Non-Atherosclerotic Brain Arterial Remodeling and Associated Vascular Dementia Risk

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Non-Atherosclerotic Brain Arterial Remodeling and Associated Vascular Dementia Risk Non-atherosclerotic brain arterial remodeling (NABAR) of the large intracranial arteries has recently emerged as a determinant of poor cognitive outcomes. Vascular aging is associated with elastin fragmentation and collagen deposition, and may present as either outward or tortuous remodeling, both of which may occur in the absence of atherosclerosis. In cross-sectional studies, non-atherosclerotic outward remodeling of the cerebral vasculature has been reported in association with diminished cognitive function. However, the extent to which brain arterial remodeling is permanent vs. reversible, or whether it progresses with age in older individuals is unknown. Mechanistic studies suggest that arterial wall thickness is regulated by intraluminal pressure and wall tension, and that arterial lumen diameter is regulated by blood flow and shear stress. Tortuous elongation has also been associated with mechanical factors, including blood flow, blood pressure, axial tension and wall changes. It is thus plausible that brain arterial remodeling may be dynamic rather than static, even in individuals of advanced age. We propose to examine prevalence and rate of change in NABAR, quantified by luminal diameters and degree of tortuosity, in older individuals from the general population who were imaged by brain MRI at 2 time points. We aim to determine whether vascular risk factors at midlife and their trajectories since midlife associate with NABAR in late life. We will also identify putative factors which may be associated with an accelerated 5-year progression of remodeling in late life. As secondary aims, we will examine the prospective relationship between NABAR and 5-year neurocognitive outcomes (change in cognition and incidence of vascular mild cognitive impairment or vascular dementia), as well as the correlation between 5- year change in NABAR and 5-year change in cognition. We will be uniquely positioned to carry out this project in the Atherosclerosis Risk in Communities study, which has collected clinical data from cohort members over the past 30 years, including multiple assessments by brain MRI and cognitive testing. We will quantify NABAR (dilation and tortuosity) in the basilar artery, middle cerebral arteries, and internal carotid arteries, using existing MRI data (TOF MRA and 3D vessel wall imaging) from ARIC study visit 5 (2011-2013, completed) and visit 6/7 (2016-2019).