Abstract & Commentary
Brain Natriuretic Peptide A Biomarker for Cognitive Decline?
By Richard S. Isaacson, MD
Associate Professor of Neurology (Education), Weill Cornell Medical College
Dr. Isaacson reports he is a retained consultant and on the speakers bureau for Novartis, and is a retained consultant for and receives grant/research support from Accera.
Synopsis: A new study has found an association between pro-brain natriuretic peptide (NT-proBNP) and cognitive decline in older adults at high risk of cardiovascular disease.
Sources: Wijsman LW, et al. N-terminal pro-brain natriuretic peptide and cognitive decline in older adults at high cardiovascular risk. Ann Neurol 2014;76:213-222. Caplan LR. Cognitive decline and brain natriuretic peptide: How are they related? Ann Neurol 2014;76:165-166.
While there are many uncertainties as to the predictors of cognitive decline, as well as uncertainty regarding the exact causes of vascular and other neurodegenerative dementias that are common with advancing age, new research has attempted to further our understanding of the myriad of potential risk factors. A prospective cohort study by Wijsman and colleagues (Leiden University Medical Center, The Netherlands) recently found that subjects with higher levels of a metabolite of brain natriuretic peptide (BNP) called N-terminal pro-BNP (NT-proBNP) had worse cognitive function and steeper cognitive decline (mean age = 75) over a mean follow-up of 3.2 years. Several cognitive domains were affected and these associations were found to be independent of cardiovascular disease and risk factors in more than 5000 participants of the PROspective Study of Pravastatin in the Elderly at Risk.
Although prior studies have also found an association of these peptides with brain function, most have focused on how NT-proBNP relates to several cardiac diagnoses. Additionally, this is the first study reporting on the association of NT-proBNP and cognitive function and decline, using a much more comprehensive, standardized cognitive test battery over several years. While it is difficult to speculate as to the reason for such an association, and further studies are warranted, these cardiovascular diseases are intimately linked to cognitive dysfunction and dementia. In the cardiovascular literature, patients who have been found to have elevated levels of either BNP or NT-proBNP have a higher risk of morbidity and mortality from heart failure, and these biomarkers may also be elevated in those with atrial fibrillation, myocardial infarction, and renal failure. Further, NT-proBNP has been used clinically to help screen for those likely to develop atrial fibrillation and lower the threshold for prolonged cardiac rhythm monitoring.
In the accompanying editorial by Dr. Louis Caplan (Beth Israel Deaconess Medical Center, Harvard Medical School), several hypotheses are discussed about potential relationships that then can be further studied to determine the pathophysiologic underpinnings of this association. For example, since elevated NT-proBNP is a recognized marker for atrial fibrillation, cognitive decline could potentially be explained by embolic infarcts over time, negatively affecting cortical function. Chronic cerebrovascular disease and associated white matter disease (although this was not specifically evaluated in this study) may be related to decline in several cognitive domains, while also contributing to mixed vascular-Alzheimer pathology (a commonly encountered condition in clinical practice). Since elevated NT-proBNP levels may be found in congestive heart failure, another potential cause could be cognitive manifestations known in the literature as "cardiac encephalopathy" (characterized by abnormalities in executive function, as well as abulia).
At this time, from a practical clinical perspective, alterations in clinical practice by ordering NT-proBNP to help stratify patients cannot yet clearly be recommended. However, these data continue to expand upon great progress over the last decade in determining modifiable, as well as non-modifiable risk factors, involved in the development of cognitive decline and dementia.1
- Oboudiyat C, et al. Alzheimer’s disease. Semin Neurol 2013;33:313-329.