Blood Angiogenesis Markers and Cognition in Older Adults at Risk for Dementia: Marqueurs sanguins de l'angiogenèse et cognition chez les personnes âgées à risque de démence.

ObjectiveChanges in angiogenesis have been shown to contribute to cognitive decline and dementia. We aimed to identify angiogenesis blood markers associated with cognitive performance in older adults with mild cognitive impairment (MCI), remitted major depressive disorder (rMDD), or both (rMDD + MCI) who are at risk for dementia.MethodWe analyzed data from participants with MCI, rMDD, or rMDD + MCI in the Prevention of Alzheimer's Dementia with Cognitive Remediation plus Transcranial Direct Current Stimulation in Mild Cognitive Impairment and Depression study. Elastic net regression was used to select variables associated with cognitive performance among 19 angiogenesis markers and 6 covariates. Linear regressions were used to determine which of the selected angiogenesis markers were associated with cognitive performance, controlling for the selected covariates. Significant angiogenesis markers were independently analyzed without other angiogenesis markers, controlling for covariates, with subgroup analyses in those with and without rMDD.ResultsAngiogenin was the only selected marker associated with cognitive performance (β = 0.28, P_adj = 0.03, f² = .02) when controlling for other selected markers (endothelial cell-specific molecule 1, e-selectin, interleukin-33 [IL-33], oncostatin M, platelet-derived growth factor-AB, IL-33 receptor, and tissue inhibitor of metalloproteinases-1) and selected covariates (age, education, apolipoprotein E ε4 status, diagnosis, and cardiovascular risk factors). When independently analyzed, angiogenin remained positively associated with cognitive performance (β = 0.21, P = 0.01, f² =.02), controlling for the covariates. In subgroup analyses, angiogenin was also associated with cognition in rMDD and rMDD + MCI participants (β =0.50, SE = 0.14, P < 0.001, f² = 0.08) and in MCI-only participants (β= 0.20, SE = 0.09, P = 0.02, f² = 0.02).ConclusionThe association of angiogenin with cognitive performance highlights a potentially novel biological pathway that could influence cognition in older adults at risk for dementia. Angiogenin may protect against cognitive decline, opening new avenues for innovative preventive, or therapeutic interventions.