Brain atrophy in patients with arterial disease. The SMART-MR study

Abstract

Brain atrophy is often observed on magnetic resonance imaging (MRI) in the elderly. This is of clinical importance since the extent and rate of progression of brain atrophy are associated with future cognitive deterioration and conversion to Alzheimer’s dementia. The overall aim of this thesis was to gain further insight in the contribution of vascular pathology and cerebral hypoperfusion to the development of brain atrophy and cognitive decline. First, we estimated brain volumes and cerebrovascular lesions on MRI in a large cohort of patients with arterial disease. The decrease in total brain volume and cortical gray matter volume with age was comparable with findings from the general population. However, white matter lesions, silent brain infarcts, and subcortical brain atrophy, were more common in patients with arterial disease. Next, we investigated whether white matter lesions and lacunar infarcts were associated with brain atrophy and cognitive impairment. We found that white matter lesions were associated with more global, subcortical and cortical brain atrophy, whereas lacunar infarcts were associated with more global and subcortical atrophy. Furthermore, we found that white matter lesions and lacunar infarcts were both associated with worse executive functioning independently of brain atrophy. White matter lesions and lacunar infarcts were not associated with worse memory. Finally, we investigated the associations between cerebral blood flow, brain atrophy and cognitive functioning. We found that a lower cerebral blood flow was associated with more subcortical brain atrophy, but only in patients with moderate to severe white matter lesions. We also found that lower cerebral blood flow was associated with worse executive performance. The association between lower cerebral blood flow and worse performance on executive functioning also became stronger with increasing volumes of white matter lesions. The studies described in this thesis showed that white matter lesions, lacunar infarcts, and subcortical brain atrophy were highly prevalent in our study population. White matter lesions seem to contribute to the development of brain atrophy, but they also appear to be an independent risk factor for impairment in executive functioning. Furthermore, white matter lesions may make persons more vulnerable to the devastating effects of cerebral hypoperfusion. The finding of a high prevalence of subcortical vascular pathology suggests that patients with arterial disease may be at increased risk of developing subcortical ischemic vascular dementia. Global and cortical brain atrophy appeared to be a less prominent feature of our population. We speculate that subcortical ischemic vascular disease is a contributing factor in the pathogenesis of cognitive decline and dementia at a stage before brain atrophy contributes to this process. This suggests that treatment of vascular risk factors may prevent or slow down the development of brain atrophy and cognitive decline.