BACKGROUND: Type 2 diabetes mellitus is associated with risk of congestive heart 
failure (CHF), cognitive dysfunction and depression. CHF itself is linked both 
to poor cognition and depression. The ventricular N-terminal pro-brain 
natriuretic peptide (NT-proBNP) is a marker of CHF, suggesting potential as a 
marker for cognitive impairment and/or depression. This was tested in the 
Edinburgh Type 2 Diabetes Study (ET2DS).
METHODOLOGY AND PRINCIPAL FINDINGS: Cross-sectional analysis of 1066 men and 
women aged 60-75 with type 2 diabetes. Results from seven neuropsychological 
tests were combined in a standardised general cognitive ability factor, 'g'. A 
vocabulary-based test estimated pre-morbid cognitive ability. The Hospital 
Anxiety and Depression Scale (HADS) assessed possible depression. After 
adjustment for age and sex, raised plasma NT-proBNP was weakly associated with 
lower 'g' and higher depression scores (ß -0.09, 95% CI -0.13 to -0.03, 
p = 0.004 and ß 0.08, 95% CI 0.04 to 0.12, p<0.001, respectively). Comparing 
extreme quintiles of NT-proBNP, subjects in the highest quintile were more 
likely to have reduced cognitive ability (within the lowest tertile of 'g') and 
'possible' depression (HADS depression ≥8) (OR 1.80; 95% CI: 1.20, 2.70; 
p = 0.005 and OR 2.18; 95% CI: 1.28, 3.71; p = 0.004, respectively). 
Associations persisted when pre-morbid ability was adjusted for, but as expected 
were no longer statistically significant following the adjustment for 
diabetes-related and vascular co-variates (β -0.02, 95% CI -0.07 to 0.03, p>0.05 
for 'g'; β 0.03, 95% CI -0.02 to 0.07, p>0.05 for depression scores).
CONCLUSION: Raised plasma NT-proBNP was weakly but statistically significantly 
associated with poorer cognitive function and depression. The prospective phases 
of the ET2DS will help determine whether or not NT-proBNP can be considered a 
risk marker for subsequent cognitive impairment and incident depression and 
whether it provides additional information over and above traditional risk 
factors for these conditions.