__Abstract__
In the 1970s, the introduction of computed tomography (CT) and magnetic resonance
imaging (MRI) in medicine, made it possible to image the living brain. These images
showed that cerebral white matter lesions and asymptomatic lacunar brain infarcts
are extremely common in elderly people. Evidence is accumulating that these lesions
are associated with an increased risk of late-life depression, gait disturbances, and
cognitive decline. Eventually, they may either by themselves or in combination with
Alzheimer’s pathology and other late life degenerative changes, lead to dementia. In
addition to clinically manifest infarcts and hemorrhages, white matter lesions and lacunar
infarcts are frequently observed on brain images, suggesting a common etiology.
Atherosclerosis-like changes and wall thickening of deep cerebral arterioles are
observed on autopsy of elderly people in areas with white matter lesions and lacunar infarcts.
Hence, these lesions are referred to as cerebral small vessel disease. The exact
etiology of white matter lesions in elderly people is unknown and a wide variety of rare
causes have been described. Nevertheless, almost all studies point to increasing
age, arterial hypertension, and indicators of systemic atherosclerosis as the main risk
factors. Post-mortem and blood-fl ow studies show ischemia and hypoperfusion in
brain areas with large white matter lesions. Reports on the evaluation of these brain
lesions over time are scarce. A better understanding of the etiology of cerebral small
vessel disease could contribute to the prevention of stroke, dementia and depression, as
well as more subtle cognitive decline, depressive symptoms and gait disturbances in a
rapidly increasing elderly population.
The objective of this thesis was to gain more insight into the etiology of cerebral
small vessel disease
