Abstract TMP96: Determining the Relationship Between Cognitive Function and ex-vivo Leptomeningeal Arteriole Function: A Study in Rapid Autopsy Brain Donors

Abstract

Impaired cerebrovascular function can lead to cognitive dysfunction and is implicated as a potential mechanism by which vascular stressors (Aβ, saturated fatty acids such as palmitic acid PA or high glucose HG) contribute to dementia. We aim to test the hypothesis that cognitive function score correlates significantly with baseline ex-vivo cerebrovascular function and dilator response to vascular stressors. Methods: Under a Brain Donation Rapid Autopsy Program, leptomeningeal arterioles were isolated from 59 donors (87.4±1.1 years, 13 cognitively normal, 46 with various neuropathologies), cannulated, pressurized and endothelium-dependent dilation (EDD, acetylcholine max 10 -4 M) and smooth muscle dilation (SMD, papaverine or DETA-Nonoate) were measured at baseline and following exposure to Aβ42 (0.5 or 2 μM, n=40), PA 150 μM (n=13) or high glucose 33 mM (n=11). Correlation analyses were performed between cognitive function score (last mini mental state examination MMSE) and baseline and post-exposure arteriole function. Results: There was no correlation between MMSE score and baseline EDD and SMD (Fig. A-B). Exposure of arterioles to Aβ and PA significantly impaired EDD (-29.1±4.6% and -27.6±9.1% vs. baseline, p<0.05) but not HG (-2.7±6.6%). Aβ and PA impaired SMD (-7.4±3 and -7.4±6.7% vs. baseline, p<0.05) but not HG (0.1±4.4%). There was no significant correlation between MMSE score and arteriole EDD and SMD response to Aβ and PA. However, there was significant correlation between MMSE score and arteriole SMD response to HG (Fig. C). Conclusions: Contrary to our hypothesis, there was no correlation between cognitive function score and baseline ex-vivo leptomeningeal arteriole function. There was significant correlation between cognitive function score and SMD response to HG (but not Aβ or PA). The role of cerebrovascular smooth muscle reserve against hyperglycemic insult in the pathophysiology of cognitive dysfunction needs to be further explored.