TY - JOUR
T1 - Growth differentiation factor 15 and nt-probnp as blood-based markers of vascular brain injury and dementia
AU - McGrath, Emer R.
AU - Himali, Jayandra J.
AU - Levy, Daniel
AU - Conner, Sarah C.
AU - Decarli, Charles
AU - Pase, Matthew P.
AU - Ninomiya, Toshiharu
AU - Ohara, Tomoyuki
AU - Courchesne, Paul
AU - Satizabal, Claudia L.
AU - Vasan, Ramachandran S.
AU - Beiser, Alexa S.
AU - Seshadri, Sudha
N1 - Funding Information:
The FHS (Framingham Heart Study) is supported by the National Heart, Lung, and Blood Institute (NHLBI) (contract Nos. N01-HC-25195, HHSN268201500001, and 75N92019D00031). This research was supported by an Alzheimer’s Association Clinician Scientist Fellowship (AACSF-18-566570), NHLBI grants R01 HL60040 and R01 HL70100, grants from the National Institute on Aging (R01 AG054076, R01 AG049607, R01 AG033193, U01 AG049505, and U01 AG052409), and grants from the National Institute of Neurological Disorders and Stroke (NS017950 and UH2 NS100605). Additional funding for the Systems Approach to Biomarker Research in Cardiovascular Disease initiative was provided by the Division of Intramural Research, NHLBI, and the Population Sciences Branch, NHLBI. None of the funding entities had any role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.
Publisher Copyright:
© 2020 The Authors.
PY - 2020/10/6
Y1 - 2020/10/6
N2 - 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.
AB - 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.
KW - Biomarker
KW - Dementia
KW - Vascular cognitive impairment
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U2 - 10.1161/JAHA.119.014659
DO - 10.1161/JAHA.119.014659
M3 - Article
C2 - 32921207
AN - SCOPUS:85092681997
SN - 2047-9980
VL - 9
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
IS - 19
M1 - e014659
ER -