P300, Gray Matter Volume and Individual Characteristics Correlates in Healthy Elderly

We investigated whether P300-ERP and cognitive test performance differ for age, sex, and education in two groups of healthy elderly, and verified whether any correlations exist between P300 amplitude and latency and gray matter volume using whole brain voxel-by-voxel-based mapping, controlling for age, education, sex and Total Intracranial Volume (TIV). We used 32 channel electroencephalograms (EEG) to record the P300 responses and 3T Magnetic Resonance Imaging (MRI) to determine gray matter volume. We recruited 36 native-Dutch speaking healthy older subjects, equally divided in two sub-groups of 52–64 and 65–76 years old, administered a battery of cognitive tests and recorded their demographics, EEGs and task performance; additionally, 16 adults from the second sub-group underwent an MRI scan. We found significant differences between age groups in their cognitive tests performance, P300 amplitudes for the frontal and parietal electrodes for the most difficult task, and P300 latencies for frontal, central and parietal electrodes for all three tasks difficulty levels. Interesting, sex and education affected cognitive and P300 results. Higher education was related to higher accuracy, and P300 amplitudes and shorter latencies. Moreover, females exhibited higher P300 amplitudes and shorter latencies, and better cognitive tasks performance compared to males. Additionally, for the 16 adults underwent to MRI scan, we found positive correlations between P300 characteristics in frontal, central and parietal areas and gray matter volume, controlling for demographic variables and TIV, but also showing that age, sex, and education correlate with gray matter volume. These findings provide support that age, sex, and education affect an individual’s cognitive, neurophysiological and structural characteristics, and therefore motivate the need to further investigate these in relation to P300 responses and gray matter volume in healthy elderly

Predicting hospitalisation-associated functional decline in older patients admitted to a cardiac care unit with cardiovascular disease: a prospective cohort study

Up to one in three of older patients who are hospitalised develop functional decline, which is associated with sustained disability, institutionalisation and death. This study developed and validated a clinical prediction model that identifies patients who are at risk for functional decline during hospitalisation. The predictive value of the model was compared against three models that were developed for patients admitted to a general medical ward.; A prospective cohort study was performed on two cardiac care units between September 2016 and June 2017. Patients aged 75 years or older were recruited on admission if they were admitted for non-surgical treatment of an acute cardiovascular disease. Hospitalisation-associated functional decline was defined as any decrease on the Katz Index of Activities of Daily Living between hospital admission and discharge. Predictors were selected based on a review of the literature and a prediction score chart was developed based on a multivariate logistic regression model.; A total of 189 patients were recruited and 33% developed functional decline during hospitalisation. A score chart was developed with five predictors that were measured on hospital admission: mobility impairment = 9 points, cognitive impairment = 7 points, loss of appetite = 6 points, depressive symptoms = 5 points, use of physical restraints or having an indwelling urinary catheter = 5 points. The score chart of the developed model demonstrated good calibration and discriminated adequately (C-index = 0.75, 95% CI (0.68-0.83) and better between patients with and without functional decline (chi; 2; = 12.8, p = 0.005) than the three previously developed models (range of C-index = 0.65-0.68).; Functional decline is a prevalent complication and can be adequately predicted on hospital admission. A score chart can be used in clinical practice to identify patients who could benefit from preventive interventions. Independent external validation is needed

Inflammatory markers are associated with quality of life, physical activity, and gait speed but not sarcopenia in aged men (40-79 years)

Background: Age-related chronic low-grade inflammation (inflammaging) is one of the proposed mechanisms behind sarcopenia. However, findings regarding inflammatory markers in sarcopenic older adults are conflicting. This study aimed to determine the association between inflammatory markers, prevalent as well as incident sarcopenia, sarcopenia-defining parameters, quality of life (QoL), and physical activity in middle-aged and older men. Methods: Men aged 40–79 years (mean 59.66 ± 11.00y) were recruited from population registers in eight European centres for participation in the European Male Aging study (EMAS). Subjects were assessed at baseline (2003–2005) and again after a median follow-up of 4.29 years. In 2577 participants, associations between baseline inflammatory markers [high-sensitive C-reactive protein (hs-CRP), white blood cell count (WBC), albumin] and baseline physical activity (PASE) and QoL (SF-36) were analysed. In the Leuven and Manchester cohort (n = 447), data were available on muscle mass (whole-body dual X-ray absorptiometry) and strength. In this subgroup, cross-sectional associations between baseline inflammatory markers and sarcopenia-defining parameters (handgrip strength, chair stand test, appendicular lean mass, and gait speed) and prevalent sarcopenia were examined. In a further subgroup (n = 277), associations with knee extensor strength were explored. Longitudinally, predictive value of baseline inflammation on functional decline, physical activity, QoL, and incident sarcopenia was examined. Subgroup analyses were performed in subgroups with chronic inflammation and stratified by age. Linear and logistic regressions were used, adjusted for age, body mass index, centre, and smoking. Results: At baseline, hs-CRP and WBC were negatively associated with PASE score (hs-CRP: β = −7.920, P < 0.001; and WBC: β = −4.552, P < 0.001) and the physical component score of SF-36 (hs-CRP: β = −1.025, P < 0.001; and WBC: β = −0.364, P < 0.001). Baseline WBC levels were negatively associated with gait speed (β = −0.013; P = 0.025), quadriceps isometric 90° (β = −5.983; P = 0.035) and isokinetic 60°/s peak torque/body weight (β = −5.532; P = 0.027). The prevalence of sarcopenia at baseline was 18.1% (n = 81). Of those without sarcopenia at baseline, 64 (18.6%) satisfied criteria for sarcopenia at follow-up. There were no significant associations between baseline inflammatory markers and either prevalent or incident sarcopenia, or change in level of sarcopenia-defining parameters between baseline and follow-up. Conclusions: In middle-aged and older men, hs-CRP and WBC were negatively associated with QoL and PASE scores, while WBC was negatively associated with gait speed and knee strength. Associations with hs-CRP remained significant in all ages, whereas WBC levels were only associated with PASE, gait speed and knee strength in older adults (60–79 years). Baseline inflammatory markers (hs-CRP, WBC and albumin) did not predict functional decline, decline in physical activity, decreased QoL or incident sarcopenia

The role of collaborative, multistakeholder partnerships in reshaping the health management of patients with noncommunicable diseases during and after the COVID-19 pandemic

Background: Policies to combat the COVID-19 pandemic have disrupted the screening, diagnosis, treatment, and monitoring of noncommunicable (NCD) patients while affecting NCD prevention and risk factor control. Aims: To discuss how the first wave of the COVID-19 pandemic affected the health management of NCD patients, identify which aspects should be carried forward into future NCD management, and propose collaborative efforts among public–private institutions to effectively shape NCD care models. Methods: The NCD Partnership, a collaboration between Upjohn and the European Innovation Partnership on Active and Healthy Ageing, held a virtual Advisory Board in July 2020 with multiple stakeholders; healthcare professionals (HCPs), policymakers, researchers, patient and informal carer advocacy groups, patient empowerment organizations, and industry experts. Results: The Advisory Board identified barriers to NCD care during the COVID-19 pandemic in four areas: lack of NCD management guidelines; disruption to integrated care and shift from hospital-based NCD care to more community and primary level care; infodemics and a lack of reliable health information for patients and HCPs on how to manage NCDs; lack of availability, training, standardization, and regulation of digital health tools. Conclusions: Multistakeholder partnerships can promote swift changes to NCD prevention and patient care. Intra- and inter-communication between all stakeholders should be facilitated involving all players in the development of clinical guidelines and digital health tools, health and social care restructuring, and patient support in the short-, medium- and long-term future. A comprehensive response to NCDs should be delivered to improve patient outcomes by providing strategic, scientific, and economic support

Symptomatic androgen deficiency develops only when both total and free testosterone decline in obese men who may have incident biochemical secondary hypogonadism: prospective results from the EMAS

Objective: Limited evidence supports the use of free testosterone (FT) for diagnosing hypogonadism when sex hormone binding globulin (SHBG) is altered. Low total testosterone (TT) is commonly encountered in obesity where SHBG is typically decreased. We aimed to assess the contribution of FT in improving the diagnosis of symptomatic secondary hypogonadism (SH), identified initially by low total testosterone (TT), and then further differentiated by normal FT (LNSH) or low FT (LLSH). Design: Prospective observational study with a median follow‐up of 4.3 years. Patients: 3369 community‐dwelling men aged 40‐79 years from eight European centres. Measurements: Subjects were categorised according to baseline and follow‐up biochemical status into persistent eugonadal (referent group; n=1880), incident LNSH (eugonadism to LNSH; n=101) and incident LLSH (eugonadism to LLSH; n=38). Predictors and clinical features associated with the transition from eugonadism to LNSH or LLSH were assessed. Results: The cumulative incidence of LNSH and LLSH over 4.3 years was 4.9% and 1.9% respectively. Baseline obesity predicted both LNSH and LLSH but the former occurred more frequently in younger men. LLSH, but not LNSH, was associated with new/worsened sexual symptoms, including low desire [OR= 2.67 (1.27‐5.60)], erectile dysfunction [OR= 4.53 (2.05‐10.01)] and infrequent morning erections [OR= 3.40 (1.48‐7.84)]. Conclusions: These longitudinal data demonstrate the importance of FT in the diagnosis of hypogonadism in obese men with low TT and SHBG. The concurrent fall in TT and FT identifies the minority (27.3%) of men with hypogonadal symptoms, which were not present in the majority developing low TT with normal FT

Pengaruh Brand Trust dan Brand Equity terhadap Loyalitas Konsumen pada Produk Kosmetik Wardah (Survey Konsumen pada PT. Paragon Technology And Innovation Cabang Pekanbaru)

The purpose of this study was to determine the influence of brand trust ( X1 ) and brand equity ( X2 ) customer loyalty ( Y ) in cosmetic products Wardah ( consumer survey on PT . Paragon technology and innovation branches pekanbaru ) . The method in this research is quantitatively using SPSS 21 program , where samples were used that consumers using cosmetic products Wardah by respondents as many as 100 people sampling technique is accidental sampling using the formula slovin . The results showed that the test results simultaneously obtained from the F count was 34.888 while the value of F table 3.090 . This means that F count> F table and significant value 0,000 < alpha of 0.05 . This means that brand trust and brand equity simultaneously significant effect on consumer loyalty to cosmetic products Wardah

Insulin-like peptide 3 (INSL3) as an indicator of leydig cell insufficiency (LCI) in Middle-aged and older men with hypogonadism: reference range and threshold

Insulin-like peptide 3 (INSL3) is a circulating biomarker for Leydig cell functional capacity in men, also indicating Leydig Cell Insufficiency (LCI) and potential primary hypogonadism. Using results from large cohort studies we explore sources of biological and technical variance, and establish a reference range for adult men. It is constitutively secreted with little within-individual variation and reflects testicular capacity to produce testosterone. The main INSL3 assays available indicate good concordance with low technical variance; there is no effect of ethnicity. INSL3 declines with age from 35 years at about 15% per decade. Like low calculated free testosterone, and to a lesser extent low total testosterone, reduced INSL3 is significantly associated with increasing age-related morbidity, including lower overall sexual function, reflecting LCI. Consequently, low INSL3 (≤0.4 ng/ml; ca. 35 years) reference range (serum) for INSL3 in the eugonadal population of 0.4 − 2.3 ng/ml, with low INSL3 prospectively identifying individuals at risk of increased future morbidity

Inflammatory markers are associated with quality of life, physical activity, and gait speed but not sarcopenia in aged men (40-79 years)

Background Age-related chronic low-grade inflammation (inflammaging) is one of the proposed mechanisms behind sarcopenia. However, findings regarding inflammatory markers in sarcopenic older adults are conflicting. This study aimed to determine the association between inflammatory markers, prevalent as well as incident sarcopenia, sarcopenia-defining parameters, quality of life (QoL), and physical activity in middle-aged and older men. Methods Men aged 40-79 years (mean 59.66 +/- 11.00y) were recruited from population registers in eight European centres for participation in the European Male Aging study (EMAS). Subjects were assessed at baseline (2003-2005) and again after a median follow-up of 4.29 years. In 2577 participants, associations between baseline inflammatory markers [high-sensitive C-reactive protein (hs-CRP), white blood cell count (WBC), albumin] and baseline physical activity (PASE) and QoL (SF-36) were analysed. In the Leuven and Manchester cohort (n = 447), data were available on muscle mass (whole-body dual X-ray absorptiometry) and strength. In this subgroup, cross-sectional associations between baseline inflammatory markers and sarcopenia-defining parameters (handgrip strength, chair stand test, appendicular lean mass, and gait speed) and prevalent sarcopenia were examined. In a further subgroup (n = 277), associations with knee extensor strength were explored. Longitudinally, predictive value of baseline inflammation on functional decline, physical activity, QoL, and incident sarcopenia was examined. Subgroup analyses were performed in subgroups with chronic inflammation and stratified by age. Linear and logistic regressions were used, adjusted for age, body mass index, centre, and smoking. Results At baseline, hs-CRP and WBC were negatively associated with PASE score (hs-CRP: beta = -7.920, P Conclusions In middle-aged and older men, hs-CRP and WBC were negatively associated with QoL and PASE scores, while WBC was negatively associated with gait speed and knee strength. Associations with hs-CRP remained significant in all ages, whereas WBC levels were only associated with PASE, gait speed and knee strength in older adults (60-79 years). Baseline inflammatory markers (hs-CRP, WBC and albumin) did not predict functional decline, decline in physical activity, decreased QoL or incident sarcopenia.</p

Association of age, hormonal, and lifestyle factors with the Leydig cell biomarker INSL3 in aging men from the European Male Aging Study cohort

Background: Aging in men is accompanied by a broad range of symptoms, including sexual dysfunction, cognitive and musculoskeletal decline, obesity, type 2 diabetes, cardiovascular disease and hypertension, organ degeneration/failure, and increasing neoplasia, some of which are associated with declining levels of Leydig cell-produced testosterone. High natural biological variance, together with multiple factors that can modulate circulating testosterone concentration, may influence its interpretation and clinical implications. Insulin-like peptide 3 is a biomarker of Leydig cell function that might provide complementary information on testicular health and its downstream outcomes. Objectives: To characterize insulin-like peptide 3 as a biomarker to assess gonadal status in aging men. Methods and materials: A large European multicenter (European Male Aging Study) cohort of community-dwelling men was analyzed to determine how insulin-like peptide 3 relates to a range of hormonal, anthropometric, and lifestyle parameters. Results and discussion: Insulin-like peptide 3 declines cross-sectionally and longitudinally within individuals at approximately 15% per decade from age 40 years, unlike testosterone (1.9% per decade), which is partly compensated by increasing pituitary luteinizing hormone production. Importantly, lower insulin-like peptide 3 in younger men appears to persist with aging. Multiple regression analysis shows that, unlike testosterone, insulin-like peptide 3 is negatively dependent on luteinizing hormone and sex hormone-binding globulin and positively dependent on follicle-stimulating hormone, suggesting a different mechanism of gonadotropic regulation. Circulating insulin-like peptide 3 is negatively associated with increased body mass index or waist circumference and with smoking, and unlike testosterone, it is not affected by weight loss in obese individuals. Geographic variation in mean insulin-like peptide 3 within Europe appears to be largely explained by differences in these parameters. The results allowed the establishment of a European-wide reference range for insulin-like peptide 3 (95% confidence interval) adjusted for increasing age. Conclusion: Insulin-like peptide 3 is a constitutive biomarker of Leydig cell functional capacity and is a robust, reliably measurable peptide not subject to gonadotropin-dependent short-term regulation and within-individual variation in testosterone

The Leydig cell biomarker INSL3 as a predictor of age-related morbidity: Findings from the EMAS cohort

Background: Insulin-like peptide 3 (INSL3) is a constitutive hormone secreted in men by the mature Leydig cells of the testes. It is an accurate biomarker for Leydig cell functional capacity, reflecting their total cell number and differentiation status. Objectives: To determine the ability of INSL3 to predict hypogonadism and age-related morbidity using the EMAS cohort of older community-dwelling men. Materials & methods: Circulating INSL3 was assessed in the EMAS cohort and its cross-sectional and longitudinal relationships to hypogonadism, here defined by testosterone (T) <10.5nmol/l, and a range of age-related morbidities determined by correlation and regression analysis. Results & discussion: While INSL3 is an accurate measure of primary hypogonadism, secondary and compensated hypogonadism also indicate reduced levels of INSL3, implying that testicular hypogonadism does not improve even when LH levels are increased, and that ageing-related hypogonadism may combine both primary and secondary features. Unadjusted, serum INSL3, like calculated free testosterone (cFT), LH, or the T/LH ratio reflects hypogonadal status and is associated with reduced sexual function, bone mineral density, and physical activity, as well as increased occurrence of hypertension, cardiovascular disease, cancer, and diabetes. Using multiple regression analysis to adjust for a range of hormonal, anthropometric, and lifestyle factors, this relationship is lost for all morbidities, except for reduced bone mineral density, implying that INSL3 and/or its specific receptor, RXFP2, may be causally involved in promoting healthy bone metabolism. Elevated INSL3 also associates with hypertension and cardiovascular disease. When unadjusted, INSL3 in phase 1 of the EMAS study was assessed for its association with morbidity in phase 2 (mean 4.3 years later); INSL3 significantly predicts 7 out of 9 morbidity categories, behaving as well as cFT in this regard. In contrast, total T was predictive in only 3 of the 9 categories. Conclusion: Together with its low within-individual variance, these findings suggest that assessing INSL3 in men could offer important insight into the later development of disease in the elderly