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To investigate the effects of inflammation on perfusion regulation and brain volumes in type 2 diabetes.A total of 147 subjects (71 diabetic and 76 nondiabetic, aged 65.2 ± 8 years) were studied using 3T anatomical and continuous arterial spin labeling magnetic resonance imaging. Analysis focused on the relationship between serum soluble vascular and intercellular adhesion molecules (sVCAM and sICAM, respectively, both markers of endothelial integrity), regional vasoreactivity, and tissue volumes.Diabetic subjects had greater vasoconstriction reactivity, more atrophy, depression, and slower walking. Adhesion molecules were specifically related to gray matter atrophy (P = 0.04) and altered vasoreactivity (P = 0.03) in the diabetic and control groups. Regionally, sVCAM and sICAM were linked to exaggerated vasoconstriction, blunted vasodilatation, and increased cortical atrophy in the frontal, temporal, and parietal lobes (P = 0.04–0.003). sICAM correlated with worse functionality.Diabetes is associated with cortical atrophy, vasoconstriction, and worse performance. Adhesion molecules, as markers of vascular health, have been indicated to contribute to altered vasoregulation and atrophy.