Background General practitioners (GPs) should regularly review patients' medications and, if necessary, deprescribe, as inappropriate polypharmacy may harm patients' health. However, deprescribing... Show moreBackground General practitioners (GPs) should regularly review patients' medications and, if necessary, deprescribe, as inappropriate polypharmacy may harm patients' health. However, deprescribing can be challenging for physicians. This study investigates GPs' deprescribing decisions in 31 countries. Methods In this case vignette study, GPs were invited to participate in an online survey containing three clinical cases of oldest-old multimorbid patients with potentially inappropriate polypharmacy. Patients differed in terms of dependency in activities of daily living (ADL) and were presented with and without history of cardiovascular disease (CVD). For each case, we asked GPs if they would deprescribe in their usual practice. We calculated proportions of GPs who reported they would deprescribe and performed a multilevel logistic regression to examine the association between history of CVD and level of dependency on GPs' deprescribing decisions. Results Of 3,175 invited GPs, 54% responded (N = 1,706). The mean age was 50 years and 60% of respondents were female. Despite differences across GP characteristics, such as age (with older GPs being more likely to take deprescribing decisions), and across countries, overall more than 80% of GPs reported they would deprescribe the dosage of at least one medication in oldest-old patients (> 80 years) with polypharmacy irrespective of history of CVD. The odds of deprescribing was higher in patients with a higher level of dependency in ADL (OR =1.5, 95%CI 1.25 to 1.80) and absence of CVD (OR =3.04, 95%CI 2.58 to 3.57). Interpretation The majority of GPs in this study were willing to deprescribe one or more medications in oldest-old multimorbid patients with polypharmacy. Willingness was higher in patients with increased dependency in ADL and lower in patients with CVD. Show less
With increasing age, blood pressure (BP) rises as a consequence of arterial stiffness. It has been debated whether it is beneficial to treat hypertension in old age especially in >75-year... Show moreWith increasing age, blood pressure (BP) rises as a consequence of arterial stiffness. It has been debated whether it is beneficial to treat hypertension in old age especially in >75-year-olds when they have multimorbidity, polypharmacy or frailty. Large trials showed that lowering BP in >60-year-olds is beneficial and lowers the risk for myocardial infarction, stroke and all-cause mortality. However, these trials lack generalizability and typically excluded multimorbid patients that are frail. At the same time, observational studies rose concerns about lowering BP too much since there are several cohort studies showing a reverse association of low BP and increased mortality especially in >75-year-olds. The general aim of this thesis is to increase the scientific knowledge about the effects of treating hypertension in >75-year-olds with frailty. This thesis has three aims: 1) to measure the prevalence of polypharmacy in older patients; 2) to test for an association between low SBP and mortality, cognitive function, daily functioning, and QoL in older patients under antihypertensive treatment; and 3) to understand the role that frailty plays in GP decisions about treating hypertension in old age across countries and see if those differences can be explained by country-specific cardiovascular disease burden and life expectancy. Show less
This thesis investigates different aspects of apathy - as a distinct clinical syndrome assessed with the Apathy Scale- in older persons with and without concurrent depression. In Chapter 2,... Show moreThis thesis investigates different aspects of apathy - as a distinct clinical syndrome assessed with the Apathy Scale- in older persons with and without concurrent depression. In Chapter 2, clinically relevant subtypes of apathy according to the Apathy Scale in older persons from the PROMODE study are examined, using data-driven Latent Class Analysis (LCA). Further, specific characteristics across the classes identified by LCA are investigated. Then, in Chapter 3, cross-sectionally the prevalence, severity and clinical profile of apathy in depressed and non-depressed older persons, in relation to various possible determinants is described. Chapter 4 examines which characteristics predict, over a 2-year period, the incidence and course of apathy in at baseline depressed older persons from the NESDO study. Chapter 5, using data of the NESDO and NESDA, investigates the presence of apathy in late-life compared to early-life depression, and various determinants of clinically relevant apathy in older compared to younger depressed persons. In Chapter 6 the association of the presence of apathy among community-dwelling older persons from the PROMODE study and a diminished quality of life is examined. All results are placed a current perspective in Chapter 7 that also discusses clinical implications, and makes some recommendations for future research. Show less
This PhD dissertation comprises a detailed study of the Anglo-Saxon cultural conceptualisation of old age as manifested and reflected by words, texts and artwork of the inhabitants of early... Show moreThis PhD dissertation comprises a detailed study of the Anglo-Saxon cultural conceptualisation of old age as manifested and reflected by words, texts and artwork of the inhabitants of early medieval England. While prior studies identified the Middle Ages as a ‘golden age for the elderly’, this dissertation offers a more complete and nuanced picture of how people considered old age over a thousand years ago. The project stands out for its multidisciplinary approach, which highlights that a study of how people thought about growing old should take into account as much of the cultural record as possible, ranging from visual arts to texts and even individual words. Individual chapters deal with early medieval definitions of the life cycle; a lexicographical study of the semantic field of old age in Old English; the merits and downsides of old age as represented in homiletic and literary texts; and the cultural roles attributed to specific social groups, such as saints, warriors, kings and women. On the whole, the Anglo-Saxons were aware of the opportunities provided by senescence (e.g., wisdom and authority), but, at the same time, they were afraid of the consequences (e.g., physical decay and sadness); they looked up to those elderly that managed to remain active despite their age, but denounced those that could not. As such, the early medieval ideas about old age may not be so different from our own. Show less
In this thesis we observe that prescription rates of lipid-lowering drugs and antithrombotic medication in secondary prevention in old age are low. According to focus-group discussions with general... Show moreIn this thesis we observe that prescription rates of lipid-lowering drugs and antithrombotic medication in secondary prevention in old age are low. According to focus-group discussions with general practitioners highly individualized care with the ultimate aim to improve quality of life, might largely explain these low prescription rates; however, improvements might be expected from structured follow up, and tailored, age-specific guidelines, reflecting the heterogeneity of clinical practice. In very old age we observed that the severity of the cardiovascular disease history is associated with unfavourable prognosis, not only with regard to (recurrent) cardiovascular disease/mortality, but also with regard to future disability and cognitive decline. Of four newer cardiovascular risk markers N-terminal pro B-type natriuretic peptide (NT-proBNP) was the strongest predictor of cardiovascular events/mortality in secondary cardiovascular prevention in very old age. NT-proBNP was also associated with cognitive and functional decline. Finally NT-proBNP predicted treatment effect of pravastatin. In order to improve patient care in older age, the following actions are recommended: vigorous ICPC coding and pro-active follow-up of all older patients with a history of cardiovascular disease. Finally, optimisation of secondary cardiovascular prevention is advised by individualised risk prediction and consciously weighing all pros and cons of preventive treatment. Show less
In this thesis we show the results of the AT-AGE study, a two-center, population based case-control study in Leiden, the Netherlands and Burlington, Vermont, US, in which consecutive patients aged... Show moreIn this thesis we show the results of the AT-AGE study, a two-center, population based case-control study in Leiden, the Netherlands and Burlington, Vermont, US, in which consecutive patients aged 70 years and older with deep venous thrombosis (DVT) in the leg or a pulmonary embolism (PE), were identified. The AT-AGE study was specifically designed to optimise the participation-rate in the older population. Therefore, we performed home visits to all participants. We showed that conventional risk factors such as immobilisation due to hospital admission, and also immobility at home, due to for instance infection and minor injury, increase the risk of venous thrombosis. Also genetic risk factors, such as Factor V Leiden (FVL, rs6025) and the prothrombin 20210A mutation (PT20210, rs1799963) increase the risk of venous thrombosis. We report the presence of age-specific risk factors: functional impairment, low hand grip strength and venous insufficiency, such as varicose veins and leg oedema. Also we identified new high risk groups in older people, e.g., recent hospital discharge in which preventive measures could be of special interest. Show less
Groeneweg-Koolhoven, I.; Comijs, H.C.; Naarding, P.; Waal, M.W.M. de; Mast, R.C. van der 2015
Knowledge of physiological changes in renal function, EPO and haemoglobin level and their impact at old age are essential for clinicians especially those working with older patients. The results of... Show moreKnowledge of physiological changes in renal function, EPO and haemoglobin level and their impact at old age are essential for clinicians especially those working with older patients. The results of the studies presented in this thesis provide more insight in the physiological aspects of age related decline in renal function and the relation with erythropoietin production and the maintenance of haemoglobin levels at old age. Furthermore, these results allow us to speculate about the predictive value of renal function, EPO and haemoglobin as markers of mortality in a clinical population of oldest old patients. Proper knowledge of these markers could contribute to increased attention of clinicians for the increased mortality risk of their oldest old patients. Furthermore, knowledge of these markers could be helpful in tailor made medicine, individual prognostication and decision making procedures, in the oldest old patients. Show less
In summary, chapter 1 of this thesis provides a background on the demographic, biologic and cardiovascular aspects of brain aging. Chapter 2 shows that higher blood pressure is associated with... Show moreIn summary, chapter 1 of this thesis provides a background on the demographic, biologic and cardiovascular aspects of brain aging. Chapter 2 shows that higher blood pressure is associated with lower cognitive decline in very old age. Findings of Chapter 3 indicate that higher blood pressure is associated with lower risk of stroke in very old subjects with higher degrees of disability. In chapter 4, we showed that visit-to-visit blood pressure variability might put subjects at a higher risk for accelerated brain aging. In Chapters 5 to 7, we observed that a strong association exists between a graded decrease in cardiac function and lower brain volumes and cognitive performance. In a meta-analysis (Chapter 8), we demonstrated that in patients with Alzheimer__s disease and vascular dementia have profound disturbances in their cerebrovascular hemodynamics. Chapter 9 shows that in late life, conventional cardiovascular risk factors loss their predictive value while impaired cognitive function better predicts risk of stroke. In Chapter 10, we showed that increased serum markers of endothelial dysfunction associate with lower cerebral blood flow in older subjects. In Chapter 11, we demonstrated that older subjects with lower cerebral blood flow have a shorter survival. Chapter 12 reviews the key findings of this thesis and discusses them in the context of current knowledge and evidence. Show less
Hegeman, J.M.; Wardenaar, K.J.; Comijs, H.C.; Waal, M.W.M. de; Kok, R.M.; Mast, R.C. van der 2012
The main objective of this thesis was to clarify the observed reversal of effect of classical risk factors for dementia and mortality with increasing age and to gain better insight in the... Show moreThe main objective of this thesis was to clarify the observed reversal of effect of classical risk factors for dementia and mortality with increasing age and to gain better insight in the biological mechanism behind the relation between both phenotypic and genetic variation in apolipoprotein E (apoE) and cognitive function. Although high cholesterol levels in midlife associate with worse cognitive function and dementia in late-life, this association attenuates and even reverses with increasing age. In memory outpatient clinic patients high blood pressure associated with better cognitive function, only in patients with structural brain damage. In the Leiden 85-Plus Study, a decline in global cognitive function preceded declines in total cholesterol levels, HDL cholesterol levels, and blood pressure, and not vice versa. Moreover, mortality was associated with larger declines in body mass index, total cholesterol levels, HDL cholesterol levels, and blood pressure. High plasma apoE levels associated with worse cognitive function, whereas offspring from Alzheimer__s disease patients had lower plasma apoE levels when measured in midlife compared to offspring from cognitively intact controls. Finally, high serum calcium levels were strongly associated with worse cognitive function in APOE _3_4 carriers, to a lesser extent in _3_3 carriers, but not in _2_3 carriers. Show less
The last decades have shown an increasing interest in treatment of high blood pressure. Copious amounts of data have been published on the mortality and morbidity risks of high blood pressure.... Show moreThe last decades have shown an increasing interest in treatment of high blood pressure. Copious amounts of data have been published on the mortality and morbidity risks of high blood pressure. Overall these data have resulted in an increasing awareness of the deleterious effects of only modest elevation of blood pressure on morbidity and mortality. Moreover, treatment of high blood pressure resulted in substantial benefits in terms of reduced morbidity and mortality. This has resulted in official guidelines about treatment for hypertension that have become stricter with every decade. However, most of the evidence has been generated from middle-aged people. Only a few trials have included people of 80 year and older. [7-9] Looking at the results in detail within that age group the evidence is not robust. Given the increasing lifespan worldwide, physicians are confronted with many elderly patients over eighty. Hence, there is an increasing urge to generate more knowledge in regard to the effects of high blood pressure in the elderly. Show less
No specific, systematic research existed focusing exclusively on late effects of surviving the Holocaust and its aftermath on the youngest child Holocaust survivors. Born between 1935 and 1944,... Show moreNo specific, systematic research existed focusing exclusively on late effects of surviving the Holocaust and its aftermath on the youngest child Holocaust survivors. Born between 1935 and 1944, they had endured persecution and deprivation in their first and most formative years. From trauma-experiential and child-developmental points of view, their peri-Holocaust experiences are different from older child survivors. They hold no recollections of a world that was peaceful and benevolent to enhance early development of basic trust. This set of studies focuses on the associations between early childhood peri-Holocaust experiences and adaptations at the beginning of old age in a __with-in design__ that compares three age cohorts in a non-convenience sample of 203 child Holocaust survivors, now living in Israel. Late-life implications of early traumatic stress for the adreno-cortical system were examined by assessing basal circadian cortisol release and cortisol reactivity to a stressor. Through several inventories severity of Holocaust survival exposure, current physical and psycho-social quality of life, and the role of Antonovsky__s Sense of Coherence as a protective factor were assessed. Results show mild to severe present-day repercussions of the Nazi persecutions, and a potentially moderating effect of the Sense of Coherence on later life impact of Holocaust survival experience. Show less
Epidural neural blockade results from processes after the administration of a local anaesthetic in the epidural space until the uptake in neural tissue. The pharmacokinetics, neural blockade and... Show moreEpidural neural blockade results from processes after the administration of a local anaesthetic in the epidural space until the uptake in neural tissue. The pharmacokinetics, neural blockade and haemodynamics after epidural anaesthesia may be influenced by several factors, with age as the most important one. Using the stable-isotope-method, the pharmacokinetics of the enantiomeric-pure local anaesthetics ropivacaine and levobupivacaine were derived and the influence of age on the pharmacokinetics was investigated. These local anaesthetics showed a bi-phasic absorption pattern. The fraction absorbed during the initial absorption process for levobupivacaine was low. The initial absorption parameters decreased with increasing age for epidurally administered levobupivacaine and ropivacaine.After epidural administration the level of analgesia was higher for levobupivacaine and ropivacaine and motor blockade was increased for ropivacaine in elderly patients. Haemodynamic changes, like the decrease in mean arterial pressure (MAP), were more pronounced in elderly patients after epidural administration of ropivacaine. It was postulated that this decrease is not only the result of the higher level of analgesia in elderly patients, but also from age-related changes in the cardiovascular and autonomic nervous system. Finally, a population pharmacokinetic/ pharmacodynamic model of the lumbar epidural space was developed that was able to demonstrate the importance of age on the spread of the sensory blockade as well as on the speed of onset/offset of blockade. Show less
