Objective

Changes 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.

Method

We 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.

Results

Angiogenin 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).

Conclusion

The 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.

Plain Language Summary

The relationship between blood markers and thinking/memory in older adults at risk for dementia.

This study aimed to identify blood markers related to angiogenesis (the process of new blood vessel formation) that could predict cognitive function (memory and thinking abilities), in older adults at risk for dementia. Angiogenesis has been linked to dementia, and understanding its associated biological factors may help in predicting cognitive decline, particularly in individuals who are at risk for dementia. Participants included adults over 50 years of age with cognitive impairment and/or a history of depression. We used the elastic net regression model to select eight out of 19 angiogenesis markers while considering five out of the six other factors (covariates) that might influence cognition, such as age, education level, apolipoprotein E genotype, diagnosis, and cardiovascular health. Among the markers studied, angiogenin, a marker that can increase angiogenesis, stood out as the only one associated with cognitive function. When considering other factors, higher levels of angiogenin were linked to better cognition. This association was present even when angiogenin was examined on its own, independent of other angiogenesis markers. Angiogenin might play a protective role in cognition in older adults at risk for dementia. Overall, the findings highlight angiogenin as a potential biomarker for cognitive health in aging adults, who were at risk with early signs of cognitive impairment and a history of depression. This suggests that angiogenin could be a target for future research into treatments aimed at preventing or slowing cognitive decline in vulnerable populations.

Search results

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