Differential effects of neurodegeneration biomarkers on subclinical cognitive decline

Abstract Introduction Neurodegeneration appears to be the biological mechanism most proximate to cognitive decline in Alzheimer's disease. We test whether t‐tau and alternative biomarkers of neurodegeneration—neurogranin and neurofilament light protein (NFL)—add value in predicting subclinical...

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Main Authors: Andrew P. Merluzzi, Nicholas M. Vogt, Derek Norton, Erin Jonaitis, Lindsay R. Clark, Cynthia M. Carlsson, Sterling C. Johnson, Sanjay Asthana, Kaj Blennow, Henrik Zetterberg, Barbara B. Bendlin
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Alzheimer’s & Dementia: Translational Research & Clinical Interventions
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Online Access:https://doi.org/10.1016/j.trci.2019.02.004
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author Andrew P. Merluzzi
Nicholas M. Vogt
Derek Norton
Erin Jonaitis
Lindsay R. Clark
Cynthia M. Carlsson
Sterling C. Johnson
Sanjay Asthana
Kaj Blennow
Henrik Zetterberg
Barbara B. Bendlin
author_facet Andrew P. Merluzzi
Nicholas M. Vogt
Derek Norton
Erin Jonaitis
Lindsay R. Clark
Cynthia M. Carlsson
Sterling C. Johnson
Sanjay Asthana
Kaj Blennow
Henrik Zetterberg
Barbara B. Bendlin
author_sort Andrew P. Merluzzi
collection DOAJ
description Abstract Introduction Neurodegeneration appears to be the biological mechanism most proximate to cognitive decline in Alzheimer's disease. We test whether t‐tau and alternative biomarkers of neurodegeneration—neurogranin and neurofilament light protein (NFL)—add value in predicting subclinical cognitive decline. Methods One hundred fifty cognitively unimpaired participants received a lumbar puncture for cerebrospinal fluid and at least two neuropsychological examinations (mean age at first visit = 59.3 ± 6.3 years; 67% female). Linear mixed effects models were used with cognitive composite scores as outcomes. Neurodegeneration interactions terms were the primary predictors of interest: age × NFL or age × neurogranin or age × t‐tau. Models were compared using likelihood ratio tests. Results Age × NFL accounted for a significant amount of variation in longitudinal change on preclinical Alzheimer's cognitive composite scores, memory composite scores, and learning scores, whereas age × neurogranin and age × t‐tau did not. Discussion These data suggest that NFL may be more sensitive to subclinical cognitive decline compared to other proposed biomarkers for neurodegeneration.
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spelling doaj-art-46a8afe7f71a495c8e6926cf841a084b2025-08-20T03:30:39ZengWileyAlzheimer’s & Dementia: Translational Research & Clinical Interventions2352-87372019-01-015112913810.1016/j.trci.2019.02.004Differential effects of neurodegeneration biomarkers on subclinical cognitive declineAndrew P. Merluzzi0Nicholas M. Vogt1Derek Norton2Erin Jonaitis3Lindsay R. Clark4Cynthia M. Carlsson5Sterling C. Johnson6Sanjay Asthana7Kaj Blennow8Henrik Zetterberg9Barbara B. Bendlin10Wisconsin Alzheimer's Disease Research CenterUniversity of Wisconsin–MadisonMadisonWIUSAWisconsin Alzheimer's Disease Research CenterUniversity of Wisconsin–MadisonMadisonWIUSADepartment of Biostatistics and Medical InformaticsUniversity of Wisconsin–MadisonMadisonWIUSADepartment of Biostatistics and Medical InformaticsUniversity of Wisconsin–MadisonMadisonWIUSAWisconsin Alzheimer's Disease Research CenterUniversity of Wisconsin–MadisonMadisonWIUSAWisconsin Alzheimer's Disease Research CenterUniversity of Wisconsin–MadisonMadisonWIUSAWisconsin Alzheimer's Disease Research CenterUniversity of Wisconsin–MadisonMadisonWIUSAWisconsin Alzheimer's Disease Research CenterUniversity of Wisconsin–MadisonMadisonWIUSADepartment of Psychiatry and NeurochemistryInstitute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of GothenburgMölndalSwedenDepartment of Psychiatry and NeurochemistryInstitute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of GothenburgMölndalSwedenWisconsin Alzheimer's Disease Research CenterUniversity of Wisconsin–MadisonMadisonWIUSAAbstract Introduction Neurodegeneration appears to be the biological mechanism most proximate to cognitive decline in Alzheimer's disease. We test whether t‐tau and alternative biomarkers of neurodegeneration—neurogranin and neurofilament light protein (NFL)—add value in predicting subclinical cognitive decline. Methods One hundred fifty cognitively unimpaired participants received a lumbar puncture for cerebrospinal fluid and at least two neuropsychological examinations (mean age at first visit = 59.3 ± 6.3 years; 67% female). Linear mixed effects models were used with cognitive composite scores as outcomes. Neurodegeneration interactions terms were the primary predictors of interest: age × NFL or age × neurogranin or age × t‐tau. Models were compared using likelihood ratio tests. Results Age × NFL accounted for a significant amount of variation in longitudinal change on preclinical Alzheimer's cognitive composite scores, memory composite scores, and learning scores, whereas age × neurogranin and age × t‐tau did not. Discussion These data suggest that NFL may be more sensitive to subclinical cognitive decline compared to other proposed biomarkers for neurodegeneration.https://doi.org/10.1016/j.trci.2019.02.004Alzheimer's diseaseBiomarkersCognitionNeurodegenerationAmyloidCognitive decline
spellingShingle Andrew P. Merluzzi
Nicholas M. Vogt
Derek Norton
Erin Jonaitis
Lindsay R. Clark
Cynthia M. Carlsson
Sterling C. Johnson
Sanjay Asthana
Kaj Blennow
Henrik Zetterberg
Barbara B. Bendlin
Differential effects of neurodegeneration biomarkers on subclinical cognitive decline
Alzheimer’s & Dementia: Translational Research & Clinical Interventions
Alzheimer's disease
Biomarkers
Cognition
Neurodegeneration
Amyloid
Cognitive decline
title Differential effects of neurodegeneration biomarkers on subclinical cognitive decline
title_full Differential effects of neurodegeneration biomarkers on subclinical cognitive decline
title_fullStr Differential effects of neurodegeneration biomarkers on subclinical cognitive decline
title_full_unstemmed Differential effects of neurodegeneration biomarkers on subclinical cognitive decline
title_short Differential effects of neurodegeneration biomarkers on subclinical cognitive decline
title_sort differential effects of neurodegeneration biomarkers on subclinical cognitive decline
topic Alzheimer's disease
Biomarkers
Cognition
Neurodegeneration
Amyloid
Cognitive decline
url https://doi.org/10.1016/j.trci.2019.02.004
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