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. 2021 Jan;1(1):114-123.
doi: 10.1038/s43587-020-00003-5. Epub 2020 Nov 30.

Individualized prognosis of cognitive decline and dementia in mild cognitive impairment based on plasma biomarker combinations

Nicholas C Cullen #  1 , Antoine Leuzy #  1 , Sebastian Palmqvist  1   2 , Shorena Janelidze  1 , Erik Stomrud  1   2 , Pedro Pesini  3 , Leticia Sarasa  3 , José Antonio Allué  3 , Nicholas K Proctor  4 , Henrik Zetterberg  5   6   7   8 , Jeffrey L Dage  4 , Kaj Blennow  5   6 , Niklas Mattsson-Carlgren  9   10   11 , Oskar Hansson  12   13
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Individualized prognosis of cognitive decline and dementia in mild cognitive impairment based on plasma biomarker combinations

Nicholas C Cullen et al. Nat Aging. 2021 Jan.

Abstract

We developed models for individualized risk prediction of cognitive decline in mild cognitive impairment (MCI) using plasma biomarkers of β-amyloid (Aβ), tau and neurodegeneration. A total of 573 patients with MCI from the Swedish BioFINDER study and the Alzheimer's Disease Neuroimaging Initiative (ADNI) were included in the study. The primary outcomes were longitudinal cognition and conversion to Alzheimer's disease (AD) dementia. A model combining tau phosphorylated at threonine 181 (P-tau181) and neurofilament light (NfL), but not Aβ42/Aβ40, had the best prognosis performance of all models (area under the curve = 0.88 for 4-year conversion to AD in BioFINDER, validated in ADNI), was stronger than a basic model of age, sex, education and baseline cognition, and performed similarly to cerebrospinal fluid biomarkers. A publicly available online tool for individualized prognosis in MCI based on our combined plasma biomarker models is introduced. Combination of plasma biomarkers may be of high value to identify individuals with MCI who will progress to AD dementia in clinical trials and in clinical practice.

Trial registration: ClinicalTrials.gov NCT01208675 NCT00106899.

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