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

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 beta-amyloid (2 mu M), palmitic acid (150 mu M), or medin (5 mu M) 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 muscledependent function. LMA endothelial function and, to a lesser extent. smooth muscle-dependent function were impaired posttreatment with -amyloid, palmitic acid, and mexlin. 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. NEW & NOTEWORTHY Here, we present novel findings that brain collateral arteriole function did not differ among subjects with normal cognition, mild cognitive impairment, and dementia (Alzheimer's disease and vascular dementia). Although arteriole function was impaired by vascular stressors (beta-amyloid, palmitic acid, and medin), responses did not differ between those with or without dementia. The cognitive dysfunction in dementia disorders is not attributable to differences in baseline brain collateral circulation function but may be influenced by vascular exposure to metabolic stressors.