The work described in this thesis had two objectives, specifically focusing on people aged 70 years and older: first, we aimed to investigate the associations between several thrombosis-related... Show moreThe work described in this thesis had two objectives, specifically focusing on people aged 70 years and older: first, we aimed to investigate the associations between several thrombosis-related risk factors described in young and middle-aged populations and the risk of venous thrombosis (VT) in the elderly; second, we aimed to provide insight into several long-term consequences (i.e., health-related quality of life (HRQoL) and long-term risk of mortality) after a first VT at old age. Show less
Pulmonary embolism (PE) is a serious and sometimes life-threatening condition that refers to a blood clot that occludes the arteries of the lung. Despite all improvements over the past decades,... Show morePulmonary embolism (PE) is a serious and sometimes life-threatening condition that refers to a blood clot that occludes the arteries of the lung. Despite all improvements over the past decades, diagnosing PE is still a difficult process due to the non-specific symptoms, which can frequently overlap with symptoms of other cardiopulmonary diseases. Currently recommended diagnostic strategies for suspected acute PE consist of standardized assessment of the clinical pre-test probability (CPTP) using validated clinical decision rules (CDRs) and D-dimer testing. PE is considered safely ruled out in patients with a non-high CPTP and a normal D-dimer test. Imaging tests as computed tomography pulmonary angiography (CTPA) are required in the case of a high CPTP and/or abnormal D-dimer test to confirm the diagnosis. The first part of this thesis describes the challenges of diagnosing PE in general and in specific clinically relevant patient subgroups. Moreover, this part evaluates the diagnostic performance of non-invasive diagnostic strategies for suspected PE in specific relevant patient subgroups. The second part of this thesis focuses on venous thrombotic complications in hospitalized patients with COVID-19. Show less
Inflammatoire darmziekten (Inflammatory Bowel Disease, IBD) zijn chronische immuun-gemedieerde ziekten van het maag-darmstelsel. Het aandeel oudere patiënten met IBD, 65 jaar of ouder, wordt... Show moreInflammatoire darmziekten (Inflammatory Bowel Disease, IBD) zijn chronische immuun-gemedieerde ziekten van het maag-darmstelsel. Het aandeel oudere patiënten met IBD, 65 jaar of ouder, wordt groter. Het behandelen van deze groep is een uitdaging, omdat zij vaak andere ziekten (comorbiditeit) hebben en geriatrische aandoeningen zoals geheugenproblemen of verminderde spiermassa. Deze aandoeningen vallen onder het begrip kwetsbaarheid, en worden gemeten met een geriatrisch assessment.Dit proefschrift richt zich op het in kaart brengen van de huidige literatuur en behandeloverwegingen bij oudere patiënten met IBD, om daarna als een van de eersten bewijs te leveren voor het invoeren van (screening naar) comorbiditeit en kwetsbaarheid bij de behandeling van oudere patiënten met IBD.Allereerst wordt onderzocht welke factoren bijdragen aan behandelbeslissingen, door behandelaren te interviewen. Leeftijd en aspecten van kwetsbaarheid beïnvloeden behandelbeslissingen, maar behandelaren verschillen onderling in hoe ze deze aspecten gebruiken. Daarnaast liet een literatuur zoektocht zien dat het bewijs over de relatie tussen kwetsbaarheid en behandeluitkomsten schaars is.Ook wordt het verband tussen comorbiditeit en veiligheid van biologicals, medicijnen die ontstekingseiwitten of afweercellen remmen, onderzocht. De aanwezigheid van meer comorbiditeit geeft een hoger risico op bijwerkingen (infecties en ziekenhuisopnames), een hogere leeftijd geeft dat niet.Tenslotte wordt de prevalentie van kwetsbaarheid in een Nederlands cohort van oudere patiënten met IBD onderzocht. Bij ongeveer de helft was er kwetsbaarheid. Hoe kwetsbaarder, hoe hoger de IBD-ziekteactiviteit en de IBD-ziektelast. Kwetsbare patiënten hadden, onafhankelijk van hun leeftijd en IBD-ziekteactiviteit, een hogere kans op ziekenhuisopnames en infecties, maar ook op achteruitgang in zelfstandigheid en kwaliteit van leven. Show less
The life expectancy of individuals has been almost doubled in the past century. The aging population brings challenges to the economic and medical burden of care-needed dependent older people... Show moreThe life expectancy of individuals has been almost doubled in the past century. The aging population brings challenges to the economic and medical burden of care-needed dependent older people limited by age-associated cognitive impairment. Age-associated cognitive decline is a meaningful experience that occurs over the lifespan.This thesis aimed to evaluate the association of cognitive performance with the risk of cardiovascular events and various causes of mortality in elderly populations. The lower cognitive function performance might be an early manifestation of clinically unrecognized cerebral and systemic vascular pathologies, which signals the future risk of cardiovascular events and mortality.In the present research, we included two longitudinal studies, the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) prospective randomized controlled trial in the elderly population of Scotland, Ireland, and the Netherlands that aimed to evaluate whether treatment with pravastatin decreases the risk of cardiovascular events, and Leiden 85-Plus Study which is a prospective population-based study of 85-year-old inhabitants of Leiden district, the Netherlands. Based on our findings and also considering results from other studies, we concluded that cognitive impairment associates with cardiovascular events and several causes of mortality in elderly individuals. Show less
In this thesis the risk factors of venous thrombosis will be discussed in the general and particularly the elderly population. The goal of this thesis is to provide insights on risk factors of... Show moreIn this thesis the risk factors of venous thrombosis will be discussed in the general and particularly the elderly population. The goal of this thesis is to provide insights on risk factors of thrombosis in the elderly population, in order to advance our basic understanding of physiological age-related changes that increase the risk of venous thrombosis and which may ultimately lead to improved personalized interventions. In this chapter firstly background information will be provided on risk factors for venous thrombosis, focussing specifically on age as a risk factor. Secondly, the role of veins and venous valves in the development of venous thrombosis will be discussed and thirdly, global assays as a potential tool to identify patients at high risk for venous thrombosis will be considered. The study populations used in this thesis will discussed, and an outline of this thesis will be provided. Show less
As a result of our ageing population, breast cancer is becoming a disease of the elderly. Unfortunately, most studies investigating the efficacy of treatment do not include older patients and are... Show moreAs a result of our ageing population, breast cancer is becoming a disease of the elderly. Unfortunately, most studies investigating the efficacy of treatment do not include older patients and are not representative for the older population. In this thesis, we investigated whether there is variation in treatment and survival among older women with breast cancer in five European countries. Moreover, we study the long term efficacy of two types of adjuvant endocrine therapy in postmenopausal women. In addition, the effect of age and comorbidities on breast cancer death in the presence of competing mortality is studied. Finally, we investigate whether other endpoints in clinical studies might be more relevant for the older population and we introduce a new endpoint for clinical research in the older population with cancer. Show less
Older women with breast cancer are underrepresented in the available evidence. Therefore, there is no solid evidence on how to treat older women with breast cancer. This thesis has three main... Show moreOlder women with breast cancer are underrepresented in the available evidence. Therefore, there is no solid evidence on how to treat older women with breast cancer. This thesis has three main conclusions: 1. There are large international differences in the treatment strategy of breast cancer among older women. These differences are not associated with a significant difference in prognosis. 2. The presence of comorbidity has an important impact on the general prognosis of older women with breast cancer. We did not show an important association between specific comorbidities or the use of co-medications and the breast cancer specific prognosis. 3. Concerning older women with breast cancer for research, there are very important methodological issues to take into account, including to avoidance of selection bias and the proper methodologies to take in to account the chance of dying from another cause of cancer: the competing risk of mortality. Future research should be done to create a tool which can assist in identifying the individualised treatment strategy for each older woman with breast cancer. This will have to take into consideration patient’s and tumour’s information, as well as the endpoints for each individual patient. Show less
Life expectancy is rising fast, but not all years gained are free of disease. Therefore, many people wonder to what extent the years that we have gained are enjoyable. Studies however show that... Show moreLife expectancy is rising fast, but not all years gained are free of disease. Therefore, many people wonder to what extent the years that we have gained are enjoyable. Studies however show that life satisfaction generally remains high at old age. We investigate this surprising phenomenon using data from two cross-sectional studies. We ask 1) which factors separate older people with a low from those with a high life satisfaction? And 2) how do older people maintain their high life satisfaction despite physical decline? Compared to earlier studies, this study used large and representative populations, and a broad array of objective health indicators. Physical decline was relatively unimportant for life satisfaction, especially when mental health (operationalised as depressive symptoms and experienced loneliness) remained high. Demographic variables and social resources also had no or a small relationship with life satisfaction. Only mental health was strongly associated with life satisfaction. By investigating various ways of measuring self-rated health, we show that older people may shift their norms and values in the face of declining health. This may thus explain their high life satisfaction, in spite of physical decline. Findings are discussed in relation to other literature and implications are given. Show less
The overriding aim of my thesis was to study the relationship between blood pressure (BP) and cognitive and psychological functioning in older persons. Observational studies indicate that lower BP... Show moreThe overriding aim of my thesis was to study the relationship between blood pressure (BP) and cognitive and psychological functioning in older persons. Observational studies indicate that lower BP increases risk for cognitive decline in older persons. Older persons are at risk for impaired cerebral autoregulation, and lowering their BP may compromise cerebral blood flow and cognitive function. Contradictory to our hypothesis, the Discontinuation of Antihypertensive Treatment in Elderly people (DANTE) Study Leiden, a community-based randomized clinical trial in older persons (aged ≥75 years) with mild cognitive deficits, did not show that discontinuation of antihypertensive treatment improves cognitive functioning. The lack of the effect of this trial may be due to the unintentional inclusion of persons with a relatively intact cerebral autoregulation. Furthermore, we demonstrated that older persons with mild cognitive deficits and with orthostatic hypotension, who discontinued all their antihypertensive medication had an increased probability of being free from orthostatic hypotension 4 months later, compared to persons who continued their medication. Finally, in the DANTE MRI sub study, the relationship between BP and both conventional features of small vessel disease (SVD) and microstructural damage was explored, as well as the relation between microstructural damage and cognitive and psychological dysfunction. Show less
With increasing age the prevalence of hypertension rises. High blood pressure at midlife is associated with cognitive impairment. Nevertheless, in older persons a lower rather than a higher... Show more With increasing age the prevalence of hypertension rises. High blood pressure at midlife is associated with cognitive impairment. Nevertheless, in older persons a lower rather than a higher blood pressure is associated with incident dementia. The main purpose of the work in this thesis was to explore the role of blood pressure in relation to cerebral structure, neurocognitive functioning and hemodynamics of the brain in old age. Therefore, we sought to determine whether discontinuation of antihypertensive therapy in persons aged 75 years and over with mild cognitive deficits and using antihypertensive medication (the Discontinuation of ANtihypertensive Treatment in Elderly people [DANTE] population) would improve their cognitive and psychological functioning. The assumption was that the increase in blood pressure after the discontinuation of antihypertensives would lead to a direct increase in cerebral blood flow and, as a consequence, to an improvement in cerebral functioning. An additional objective was to investigate possible underlying mechanisms in the relation between blood pressure and neurocognitive functioning. To enable this, brain MRI was used to determine whether (lower) blood pressure was associated with (micro)structural damage, cerebral small vessel disease and blood flow in the brain, and also whether the presence of cerebral (micro)structural damage was related to neurocognitive functioning. Show less
Breast cancer is the most common malignancy and the leading cause of cancer related death in women of the western world. For most women, increasing age is the primary risk factor for breast... Show more Breast cancer is the most common malignancy and the leading cause of cancer related death in women of the western world. For most women, increasing age is the primary risk factor for breast cancer. Therefore, the number of breast cancer patients is expected to further increase in the coming years. The work presented in this thesis is part of the collaborative FOCUS project, seeking insight into breast cancer disease (in the elderly), aiming to define normal tissue, breast cancer, and therapeutic sensitivity differences in observational, population-based cohorts consisting of elderly breast cancer patients. Topics discussed in this thesis are differences and clinical value of molecular differentiation, immune evasion, proliferative and apoptotic signaling; but also the predictive value of IGF1R and HER2 expression on the breast tumors. Last but not least, we discuss the effects of aging on tumorgenesis and the road to precision medicine. Only when all medical specialties bound to the care and cure of older cancer patients join forces, known as a multidisciplinary oncogeriatric battlefront, treatment goals, and implementation hereof will be achieved. 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
The role of computed tomography in the development of transcatheter aortic valve implantation (TAVI)has been crucial. Post-TAVI computed tomography data has helped us to understand the underlying... Show moreThe role of computed tomography in the development of transcatheter aortic valve implantation (TAVI)has been crucial. Post-TAVI computed tomography data has helped us to understand the underlying mechanisms of specific complications related to TAVI. The future of TAVI is promising in subgroups of patients that would intialy have been excluded from this procedure. In this future, the role of imaging is pivotal Show less
Breast cancer is the most common malignancy diagnosed in women1. The incidence of breast cancer increases with age; currently, in developed countries more than 40% of breast cancer patients is 65... Show moreBreast cancer is the most common malignancy diagnosed in women1. The incidence of breast cancer increases with age; currently, in developed countries more than 40% of breast cancer patients is 65 years or older at diagnosis1. In the Netherlands in 2011, 5,441 women aged 65 years or older were diagnosed with breast cancer2. The remaining life expectancy of persons aged 65 is still increasing, from almost 19 years in 1980, up to more than 21 years in 2010. Moreover, in last decades the birth rate has decreased, resulting in a higher proportion of older persons in the general population3. Both an increasing life expectancy and the increasing number of elderly in the population will further enhance the number of elderly women confronted with breast cancer Show less
Colorectal cancer is one of the most common cancers worldwide. Although there have been several improvements in screening, staging, and treatment in the past decades, survival differences remain.... Show moreColorectal cancer is one of the most common cancers worldwide. Although there have been several improvements in screening, staging, and treatment in the past decades, survival differences remain. For example among certain subgroups of patients, such as elderly patients and patients with comorbidities. Besides, inequalities in the quality of care between European countries remain. Quality control on surgery, radiotherapy, and pathology have been introduced in trials, followed by incorporation in the general care. Another option to incorporate improved quality of care is via an audit structure in which hospitals and clinicians can improve their results by learning from their own outcome statistics and those from colleagues treating a similar patient group. Although all these audit structures have achieved excellent results within countries, differences in outcome between European countries remain. A next step will b e to combine these national audits. The combined audit structure will provide a network in which __best practices__ can be compared and identified, including for certain subgroups, which has been initiated as European Registration of Cancer Care (EURECCA). To achieve optimal care for all patients, multidisciplinary care is the only way. By comparing multidisciplinary audit structures across countries, optimal treatment strategies within subgroups can be identified Show less
This thesis describes the PROMODE-study, which investigated in a pragmatic way whether a pro-active approach in primary care by screening for depressive symptoms, followed by an intervention offer... Show moreThis thesis describes the PROMODE-study, which investigated in a pragmatic way whether a pro-active approach in primary care by screening for depressive symptoms, followed by an intervention offer to persons of 75 years and over who screened positive, is (cost)effective to detect and relieve suffering from depressive symptoms at old age. We compared two screening methods regarding yield and costs. Furthermore, we found that scores of the 15-item Geriatric Depression Scale were higher when this screening questionnaire was self-administered than when interviewer-administered. In our intervention study, a cluster-randomised controlled trial, we found that the stepped-care intervention program was not (cost)effective compared with usual care in general practice, possibly due to a low uptake of the offered course being the main part of the intervention. In a qualitative study we explored the limiting and motivating factors for accepting course participation. This revealed that most persons were not (yet) prepared to accept the unsolicited intervention offer, although perceived needs to relieve depressive symptoms seemed to largely match the elements of the course. It is discussed that a more selective approach, aimed at high risk-groups and focussing on need for and readiness to accept help, might increase efficiency of a combined screening-intervention program. Show less
This thesis focuses on quality assurance of rectal cancer treatment, in particular of the surgical treatment. Both oncological short-term and long-term outcome parameters are studied, but also... Show moreThis thesis focuses on quality assurance of rectal cancer treatment, in particular of the surgical treatment. Both oncological short-term and long-term outcome parameters are studied, but also other end-points which are important for quality assurance are investigated, such as anastomotic leakage and stoma reversal. The introduction of total mesorectal excision (TME) surgery resulted in an improved survival of patients with rectal cancer. However, survival of the elderly patients and patients treated with an abdominoperineal resection improved less. For frail elderly patients, postoperative mortality is an important competitive risk factor and other treatment schedules might be more appropriate. The abdominoperineal resection itself was associated with a nonradical resection, decreased local control and decreased survival compared to patients treated with a low anterior resection. To improve these results, in selected cases preoperative treatment should consist of chemoradiotherapy and/or a widened resection. Anastomotic leakage is a feared complication after colorectal surgery. After surviving this complication, the overall survival rate in the long-term is still reduced. However, oncological outcome was not significantly affected. The presence of a stoma resulted in a lower symptomatic leakage rate. 20% of stomas was never reversed. Standardised postoperative surveillance resulted in an earlier confirmation of the diagnosis anastomotic leakage. Show less
In the Netherlands the Coping with Depression (CWD; Lewinsohn & Clark, 1984) course for elderly has been implemented in the prevention arm of the community-based mental health care system. The... Show moreIn the Netherlands the Coping with Depression (CWD; Lewinsohn & Clark, 1984) course for elderly has been implemented in the prevention arm of the community-based mental health care system. The study’s aim was the effectiveness (immediate and long-term) of the course in this real life setting. Enrolment of all 318 participants was the responsibility of the mental health care professionals in charge of the course. The immediate effect was studied in a random design using a waitlist group as control group; the long-term effect was analyzed in a naturalistic design. The Center for Epidemiological studies Depression scale (CES-D; Radloff, 1977) was used as the outcome measure. A wide range of variables related to incidence, severity, course and remittance of depression were included as predictors of immediate and long-term outcome. Results. The level of depressive symptoms varied from slight to being severely depressed i.e., meeting the criteria for a major depressive episode (MDE). Effect size: for non-depressed 0.32, for those with a MDE 0.92. The four predictors – anxiety, MDE, previous MDE, and education level - that were statistically significant had no clinical significance and did not justify further triage at intake. At the conclusion of the course 62% still had a CES-D score above 16, which is an indication that a clinical relevant depression is persisting. These participants should be advised to seek further treatment. Show less
Aging of the brain was studied by comparing follow-up MRI scans in 554 persons aged 70-82 years. Mean interval time between these scans was three years and scans were looked for changes in cerebral... Show moreAging of the brain was studied by comparing follow-up MRI scans in 554 persons aged 70-82 years. Mean interval time between these scans was three years and scans were looked for changes in cerebral infarcts, white matter lesions, cerebral blood flow, and brain volume. Besides this, the preventive effect of pravastatin on these changes was studied. During the study time there was progression of cerebral infarcts, white matter lesions and there was decline of cerebral blood flow and progression of brain atrophy. Treatment with pravastatin 40 mg/daily did not have a protective effect on these changes. Show less
