Purpose: This study aimed to quantify the extent to which age was associated with joint position sense (JPS) of the asymptomatic shoulder as measured by joint position reproduction (JPR) tasks and... Show morePurpose: This study aimed to quantify the extent to which age was associated with joint position sense (JPS) of the asymptomatic shoulder as measured by joint position reproduction (JPR) tasks and assess the reproducibility of these tasks. Methods: 120 Asymptomatic participants aged 18-70 years each performed 10 JPR-tasks. Both contralateral and ipsilateral JPR-tasks were evaluated on accuracy of JPR under active-and passive conditions at two levels within the shoulder forward flexion trajectory. Each task was performed three times. In a subgroup of 40 participants, the reproducibility of JPR-tasks was assessed one week after initial measurement. Reproducibility of JPR-tasks was evaluated by both reliability (intra-class correlation coefficients (ICC's)) and agreement (standard error of measurement (SEM)) measures. Results: Age was not associated with increased JPR-errors for any of the contralateral or ipsilateral JPR-tasks. ICC's ranged between 0.63 and 0.80 for contralateral JPR-tasks, and from 0.32 to 0.48 for ipsilateral tasks, except for one ipsilateral task where the reliability was similar to contralateral tasks (0.79). The SEM was comparable and small for all JPR-tasks, ranging between 1.1 and 2.1. Conclusion: No age-related decline in JPS of the asymptomatic shoulder was found, and good agreement between test and re-test measurements for all JPR-tasks as indicated by the small SEM. Show less
Geurkink, T.H.; Overbeek, C.L.; Marang-van de Mheen, P.J.; Nagels, J.; Nelissen, R.G.H.H.; Groot, J.H. de 2023
PurposeThis study aimed to quantify the extent to which age was associated with joint position sense (JPS) of the asymptomatic shoulder as measured by joint position reproduction (JPR) tasks and... Show morePurposeThis study aimed to quantify the extent to which age was associated with joint position sense (JPS) of the asymptomatic shoulder as measured by joint position reproduction (JPR) tasks and assess the reproducibility of these tasks.Methods120 Asymptomatic participants aged 18–70 years each performed 10 JPR-tasks. Both contralateral and ipsilateral JPR-tasks were evaluated on accuracy of JPR under active- and passive conditions at two levels within the shoulder forward flexion trajectory. Each task was performed three times. In a subgroup of 40 participants, the reproducibility of JPR-tasks was assessed one week after initial measurement. Reproducibility of JPR-tasks was evaluated by both reliability (intra-class correlation coefficients (ICC’s)) and agreement (standard error of measurement (SEM)) measures.ResultsAge was not associated with increased JPR-errors for any of the contralateral or ipsilateral JPR-tasks. ICC’s ranged between 0.63 and 0.80 for contralateral JPR-tasks, and from 0.32 to 0.48 for ipsilateral tasks, except for one ipsilateral task where the reliability was similar to contralateral tasks (0.79). The SEM was comparable and small for all JPR-tasks, ranging between 1.1 and 2.1.ConclusionNo age-related decline in JPS of the asymptomatic shoulder was found, and good agreement between test and re-test measurements for all JPR-tasks as indicated by the small SEM. Show less
Geurkink, T.H.; Overbeek, C.L.; Marang-van de Mheen, P.J.; Nagels, J.; Nelissen, R.G.H.H.; Groot, J.H. de 2023
Purpose: This study aimed to quantify the extent to which age was associated with joint position sense (JPS) of the asymptomatic shoulder as measured by joint position reproduction (JPR) tasks and... Show morePurpose: This study aimed to quantify the extent to which age was associated with joint position sense (JPS) of the asymptomatic shoulder as measured by joint position reproduction (JPR) tasks and assess the reproducibility of these tasks.Methods: 120 Asymptomatic participants aged 18-70 years each performed 10 JPR-tasks. Both contralateral and ipsilateral JPR-tasks were evaluated on accuracy of JPR under active-and passive conditions at two levels within the shoulder forward flexion trajectory. Each task was performed three times. In a subgroup of 40 participants, the reproducibility of JPR-tasks was assessed one week after initial measurement. Reproducibility of JPR-tasks was evaluated by both reliability (intra-class correlation coefficients (ICC's)) and agreement (standard error of measurement (SEM)) measures. Results: Age was not associated with increased JPR-errors for any of the contralateral or ipsilateral JPR-tasks. ICC's ranged between 0.63 and 0.80 for contralateral JPR-tasks, and from 0.32 to 0.48 for ipsilateral tasks, except for one ipsilateral task where the reliability was similar to contralateral tasks (0.79). The SEM was comparable and small for all JPR-tasks, ranging between 1.1 and 2.1.onclusion: No age-related decline in JPS of the asymptomatic shoulder was found, and good agreement between test and re-test measurements for all JPR-tasks as indicated by the small SEM. Show less
Currently immunomodulatory compounds are under investigation for use in patients with cardiovascular disease, caused by atherosclerosis. These trials, using recurrent cardiovascular events as... Show moreCurrently immunomodulatory compounds are under investigation for use in patients with cardiovascular disease, caused by atherosclerosis. These trials, using recurrent cardiovascular events as endpoint, require enrollment of large patient groups. We investigated the effect of key risk factors for atherosclerosis development, ageing and smoking, on the immune system, with the objective to identify biomarkers differentiating between human populations, and potentially serving as endpoints for future phase 1B trials with immunomodulatory compounds. Blood was collected from young healthy volunteers (aged 18-25 years, n=30), young smokers (18-25 years, n=20), elderly healthy volunteers (>60 years, n=20), heavy smokers (>45 years, 15 packyears, n=11) and patients with stable coronary artery disease (CAD) (>60 years, n=27). Circulating immune cell subsets were characterized by flow cytometry, and collected plasma was evaluated by proteomics (Olink). Clear ageing effects were observed, mostly illustrated by a lower level in CD8+ and naïve CD4+ and CD8+ T cells, with an increase in CD4+ and CD8+ effector memory T cells in elderly healthy volunteers compared to young healthy volunteers. Heavy smokers showed a more inflammatory cellular phenotype, especially a shift in Th1/Th2 ratio: higher Th1 and lower Th2 percentages compared to young healthy volunteers. A significant decrease in circulating atheroprotective oxLDL-specific IgM was found in patients with CAD compared to young healthy volunteers. Elevated pro-inflammatory and chemotactic proteins TREM1 and CCL11 were observed in elderly volunteers compared to young volunteers. In addition, heavy smokers had an increase in pro-inflammatory cytokine IL-6 and lysosomal protein LAMP3. These data show that ageing and smoking are associated with an inflammatory immunophenotype, and that heavy smokers or aged individuals may serve as potential populations for future clinical trials investigating immunomodulatory drugs targeted for cardiovascular disease. Show less
Background Health-related quality of life (HRQoL) is an important outcome measure when considering medical treatment; however, the impact of polypharmacy on trajectories of HRQoL over time is... Show moreBackground Health-related quality of life (HRQoL) is an important outcome measure when considering medical treatment; however, the impact of polypharmacy on trajectories of HRQoL over time is unknown. This study aimed to investigate the association between polypharmacy status and trajectories of HRQoL in older adults. Methods A longitudinal cohort study of 2181 community-dwelling adults, 65 years and older, who participated in the 2013 to 2017 waves of the Household Income and Labour Dynamics in Australia (HILDA) Survey. Polypharmacy was defined as the regular use of >= 5 prescription medications. Polypharmacy status was categorised into no polypharmacy, in 2013 only (baseline only polypharmacy), in 2017 only (incident polypharmacy) or at both time points (persistent polypharmacy). HRQoL was assessed through the SF-36 questionnaire generating two summary scores: physical component summary (PCS) and mental component summary (MCS). Linear mixed-effects models stratified according to polypharmacy status and change in comorbidities were used to assess trajectories of HRQoL. Results Older adults with persistent polypharmacy had lowest scores for HRQoL measures from 2013 to 2017. After adjusting for all covariates, those with incident polypharmacy had the steepest annual decline in both the PCS and MCS: - 0.86 in PCS and - 0.76 in MCS for those with decreasing or stable comorbidities, and - 1.20 in PCS and - 0.75 in MCS for those with increasing comorbidities. Conclusions Polypharmacy was associated with poorer HRQoL, even after adjusting for confounders. Incident polypharmacy was found to be associated with a clinically important decline in HRQoL and this should be considered when prescribing additional medication to older adults. Show less
Introduction: Although increased cholesterol level has been acknowledged as a risk factor for dementia, evidence synthesis based on published data has yielded mixed results. This is especially... Show moreIntroduction: Although increased cholesterol level has been acknowledged as a risk factor for dementia, evidence synthesis based on published data has yielded mixed results. This is especially relevant in older adults where individual studies report non-linear relationships between cholesterol and cognition and, in some cases, find higher cholesterol associated with a lower risk of subsequent cognitive decline or dementia. Prior evidence synthesis based on published results has not allowed us to focus on older adults or to standardize analyses across studies. Given our ageing population, an increased risk of dementia in older adults, and the need for proportionate treatment in this age group, an individual participant data (IPD) meta-analysis is timely. Method: We combined data from 8 studies and over 21,000 participants aged 60 years and over in a 2-stage IPD to examine the relationship between total, high-density, and low-density lipoprotein (HDL and LDL) cholesterol and subsequent incident dementia or cognitive decline, with the latter categorized using a reliable change index method. Results: Meta-analyses found no relationship between total, HDL, or LDL cholesterol (per millimoles per litre increase) and risk of cognitive decline in this older adult group averaging 76 years of age. For total cholesterol and cognitive decline: odds ratio (OR) 0.93 (95% confidence interval [CI] 0.86: 1.01) and for incident dementia: OR 1.01 [95% CI 0.89: 1.13]. This was not altered by rerunning the analyses separately for statin users and non-users or by the presence of an APOE e4 allele. Conclusion: There were no clear consistent relationships between cholesterol and cognitive decline or dementia in this older adult group, nor was there evidence of effect modification by statin use. Further work is needed in younger populations to understand the role of cholesterol across the life-course and to identify any relevant intervention points. This is especially important if modification of cholesterol is to be further evaluated for its potential influence on risk of cognitive decline or dementia. Show less
Bacalini, M.G.; Reale, A.; Malavolta, M.; Ciccarone, F.; Moreno-Villanueva, M.; Dolle, M.E.T.; ... ; Zampieri, M. 2021
Ageing leaves characteristic traces in the DNA methylation make-up of the genome. However, the importance of DNA methylation in ageing remains unclear. The study of subtelomeric regions could give... Show moreAgeing leaves characteristic traces in the DNA methylation make-up of the genome. However, the importance of DNA methylation in ageing remains unclear. The study of subtelomeric regions could give promising insights into this issue. Previously reported associations between susceptibility to age-related diseases and epigenetic instability at subtelomeres suggest that the DNA methylation profile of subtelomeres undergoes remodelling during ageing. In the present work, this hypothesis has been tested in the context of the European large-scale project MARK-AGE. In this cross-sectional study, we profiled the DNA methylation of chromosomes 5 and 21 subtelomeres, in more than 2000 age-stratified women and men recruited in eight European countries. The study included individuals from the general population as well as the offspring of nonagenarians and Down syndrome subjects, who served as putative models of delayed and accelerated ageing, respectively. Significant linear changes of subtelomeric DNA methylation with increasing age were detected in the general population, indicating that subtelomeric DNA methylation changes are typical signs of ageing. Data also show that, compared to the general population, the dynamics of age-related DNA methylation changes are attenuated in the offspring of centenarian, while they accelerate in Down syndrome individuals. This result suggests that subtelomeric DNA methylation changes reflect the rate of ageing progression. We next attempted to trace the age-related changes of subtelomeric methylation back to the influence of diverse variables associated with methylation variations in the population, including demographics, dietary/health habits and clinical parameters. Results indicate that the effects of age on subtelomeric DNA methylation are mostly independent of all other variables evaluated. Show less
Purpose The tumour microenvironment in older patients is subject to changes. The tumour-stroma ratio (TSR) was evaluated in order to estimate the amount of intra-tumoural stroma and to evaluate the... Show morePurpose The tumour microenvironment in older patients is subject to changes. The tumour-stroma ratio (TSR) was evaluated in order to estimate the amount of intra-tumoural stroma and to evaluate the prognostic value of the TSR in older patients with breast cancer (>= 70 years). Methods Two retrospective cohorts, the FOCUS study (N = 619) and the Nottingham Breast Cancer series (N = 1793), were used for assessment of the TSR on haematoxylin and eosin stained tissue slides. Results The intra-tumoural stroma increases with age in the FOCUS study and the Nottingham Breast Cancer series (B 0.031, 95% CI 0.006-0.057, p = 0.016 and B 0.034, 95% CI 0.015-0.054, p < 0.001, respectively). Fifty-one per cent of the patients from the Nottingham Breast Cancer series < 40 years had a stroma-high tumour compared to 73% of the patients of >= 90 years from the FOCUS study. The TSR did not validate as an independent prognostic parameter in patients >= 70 years. Conclusions The intra-tumoural stroma increases with age. This might be the result of an activated tumour microenvironment. The TSR did not validate as an independent prognostic parameter in patients >= 70 years in contrast to young women with breast cancer as published previously. Show less
Introduction: The ageing process can be influenced by different dietary patterns and dietary factors.Aim: To analyse the association of dietary factors, which include the Mediterranean diet... Show moreIntroduction: The ageing process can be influenced by different dietary patterns and dietary factors.Aim: To analyse the association of dietary factors, which include the Mediterranean diet adherence, the compliance with the "Sociedad Espanola de Nutricion Comunitaria" food portion recommendations, and the intake of different food groups, with the secreted form of the alpha-Klotho gene (S-Klotho as an anti-ageing marker) in middle-aged sedentary adults.Methods: A total of 74 (39 women) middle-aged sedentary adults participated in the study. Dietary factors were assessed with a food frequency questionnaire and the PREDIMED questionnaire. The S-Klotho plasma levels were measured using a soluble alpha-Klotho ELISA assay kit.Results: We observed: (i) a negative association between the adherence to the Mediterranean diet and the S-Klotho plasma levels (beta = - 53.219; R-2 = 0.078; P = 0.020), (ii) a higher intake of wine (> 7 glasses/week), was associated with lower S-Klotho plasma levels (P = 0.039), and (iii) a positive association between nuts portion intake and the S-Klotho plasma levels (beta = 26.087; R-2 = 0.070; P = 0.029). All the associations disappeared after controlling for lean mass index (LMI) (all P > 0.05).Conclusion: Our study suggests that, although dietary factors could be related to S-Klotho plasma levels in middle-aged sedentary adults, LMI is the main determinant in this regard. Show less
Kolk, A.; Zwaal, P. van der; Thomassen, B.J.W.; Kamp, E.W.C. van de; Stijnen, T.; Groot, J.H. de; Nelissen, R.G.H.H. 2018
Background: muscle strength measured as handgrip strength declines with increasing age and predicts mortality. While handgrip strength is determined by lifestyle through nutrition and physical... Show moreBackground: muscle strength measured as handgrip strength declines with increasing age and predicts mortality. While handgrip strength is determined by lifestyle through nutrition and physical activity, it has almost exclusively been studied in western populations with a sedentary lifestyle. This study aims to investigate the relation between handgrip strength, ageing and mortality in a population characterised by a predominance of malnutrition and manual labour. Design: a population-based longitudinal study. Setting: a traditional African rural population in Ghana. Subjects: nine hundred and twenty-three community-dwelling individuals aged 50 and older. Methods: demographic characteristics were registered. At baseline, height, body mass index (BMI) and handgrip strength were measured and compared with those in a western reference population. Survival of the participants was documented during a period of up to 2 years. Results: handgrip strength was dependent on age, sex, height and BMI. Compared with the western reference population, handgrip strength was lower due to a lower height and BMI but declined over age similarly. Risk of mortality was lower in participants having higher handgrip strength, with a hazard ratio of 0.94 per kg increase (P = 0.002). After adjustment for age, sex, tribe, socio-economic status, drinking water source, height and BMI, only handgrip strength remained predictive of mortality. Conclusion: in a traditional rural African population characterised by malnutrition and manual labour, handgrip strength declines over age and independently predicts mortality similar to western populations. Handgrip strength can be used as a universal marker of ageing. Show less
Engelaer, F.M.; Bodegom, D. van; Westendorp, R.G.J. 2013
