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

Author:

Cronjé Héléne T.1ORCID,Liu Xiaojuan2,Odden Michelle C.2,Moseholm Kristine F.1,Seshadri Sudha34,Satizabal Claudia L.34,Lopez Oscar L.5,Bis Joshua C.6,Djoussé Luc78,Fohner Alison E.6910,Psaty Bruce M.611,Tracy Russell P.12,Longstreth W. T913,Jensen Majken K.18,Mukamal Kenneth J.814

Affiliation:

1. Department of Public Health, Section of Epidemiology University of Copenhagen Copenhagen Denmark

2. Department of Epidemiology and Population Health Stanford University Stanford California USA

3. Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases University of Texas San Antonio Texas USA

4. Department of Neurology Boston University School of Medicine Boston Massachusetts USA

5. Departments of Neurology and Psychiatry University of Pittsburgh Pittsburgh Pennsylvania USA

6. Cardiovascular Health Research Unit Department of Medicine University of Washington Seattle Washington USA

7. Division of Aging Department of Medicine Brigham and Women's Hospital and Harvard Medical School Boston Massachusetts USA

8. Department of Nutrition Harvard T.H. Chan School of Public Health Boston Massachusetts USA

9. Department of Epidemiology University of Washington Seattle Washington USA

10. Institute of Public Health Genetics University of Washington Seattle Washington USA

11. Departments of Epidemiology and Health Systems and Population Health University of Washington Seattle Washington USA

12. Department of Pathology Laboratory Medicine Larner College of Medicine University of Vermont Burlington Vermont USA

13. Department of Neurology University of Washington Seattle Washington USA

14. Division of General Medicine Beth Israel Deaconess Medical Center Boston Massachusetts USA

Abstract

AbstractINTRODUCTIONCirculating 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.METHODSWe 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.RESULTSIn 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.DISCUSSIONCirculating NfL and GFAP may, independently and jointly, provide useful clinical insight regarding dementia risk and prognosis.

Funder

National Heart, Lung, and Blood Institute

National Institute on Aging

Novo Nordisk Fonden

Alzheimer's Association

Publisher

Wiley

Subject

Psychiatry and Mental health,Cellular and Molecular Neuroscience,Geriatrics and Gerontology,Neurology (clinical),Developmental Neuroscience,Health Policy,Epidemiology

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