Vascular burden and integrity of brain structural parameters in ageing and in early Alzheimer's disease

Abstract

Pure cases of Alzheimer’s Disease (AD) seldom exist by itself and generally AD tends to coexist with cerebrovascular disease or other vascular risk factors. This suggests that most of the structural damage caused to grey matter and white matter cannot be due simply to neurodegenerative pathology but would also reflect the presence of vascular pathology causing additional damage to these structures at the macro as well as micro level. This damage is different to the damage caused by AD and it is also manifested through changes in the cognitive phenotype. The aim of this thesis is to explain the cumulative contribution of several vascular risk factors as measured using a composite score (vascular burden) and to examine the type of damage inflicted by low or high vascular burden at the macro level (grey and white matter volume) and also at the micro level (white matter microstructural alterations). In addition, the interaction between a genetic risk factor for AD, i.e., carrying the 4 allelic variant of the apolipoprotein E and vascular burden on structure was examined. Finally, a separate chapter was dedicated to examining the beneficial effects of physical activity on white matter integrity given that both epidemiological and longitudinal studies show it delays the onset of cognitive decline in AD. The evidence from the voxel-based analysis at the macro level from GMV suggests that vascular burden tends to be additive. At the micro level, vascular pathology again tends to show additive features, affecting late-myelinating association tracts followed by projection tracts and this damage is inflicted at a macro scale. Specifically, in relation to the projection tracts, there is a rightward asymmetry. Furthermore, an interaction between APOE status and vascular burden suggests that the non-carriers with high vascular burden tend to show the greatest damage. The beneficial effect of physical activity too was seen at a macro scale on several white matter tracts.