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

German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Duesseldorf, Germany.
PLoS ONE (Impact Factor: 3.53). 09/2012; 7(9):e44569. DOI: 10.1371/journal.pone.0044569
Source: PubMed

ABSTRACT 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).

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.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Rates of depression are significantly increased in diabetic patients, and even more in the elderly. About 20-30 % of patients with diabetes suffer from clinically relevant depressive disorders, 10 % of which being affected by the major depression disorder. Moreover, people with depression seem to be more prone to develop an associated diabetes mellitus, and depression can worsen glycemic control in diabetes, with higher risk to develop complications and adverse outcomes, whereas improving depressive symptoms is generally associated with a better glycemic control. Thus, the coexistence of depression and diabetes has a negative impact on both lifestyle and quality of life, with a reduction of physical activity and an increase in the request for medical care and prescriptions, possibly increasing the healthcare costs and the susceptibility to further diseases. These negative aspects are particularly evident in the elderly, with further decrease in the mobility, worsening of disability, frailty, geriatric syndromes and increased mortality. Healthcare providers should be aware of the possible coexistence of depression and diabetes and of the related consequences, to better manage the patients affected by these two pathological conditions.
    Endocrine 06/2014; 48(1). DOI:10.1007/s12020-014-0323-x · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: 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 5205 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 (≥ 450 ng/L) had a worse baseline cognitive function including reaction time (mean difference high vs. low group (95% CI)) 3.07 seconds (0.83; 5.32); processing speed -1.02 digits coded (-1.65; -0.39) and immediate memory -0.13 pictures remembered (-0.29; 0.04). There was no significant difference in delayed memory (-0.14 (-0.38; 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 (95% CI)) 0.60 seconds (0.14; 1.07); processing speed -0.15 digits coded (-0.25; -0.05); immediate memory -0.05 pictures remembered (-0.09; 0.00); delayed memory -0.05 pictures remembered (-0.11; 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. ANN NEUROL 2014. © 2014 American Neurological Association.
    Annals of Neurology 06/2014; 76(2). DOI:10.1002/ana.24203 · 11.91 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In the aging society, it is important to identify very old persons at high risk of functional decline, cardiovascular disease and mortality. However, traditional risk markers lose their predictive value with age. We investigated whether plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels predict change in functional status, cardiovascular morbidity and mortality in very old age. Here we present an observational prospective cohort study (Leiden 85-plus Study, 1997-2004) in a population-based sample of 560 individuals aged 85 years with a 5-year complete follow-up for functional status, cardiovascular morbidity and cause-specific mortality. Median NT-proBNP for men was 351 pg/ml (cutoff values for low-medium tertiles 201 pg/ml and medium-high tertiles 649 pg/ml) and, for women, 297 pg/ml (cutoffs 204 and 519 pg/ml, respectively). During the 5-year follow-up, participants with high NT-proBNP had an accelerated cognitive decline and increase of activities of daily living (ADL) disability over time (all at p < 0.01) and an increased risk of incident heart failure [hazard ratio (HR) 3.3 (95 % confidence interval (CI) 1.8-6.1)], atrial fibrillation [HR 4.1 (2.0-8.7)], myocardial infarction [HR 2.1 (1.2-3.7)], stroke [HR 3.4 (1.9-6.3)], cardiovascular mortality [HR 5.5 (3.1-10)], non-cardiovascular mortality [HR 2.0 (1.4-3.0)] and all-cause mortality [HR 2.9 (2.1-4.0)], independent of other known risk markers. All results remained similar after exclusion of participants with heart failure at baseline. In very old age, high-NT-proBNP levels predict accelerated cognitive and functional decline, as well as cardiovascular morbidity and mortality. Results suggest that NT-proBNP can help clinicians to identify very old people at high risk of functional impairment and incident cardiovascular morbidity.
    Age 05/2014; 36(3). DOI:10.1007/s11357-014-9660-1 · 3.45 Impact Factor

Full-text (2 Sources)

Available from
May 21, 2014