Greater Rate Of Decline Research Articles

Neural and muscular contributions to the age-related differences in peak power of the knee extensors in men and women.

The mechanisms for the loss in limb muscle power output in old (60-79 yr) and very old (≥80 yr) adults and whether the mechanisms differ between men and women are not well understood. We compared maximal peak power of the knee extensor muscles between young, old, and very old men and women and identified the neural and muscular factors contributing to the age-related differences in power. Thirty-one young (22.9 ± 3.0 yr, 15 women), 82 old (70.3 ± 4.9 yr, 38 women), and 16 very old adults (85.8 ± 4.2 yr, 9 women) performed maximal isokinetic contractions at 14 different velocities (30-450°/s) to identify peak power. Voluntary activation (VA) and contractile properties were assessed with transcranial magnetic stimulation to the motor cortex and electrical stimulation of the femoral nerve. The age-related loss in peak power was ∼6.5 W·yr-1 for men (R2 = 0.62, P < 0.001), which was a greater rate of decline (P = 0.002) than the ∼4.2 W·yr-1 for women (R2 = 0.77, P < 0.001). Contractile properties were the most closely associated variables with peak power for both sexes, such as the rate of torque development of the potentiated twitch (men: R2 = 0.69, P < 0.001; women: R2 = 0.57, P < 0.001). VA was weakly associated with power in women (R2 = 0.13, P = 0.012) but not in men (P = 0.191). Similarly, neuromuscular activation [rates of electromyography (EMG) rise] during the maximal power contraction was associated with power in women (R2 = 0.07, P = 0.042) but not in men (P = 0.456). These data suggest that the age-related differences in maximal peak power of the knee extensor muscles are due primarily to factors within the muscle for both sexes, although neural factors may play a minor role in older women.NEW & NOTEWORTHY The greater age-related loss in power relative to the loss in muscle mass of the knee extensors was primarily due to factors altering the contractile properties of the muscle for both old and very old (≥80 yr) adults. The mechanisms for the decrements in power with aging appear largely similar for men and women, although neural factors may play more of a role in older women.

A global approach to the epidemiology of cognitive ageing and dementia: Cohort Studies of Memory in International Consortium (COSMIC)

AbstractCOSMIC (COhort Studies of Memory in International Consortium) is an international consortium of longitudinal studies of cognitive aging and dementia, currently comprising 57 cohorts from 39 countries across 6 continents, comprising 186,000 participants (49% White, 8% Black, 21% Asian, 20% Hispanic, 2% Other). COSMIC embraces the power of collaboration through horizontal partnerships, with pooled and coordinated analyses after rigorous harmonization to examine ethno‐geographic differences in risk/protective factors and biomarkers, harness data from under‐represented populations, and permit cross‐validation in a field notorious for non‐replicable results. Analyses thus far have demonstrated that the cross‐national variation in prevalence of MCI is lower than generally reported, with commonality of most risk factors. The effect sizes of risk factors do, however, vary in populations, with APOE*4 and diabetes being associated with greater rates of decline in Asian than White populations. High school education is a significant threshold for protection against cognitive decline in later life, especially in Black and Asian populations. Physical activity shows a dose‐dependent relationship with incident dementia, suggesting that older adults should do three to six hours of physical activity per week for maximum cognitive benefits. The range and depth of such findings continues to grow, as is the community of researchers in both high and low‐middle income countries. With its global reach, open sharing of data and diverse network of researchers, COSMIC is creating a truly global epidemiology of dementia that is needed to deal with the world‐wide inequity in research, and meet the ambitious goals of the 2017 World Health Assembly to address the global epidemic of dementia and the hopes of people at risk of dementia everywhere.

Abstract 16797: The Role of Adiposity on Microvascular Dysfunction and Arterial Stiffness in Patients With New Onset Breast Cancer

INTRODUCTION: Increased adiposity is a risk factor for both cardiovascular disease (CVD) and cancer. Microvascular endothelial dysfunction and arterial stiffness are independent risk factors for CVD and can accelerate vascular aging. Whether or not adiposity plays a role in vascular aging over time in patients with new-onset breast cancer (BC) has yet to be elucidated. Hypothesis: Adiposity impacts microvascular dysfunction and arterial stiffness differently in women undergoing therapy for recent BC diagnoses. Methods: Two lean (L; BMI &lt; 25 kg/m 2 ) and four overweight and obese (Ow/Ob; BMI &gt; 25 kg/m 2 ) women diagnosed with BC within the last 3 months participated in the study. Using laser Doppler imaging, microvascular endothelial function was assessed with three protocols: 1) cutaneous post-occlusion reactive hyperemia (PORH), 2) local thermal heating (LTH), and 3) iontophoresis of acetylcholine. Arterial stiffness was assessed using pulse wave velocity (PWV) and pulse wave analysis (PWA). Assessments were made at baseline and at 3 and 6 months following enrollment. Data are reported as means ± SE. Results: No differences in age, height, blood pressure, or total cholesterol (all p &gt;0.05) were observed between L and Ow/Ob groups. Microvascular function and arterial stiffness were similar at baseline between groups. There was a greater decrease in LTH responses from baseline to 6 months post-baseline in Ow/Ob women (Δ-48±4 PU; p =0.001) compared to L women (Δ-16±13 PU; p =0.125). Similar responses in both groups were noted for PORH ( p =0.886) and iontophoresis ( p =0.784). PWV was similar from baseline to 6 months post-baseline in both groups; however, the PWA tended to increase over time in Ow/Ob women (Δ2.5±4.7) and decrease in L women (Δ-3.0±5.0). CONCLUSION: Ow/Ob women have a greater rate of decline in LTH responses compared with L women, whereas similar responses between L and OW/OB women were observed over time for PORH and iontophoresis. In addition, central aortic stiffness increased in Ow/Ob women and decreased in L women, while no change in PWV was observed. These findings suggest that adiposity may impact vascular beds differently over time following the initial diagnosis of breast cancer.

Decline in forced vital capacity as a surrogate for mortality in patients with pulmonary fibrosis.

Surrogate endpoints enable determination of meaningful treatment effects more efficiently than applying the endpoint of ultimate interest. We used data from trials of nintedanib in subjects with pulmonary fibrosis to assess decline in forced vital capacity (FVC) as a surrogate for mortality. Data from the nintedanib and placebo groups of trials in subjects with idiopathic pulmonary fibrosis, other forms of progressive pulmonary fibrosis, and pulmonary fibrosis due to systemic sclerosis (NCT00514683, NCT01335464, NCT01335477, NCT01979952, NCT02999178, NCT02597933) were pooled. Using joint models for longitudinal and time-to-event data, we assessed the association between decline in FVC % predicted and time to death over 52 weeks. The rate of change in FVC % predicted and the current value of FVC % predicted were modelled longitudinally and estimates applied as predictors in time-to-event models. Among 2583 subjects with pulmonary fibrosis, both a greater rate of decline in FVC % predicted and a lower current value of FVC % predicted were associated with an increased risk of death over 52 weeks (HR 1.79 [95% CI: 1.57, 2.03] and HR 1.24 [1.17, 1.32] per 5-percentage point decrease, respectively). Associations between the rate of change in FVC % predicted and the risk of death were consistent between patients with IPF and other ILDs. Data from clinical trials in subjects with pulmonary fibrosis of diverse aetiology demonstrate a strong association between decline in FVC % predicted and mortality over 52 weeks, supporting FVC decline as a surrogate for mortality in these patients.

Lung function trajectories in patients with idiopathic pulmonary fibrosis

BackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease characterised by decline in lung function. We evaluated trajectories of forced vital capacity (FVC) and diffusing capacity (DLco) in a cohort of patients with IPF.MethodsPatients with IPF that was diagnosed or confirmed at the enrolling centre in the previous 6 months were enrolled into the IPF-PRO Registry between June 2014 and October 2018. Patients were followed prospectively, with lung function data collected as part of routine clinical care. Mean trajectories of FVC and DLco % predicted in all patients and in subgroups by characteristics assessed at enrolment were estimated using a joint model that accounted for factors such as disease severity and visit patterns.ResultsOf 1002 patients in the registry, 941 had ≥ 1 FVC and/or DLco measurement after enrolment. The median (Q1, Q3) follow-up period was 35.1 (18.9, 47.2) months. Overall, mean estimated declines in FVC and DLco % predicted were 2.8% and 2.9% per year, respectively. There was no evidence that the mean trajectories of FVC or DLco had a non-linear relationship with time at the population level. Patients who were male, white, had a family history of ILD, were using oxygen, or had prior/current use of antifibrotic therapy at enrolment had greater rates of decline in FVC % predicted. Patients who were male or white had greater rates of decline in DLco % predicted.ConclusionsData from the IPF-PRO Registry suggest a constant rate of decline in lung function over a prolonged period, supporting the inexorably progressive nature of IPF. A graphical abstract summarising the data in this manuscript is available at: https://www.usscicomms.com/respiratory/IPF-PRORegistry_LungFunctionTrajectories.Trial registrationNCT01915511.

Cirrhosis-related sarcopenia may not resolve after liver transplantation

Sarcopenia has significant burden in cirrhosis and has been shown to worsen short-term post-liver transplantation (LT). This study aims to evaluate the long-term change in sarcopenia post-LT along with its associations and predictors. A retrospective study of adult patients who underwent LT at a tertiary centre between 1/1/2009 and 12/31/2018. Relevant demographic and clinical data were collected. Skeletal muscle index (SMI) was calculated using standard of care computerised tomography (CT) scans pre- and post-LT. Sarcopenia was defined using previously established cut-points. The primary outcome was SMI change post-LT and secondary outcome was post-LT mortality. Out of 1165 patients, 401 met inclusion criteria (1,205 CT scans reviewed). The average age at transplant was 57 years; 63% were male. The average BMI was 28kg/m2. Thirteen percent of females and 32% of males had sarcopenia pre-LT. Post-LT SMI declined by 4.7cm2/m2 in the first year then by 0.39cm2/m2 per year thereafter. Females had greater rate of decline in SMI after the first year compared with males (0.87cm2/m2 per year vs. 0.17cm2/m2 per year, respectively, p= 0.02). Post-LT physical rehabilitation, infection, and readmissions were not associated with SMI trajectory. At 3 years post-LT, 31% of females and 48% of males had sarcopenia. Baseline sarcopenia was the only predictor of long-term post-LT sarcopenia on multivariable analysis, but it was not associated with mortality. Sarcopenia does not appear to resolve post-LT and likely worsens leading to nearly doubling its prevalence in those with long-term follow-up. Immediate post-LT physical rehabilitation was not associated with SMI trajectory in our cohort. The prevalence of sarcopenia is high among patients with cirrhosis; however, data are mixed on the impact of sarcopenia on post-liver transplant (LT) course and there have been no studies evaluating the long-term evolution of sarcopenia post-LT beyond 1 year. In this study, we analysed changes in muscle mass up to 3 years after transplant in 401 patients and found that sarcopenia did not resolve in most liver transplant recipients and skeletal muscle mass tended to worsen after transplant with the greatest decline in muscle mass in the first year post-LT. Interestingly, sarcopenia did not influence post-transplant outcomes. Future prospective studies are needed to further understand the natural course of sarcopenia post-LT to guide interventions aiming at reversing post-LT sarcopenia.

EFFECT OF THE RUSSIAN MILITARY INVASION ON THE ENDOGENOUS POTENTIAL OF UKRAINE

The research determines main risks for the endogenous development of the regions of Ukraine in the war conditions. It is stressed that the highest rate of decrease was demonstrated by the export of agricultural and metallurgical products. In the conditions of war, the main risks for the endogenous development of the regions of Ukraine have been identified. It was emphasized that the greatest rate of decline is demonstrated by exports of agricultural and metallurgical products. The growing risks of loss of the export market of Ukraine because of the war was the main reason for export reduction in the first half of 2022. The work specifies structure of the main export goods of Ukraine and defines geographical and commodity structure of the foreign trade of Ukraine in the first half of 2022. It is noted that blockade of export routes for agricultural products increased tension at the international food market. The author analyzes behaviour of companies during the war.

Direct Connection to the ECMO Circuit versus a Hemodialysis Catheter Is Associated with Improved Urea Nitrogen Ultrafiltration during Continuous Renal Replacement Therapy for Patients on Extracorporeal Membrane Oxygenation.

For patients on extracorporeal membrane oxygenation (ECMO) who require renal replacement therapy (RRT), dialysis can be achieved through a dedicated hemodialysis (HD) catheter or direct connection to the ECMO circuit. The relative effect of each on filtration efficacy is not known. We conducted a retrospective single-center analysis of patients on ECMO who required CRRT. We examined the outcomes of blood biomarkers and transmembrane filter pressures, comparing sessions by attachment approach. All analyses were clustered by patient. Of the 33 patients (7 ECMO access and 23 HD catheter access) that met the inclusion criteria, there were a total of 493 CRRT sessions (93 ECMO access and 400 HD catheter access). At the end of the first 12 h of CRRT therapy, the ECMO group had a greater rate of decline in serum BUN than the HD catheter access group (2.5 mg/dl (SD 11) vs. 2 mg/dl (SD 6), p = 0.035). Additionally, the platelet level was significantly higher in the ECMO group compared to the HD catheter access group after 72 h (94.5 k/uL (SD 41) vs. 71 k/uL (SD 29), p = 0.008). Utilizing the ECMO circuit as direct venous access for CRRT was associated with some improved filtration proximal outcomes.

The trajectory of mental health problems for UK emerging adults during COVID-19

Initial COVID-19 restrictions were associated with declining mental health, particularly in UK emerging adults. Prior research has yet to examine changes in mental health in this demographic over the entire course of the three UK national lockdowns. Drawing upon the Understanding Society COVID-19 Survey, this study examined the trajectory of mental health problems for emerging adults (18-29-year-olds) from April 2020–September 2021. Mental health problems were assessed at nine time-points using the General Health Questionnaire. The analytic sample included 1018 participants (304 males, 714 females). Growth curve modelling was used to examine the trajectory of mental health problems and the associated sociodemographic and health covariates. Females and those with fewer household members, lower income, no private garden, and pre-existing mental or physical health diagnoses reported more mental health problems. Gender differences were evident in the rate of change. Females' mental health problems declined from the first lockdown until just after the relaxation of initial restrictive measures (September 2020), increased until April 2021 (constituting lockdowns two and three), and then slightly decreased until September 2021 during the phased exit from restrictions. Males’ mental health problems followed a similar trajectory, with a greater rate of increase in mental health problems from July 2020–April 2021, and a greater rate of decline from April–September 2021. Females reported more mental health problems throughout the three national lockdowns than males. These findings can inform public health policies targeted toward young adult populations and highlight sub-populations at greater risk of worsening mental health.

Time Course of Performance Fatigability during Exercise below, at, and above the Critical Intensity in Females and Males.

This study aimed to investigate the time course and amplitude of performance fatigability during cycling at intensities around the maximal lactate steady state (MLSS) until task failure (TTF). Ten females and 11 males were evaluated in eight visits: 1) ramp incremental test; 2-3) 30-min constant power output (PO) cycling for MLSS determination; and 4-8) cycling to TTF at PO relative to the MLSS of (i) -15%, (ii) -10 W, (iii) at MLSS, and (iv) +10 W, and (v) +15%. Performance fatigability was characterized by femoral nerve electrical stimulation of knee extensors at baseline; minutes 5, 10, 20, and 30; and TTF. Oxygen uptake, blood lactate concentration, muscle oxygen saturation, and perceived exertion were evaluated. Approximately 75% of the total performance fatigability occurred within 5 min of exercise, independently of exercise intensity, followed by a further change at minute 30. Contractile function declined more in males than females (all P < 0.05). At task failure, exercise duration declined from MLSS -15% to MLSS +15% (all P < 0.05), accompanied by a greater rate of decline after MLSS +15% and MLSS +10 compared with MLSS, MLSS -10 , and MLSS -15% for voluntary activation (-0.005 and -0.003 vs -0.002, -0.001 and -0.001%·min -1 , respectively) and contractile function (potentiated single twitch force, -0.013 and -0.009 vs -0.006, -0.004 and -0.004%·min -1 , respectively). Whereas the time course of performance fatigability responses was similar regardless of exercise intensity and sex, the total amplitude and rate of change were affected by the distinct metabolic disturbances around the MLSS, leading to different performance fatigability etiologies at task failure.

The effect of digoxin on renal function in patients with heart failure

IntroductionDigoxin is used in patients with chronic heart failure (CHF) who remain symptomatic despite optimal medical treatment. Impaired renal function is commonly associated with CHF. We investigated the relation between digoxin use and change in renal function over time in patients with CHF.MethodsOne thousand two hundred forty-one patients with symptoms and signs of CHF (average age 72 years (64% male), and median NTproBNP 1426 ng/l (interquartile range 632–2897) were divided into four groups: never on digoxin (N = 394); digoxin throughout (N = 449); started digoxin at some point after baseline (N = 367); and stopped digoxin at some point after baseline (N = 31). The rate of change of estimated glomerular filtration rate (eGFR) was calculated using linear regression.ResultsPatients on digoxin throughout had a significantly greater rate of decline in eGFR per year than patients not on digoxin throughout (mean (± standard deviation); − 5 (14) ml/min/1.73m2 per year v − 2 (11) ml/min/1.73m2 per year, P = 0.02). In those patients who started digoxin during follow up, there was no significant difference in the rate of decline in eGFR before and after starting digoxin. There was no correlation between baseline eGFR (or rate of decline in eGFR) and age, haemoglobin or NTproBNP. Compared to patients taking both angiotensin-converting-enzyme inhibitor (ACEi) or angiotensin receptor blockers (ARB) and beta-blocker (BB), patients who were not taking an ACEi/ARB or BB had a numerically faster rate of decline in eGFR, although this was not statistically significant.ConclusionThe rate of decline in renal function is greater in patients with CHF who are taking digoxin.

Plasma Neurofilament Light and Future Declines in Cognition and Function in Alzheimer’s Disease in the FIT-AD Trial

Background:Utilities of blood-based biomarkers in Alzheimer’s disease (AD) clinical trials remain unknown.Objective:To evaluate the ability of plasma neurofilament light chain (NfL) to predict future declines in cognition and activities of daily living (ADL) outcomes in 26 older adults with mild-to-moderate AD dementia from the FIT-AD Trial.Methods:Plasma NfL was measured at baseline and 3 and 6 months. Cognition and ADL were assessed using the AD Assessment Scale-Cognition (ADAS-Cog) and AD Uniform Dataset Instruments and Disability Assessment for Dementia (DAD), respectively, at baseline, 3, 6, 9, and 12 months. Linear mixed effects models were used to examine the associations between baseline or change in plasma NfL and changes in outcomes.Results:Higher baseline plasma NfL was associated with greater rate of decline in ADAS-Cog from baseline to 6 months (standardized estimate of 0.00462, p = 0.02853) and in ADL from baseline to 12 months (standardized estimate of –0.00284, p = 0.03338). Greater increase in plasma NfL in short term from baseline to 3 months was associated with greater rate of decline in memory and ADL from 3 to 6 months (standardized estimate of –0.04638 [0.003], p = 0.01635; standardized estimate of –0.03818, p = 0.0435) and greater rate of decline in ADL from 3 to 12 month (standardized estimate of –0.01492, p = 0.01082).Conclusion:This study demonstrated that plasma NfL might have the potential to predict cognitive and function decline up to 12 months. However, future studies with bigger sample sizes need to confirm the findings.

SARS-CoV-2 antibody persistence in COVID-19 convalescent plasma donors: Dependency on assay format and applicability to serosurveillance.

BackgroundAntibody response duration following severe acute respiratory syndrome coronavirus 2 infection tends to be variable and depends on severity of disease and method of detection.Study design and methodsCOVID‐19 convalescent plasma from 18 donors was collected longitudinally for a maximum of 63–129 days following resolution of symptoms. All the samples were initially screened by the Ortho total Ig test to confirm positivity and subsequently tested with seven additional direct sandwich or indirect binding assays (Ortho, Roche, Abbott, Broad Institute) directed against a variety of antigen targets (S1, receptor binding domain, and nucleocapsid [NC]), along with two neutralization assays (Broad Institute live virus PRNT and Vitalant Research Institute [VRI] Pseudovirus reporter viral particle neutralization [RVPN]).ResultsThe direct detection assays (Ortho total Ig total and Roche total Ig) showed increasing levels of antibodies over the time period, in contrast to the indirect IgG assays that showed a decline. Neutralization assays also demonstrated declining responses; the VRI RVPN pseudovirus had a greater rate of decline than the Broad PRNT live virus assay.DiscussionThese data show that in addition to variable individual responses and associations with disease severity, the detection assay chosen contributes to the heterogeneous results in antibody stability over time. Depending on the scope of the research, one assay may be preferable over another. For serosurveillance studies, direct, double Ag‐sandwich assays appear to be the best choice due to their stability; in particular, algorithms that include both S1‐ and NC‐based assays can help reduce the rate of false‐positivity and discriminate between natural infection and vaccine‐derived seroreactivity.

Regional differences in pediatric asthma hospital admissions: National data from Israel 1996-2017.

Asthma is a common chronic childhood illness and frequent cause of hospitalization. A decline in hospital admission rates was noted up to the 1990s, however, trends are not as clear since the turn of the century. This study aimed to assess the rates and regional differences of asthma admissions over more than two decades using the national Ministry of Health database, which registers data from all the hospitals. A retrospective cohort study, analysis of all pediatric asthma admissions, for Patients 1-14 years old, between 1996 and 2017 as recorded by the National Hospital Discharge Registry, was performed. Asthma admission rates were calculated per 1000 age adjusted residents, using the number of admission cases as the numerator, and age specific population size as the denominator. The annual asthma hospitalization rate decreased in the entire pediatric population from 2.14 in 1996-0.89 in 2017. Children in the 1-4 year age group comprised most of the hospital admissions, and most of the decline was attributable to this age group. Significant differences in hospitalizations were found between different regions as well as differences in the rate of decline in asthma hospitalizations with the lowest admission rate in the Jerusalem district, highest in Haifa, northern and southern Israeli regions and the greatest rate of decline in the Tel-Aviv district. This nationwide study, over more than two decades, shows clear regional differences in the rates of asthma admissions as well as regional differences in the rates of decline.

Schizophrenia polygenic risk predicts general cognitive deficit but not cognitive decline in healthy older adults

There has been a long argument over whether schizophrenia is a neurodegenerative disorder associated with progressive cognitive impairment. Given high heritability of schizophrenia, ascertaning if genetic susceptibility to schizophrenia is also associated with cognitive decline in healthy people would support the view that schizophrenia leads to an accelerated cognitive decline. Using the population representative sample of 6817 adults aged >50 years from the English Longitudinal Study of Ageing, we investigated associations between the biennial rate of decline in cognitive ability and the schizophrenia polygenic score (SZ-PGS) during the 10-year follow-up period. SZ-PGS was calculated based on summary statistics from the Schizophrenia Working Group of the Psychiatric Genomics Consortium. Cognition was measured sequentially across four time points using verbal memory and semantic fluency tests. The average baseline verbal memory was 10.4 (SD = 3.4) and semantic fluency was 20.7 (SD = 6.3). One standard deviation (1-SD) increase in SZ-PGS was associated with lower baseline semantic fluency (β = −0.25, 95%CI = −0.40 to −0.10, p = 0.002); this association was significant in men (β = −0.36, 95%CI = −0.59 to −0.12, p = 0.003) and in those who were aged 60–69 years old (β = −0.32, 95%CI = −0.58 to −0.05, p = 0.019). Similarly, 1-SD increase in SZ-PGS was associated with lower verbal memory score at baseline in men only (β = −0.12, 95%CI = −0.23 to −0.01, p = 0.040). However, SZ-PGS was not associated with a greater rate of decline in these cognitive domains during the 10-year follow-up. Our findings highlight that while genetic susceptibility to schizophrenia conveys developmental cognitive deficit, it is not associated with an ongoing cognitive decline, at least in later life. These results do not support the neo-Kraepelinian notion of schizophrenia as a genetically determined progressively deteriorating brain disease.

The Association Between Dietary Pattern Adherence, Cognitive Stimulating Lifestyle, and Cognitive Function Among Older Adults From the Quebec Longitudinal Study on Nutrition and Successful Aging.

This study examined the effect of dietary patterns and engagement in cognitive stimulating lifestyle (CSL) behaviors on the trajectory of global cognition, executive function (EF), and verbal episodic memory (VEM). Western and prudent dietary patterns were empirically derived using food frequency questionnaire responses from 350 community-dwelling older adults (mean age: 73.7 years) participating in the Quebec Longitudinal Study on Nutrition and Successful Aging. CSL was represented by a binary composite indicator based on education, occupational complexity, and social engagement. Global cognition, EF, and VEM were assessed prospectively. Primary effect models revealed an association between higher Western dietary pattern score and a greater rate of decline in global cognition and EF. Higher Western dietary pattern adherence was also associated with poorer baseline VEM. Primary effect models also revealed that CSL was independently associated with baseline global cognition and EF. Effect modification models suggested an interactive effect between Western dietary pattern and CLS on global cognition only. No associations were found for prudent dietary pattern score. Contributing to existing research supporting the negative impact of consuming an unhealthy diet on cognitive function, the current study suggests increased vulnerability among older adults who do not engage in a CSL. These findings can inform the development of lifestyle intervention programs that target brain health in later adulthood.

THE COGNITIVE IMPPAIRMENT AND ITS RELATED FACTORS AMONG FACTORS AMONG ELDERLY HYPERTENSIVE IN TWO RURAL DISTRICTS AREAS, MALAYSIA

As cognition declines with age, cognitive impairment rates are expected to increase ranging from 100% to 300% in this region. It could be higher among elderly who had any chronic diseases. The aim of the present work was to determine the prevalence and associated factors of cognitive impairment among elderly with hypertension. A clinic-based, cross-sectional study was conducted at several community clinics in Sabak Bernam and Hilir Perak districts from July to December 2015. A total of 480 patients were recruited. The prevalence of cognitive impairment was 13.13% (95%CI: 13.11, 13.15). Factors associated with cognitive impairment among elderly hypertensive were no formal educational level [OR: 3.95 (95%CI: 1.80, 8.67)]; history of high cholesterol [OR: 3.24 (95%CI: 1.15, 9.16)]; underweight [adj. OR: 4.88 (95%CI: 1.34, 17.67)]; and increasing age [OR: 1.03 (95%CI: 1.01, 1.06)]. Public health policy makers and geriatric practitioners should emphasise on early cognitive function assessment among elderlies who are hypertensive, unemployed, poor educational background, males, high cholesterol level and underweight to enhance the quality of geriatric services. Earlier establishment of diagnosis may prevent from greater rate of decline in cognitive functioning among this vulnerable group.

Decline in Muscle Strength and Performance Predicts Fracture Risk in Elderly Women and Men.

Muscle strength and performance are associated with fractures. However, the contribution of their rate of decline is unclear. To assess the independent contribution of the rate of decline in muscle strength and performance to fracture risk. Community-dwelling women (n = 811) and men (n = 440) aged 60 years or older from the prospective Dubbo Osteoporosis Epidemiology Study followed from 2000 to 2018 for incident fracture. Clinical data, appendicular lean mass/height2 (ht)2, bone mineral density, quadricep strength/ht (QS), timed get-up-and-go (TGUG), 5 times repeated sit-to-stand (5xSTS), and gait speed (GS) measured biennially. Rates of decline in muscle parameters were calculated using ordinary least squares regression and fracture risk was assessed using Cox's models. Incident low-trauma fracture ascertained by x-ray report. Apart from lean mass in women, all muscle parameters declined over time. Greater rates of decline in physical performance were associated with increased fracture risk in women (Hazard ratios [HRs] ranging from 2.1 (95% CI: 1.5-2.9) for GS to 2.7 (95% CI: 1.9-3.6) for 5xSTS, while in men only the decline in GS was associated with fracture risk (HR: 3.4 [95% CI: 1.8-6.3]). Baseline performance and strength were also associated with increased fracture risk in men (HRs ranging from 1.8 (95% CI: 1.1-3.0) for QS to 2.5 (95% CI: 1.5-4.1) for TGUG, but not in women. Rate of decline in physical performance in both genders, and baseline strength and performance in men, contributed independently to fracture risk. Sit-to-stand and GS were the tests most consistently associated with fractures. Further studies are required to determine whether muscle strength and/or performance improve the predictive accuracy of fracture prediction models.

SAT0345 IS THERE A DIFFERENCE BETWEEN THE SEXES IN THE RATE OF PROGRESSION OF SYSTEMIC SCLEROSIS-ASSOCIATED ILD (SSC-ILD)? DATA FROM THE SENSCIS TRIAL

Background:Previous studies suggested that male sex may be associated with a greater rate of decline in FVC in patients with SSc-ILD. In the SENSCIS trial, nintedanib reduced the rate of FVC decline over 52 weeks vs placebo.Objectives:Analyse the rate of decline in FVC and the efficacy and safety of nintedanib in the SENSCIS trial in subgroups by sex.Methods:Patients with SSc-ILD with first non-Raynaud symptom &lt;7 years before screening and ≥10% fibrosis of the lungs on HRCT were randomised to nintedanib or placebo. We analysed the rate of decline in FVC (mL/year) and adverse events over 52 weeks in male and female patients.Results:Of 576 patients, 433 (75.2%) were female. Compared with males, the female subgroup included a smaller proportion of White patients (64.7% vs 74.8%), a smaller proportion on mycophenolate at baseline (46.9% vs 53.1%), a greater proportion of ATA positive patients (63.3% vs 53.1%), and had a lower mean weight at baseline (66.6 vs 79.1 kg). FVC % predicted (72.8% vs 71.7%) and mRSS (11.2 vs 10.8) were similar in females and males. The adjusted annual rate of decline in FVC in the placebo group was numerically greater in male than female patients (-126.8 [SE 29.0] vs -82.0 [16.2] mL/year). The estimated effect of nintedanib vs placebo on reducing the rate of decline in FVC was numerically more pronounced in males than females (difference: 58.6 [95% CI -18.0, 135.1] vs 34.6 [-9.3, 78.4] mL/year), but the interaction p-value did not indicate heterogeneity in the treatment effect between subgroups (p=0.59). Among nintedanib-treated patients, diarrhoea was reported in similar proportions of females and males (74.7% vs 79.1%); nausea, vomiting and liver test abnormalities were reported in greater proportions of females vs males (35.3% vs 19.4%, 28.1% vs 13.4%, and 15.4% vs 9.0%), while serious adverse events were more frequent in males (32.8% vs 21.3%). In the nintedanib and placebo groups, respectively, adverse events leading to treatment discontinuation were reported in 16.7% and 8.5% of females and 13.4% and 9.2% of males.Conclusion:In the SENSCIS trial in patients with SSc-ILD, the annual rate of decline in FVC in the placebo group was numerically greater in male than female patients. The rate of FVC decline was lower with nintedanib than placebo both in males and females. The safety profile of nintedanib was similar between males and females.Disclosure of Interests:Elizabeth Volkmann Grant/research support from: Forbius, Corbus Pharmaceuticals, Consultant of: Boehringer Ingelheim, Forbius, Speakers bureau: Boehringer Ingelheim, Serena Vettori Consultant of: Boehringer Ingelheim, John Varga Grant/research support from: John Varga is awaiting grants from Boehringer Ingelheim and has received grants from Bristol-Myers Squibb, Pfizer, Takeda, and TeneoBio, Consultant of: John Varga has acted as a consultant for Boehringer Ingelheim, Bristol-Myers Squibb, Emerald Health, and TeneoBio, Ariane Herrick: None declared, Maurizio Cutolo Grant/research support from: Bristol-Myers Squibb, Actelion, Celgene, Consultant of: Bristol-Myers Squibb, Speakers bureau: Sigma-Alpha, Ana Cordeiro Consultant of: Ana Cordeiro has acted as a consultant for Roche, Speakers bureau: Ana Cordeiro has received speaker fees from Boehringer Ingelheim, Lilly, and Vitoria, Valderilio F Azevedo Grant/research support from: Abbvie, Janssen, Bristol-Myers Squibb, Boehringer-Ingelheim, Lilly and Novartis, Consultant of: Lilly, Novartis, Janssen, Boehringer-Ingelheim, Amgen, Pfizer and Abbvie, Speakers bureau: Sandoz, Celltrion, Lilly, Novartis, Janssen, Boehringer-Ingelheim, Amgen, Pfizer and Abbvie, Sindhu Johnson Grant/research support from: Boehringer Ingelheim, Corbus Pharmaceuticals, GlaxoSmithKline, Roche, Merck, Bayer, Consultant of: Boehringer Ingelheim, Ikaria, Christian Stock Employee of: Employee of Boehringer Ingelheim, Martina Gahlemann Employee of: Employee of Boehringer Ingelheim, Lizette Moros Employee of: Lizette Moros is an employee of Boehringer Ingelheim, Margarida Alves Employee of: Employee of Boehringer Ingelheim, Maureen Mayes Grant/research support from: Maureen Mayes has received grants from Boehringer Ingelheim, Corbus, CSL Behring, Eicos, and Galapagos, Consultant of: Maureen Mayes has acted as a consultant for Boehringer Ingelheim, Eicos, and Galapagos. She was a member of the SENSCIS trial Steering Committee (Boehringer Ingelheim)

Average rate of lung function decline in adults with cystic fibrosis in the United Kingdom: Data from the UK CF registry

BackgroundRate of change in lung function is used as a measure of disease progression and a predictor of mortality in individuals with cystic fibrosis (CF). The aim of this study was to determine the national rate of decline in percent predicted Forced Expiratory Volume in 1 second (ppFEV1) in adults in the UK accounting for age, sex and pancreatic status. MethodsData on ppFEV1 for adults with CF, excluding those post lung transplantation, was extracted from the UK CF registry between 2015 and 2017. Multilevel modelling was conducted to calculate the annual rate of change in ppFEV1 accounting for age, sex and pancreatic status. ResultsOverall annual ppFEV1 decline was -1.52% (95% CI: -1.66 to -1.38%) and -0.55% (95% CI: -0.86 to -0.23%) in pancreatic insufficient (PI) and sufficient (PS) adults respectively. In PI individuals, females had a greater rate of decline in ppFEV1. There were differences between age groups. The fastest rate of decline was observed in the 18–28 years group, declining -1.76% (95% CI: -2.06 to -1.46) and -1.61% (95% CI: -1.91 to -1.31) per year in PI females and males respectively. The pattern between the sexes and age categories was more inconsistent in the PS group. ConclusionsThe average annual rates of decline in lung function in adults with CF in the UK are similar to reports from other large international cohorts. Pancreatic status has a marked impact on average rate of decline. Younger adults, especially females, have a faster rate of decline and need close monitoring.