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
