Assessing the cumulative impact of vascular burden on structural changes in the brain during ageing

Abstract

AbstractBackgroundAlzheimer’s disease (AD) is the most common cause of dementia. Yet more recent findings from epidemiological and neuropathological studies have revealed the presence of vascular pathology in AD. There is overwhelming evidence from pathological examinations that indicates the presence of ‘mixed cases’ at autopsy. The study aim was to examine whether overall vascular burden measured by the Framingham General Cardiovascular Risk Score (FGCRS) is associated with brain structural changes.MethodIn the first analysis a Voxel Based Morphometry (VBM) multiple regression model was used with group status (60 controls, 74 Mild Cognitive Impairment and 51 AD) and Framingham vascular risk scores as predictors while accounting for age, total intracranial volume, years of education. In the second model a 2x2x2 factorial design with different group comparisons was used with group, APOE ε4 carrier status and Vascular Burden (low vs high load) to understand the interactions across the factors.ResultThe VBM regression model implicated regions that included the thalamus, subcallosal gyrus, precentral and postcentral gyrus, cerebellum, occipital gyri, inferior frontal gyrus, insula and the cuneus.The factorial analysis revealed two different set of interaction effects. There was a APOE x Vascular Burden interaction effect between controls and MCI. The regions implicated in this analysis included the cerebellum, right inferior occipital gyrus, right thalamus, left brainstem, left fusiform gyrus, left precentral and postcentral gyrus and left Insula. There also was a Group x APOE Status x Vascular Burden interaction effect that involved the left brainstem and left parahippocampal gyrus during the transition from MCI and AD.ConclusionThe voxel‐based regression model and the first factorial analysis implicated areas that comprises both cerebellar and subcortical regions that have been previously implicated in dementia with vascular pathology. The areas implicated by vascular pathology have been shown to affect primarily gait, movement and visuospatial abilities. But given that the brainstem and its nuclei are also involved, future studies should look at examining the role of vascular pathology and how it affects the neuromodulatory systems of the brainstem and whether these projections have any effect on the efficient functioning of large‐scale brain networks.