Microvascular Endothelial Function and Neurocognition Among Adults With Major Depressive Disorder

Cardiovascular risk factors (CVRFs) and endothelial dysfunction have been associated independently with poorer neurocognition in middle-aged adults, particularly on tests of frontal lobe function. However, to our knowledge, no studies have examined markers of microvascular dysfunction on neurocognition or the potential interaction between macro- and microvascular biomarkers on neurocognition in middle-aged and older adults with major depressive disorder (MDD).

Participants included 202 adults with MDD who were not receiving mental health treatment. Microvascular endothelial function was assessed using a noninvasive marker of forearm reactive hyperemia velocity while macrovascular endothelial function was assessed using flow-mediated dilation (FMD) of the brachial artery. CVRFs were assessed using the Framingham Stroke Risk Profile and fasting lipid levels. A standardized neurocognitive assessment battery was used to assess three cognitive domains: executive function, working memory, and verbal memory.

Greater microvascular dysfunction was associated with poorer neurocognition across all three domains. Microvascular function continued to predict verbal memory performance after accounting for background factors and CVRFs. Macro- and microvascular function interacted to predict working memory performance (F = 4.51_{1, 178}, p = 0.035), with a similar nonsignificant association for executive function (F = 2.73_{1, 178}, p = 0.095), with moderate associations observed between microvascular function and neurocognition in the presence of preserved FMD (r₆₁ = 0.40, p = 0.001), but not when FMD was impaired (r₆₃ = -0.05, p = 0.675).

Greater microvascular dysfunction is associated with poorer neurocognition among middle-aged and older adults. This association was strongest in participants with preserved macrovascular function.