The general aim of this thesis was to study the frequency, causes and consequences of pathologic brain aging specifically focusing on sub-clinical and clinical MRI manifestations of vascular (small... Show moreThe general aim of this thesis was to study the frequency, causes and consequences of pathologic brain aging specifically focusing on sub-clinical and clinical MRI manifestations of vascular (small vessel disease) and neurodegenerative (brain atrophy) disease. A second aim was to improve the accuracy of the tools to quantify brain tissue so to better reflect the imaging characteristics of older people. All data presented in this thesis are from the AGES-Reykjavik Study including 5764 elderly men and women. The data is based on cross-sectional and longitudinal assessments of the brain with MRI measures. Show less
Worldwide, life expectancy has increased, which also resulted in an increasing number of people reaching old age. With aging, several age-related diseases commonly occur, such as dementia,... Show moreWorldwide, life expectancy has increased, which also resulted in an increasing number of people reaching old age. With aging, several age-related diseases commonly occur, such as dementia, osteoporosis and cardiovascular disease. The occurence of these diseases with age is highly heterogeneous. The research described in this thesis assessed the role of thyroid hormones in the etiology of age-related diseases. Based on the results, variation in blood levels of thyroid hormones do not appear to play a major role in the development of cogniitve decline, osteoporosis, anemia, diabetes mellitus or cardiovascular disease. Therefore, we conclude that is unlikely that thyroid hormones are a modifiable risk factor in the aging process. Nevertheless, many other research questions remain regarding thyroid hormones and older individuals. Show less
The experimental research in this thesis aims to gain more understanding of how the SCN network is organized and what is needed for network changes. More specifically, this work focused on the... Show moreThe experimental research in this thesis aims to gain more understanding of how the SCN network is organized and what is needed for network changes. More specifically, this work focused on the potential role of GABA and the GABAeric E/I balance in SCN network plasticity. Communication and synchronization in the SCN are important for the generation of a strong and coherent output signal. Under certain conditions, like long photoperiod, the phases of the individual SCN cells are more dispersed over the 24 hour cycle as evidenced by measurements of electrical activity and clock gene expression. Aging is also known to affect the network organization of the SCN with deterioration in synchronization among the individual SCN neurons. In this thesis, I present work that contributes to research questions regarding the effect of light exposure and/or aging on several characteristics of SCN network plasticity. Show less
My research projects include the investigation of effects of different environmental factors on sleep and the circadian clock in the course of aging (such as light levels, exercise, diet and... Show moreMy research projects include the investigation of effects of different environmental factors on sleep and the circadian clock in the course of aging (such as light levels, exercise, diet and pharmacological substances including caffeine and diazepam). Investigating thebeneficial or adverse effects in the course of aging provides significant insights that could accelerate, hinder or ameliorate parts of the aging process allowing for a healthier and longer life span.Chronic consupmtion of high-caloric diet, eventually leading to obesity, alters the sleep homeostasis as well as the sleep architecture denoting a potentially enhanced aging phenotype.In addition to dietary preferences, light levels particularly at night significantly affect sleep and the sleep electroencephalogram across a wide age span, impactingthe sleep regulatory system as well as the brain integrity.Factors that induce beneficial effects include exercise and caffeine intake. Long-term exercise was able to lead to a younger brain phenotype across all ages while caffeine generally ameliorated sleep health. Show less
The subject of this Thesis is the role of the immune system in age-related eye diseases, such as glaucoma. Glaucoma is a disease that afflicts nearly 70 million people worldwide. Little is known... Show moreThe subject of this Thesis is the role of the immune system in age-related eye diseases, such as glaucoma. Glaucoma is a disease that afflicts nearly 70 million people worldwide. Little is known about the origins of the disease, which damages the retina and optic nerve and can lead to blindness. One of the biggest risk factors for glaucoma is elevated eye pressure. Our study found that glaucoma may in fact be an autoimmune disorder. We found that the body’s own T cells are responsible for the progressive retinal degeneration seen in glaucoma. Furthermore these T cells appear to be primed to attack retinal neurons as the result of previous interactions with bacteria that normally live in our body. This opens a new approach to prevent and treat glaucoma. Currently most treatments focus on lowering eye pressure. However, in many patients, the disease worsens even after intraocular pressure returns to normal. We showed that when we blocked these autoreactive T cells in the eye, not only does it diminish the loss of retinal ganglion cells and axons, but it also preserves retinal function. Show less
Thoracale epidurale anesthesie (TEA), ook wel ruggenprik genoemd, zorgt voor een uitstekende pijnstilling rondom operaties en wordt als zodanig veelvuldig toegepast binnen de cardiothoracale... Show moreThoracale epidurale anesthesie (TEA), ook wel ruggenprik genoemd, zorgt voor een uitstekende pijnstilling rondom operaties en wordt als zodanig veelvuldig toegepast binnen de cardiothoracale chirurgie. TEA heeft echter ook effecten op het hart en de bloedsomloop. Hoewel in fysiologische studies is aangetoond dat thoracale epidurale anesthesie gunstige effecten heeft op het hart, heeft zich dit in grote klinische studies niet vertaald in een betere uitkomst. Dit proefschrift beschrijft de anatomie en fysiologie van het hart tijdens TEA bij patiënten die een long ingreep ondergaan. Het doel van dit proefschrift is het bepalen van de bijwerkingen van TEA op het hart en de bloedsomloop waarbij deze effecten van TEA zowel tijdens rust als gedurende omstandigheden van stress (zoals tijdens operatie of inspanning) onderzocht werden. De resultaten van dit proefschrift tonen aan dat TEA de functie van de rechter hartkamer vermindert. Dit proefschrift toont ook aan dat de toename van de linker- en rechter kamerfunctie tijdens inspanning nauwelijks wordt beïnvloed door TEA. Leeftijd lijkt geen duidelijke invloed te hebben op de bijwerkingen van TEA. Het is nog niet duidelijk in hoeverre deze resultaten klinisch relevant zijn. Echter, de resultaten uit dit proefschrift zouden kunnen helpen bij het maken van weloverwogen besluiten rond het gebruik van TEA bij cardiothoracale chirurgie. 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
The aim of this thesis is to investigate the role of chronic inflammation as well as acute inflammatory response on muscle aging. We conclude that high chronic inflammation is associated with low... Show moreThe aim of this thesis is to investigate the role of chronic inflammation as well as acute inflammatory response on muscle aging. We conclude that high chronic inflammation is associated with low muscle strength, while high acute pro-inflammatory response is associated with high muscle strength. Show less
