N-Terminal Pro-Brain Natriuretic Peptide and Cognitive Decline in Older Adults at High Cardiovascular Risk

Objective: Elevated levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) are associated with cognitive impairment, which might be explained by cardiovascular diseases or risk factors. The aim of this study was to investigate the association of NT-proBNP with cognitive function and decline in older adults at high risk of cardiovascular disease. Methods: We studied 5,205 men and women (mean age = 75 years) who were recruited into the PROspective Study of Pravastatin in the Elderly at Risk. All participants had pre-existing cardiovascular disease or risk factors thereof. Four domains of cognitive function were tested at baseline and repeated during a follow-up period of 3.2 years. Results: Participants with higher NT-proBNP (>= 450ng/l) had worse baseline cognitive function, including reaction time (mean difference high vs low group = 3.07 seconds, 95% confidence interval [CI] = 0.83 to 5.32), processing speed (-1.02 digits coded, 95% CI = -1.65 to -0.39), and immediate memory (-0.13 pictures remembered, 95% CI= -0.29 to 0.04). There was no significant difference in delayed memory (-0.14, 95% CI=-0.38 to 0.10) between the NT-proBNP groups. Participants with higher NT-proBNP had a steeper cognitive decline, including reaction time (mean annual change high vs low group = 0.60 seconds, 95% CI = 0.14 to 1.07), processing speed (-0.15 digits coded, 95% CI = -0.25 to -0.05), immediate memory (-0.05 pictures remembered, 95% CI=-0.09 to 0.00), and delayed memory (-0.05 pictures remembered, 95% CI=-0.11 to 0.01). Associations were independent of cardiovascular diseases and risks. Interpretation: Higher NT-proBNP associates with worse cognitive function and steeper cognitive decline, independent of cardiovascular diseases and risks. Further studies to unravel the underlying mechanisms are warranted.