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 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.Financial support for printing of this thesis was provided by the Leiden University Medical Centre, Leyden Academy on Vitality and Ageing, and Internationale Stichting Alzheimer Onderzoek (ISAO.UBL - phd migration 201
