Growth Differentiation Factor 15 and NT‐proBNP as Blood‐Based Markers of Vascular Brain Injury and Dementia

Background GDF15 (growth differentiation factor 15) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) may offer promise as biomarkers for cognitive outcomes, including dementia. We determined the association of these biomarkers with cognitive outcomes in a community-based cohort. Methods and...

Full description

Saved in:
Bibliographic Details
Published in:Journal of the American Heart Association Vol. 9; no. 19; p. e014659
Main Authors: McGrath, Emer R., Himali, Jayandra J., Levy, Daniel, Conner, Sarah C., DeCarli, Charles, Pase, Matthew P., Ninomiya, Toshiharu, Ohara, Tomoyuki, Courchesne, Paul, Satizabal, Claudia L., Vasan, Ramachandran S., Beiser, Alexa S., Seshadri, Sudha
Format: Journal Article
Language:English
Published: England John Wiley and Sons Inc 20.10.2020
Wiley
Subjects:
Aged
biomarker
Biomarkers - blood
Cerebrovascular Trauma - blood
Cerebrovascular Trauma - diagnostic imaging
dementia
Dementia - blood
Dementia - diagnostic imaging
Female
Growth Differentiation Factor 15 - blood
Humans
Magnetic Resonance Imaging
Male
Natriuretic Peptide, Brain - blood
Neuroimaging
Original Research
Peptide Fragments - blood
Proportional Hazards Models
Prospective Studies
vascular cognitive impairment
vascular cognitive impairment
biomarker
dementia
ISSN:2047-9980, 2047-9980
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Background GDF15 (growth differentiation factor 15) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) may offer promise as biomarkers for cognitive outcomes, including dementia. We determined the association of these biomarkers with cognitive outcomes in a community-based cohort. Methods and Results Plasma GDF15 (n=1603) and NT-proBNP levels (n=1590) (53% women; mean age, 68.7 years) were measured in dementia-free Framingham Offspring cohort participants at examination 7 (1998-2001). Participants were followed up for incident dementia. Secondary outcomes included Alzheimer disease dementia, magnetic resonance imaging structural brain measures, and neurocognitive performance. During a median 11.8-year follow-up, 131 participants developed dementia. On multivariable Cox proportional-hazards analysis, higher circulating GDF15 was associated with an increased risk of incident all-cause and Alzheimer disease dementia (hazard ratio [HR] per SD increment in natural log-transformed biomarker value, 1.54 [95% CI, 1.22-1.95] and 1.37 [95% CI, 1.03-1.81], respectively), whereas higher plasma NT-proBNP was also associated with an increased risk of all-cause dementia (HR, 1.32; 95% CI, 1.05-1.65). Elevated GDF15 was associated with lower total brain and hippocampal volumes, greater white matter hyperintensity volume, and poorer cognitive performance. Elevated NT-proBNP was associated with greater white matter hyperintensity volume and poorer cognitive performance. Addition of both biomarkers to a conventional risk factor model improved dementia risk classification (net reclassification improvement index, 0.25; 95% CI, 0.05-0.45). Conclusions Elevated plasma GDF15 and NT-proBNP were associated with vascular brain injury on magnetic resonance imaging, poorer neurocognitive performance, and increased risk of incident dementia in individuals aged >60 years. Both biomarkers improved dementia risk classification beyond that of traditional clinical risk factors, indicating their potential value in predicting incident dementia.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Current address: Turner Institute, Monash University, Clayton, Victoria, Australia and Harvard University, Boston, MA.For Sources of Funding and Disclosures, see page 9.
Supplementary materials for this article are available at https://www.ahajo​urnals.org/doi/suppl/​10.1161/JAHA.119.014659
ISSN:2047-9980
2047-9980
DOI:10.1161/JAHA.119.014659