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.