamine loss. In this study, we explored the functional brain network associated with motor reserve in early-stage PD.

Pre-operative frailty is predictive of adverse post-operative outcomes in colorectal cancer patients.

An increasing number of elderly patients are presenting for elective surgery. Pre-operative risk assessment in this population is inexact due to the complex interplay between age, comorbidity and functional status. Frailty assessment may provide a surrogate measure of a patient's physiological reserve and aid operative decision-making. The aim of this study is to determine the association between pre-operative frailty, as assessed using the Edmonton Frail Scale, and post-operative outcomes in elderly patients undergoing elective colorectal cancer surgery. A prospective analysis of 86 patients over the age of 65 undergoing elective colorectal cancer surgery at a tertiary centre between October 2017 and October 2018 was performed. Frailty assessment was conducted pre-operatively using the Edmonton Frail Scale. Primary outcomes included length of stay and post-operative complication rates. Multivariable logistic regression analyses were used to determine the influence of frailty on post-operative outcomes including mortality, prolonged hospital admission, complication rates and quality of life. Of 86 patients, 12 (14.0%) were identified as frail. Frailty was associated with a significantly increased median length of stay (20 days versus 6 days, incidence rate ratio 2.83, P < 0.01) and a significantly increased risk of major post-operative complications (50.0% versus 6.7%, odds ratio 13.8, P < 0.01). Frailty was not associated with a significant reduction in quality of life scores at 30 and 90 days post-operatively. Frailty is associated with adverse post-operative outcomes in elderly patients undergoing elective colorectal cancer surgery. Frailty assessment is an important component of pre-operative risk assessment and may identify targets for pre-operative optimisation.

Abstract 5694: Complete regression of murine breast tumors by hetIL-15FC monotherapy correlates with infiltration by T, NK, cDC1 cells and a novel population of dendritic cells

Abstract Introduction: IL-15 cytokine stimulates the proliferation and cytotoxic function of CD8+ T and NK cells. Several preclinical models have supported the anti-tumor activity of IL-15. We have produced the native heterodimeric IL-15 (hetIL-15) of human, macaque or mouse and also fusions to the Fc antibody fragments (hetIL-15FC). Experimental procedures: We studied the therapeutic efficacy of hetIL-15 or hetIL-15FC immunotherapy in the murine EO771 orthotopic breast cancer model in syngeneic C57BL/6 mice. The effects of hetIL-15FC on immune cells were compared in tumors, lymph nodes and spleen by flow cytometry, immunohistochemistry (IHC) and gene expression profiling (Nanostring). We also assessed the metabolic profile of tumor infiltrating T cells. Results: hetIL-15 therapy delayed the primary tumor growth and increased overall survival. hetIL-15 or hetIL-15FC peritumoral administration resulted in tumor regression in 40% of the treated animals and resistance to tumor re-challenge. Therefore, monotherapy induced long term immunological memory able to block tumor growth. Both CD8+ T and NK cells were increased in hetIL-15FC treated tumors; phenotypic analysis showed they were activated and in an active proliferation state. Transcriptomic analysis confirmed the activated state of the T and NK cells, whereas metabolic flux analysis of the infiltrated CD8+T cells from treated mice confirmed a rise in oxygen consumption rate (OCR) with substantial increase of spare respiratory capacity (as a measure of mitochondrial reserve), which supports an activated/non exhausted phenotype of these hetIL-15 treated effector cells. In addition, peritumoral hetIL-15FC administration resulted in an increase of infiltrating, conventional type 1 dendritic cells (cDC1s), suggesting mechanisms of DC-lymphocyte interactions in the tumor. We also observed a new population of intra-tumoral DCs induced by hetIL-15, CD24+ F4/80high cDC2s (F4/80high DCs). The new DC population was negatively correlated with the tumor size of EO771 tumor bearing mice. Phenotypic profiling of F4/80high DCs identified expression of several cDC1 specific markers, including CD103 and IRF8 and t-SNE analysis clustered F4/80high DCs close to cDC1s and macrophages. Conclusion: Our results show complete eradication of EO771 tumors by hetIL-15FC treatment, correlating with different tumor infiltrating immune cell types. We propose that the anti-cancer activity of hetIL-15 in primary tumors is orchestrated by the interplay of CD8+T cells, cDC1s and a novel subset of antigen presenting cells with a distinct phenotypic profile. hetIL-15 supported a favorable metabolic profile of intra-tumoral effector lymphocytes, important for their function. Effective hetIL-15 treatment leads to development of long-term anti-tumor memory. Citation Format: Sevasti Karaliota, Dimitris Stellas, Vasiliki Stravokefalou, Bethany Nagy, Cristina Bergamaschi, Barbara K. Felber, George N. Pavlakis. Complete regression of murine breast tumors by hetIL-15FC monotherapy correlates with infiltration by T, NK, cDC1 cells and a novel population of dendritic cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5694.

Hydroxycarbamide exposure and ovarian reserve in women with sickle cell disease in the Multicenter Study of Hydroxycarbamide.

The application of modern ovarian reserve measures to women with sickle cell disease (SCD) may help answer longstanding questions about whether SCD or hydroxycarbamide (HC; also known as hydroxyurea) affect women's reproductive lifespan. Anti-Müllerian hormone (AMH), an established marker of ovarian reserve, is used to assess the ovarian follicle pool. We used a standard clinical assay to measure AMH in 285 banked samples from 93 female subjects with haemoglobin SS from the historic Multicenter Study of Hydroxyurea (MSH), which led to the United States Food and Drug Administration approval of HC for adults with SCD. No samples from the randomised portion of the MSH remain, so samples from the decade-long MSH follow-up studies were analysed. Most subjects were exposed to HC (86/93). The median AMH levels were lower in study subjects than in age- and sex-matched reference values. The median AMH levels consistent with diminished ovarian reserve, a risk factor for infertility, occurred in subjects starting at the age of 25-30years; in healthy women, this occurs after the age of 40years. In multivariate analysis, taking HC was independently associated with a low AMH (β = 0·001, 95% confidence interval -0·002 to 0·000; P=0·006). These results suggest that ovarian reserve is prematurely reduced in women with haemoglobin SS and raise the possibility that HC contributes to this finding.

Exercise as a diagnostic and therapeutic tool for preventing cardiovascular morbidity in breast cancer patients\u2013 the BReast cancer EXercise InTervention (BREXIT) trial protocol

BackgroundAnthracycline chemotherapy (AC) is an efficacious (neo) adjuvant treatment for early-stage breast cancer (BCa), but is associated with an increased risk of cardiac dysfunction and functional disability. Observations suggest that regular exercise may be a useful therapy for the prevention of cardiovascular morbidity but it is yet to be interrogated in a large randomised trial.The primary aims of this study are to: 1) determine if 12-months of ET commenced at the onset of AC can reduce the proportion of BCa patients with functional disability (peak VO2, < 18 ml/kg/min), and 2) compare current standard-of-care for detecting cardiac dysfunction (resting left-ventricular ejection fraction assessed from 3-dimensional echocardiography) to measures of cardiac reserve (peak exercise cardiac output assessed from exercise cardiac magnetic resonance imaging) for predicting the development of functional disability 12-months following AC. Secondary aims are to assess the effects of ET on VO2peak, left ventricular morphology, vascular stiffness, cardiac biomarkers, body composition, bone mineral density, muscle strength, physical function, habitual physical activity, cognitive function, and multidimensional quality of life.MethodsOne hundred women with early-stage BCa (40–75 years) scheduled for AC will be randomized to 12-months of structured exercise training (n = 50) or a usual care control group (n = 50). Participants will be assessed at baseline, 4-weeks following completion of AC (4-months) and at 12-months for all measures.DiscussionWomen diagnosed with early-stage BCa have increased cardiac mortality. More sensitive strategies for diagnosing and preventing AC-induced cardiovascular impairment are critical for reducing cardiovascular morbidity and improving long-term health outcomes in BCa survivors.Trial registrationAustralia & New Zealand Clinical Trials Registry (ANZCTR), ID: 12617001408370. Registered on 5th of October 2017.

The role of cognitive reserve as mediator for addition and multiplication skills in late adulthood.

The role played by cognitive reserve for the maintenance of numeracy skills in late adulthood is still not sufficiently explored. This study mainly investigated whether cognitive reserve (i.e., vocabulary) mediates on the relationship between non-verbal reasoning and addition and multiplication skills of older individuals. Moreover, the impact of schooling and gender on written calculation was examined, controlling for the effect of cognitive decline. One hundred and six 68-94-year-old participants completed a battery of tests assessing numeracy, executive functions, and cognitive reserve skills. Significant correlations were found between age, cognitive reserve, numeracy, and executive functions measures. Besides, mediation analyses indicated that cognitive reserve and non-verbal reasoning explain 23% and 29% of the variance in written addition and multiplication conditions, respectively. Finally, more educated individuals performed better numeracy tasks, whereas the solution of additions and multiplications was not impact by gender. Cognitive reserve impacts numeracy in late adulthood.

P0677CONTRAST-ENHANCED ULTRASOUND TO ASSESS RENAL MICROCIRCULATION IN PATIENTS WITH CHRONIC KIDNEY DISEASE

Abstract Background and Aims Vascular factors such as capillary rarefaction, increased vascular stiffness and reduced vasodilatation due to endothelial dysfunction probably play an important role in the pathophysiology of chronic kidney disease (CKD). However, our understanding of the underlying mechanisms is hampered by the lack of non-invasive techniques to quantify renal microvasculature in humans. The aim of this study was to assess whether contrast-enhanced ultrasonography (CEUS) can identify (1) differences in renal microcirculation and (2) the degree of nitroglycerin-induced vasodilatation (NIV) as a measure of renal flow reserve between CKD-patients and age-matched healthy volunteers. Method All participants underwent CEUS under standardized conditions. Sonovue© (0.015 ml/kg/min) was perfused as contrast agent until a steady state was obtained, followed by four destruction-refilling sequences. Outcome measure of CEUS was the mean (change in) perfusion index (PI) of the outer renal cortex (see figure for an example). In a subgroup of participants, CEUS was repeated before and five minutes after the sublingual administration of nitroglycerin (0.2mg). Renal resistive index (RRI) as a measure of vascular stiffness was also measured at each time point with Doppler ultrasound. Results A total of 38 healthy volunteers (aged 50±8 years, eGFR 95±13 ml/min/1.73 m, 69% women) and 18 CKD stage 2-3 patients (aged 55±15 years, eGFR 64±32 ml/min/1.73m, 56% women) were included. Renal PI was significantly lower in CKD patients (1304±762 vs 2989 ±2503 arbitrary units, p=0.034), whereas RRI did not differ (0.66± 0.07 vs 0.63± 0.04), p=0.10). PI was lower in CKD due to vascular nephropathy (n=3) or interstitial nephritis (n=4) than CKD due to diabetes (n=4) or other causes (7). In continuous analysis, PI correlated with eGFR (spearman’s r=0.54, p=0.005) but not with blood pressure. Renal PI did not change after nitroglycerin in both groups; RRI decreased in healthy (from 0.64±0.03 to 0.61±0.02, p=0.01) but not in CKD patients. Conclusion In this study, contrast-enhanced ultrasound identified important alterations in renal microperfusion in patients with moderate CKD. Whether a low perfusion index predicts renal function decline needs further study. Sublingual nitroglycerin seems to have limited potential as a new test of renal flow reserve.

The association between cognitive reserve and performance-related brain activity during episodic encoding and retrieval across the adult lifespan

Remembering associations between encoded items and their contextual setting is a feature of episodic memory. Although this ability generally deteriorates with age, there is substantial variability in how older individuals perform on episodic memory tasks. A current topic of debate in the cognitive neuroscience of aging literature revolves around whether this variability may stem from genetic and/or environmental factors related to reserve, allowing some individuals to compensate for age-related decline through differential recruitment of brain regions. In this fMRI study spanning a large adult lifespan sample (N = 154), we tested whether higher cognitive reserve was associated with better task-fMRI context memory performance, and functional compensatory activity patterns in the aging brain. We used multivariate Behaviour Partial Least Squares (B-PLS) analysis to examine how age, retrieval accuracy, and a proxy measure of cognitive reserve [i.e., a composite score consisting of years of education (EDU) and crystallized IQ], impacted brain activity during the encoding and retrieval of spatial and temporal contextual details. The results indicated that age-related increases in encoding activity within anterior and lateral frontal, inferior parietal, occipito-temporal and medial temporal cortices, was correlated with better subsequent memory performance; and may be indicative of age-related functional compensation at encoding. Interestingly this compensatory pattern was not correlated with our proxy measure of cognitive reserve but was associated with total brain volume (a measure of brain reserve). However, cognitive reserve was associated with age-invariant and task-general activity in superior temporal, occipital, and left inferior frontal regions. We conclude that the relationship between cognitive reserve, brain reserve and age-related functional compensation is complex, and that EDU and IQ may not fully account for individual differences in cognitive reserve when studying well educated, healthy aging cohorts.

Expanding the role of education in frontotemporal dementia: a functional dynamic connectivity (the chronnectome) study

In the present study, we aim at investigating whether education modulates dynamical properties of time-varying whole-brain network connectivity (the chronnectome) in frontotemporal dementia (FTD) at a given level of symptom severity. Dynamic connectivity parameters were evaluated in 128 patients with FTD using independent component analysis, sliding-time window correlation, and k-means approach to resting state–magnetic resonance imaging data. We evaluated the relationship between education, a proxy measure of cognitive reserve, and 4 indexes of metastate dynamic connectivity: (1) the number of distinct metastates a patient passes through, (2) the number of switches from one metastate to another, (3) the span of the realized metastates, and (4) the total distance traveled in the state space. We found a significant inverse correlation between years of education and the 4 indexes of metastate dynamic fluidity (all p-values ≤ 0.03, false discovery rate–corrected). This study suggests that patients with FTD with higher education but comparable clinical severity show more global functional brain impairment, suggesting that patients with higher cognitive reserve can cope with more global brain fluidity reduction.

Validation of quantitative measure of repolarization reserve as a novel marker of drug induced proarrhythmia

Repolarization reserve, the robustness of a cell to repolarize even when one of the repolarization mechanisms is failing, has been described qualitatively in terms of ionic currents, but has not been quantified by a generic metric that is applicable to drug screening. Prolonged repolarization leading to repolarization failure is highly arrhythmogenic. It may lead to ventricular tachycardia caused by triggered activity from early afterdepolarizations (EADs), or it may promote the occurrence of unidirectional conduction block and reentry. Both types of arrhythmia may deteriorate into ventricular fibrillation (VF) and death. We define the Repolarization Reserve Current (RRC) as the minimum constant current necessary to prevent normal repolarization of a cell. After developing and testing RRC for nine computational ionic models of various species, we applied it experimentally to atrial and ventricular human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM), and isolated guinea-pig ventricular cardiomyocytes. In simulations, repolarization was all-or-none with a precise, model-dependent critical RRC, resulting in a discrete shift in the Action Potential Duration (APD) - RRC relation, in the occurrence of EADs and repolarization failure. These data were faithfully reproduced in cellular experiments.RRC allows simple, fast, unambiguous quantification of the arrhythmogenic propensity in cardiac cells of various origins and species without the need of prior knowledge of underlying currents and is suitable for high throughput applications, and personalized medicine applications.

Reduction of functional cardiovascular reserve in the stages of chronic kidney disease.

Patients with chronic kidney disease (CKD) present reduced oxygen consumption at peak exercise (VO2 peak). No studies have evaluated objective measures of the cardiovascular reserve, besides VO2 peak and VO2 at the anaerobic threshold (VO2 AT), and compared these measures among ckd patients at different stages of the disease. Fifty-eight patients [pre-dialysis group (PD)=26, hemodialysis group (HD)=20, and post-kidney transplant group (KT)=12] were included. The following measures of cardiovascular reserve were obtained: 1) peak heart rate (HR); 2) peak systolic blood pressure (SBP); 3) VO2 peak and % predicted; 4) VO2 AT and % of predicted VO2; 5) peak circulatory power; 6) ventilatory efficiency for the production of carbon dioxide (VE/VCO2 slope); 7) oxygen uptake efficiency slope (OUES); and 8) recovery of gas exchange. The VO2 peak and VO2 AT in the PD, HD, and KT groups were reduced to 86% and 69%, 70% and 57%, and 79% and 64% of the predicted value, respectively. Patients in the HD group had lower VO2 peak (17.5±5.9 vs. 23.2±8.2 [p-value=0.036]) and VO2 AT (14.0±5.2 vs. 18.3±4.7 [p-value=0.039]) compared to patients in the KT group. OUES was significantly lower in the HD group compared to the KT group (p-value=0.034). Age in the PD, HD, and KT groups and sedentary lifestyle in the KT group were predictors of VO2 peak. CKD patients presented a reduction in cardiovascular reserve regardless of the stage of the disease. However, hemodialysis patients presented a greater reduction of cardiovascular reserve when compared to post-kidney transplant patients.

Resting State Glucose Utilization and Adult Reading Test Performance.

Adult reading tests (ART) have been widely used in both research and clinical settings as a measure of premorbid cognitive abilities or cognitive reserve. However, the neural substrates underlying ART performance are largely unknown. Furthermore, it has not yet been examined whether the neural substrates of ART performance reflect the cortical regions associated with premorbid intelligence or cognitive reserve. The aim of the study is to identify the functional neural correlates of ART performance using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging in the cognitively normal (CN) middle- and old-aged adults. Voxel-wise analyses revealed positive correlations between glucose metabolism and ART performance in the frontal and primary somatosensory regions, more specifically the lateral frontal cortex, anterior cingulate cortex and postcentral gyrus (PCG). When conducted again only for amyloid-β (Aβ)-negative individuals, the voxel-wise analysis showed significant correlations in broader areas of the frontal and primary somatosensory regions. This is the first neuroimaging study to directly demonstrate the cerebral resting-state glucose utilization associated with ART performance. Our findings provide important evidence at the neural level that ART predicts premorbid general intelligence and cognitive reserve, as brain areas that showed significant correlations with ART performance correspond to regions that have been associated with general intelligence and cognitive reserve.

Frailty predicts surgical complications after kidney transplantation. A propensity score matched study.

Surgical complications after kidney transplantation can lead to catastrophic outcomes. Frailty has been associated with important kidney transplantation outcomes; however, there are no studies assessing this measure of physiological reserve as a specific predictor of surgical complications in this population. Such an assessment was, therefore, the objective of the present study. A total of 87 individuals aged ≥ 18 years who underwent kidney transplantation between March 2017 and March 2018 were included. At the time of admission for kidney transplantation, demographic, clinical, and kidney transplantation data were collected, and the frailty score was calculated according to Fried et al., which comprises five components: shrinking, weakness, exhaustion, low activity, and slowed walking speed. Urological, vascular, and general surgical complications were assessed three months later, or until graft loss or death. The propensity score was used to achieve a better homogeneity of the sample, and new analyses were performed in this new, balanced sample. Of the 87 individuals included, 30 (34.5%) had surgical complications. After propensity score matching, the risk of surgical complications was significantly higher among the frail individuals (RR 2.14; 95% CI 1.01-4.54; p = 0.035); specifically, the risk of noninfectious surgical complications was significantly higher among these individuals (RR 2.50; 95% CI 1.11-5.62; p = 0.017). The results showed that individuals with some degree of frailty before kidney transplantation were more subject to surgical complications. The calculation of the frailty score for transplant candidates and the implementations of measures to increase the physiological reserve of these patients at the time of kidney transplantation may possibly reduce the occurrence of surgical complications.

Identifying the Functional Brain Network of Motor Reserve in Early Parkinson's Disease.

The severity of motor symptoms in Parkinson's disease (PD) does not always correlate with the degree of nigral dopaminergic neuronal loss. Individuals with greater motor reserve may have milder motor signs than their striatal dopamine loss. In this study, we explored the functional brain network associated with motor reserve in early-stage PD. We analyzed 134 patients with de novo PD who underwent dopamine transporter scans and resting-state functional magnetic resonance imaging. We estimated individual motor reserve based on initial motor deficits and striatal dopamine depletion using a residual model. We applied network-based statistic analysis to identify the functional brain network associated with the measure of motor reserve (ie, motor reserve network). We also assessed the effect of motor reserve network connectivity strength on the longitudinal increase in levodopa-equivalent dose during the 2-year follow-up period. Network-based statistic analysis identified the motor reserve network composed of the basal ganglia, inferior frontal cortex, insula, and cerebellar vermis at a primary threshold of P value 0.001. Patients with an increased degree of functional connectivity within the motor reserve network had greater motor reserve. There was a significant interaction between the motor reserve network strength and time in the linear mixed model, indicating that higher motor reserve network strength was associated with slower longitudinal increase in levodopa-equivalent dose. The present study revealed the functional brain network associated with motor reserve in patients with early-stage PD. Functional connections within the motor reserve network are associated with the individual's capacity to cope with PD-related pathologies. © 2020 International Parkinson and Movement Disorder Society.

Reduced Exercise Capacity in Diabetes Mellitus Is Not Associated with Impaired Deformation or Twist

Exercise capacity is frequently reduced in people with diabetes mellitus (DM) and may be due to subclinical cardiac dysfunction. Speckle-tracking echocardiography is now widely available; however, the clinical utility and significance of left ventricular (LV) strain and twist parameters remain uncertain. We hypothesized that LV strain and twist would be reduced in DM subjects during exercise. Adults with type 1 or type 2 DM and age- and sex-matched controls performed cardiopulmonary exercise testing (VO2 peak) and supine bicycle exercise echocardiography. Detailed echocardiographic assessment of biventricular function was performed at baseline and repeated during incremental exercise to maximal intensity. Of the 60 participants completing the study protocol, 51 (34 DM, 17 controls; mean age, 42±13years; 69% male; DM duration, 16±10years) had sufficient image quality to assess LV deformation and twist mechanics at rest. Of these, 38 (25 DM, 13 controls) were able to be assessed immediately after exercise. Baseline LV systolic and diastolic function using standard echocardiography measurements were similar between groups. Resting LV global longitudinal strain, twist, twist rate and untwist rate, and the corresponding peak exercise and reserve measures did not differ significantly. As compared with the control subjects, exercise capacity was reduced in the DM cohort (VO2 peak 33±10 vs 41±12mL/minute/kg; P=.02); however, no correlation was observed between VO2 peak and LV twist reserve (R=0.28, P=.09), LV twist rate reserve (R=0.14, P=.39), or LV untwist rate reserve (R=0.24, P=.14). Despite reduced VO2 peak, LV twist mechanics at rest and after maximal intensity exercise did not differ significantly in a cohort of asymptomatic DM subjects with normal resting LV systolic and diastolic function compared with age- and sex-matched controls. This would suggest that exercise capacity can be reduced in the absence of subclinical cardiac dysfunction and that noncardiac factors should be considered as alternative explanations.

Comparison between AMH level in Multipara and Nullipara in Women More than 40 Years Old

Decreased ovarian reserve is considered as one of the main causes of infertility. It is about the availability of preovulatory oocytes in the ovaries. With increase age, ovarian reserve decreases. Nowadays, “ovarian reserve” assessment became a strategy to assess female infertility.Objective: The current study aims to find the relationship between age and infertility type with measures of ovarian reserve (FSH, AMH and AFC) in infertile patients.Material and Method: The cross-sectional study design was used for this study and a survey was conducted among 100 infertile women.Result: Results revealed that Relationships between age and ovarian reserve indicators show a highly significant negative correlation with AFC (p= 0.001) and AMH (p= 0.007) level while positive correlation is found with FSH level (p= 0.001). The relation between age and FSH was moderate (rs=0.38, p&lt;0.0001) and revealed that AMH and AFC level decreases while FSH level increases with age.Conclusion Study of AMH level is the most reliable source to measure age-specific changes.

Relationship Between Risk Factors and Brain Reserve in Late Middle Age: Implications for Cognitive Aging

BackgroundBrain reserve can be defined as the individual variation in the brain structural characteristics that later in life are likely to modulate cognitive performance. Late midlife represents a point in aging where some structural brain imaging changes have become manifest but the effects of cognitive aging are minimal, and thus may represent an ideal opportunity to determine the relationship between risk factors and brain imaging biomarkers of reserve.ObjectiveWe aimed to assess neuroimaging measures from multiple modalities to broaden our understanding of brain reserve, and the late midlife risk factors that may make the brain vulnerable to age related cognitive disorders.MethodsWe examined multimodal [structural and diffusion Magnetic Resonance Imaging (MRI), FDG PET] neuroimaging measures in 50–65 year olds to examine the associations between risk factors (Intellectual/Physical Activity: education-occupation composite, physical, and cognitive-based activity engagement; General Health Factors: presence of cardiovascular and metabolic conditions (CMC), body mass index, hemoglobin A1c, smoking status (ever/never), CAGE Alcohol Questionnaire (>2, yes/no), Beck Depression Inventory score), brain reserve measures [Dynamic: genu corpus callosum fractional anisotropy (FA), posterior cingulate cortex FDG uptake, superior parietal cortex thickness, AD signature cortical thickness; Static: intracranial volume], and cognition (global, memory, attention, language, visuospatial) from a population-based sample. We quantified dynamic proxies of brain reserve (cortical thickness, glucose metabolism, microstructural integrity) and investigated various protective/risk factors.ResultsEducation-occupation was associated with cognition and total intracranial volume (static measure of brain reserve), but was not associated with any of the dynamic neuroimaging biomarkers. In contrast, many general health factors were associated with the dynamic neuroimaging proxies of brain reserve, while most were not associated with cognition in this late middle aged group.ConclusionBrain reserve, as exemplified by the four dynamic neuroimaging features studied here, is itself at least partly influenced by general health status in midlife, but may be largely independent of education and occupation.