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 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:9 |
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| Enthalten in: |
Journal of the American Heart Association - 9(2020), 19 vom: 20. Okt., Seite e014659 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
McGrath, Emer R [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 15.03.2021 Date Revised 15.03.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1161/JAHA.119.014659 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM314932909 |
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| 100 | 1 | |a McGrath, Emer R |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Growth Differentiation Factor 15 and NT-proBNP as Blood-Based Markers of Vascular Brain Injury and Dementia |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 700 | 1 | |a Himali, Jayandra J |e verfasserin |4 aut | |
| 700 | 1 | |a Levy, Daniel |e verfasserin |4 aut | |
| 700 | 1 | |a Conner, Sarah C |e verfasserin |4 aut | |
| 700 | 1 | |a DeCarli, Charles |e verfasserin |4 aut | |
| 700 | 1 | |a Pase, Matthew P |e verfasserin |4 aut | |
| 700 | 1 | |a Ninomiya, Toshiharu |e verfasserin |4 aut | |
| 700 | 1 | |a Ohara, Tomoyuki |e verfasserin |4 aut | |
| 700 | 1 | |a Courchesne, Paul |e verfasserin |4 aut | |
| 700 | 1 | |a Satizabal, Claudia L |e verfasserin |4 aut | |
| 700 | 1 | |a Vasan, Ramachandran S |e verfasserin |4 aut | |
| 700 | 1 | |a Beiser, Alexa S |e verfasserin |4 aut | |
| 700 | 1 | |a Seshadri, Sudha |e verfasserin |4 aut | |
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