Cerebral white matter injury in small vessel and Alzheimer’s disease

Alzheimer’s disease and small vessel disease are the most common causes of ageing-related cognitive impairment and dementia. In order to better understand these diseases, there is a need for sensitive brain injury markers. Measures of white matter integrity derived from diffusion MRI have been suggested as an injury marker in both conditions. The overarching aim of this thesis was to study the microstructural integrity of the white matter in Alzheimer’s disease and small vessel diseases to better understand brain injury and cognitive decline in these conditions.

Four key findings emerged from my thesis: 1) small vessel diseases more than Alzheimer’s disease determine white matter diffusion MRI alterations in memory clinic patients. 2) small vessel diseases and Alzheimer’s disease could not be disentangled based on their white matter diffusion signature with the techniques we used. 3) For neither disease, critical network connections were not found to be extra vulnerable compared to non-critical connections. The effects of both small vessel diseases and Alzheimer’s disease on the white matter network seem quite diffuse. 4) Diffusion-based measures of white matter integrity appear to be a strong determinant of cognition in small vessel diseases and white matter integrity mediates the relationship between small vessel diseases burden and cognition.

The work in this thesis shows that for small vessel diseases, diffusion measures are strong markers, capable of capturing relevant information about the disease. For Alzheimer’s disease, there are currently alternative markers that provide more information on relevant aspects of the disease processes and injury and are more specific to Alzheimer’s disease than diffusion measures of the white matter.