Human cerebral collateral arteriole function in subjects with normal cognition, mild cognitive impairment, and dementia



Migrino, Raymond Q, Truran, Seth, Karamanova, Nina, Davies, Hannah, Madine, J ORCID: 0000-0001-9963-5871, Reaven, Peter and Beach, Thomas G
(2018) Human cerebral collateral arteriole function in subjects with normal cognition, mild cognitive impairment, and dementia. American Journal of Physiology: Heart and Circulatory Physiology, 315 (2). H284 - H290.

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Abstract

Clinical and preclinical studies have suggested a link between cardiovascular disease and dementia disorders, but the role of the collateral brain circulation in cognitive dysfunction remains unknown. We aimed to test the hypothesis that leptomeningeal arteriole (LMA) function and response to metabolic stressors differ among subjects with dementia, mild cognitive impairment (MCI), and normal cognition (CN). After rapid autopsy, LMAs were isolated from subjects with CN (n = 10), MCI (n = 12), or dementia [n = 42, Alzheimer’s disease (AD), vascular dementia (VaD), or other dementia], and endothelial and smooth muscle-dependent function were measured at baseline and after exposure to β-amyloid (2 μM), palmitic acid (150 μM), or medin (5 μM) and compared. There were no differences among the groups in baseline endothelial function (maximum dilation to acetylcholine, CN: 74.1 ± 9.7%, MCI: 67.1 ± 4.8%, AD: 74.7 ± 2.8%, VaD: 72.0 ± 5.3%, and other dementia: 68.0 ± 8.0%) and smooth muscle-dependent function (CN: 93.4 ± 3.0%, MCI: 83.3 ± 4.1%, AD: 91.8 ± 1.7%, VaD: 91.7 ± 2.4%, and other dementia: 87.9 ± 4.9%). There was no correlation between last cognitive function score and baseline endothelial or smooth muscle-dependent function. LMA endothelial function and, to a lesser extent, smooth muscle-dependent function were impaired posttreatment with β-amyloid, palmitic acid, and medin. Posttreatment LMA responses were not different between subjects with CN/MCI vs. dementia. Baseline responses and impaired vasoreactivity after treatment with metabolic stressors did not differ among subjects with CN, MCI, and dementia. The results suggest that the cognitive dysfunction in dementia disorders is not attributable to differences in baseline brain collateral circulation function but may be influenced by exposure of the vasculature to metabolic stressors.

Item Type: Article
Uncontrolled Keywords: Alzheimer’s disease, cerebrovascular disease, disease model, endothelial function, vascular dementia
Depositing User: Symplectic Admin
Date Deposited: 24 May 2018 13:50
Last Modified: 09 Jan 2021 05:29
DOI: 10.1152/ajpheart.00206.2018
Open Access URL: https://www.physiology.org/doi/abs/10.1152/ajphear...
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3021714