Association of N-Terminal Pro-Brain Natriuretic Peptide with Cognitive Function and Depression in Elderly People with Type 2 Diabetes

Edinburgh Type 2 Diabet Study Inve, Insa Feinkohl*, Naveed Sattar, Paul Welsh, Rebecca M. Reynolds, Ian Deary, Mark W. J. Strachan, Jackie F. Price

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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 (beta -0.09, 95% CI -0.13 to -0.03, p = 0.004 and beta 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 (beta -0.02, 95% CI 20.07 to 0.03, p > 0.05 for 'g'; beta 0.03, 95% CI 20.02 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.

Original languageEnglish
Article numberARTN e44569
Number of pages7
JournalPLoS ONE
Issue number9
Publication statusPublished - 4 Sep 2012




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