White matters : a longitudinal study on causes and consequences of
white matter hyperintensities in the elderly.
Heuvel, D.M.J. van den
Citation
Heuvel, D. M. J. van den. (2005, November 17). White matters : a longitudinal study on
causes and consequences of white matter hyperintensities in the elderly. Retrieved from
https://hdl.handle.net/1887/3729
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Corrected Publisher’s Version
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Institutional Repository of the University of Leiden
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Chapter
1
CHAPTER 1
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The brain is the supervisory centre of the nervous system that is involved in all our human activities. It consists for about 60% of white matter that is located in the central and subcortical regions of the cerebral and cerebellar hemispheres. White matter is primarily made up of myelin sheated axons, which are extensions of nerve cell bodies that reside within the cerebral cortex. White matter is respon-sible for the transmission of impulses between different areas in the brain and thus, as part of a complex association network, plays a critical role in the func-tioning of the brain1.
The introduction of modern imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) in the 1970’s and 1980’s made it possible to obtain detailed images of the cerebral white matter. Especially, MRI was found to be highly sensitive to detect pathological changes in the white mat-ter2. Many of these white matter lesions appear as hyperintense areas on conven-tional Proton Density (PD), T2-weighted or Fluid Attenuated Inversion Recovery (FLAIR) images and are therefore referred to as white matter hyperintensities (WMH) in literature. WMHs occur with a high frequency in elderly individuals. They are common observations on MR scans of demented patients and patients presenting with stroke and lacunar infarcts3-8. Moreover, it soon became evident that WMHs are also common in non-demented and otherwise healthy elderly9-11. In individual cases, WMHs do not seem to be associated with obvious neurologi-cal or cognitive symptoms. However, mounting evidence indicates that these WMHs may be of clinical importance12, 13.
Numerous neuroimaging studies have reported on the etiology of WMHs. A major-ity of studies has pointed out that age is the major independent risk factor for developing WMHs. Furthermore, classical cerebrovascular risk factors like hyper-tension, diabetes, artherosclerosis, and smoking have been associated with the presence of WMHs9, 10, 14-17. As major consequences of WMHs reduced mental pro-cessing speed and reduced attention have been reported. In addition, subtle memory dysfunction and deficits in executive functioning have been attributed to WMHs. Other deficits like depression and gait disturbances have also been report-ed in subjects with WMHs.
in combination with serial cerebral MRI21-24. Still, these studies suffer from a lack of statistical power due to small sample sizes and underestimation of WMH pro-gression due to visual assessment of WMH propro-gression.
The studies in this thesis were undertaken in the context of a longitudinal study with serial measurements of WMHs. In addition, our study benefits from a large sample of elderly subjects and a semiautomated quantitative measurement of WMH volumes.
Outline of the thesis
The general objective of this thesis was to prospectively investigate possible caus-es and consequenccaus-es of WMHs in a group of non-demented elderly individuals with pre-existing vascular disease or at risk of developing this condition. The studies presented in this thesis are based on the MRI substudy of the PROspective Study of the Elderly at Risk (PROSPER). A brief overview of the PROSPER study is given in chapter 2.
The thesis consists of seven studies focussing on i) the methods for quantifying WMH, ii) the causes of WMHs, iii) the impact of WMHs on cognitive functioning and, iv) the prevention of progression of WMHs and infarcts by pharmacological intervention.
In chapter 3 and 4 we report on the methods used for measuring longitudinal WM changes. In chapter 3 an inhouse developed quantitative volumetric measure-ment method to study longitudinal WM changes is introduced. In chapter 4 this quantitative volumetric measurement method is compared to a widely used semi-quantitative visual rating scale in the ability to measure longitudinal WM changes. Chapter 5 reports the differences between elderly men and women in their pro-gression rates for white matter hyperintensities. Chapters 6 and 7 focus on the association between possible vascular and cerebrovascular determinants and the presence and progression of WMHs. More specifically, in chapter 6 we studied the association between cerebral blood flow and WMHs, whereas in chapter 7 the influence of history of vascular disease and current risk factors for vascular dis-ease on the presence and progression of WMHs was studied. Whether WMHs have consequences for cognitive functioning in a non-demented population is explored in chapter 8. Finally, in chapter 9 we studied the benefits of treatment with pravastatin on the progression of ischemic brain lesions (infarcts and WMHs). In chapter 10, our main conclusions are summarized and discussed.
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Reference List
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