Cerebral white matter changes : Differentiating vascular and degenerative cognitive impairment

Abstract

Different types of dementia are difficult to identify in vivo, especially at early stages and partly due to the frequent co-existence of various etiologies. Recent techniques, including examination of biomarkers in cerebrospinal fluid (CSF) and advanced brain imaging techniques facilitate a more precise diagnosis of a given type of dementia. As previous diagnostic criteria for the Alzheimer type of dementia (AD) only captured the disease after dementia occured, new criteria involving recent biomarkers aim to arrive at a diagnosis at early stages, even prior to the onset of overt dementia. Along with episodic memory impairment, neuroimaging and CSF analysis have been proposed as reliable and important tools to make an accurate AD diagnosis possible, including forms of AD with co-existing cerebrovascular disease. The objective of this thesis aims to exploit the posssibilities of CSF analysis and neuroimaging in order to better understand the relationship between cerebrovascular and degenerative changes and cognition. To do so, measures of cerebral white matter changes from magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) were studied in cognitively impaired patients and compared to levels of CSF biomarkers and cognition. In degenerative and vascular cognitive impairment, risk factors and pathological disease processes have been well mapped. However, it remains unclear which exact mechanisms trigger these processes and in which way white matter changes and cortical events are connected. Improved early diagnostic specificity and better knowledge of interaction between vascular and degenerative changes may give rise to specific approaches to prevention and therapy, based upon individual risk-profiles.