Lesion-symptom mapping in vascular cognitive impairment

Abstract

Cerebral vascular disease (CVD) is an important cause of cognitive decline and dementia, either alone or in combination with neurodegenerative diseases, such as Alzheimer's Disease (AD). The contribution of CVD to cognitive decline and dementia is referred to as Vascular Cognitive Impairment (VCI). This thesis focuses on the role of lesion location in the cognitive impact of vascular brain injury. In the first part of this thesis, I aim to determine the neural substrates of several specific cognitive processes by applying lesion-symptom mapping to patients with acute ischemic stroke. In lesion-symptom mapping, the cognitive deficit that is observed in a patient is 'mapped' to the damaged brain region. In this context, stroke is used as a 'model condition' to study the neural substrates of certain cognitive processes and to get a more complete picture of the cognitive architecture of complex mental processes. In the second part of this thesis, I focus on the relation between vascular lesion location and cognitive functioning in patients with white matter hyperintensities (WMH) and lacunes. A common observation in clinical practice is that some patients with extensive WMH are cognitively intact, whereas others have severe cognitive impairment. A probable explanation for this discrepancy is that the cognitive impact of these lesions depends on location. In part II of this thesis, I aim to provide statistical proof for this hypothesis and identify strategic white matter tracts in which vascular lesion disproportionally affect cognitive functioning. Results and conclusions: The studies of part I identify, for the first time, the neural substrate of visuocontruction proper, and discriminability and criterion setting in verbal recognition memory, and reveal that the right inferior frontal gyrus is crucially involved in semantic, but not phonemic verbal fluency. These findings provide novel insights into the cognitive architecture of the human brain, and further clarify the interplay between cognitive subcomponents in visuospatial construction and recognition memory. The studies of part II provide solid proof for the concept that the impact of WMH and lacunes on cognitive functioning depends on location and demonstrated the added value of DTI-based assessment of the white matter. As such, shifting from a global assessment of MRI markers for brain injury towards the assessment of lesion volumes and microstructural characteristics of strategic brain regions has the potential to improve the diagnostic work-up of memory clinic patients