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Background: Coated-platelets, a subset of procoagulant platelets observed upon dual agonist stimulation with collagen and thrombin, are elevated in patients with incident and recurrent stroke/TIA and mild cognitive impairment. We now report the association between coated-platelets and brain imaging correlates of vascular cognitive impairment in a pilot study of cognitive impairment among Native Americans Veterans.Methods: Coated-platelets, reported as percentage of cells converted to coated-platelets, were assayed in 60 Native American veterans with ≥2 vascular risk factors. The Montreal Cognitive Assessment (MoCA) and the Beck Depression Inventory-II were administered to screen for cognitive impairment and depression. Brain CT or MRI performed within 12 months of enrollment were reviewed for silent brain infarction (SBI), small vessel disease and/or atrophy. SBI was defined as focal, ≥ 3mm, cavitary lesion with T1 hypointensity and T2 hyperintensity features on MRI or hypodense on CT and not associated with stroke history or focal neurologic findings. Differences in mean coated-platelet levels by imaging results were determined using the Kruskal-Wallis test.Results: MoCA scores were abnormal (<26) in 23 of 51 subjects (44%, 95%CI: 30%-59%) after excluding 9 with depression. Brain imaging was available for 36 subjects (97% male, mean age 63 range 50-86). Twelve (33%, 95%CI: 19%-51%) had normal results, 19 (53%, 35%-70%) had small vessel disease and/or atrophy, and 5 (14%, 5%-30%) had SBI. Median coated-platelets were significantly higher among those with SBI (51%, IQR 48%-59%) versus those without SBI having either normal results (36.5%, IQR 30.5%-48.1%) or small vessel disease and/or atrophy (33.6%, IQR 24.4%-47.3%), overall p=0.045.Conclusion: Platelet procoagulant potential is increased among Native American veterans with vascular risk factors and SBI versus those with normal scans or with small vessel disease and/or atrophy. These results suggest a role for coated-platelets as a biomarker of SBI in vascular cognitive impairment, and are consistent with previous findings of increased risk of ischemic stroke among non-Native Americans. Further studies are warranted to confirm these results and explore mechanisms involved.