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- W2085165058 abstract "To examine the association between longitudinal changes in total and regional brain volumes and pathology. Research participants of the Oregon Alzheimer's Disease Center were followed on average for 7 years with annual MRI scans until death. Initial MRI was obtained before onset of dementia and last MRI within a mean of 15 months of death. Average age at death was 95 years. Using mixed-effects models the relationship between longitudinal changes in regional brain volumes (ventricular, total brain, and hippocampal) and pathology (neurofibrillary tangles (NFTs), neuritic plaques (NPs), gross infarcts, microinfarcts, amyloid angiopathy, Lewy Bodies) was examined adjusting for APOE status, diagnosis, duration of follow up and age at death. In a subset of participants the relationship between white matter hyperintensity (WMH) accumulation and pathology (myelin pallor, arteriolosclerosis, atherosclerosis, microvascular disease, microinfarcts, large vessel infarcts, lacunar infarcts, amyloid angiopathy, NFTs and NPs) was examined using a similar statistical approach. Ventricular enlargement over time was associated with infarcts (p<.001), NFTs (p=.015), NPs (p=.001), age (p<.001), and presence of the ε4 allele (p<.001). Ventricular enlargement accelerated in mild cognitive impairment (MCI) (p=.04) and dementia (p<.001) compared to normal cognition. Total brain atrophy was associated with age (p<.001), amyloid angiopathy (p=.03) and infarcts (p=.04) and also accelerated in MCI (p=.004) and dementia (p=.02). Longitudinal hippocampal atrophy was only associated with amyloid angiopathy (p=.009). WMH accrual was associated with arteriolosclerosis (p<.0001), myelin pallor (p=.04), NFTs (p=.008) and presence of the ε4 allele (p=.02). In post-hoc analysis, those with highest NFT burden had significantly more atherosclerosis compared to those with lowest NFT burden. Ventricular volume trajectory is more sensitive than total brain and hippocampal atrophy as a marker of accruing Alzheimer's and cerebrovascular disease pathology in the oldest old. Because MCI and dementia diagnosis contributed to more brain atrophy despite adjusting for pathology, other unmeasured factors are likely contributing to brain atrophy. Last, while arteriolosclerosis is the main driver of WMH accumulation, the observed association between NFTs and WMH accumulation supports a link between cerebrovascular disease and Alzheimer's disease." @default.
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- W2085165058 date "2014-07-01" @default.
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- W2085165058 title "S1-01-01: PATHOLOGY UNDERLYING REGIONAL BRAIN ATROPHY" @default.
- W2085165058 doi "https://doi.org/10.1016/j.jalz.2014.04.035" @default.
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