The objective of the studies described in this thesis was to investigate with magnetic resonance imaging (MRI) brain changes that may function as preclinical imaging markers for neurodegenerative and cerebrovascular disease. For this goal, advanced MRI techniques were applied in the Rotterdam Scan Study, a large population-based brain imaging study among middle-aged and elderly persons. We studied the prevalence and distribution of age-related brain changes on MRI, investigated associated risk factors and related these brain changes to cognitive functioning. We found that cerebral microbleeds were present in 1 in 5 persons over age of 60. This prevalence is much higher than reported previously, which in part may be explained by the use of a more sensitive MRI sequence. Furthermore, we showed that risk factors for microbleeds varied according to the location of microbleeds in the brain. By measuring cerebral blood flow, we assessed that persons with low total brain perfusion had significantly more white matter lesions compared to those with high total brain perfusion. This suggests that tissue hypoperfusion may contribute to white matter lesion pathogenesis. Microstructural integrity within white matter lesions or normal-appearing white matter was associated with cognitive function, even when taking into account volume of white matter lesions and white matter atrophy. This indicates that the deleterious effect of white matter changes on cognition not only depends on lesion burden or amount of atrophy, but also on characteristics that are not easily evaluated by conventional MRI. The studies described in this thesis have identified several age-related brain changes that have potential to serve as imaging markers for neurodegenerative or cerebrovascular disease.

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Erasmus MC, Netherlands Organization for Scientific Research (NWO), Netherlands Organization for Health Research and Development (ZonMw), Research Institute for Diseases in the Elderly (RIDE), Ministry of Education, Culture and Science, Ministry of Health, Welfare and Sports, European Commission (DG XII) , Municipality of Rotterdam, General Electric Healthcare, Remmert Adriaan Laan Fonds, J.E. Jurriaanse Stichting, Internationale Stichting Alzheimer Onderzoek, Janssen-Cilag BV, AstraZeneca BV, Bayer, Schering Pharma, Stichting Alzheimer Nederland.
G.P. Krestin (Gabriel) , M.M.B. Breteler (Monique)
Erasmus University Rotterdam
Erasmus MC: University Medical Center Rotterdam

Vernooij, M. (2009, March 11). Imaging of Age-related Brain Changes: A Population-based Approach. Retrieved from