Cholesterol-lowering medications aim to prevent cardiovascular events, caused by arteriosclerosis. Older adults (75 years and older) have a high cardiovascular risk based on age alone, and it is... Show moreCholesterol-lowering medications aim to prevent cardiovascular events, caused by arteriosclerosis. Older adults (75 years and older) have a high cardiovascular risk based on age alone, and it is estimated that 1 in 3 older adults use cholesterol-lowering medication. The vast majority (96% in the Netherlands) use a statin.The appropriateness of cholesterol-lowering medication for older adults is under debate. While there is strong evidence for the benefits of statins in relatively healthy older adults with a history of cardiovascular disease, for other groups the evidence is less convincing. Also, statins are associated with hindering side effects. In this thesis, various aspects of the appropriateness of cholesterol-lowering medication for older adults were studied, using different research designs. Five recurrent themes were of the utmost importance in the assessment of the appropriateness of cholesterol-lowering medication in older adults; 1) the individual context of a patient, 2) life expectancy, 3) hindering side effects, 4) cardiovascular history, and 5) the complexity of health problems. Based in these five themes, five key questions were distilled that can be used in a systematic evaluation of the appropriateness of cholesterol- lowering treatment for an individual patient. Show less
PurposePre-stroke frailty in older adults is associated with adverse outcomes after stroke in community-based and hospital-based populations. The aim of our study was to investigate the prevalence... Show morePurposePre-stroke frailty in older adults is associated with adverse outcomes after stroke in community-based and hospital-based populations. The aim of our study was to investigate the prevalence of pre-stroke frailty among older stroke survivors receiving medical specialistic rehabilitation and its association with outcomes and recovery.MethodsPre-stroke frailty was measured by the Groningen Frailty Indicator (GFI, score ≥ 4 indicates frailty) in patients ≥ 65 years receiving stroke medical specialistic rehabilitation. Baseline, follow-up and change (i.e. recovery) scores of the Barthel index (BI), Stroke Impact Scale (SIS) ‘mobility’, ‘communication’, and ‘memory and thinking’, Hospital Anxiety and Depression Scale (HADS) and the EuroQoL-5 dimensions (EQ-5D) were compared between frail and non-frail patients with a multivariable regression model adjusting for confounders.ResultsOf 322 included patients (34.2% females, median age 70 years), 43 (13.4%) patients reported pre-stroke frailty. There were no differences in BI or in destination of discharge between pre-stroke frail and non-frail stroke survivors receiving inpatient rehabilitation. However, pre-stroke frailty was associated with worse follow-up scores for all other measures. Recovery in pre-stroke frail patients was less favorable compared to non-frail patients for SIS mobility, HADS subscales and EQ-5D index and visual analogue scale.ConclusionPre-stroke frailty was present in a minority of older stroke survivors receiving medical specialistic rehabilitation. BI and destination of discharge did not differ. Nevertheless, pre-stroke frailty was associated with worse functioning at follow-up for most measures of health status and with smaller improvements in mobility, mood and quality of life. Show less
Kuiper, L.M.; Polinder-Bos, H.A.; Bizzarri, D.; Vojinovic, D.; Vallerga, C.L.; Beekman, M.; ... ; Meurs, J.B.J. van 2023
Biological age captures a person’s age-related risk of unfavorable outcomes using biophysiological information. Multivariate biological age measures include frailty scores and molecular biomarkers... Show moreBiological age captures a person’s age-related risk of unfavorable outcomes using biophysiological information. Multivariate biological age measures include frailty scores and molecular biomarkers. These measures are often studied in isolation, but here we present a large-scale study comparing them. In 2 prospective cohorts (n = 3 222), we compared epigenetic (DNAm Horvath, DNAm Hannum, DNAm Lin, DNAm epiTOC, DNAm PhenoAge, DNAm DunedinPoAm, DNAm GrimAge, and DNAm Zhang) and metabolomic-based (MetaboAge and MetaboHealth) biomarkers in reflection of biological age, as represented by 5 frailty measures and overall mortality. Biomarkers trained on outcomes with biophysiological and/or mortality information outperformed age-trained biomarkers in frailty reflection and mortality prediction. DNAm GrimAge and MetaboHealth, trained on mortality, showed the strongest association with these outcomes. The associations of DNAm GrimAge and MetaboHealth with frailty and mortality were independent of each other and of the frailty score mimicking clinical geriatric assessment. Epigenetic, metabolomic, and clinical biological age markers seem to capture different aspects of aging. These findings suggest that mortality-trained molecular markers may provide novel phenotype reflecting biological age and strengthen current clinical geriatric health and well-being assessment. Show less
Ploeg, M.A. van der; Poortvliet, R.K.E.; Bogaerts, J.M.K.; Klei, V.M.G.T.H. van der; Kerse, N.; Rolleston, A.; ... ; TULIPS Consortium 2023
BackgroundIn the general population, an increase in low-density lipoprotein cholesterol (LDL-C) predicts higher cardiovascular disease risk, and lowering LDL-C can prevent cardiovascular disease... Show moreBackgroundIn the general population, an increase in low-density lipoprotein cholesterol (LDL-C) predicts higher cardiovascular disease risk, and lowering LDL-C can prevent cardiovascular disease and reduces mortality risk. Interestingly, in cohort studies that include very old populations, no or inverse associations between LDL-C and mortality have been observed. This study aims to investigate whether the association between LDL-C and mortality in the very old is modified by a composite fitness score.MethodsA 2-stage meta-analysis of individual participant data from the 5 observational cohort studies. The composite fitness score was operationalized by performance on a combination of 4 markers: functional ability, cognitive function, grip strength, and morbidity. We pooled hazard ratios (HR) from Cox proportional-hazards models for 5-year mortality risk for a 1 mmol/L increase in LDL-C. Models were stratified by high/low composite fitness score.ResultsComposite fitness scores were calculated for 2 317 participants (median 85 years, 60% females participants), of which 994 (42.9%) had a high composite fitness score, and 694 (30.0%) had a low-composite fitness score. There was an inverse association between LDL-C and 5-year mortality risk (HR 0.87 [95% CI: 0.80–0.94]; p < .01), most pronounced in participants with a low-composite fitness score (HR 0.85 [95% CI: 0.75–0.96]; p = .01), compared to those with a high composite fitness score (HR = 0.98 [95% CI: 0.83–1.15]; p = .78), the test for subgroups differences was not significant.ConclusionsIn this very old population, there was an inverse association between LDL-C and all-cause mortality, which was most pronounced in participants with a low-composite fitness scores. Show less
Background: There is a lack of information on mental health outcomes for the increasing older population. Therefore, the aim of the current study is to assess depressive symptoms, loneliness, and... Show moreBackground: There is a lack of information on mental health outcomes for the increasing older population. Therefore, the aim of the current study is to assess depressive symptoms, loneliness, and apathy in older patients with breast cancer within the first 5 years after diagnosis.Methods: Women aged >= 70 years with early-stage breast cancer were included. Multivariate linear mixed models were used to assess longitudinal changes in symptoms of depression (according to the 15-item Geriatric Depression Scale), loneliness (according to the De Jong Gierveld Loneliness Scale) and apathy (according to the Starkstein Apathy Scale) over time at 3, 9, 15, 27 and 60 months follow-up.Results: In total, 299 patients were included (mean [standard deviation (SD)] age: 75.8 [5.2] years). At 3 months follow-up, shortly after the acute treatment, 10% of patients had sig-nificant depressive symptoms, while loneliness and apathy were present in 31% and 41% of all patients, respectively. Depression, loneliness and apathy scores showed no clinically relevant changes over time in the whole cohort. Patients who received adjuvant systemic therapies (i.e. endocrine therapy and/or chemotherapy and/or targeted therapy (trastuzumab)) had si-milar mental health outcomes as those who did not. However, frail patients had more symptoms (p < 0.001) and were more prone to develop depressive symptoms over time than non-frail patients (p = 0.002).Discussion: Depression, loneliness and apathy were frequently observed in older women with breast cancer and did not change over time. Patients who received adjuvant systemic therapies had similar mental health outcomes as those who did not. However, frail patients were at higher risk to experience these symptoms.(c) 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
This thesis addresses current treatment strategies in older cancer patients, as well as the consequences of these decisions for clinical outcomes. In addition, this thesis investigated the value of... Show moreThis thesis addresses current treatment strategies in older cancer patients, as well as the consequences of these decisions for clinical outcomes. In addition, this thesis investigated the value of frailty assessment in different cancer populations and described the implementation of a multidisciplinary team approach in frail older cancer patients. Show less
The emphasis of this thesis lies on complex survival data and on the modelling of this kind of data. Statistical models are developed or adapted and applied to five different real data sets, which... Show moreThe emphasis of this thesis lies on complex survival data and on the modelling of this kind of data. Statistical models are developed or adapted and applied to five different real data sets, which all contain repeated censored measurements. To take into account the correlation between these repeated data, a frailty is considered in all statistical analysis used. Extensions of and alternatives for frailty models are considered. The centre-effect on survival after bone marrow transplantation is studied in chapter 2. Models that are able to take into account a time-dependent frailty are proposed and compared. In chapter 3 survival analysis approaches are used for modelling an ecological capture-recapture data set. In chapter 4, the emphasis lies on the frailty model used in a genetic context. Our model is applied on age at onset of Huntington disease. Chapter 5 concerns the estimation of the correlation between processes with frailties. The approach is applied on the Dutch part of the data set from the Caprie trial, involving cardiac, cerebral and peripheral atherosclerosis. In chapter 6, the point of interest is the marginal survivor curve in different simulated balanced and unbalanced longitudinal situations. Finally, in chapter 7 a general summary can be found. Show less
