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In contrast, patients with WMH progression presented a steeper decline in MET over time. Furthermore, cases showed higher MMP9 and lower ASAH2 levels than controls at the follow-up. These results indicate that MMP9, MET, and ASAH2 are potentially associated with the progression of WMH, and could therefore be interesting candidates to validate in future studies.Multiple theories have proposed that increasing central arousal through the brain's locus coeruleus-norepinephrine system may facilitate cognitive control and memory. However, the