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

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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.
Funding Information
  • National Heart, Lung, and Blood Institute (U01HL080295, U01HL130114, HHSN268201200036C, HHSN268200800007C, HHSN268201800001C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, N01HC15103, 75N92021D00006)
  • National Institute on Aging (R01AG20098, R01AG023629, R01AG053325, P30AG066546, K24AG065525, K01AG071689)
  • Novo Nordisk Fonden (NNF17OC0027812)
  • Alzheimer's Association (AARF-21-851606)

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