Associations of Cerebrovascular and Alzheimer’s Disease Pathology with Brain Atrophy

Cortical atrophy and brain vascular disease are both associated with dementia, but there are only limited pathological data on the association of brain vascular disease with cortical atrophy. We studied pathological material from the Rush Memory and Aging Project (MAP, N = 445). Cortical and hippocampal atrophy, and atherosclerosis at the circle of Willis (large vessel disease, LVD) and arteriolosclerosis (small vessel disease, SVD) were rated by neuropathologists unaware of this study's hypothesis. Quantitative measures of Alzheimer's disease (AD) pathology, specifically neuronal neurofibrillary tangles (NFT) and amyloid-beta (Aβ) burden, were also obtained. Chronic micro and macroscopic infarcts were noted. In ordinal logistic regression models that included age at death, sex, apoE genotype, statin-use, Aβ and NFT, more severe LVD was significantly associated with more severe cortical and hippocampal atrophy. The odds ratio for the association of the most severe LVD (compared to the least) with cortical atrophy was 2.7 (CI: 1.5-4.7) p = 0.001; for hippocampal atrophy the odds ratio was 2.8 (CI: 1.5-5.2), p = 0.001. The association of SVD with atrophy did not follow a consistent pattern. Neither macroscopic infarcts nor microscopic infarcts were associated with cortical or hippocampal atrophy (p's > 0.15). Tangle density was associated with cortical (p = 0.014) and hippocampal atrophy (p < 0.001). In contrast, amyloid burden was associated with less cortical (p = 0.02) or hippocampal (p = 0.002) atrophy. In this large autopsy study LVD was associated with cortical and hippocampal atrophy. The relationship between SVD and atrophy requires further study.