Serum NfL and GFAP are associated with incident dementia and dementia mortality in older adults: The cardiovascular health study

Héléne T Cronjé; Xiaojuan Liu; Michelle C Odden; Kristine F Moseholm; Sudha Seshadri; Claudia L Satizabal; Oscar L Lopez; Joshua C Bis; Luc Djoussé; Alison E Fohner; Bruce M Psaty; Russell P Tracy; W T Longstreth; Majken K Jensen; Kenneth J Mukamal

doi:10.1002/alz.13367

Serum NfL and GFAP are associated with incident dementia and dementia mortality in older adults: The cardiovascular health study

Héléne T Cronjé
, Xiaojuan Liu
, Michelle C Odden
, Kristine F Moseholm
, Sudha Seshadri
, Claudia L Satizabal
, Oscar L Lopez
, Joshua C Bis
, Luc Djoussé
, Alison E Fohner
, Bruce M Psaty
, Russell P Tracy
, W T Longstreth
, Majken K Jensen
, Kenneth J Mukamal

Research output: Contribution to journal › Article › peer-review

38 Scopus citations

Abstract

INTRODUCTION: Circulating neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) have been independently associated with dementia risk. Their additive association, and their associations with dementia-specific mortality, have not been investigated.

METHODS: We associated serum NfL, GFAP, total tau ,and ubiquitin carboxyl-terminal hydrolase-L1, measured in 1712 dementia-free adults, with 19-year incident dementia and dementia-specific mortality risk, and with 3-year cognitive decline.

RESULTS: In adjusted models, being in the highest versus lowest tertile of NfL or GFAP associated with a hazard ratio (HR) of 1.49 (1.20-1.84) and 1.38 (1.15-1.66) for incident dementia, and 2.87 (1.79-4.61) and 2.76 (1.73-4.40) for dementia-specific mortality. Joint third versus first tertile exposure further increased risk; HR = 2.06 (1.60-2.67) and 9.22 (4.48-18.9). NfL was independently associated with accelerated cognitive decline.

DISCUSSION: Circulating NfL and GFAP may, independently and jointly, provide useful clinical insight regarding dementia risk and prognosis.

Original language	English (US)
Journal	Alzheimer's and Dementia
DOIs	https://doi.org/10.1002/alz.13367
State	E-pub ahead of print - Jul 1 2023

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Cronjé, H. T., Liu, X., Odden, M. C., Moseholm, K. F., Seshadri, S., Satizabal, C. L., Lopez, O. L., Bis, J. C., Djoussé, L., Fohner, A. E., Psaty, B. M., Tracy, R. P., Longstreth, W. T., Jensen, M. K., & Mukamal, K. J. (2023). Serum NfL and GFAP are associated with incident dementia and dementia mortality in older adults: The cardiovascular health study. Alzheimer's and Dementia. Advance online publication. https://doi.org/10.1002/alz.13367

Cronjé, HT, Liu, X, Odden, MC, Moseholm, KF, Seshadri, S, Satizabal, CL, Lopez, OL, Bis, JC, Djoussé, L, Fohner, AE, Psaty, BM, Tracy, RP, Longstreth, WT, Jensen, MK & Mukamal, KJ 2023, 'Serum NfL and GFAP are associated with incident dementia and dementia mortality in older adults: The cardiovascular health study', Alzheimer's and Dementia. https://doi.org/10.1002/alz.13367

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title = "Serum NfL and GFAP are associated with incident dementia and dementia mortality in older adults: The cardiovascular health study",

abstract = "INTRODUCTION: Circulating neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) have been independently associated with dementia risk. Their additive association, and their associations with dementia-specific mortality, have not been investigated.METHODS: We associated serum NfL, GFAP, total tau ,and ubiquitin carboxyl-terminal hydrolase-L1, measured in 1712 dementia-free adults, with 19-year incident dementia and dementia-specific mortality risk, and with 3-year cognitive decline.RESULTS: In adjusted models, being in the highest versus lowest tertile of NfL or GFAP associated with a hazard ratio (HR) of 1.49 (1.20-1.84) and 1.38 (1.15-1.66) for incident dementia, and 2.87 (1.79-4.61) and 2.76 (1.73-4.40) for dementia-specific mortality. Joint third versus first tertile exposure further increased risk; HR = 2.06 (1.60-2.67) and 9.22 (4.48-18.9). NfL was independently associated with accelerated cognitive decline.DISCUSSION: Circulating NfL and GFAP may, independently and jointly, provide useful clinical insight regarding dementia risk and prognosis.",

author = "Cronj{\'e}, \{H{\'e}l{\'e}ne T\} and Xiaojuan Liu and Odden, \{Michelle C\} and Moseholm, \{Kristine F\} and Sudha Seshadri and Satizabal, \{Claudia L\} and Lopez, \{Oscar L\} and Bis, \{Joshua C\} and Luc Djouss{\'e} and Fohner, \{Alison E\} and Psaty, \{Bruce M\} and Tracy, \{Russell P\} and Longstreth, \{W T\} and Jensen, \{Majken K\} and Mukamal, \{Kenneth J\}",

note = "{\textcopyright} 2023 The Authors. Alzheimer's \& Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.",

year = "2023",

month = jul,

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doi = "10.1002/alz.13367",

language = "English (US)",

journal = "Alzheimer's and Dementia",

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TY - JOUR

T1 - Serum NfL and GFAP are associated with incident dementia and dementia mortality in older adults

T2 - The cardiovascular health study

AU - Cronjé, Héléne T

AU - Liu, Xiaojuan

AU - Odden, Michelle C

AU - Moseholm, Kristine F

AU - Seshadri, Sudha

AU - Satizabal, Claudia L

AU - Lopez, Oscar L

AU - Bis, Joshua C

AU - Djoussé, Luc

AU - Fohner, Alison E

AU - Psaty, Bruce M

AU - Tracy, Russell P

AU - Longstreth, W T

AU - Jensen, Majken K

AU - Mukamal, Kenneth J

PY - 2023/7/1

Y1 - 2023/7/1

N2 - INTRODUCTION: Circulating neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) have been independently associated with dementia risk. Their additive association, and their associations with dementia-specific mortality, have not been investigated.METHODS: We associated serum NfL, GFAP, total tau ,and ubiquitin carboxyl-terminal hydrolase-L1, measured in 1712 dementia-free adults, with 19-year incident dementia and dementia-specific mortality risk, and with 3-year cognitive decline.RESULTS: In adjusted models, being in the highest versus lowest tertile of NfL or GFAP associated with a hazard ratio (HR) of 1.49 (1.20-1.84) and 1.38 (1.15-1.66) for incident dementia, and 2.87 (1.79-4.61) and 2.76 (1.73-4.40) for dementia-specific mortality. Joint third versus first tertile exposure further increased risk; HR = 2.06 (1.60-2.67) and 9.22 (4.48-18.9). NfL was independently associated with accelerated cognitive decline.DISCUSSION: Circulating NfL and GFAP may, independently and jointly, provide useful clinical insight regarding dementia risk and prognosis.

AB - INTRODUCTION: Circulating neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) have been independently associated with dementia risk. Their additive association, and their associations with dementia-specific mortality, have not been investigated.METHODS: We associated serum NfL, GFAP, total tau ,and ubiquitin carboxyl-terminal hydrolase-L1, measured in 1712 dementia-free adults, with 19-year incident dementia and dementia-specific mortality risk, and with 3-year cognitive decline.RESULTS: In adjusted models, being in the highest versus lowest tertile of NfL or GFAP associated with a hazard ratio (HR) of 1.49 (1.20-1.84) and 1.38 (1.15-1.66) for incident dementia, and 2.87 (1.79-4.61) and 2.76 (1.73-4.40) for dementia-specific mortality. Joint third versus first tertile exposure further increased risk; HR = 2.06 (1.60-2.67) and 9.22 (4.48-18.9). NfL was independently associated with accelerated cognitive decline.DISCUSSION: Circulating NfL and GFAP may, independently and jointly, provide useful clinical insight regarding dementia risk and prognosis.

U2 - 10.1002/alz.13367

DO - 10.1002/alz.13367

M3 - Article

C2 - 37392405

SN - 1552-5260

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

ER -

Serum NfL and GFAP are associated with incident dementia and dementia mortality in older adults: The cardiovascular health study

Abstract

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