Clinical and demographic factors modify the association between plasma phosphorylated tau‐181 and cognition

Abstract INTRODUCTION Plasma phosphorylated tau‐181 (p‐tau181) associations with global cognition and memory are clear, but the link between p‐tau181 with other cognitive domains and subjective cognitive decline (SCD) across the clinical spectrum of Alzheimer's disease (AD) and how this associa...

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Main Authors: Corey J. Bolton, Marilyn Steinbach, Omair A. Khan, Dandan Liu, Julia O'Malley, Logan Dumitrescu, Amalia Peterson, Angela L. Jefferson, Timothy J. Hohman, Henrik Zetterberg, Katherine A. Gifford, for the Alzheimer's Disease Neuroimaging Initiative
Format: Article
Language:English
Published: Wiley 2024-10-01
Series:Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring
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Online Access:https://doi.org/10.1002/dad2.70047
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author Corey J. Bolton
Marilyn Steinbach
Omair A. Khan
Dandan Liu
Julia O'Malley
Logan Dumitrescu
Amalia Peterson
Angela L. Jefferson
Timothy J. Hohman
Henrik Zetterberg
Katherine A. Gifford
for the Alzheimer's Disease Neuroimaging Initiative
author_facet Corey J. Bolton
Marilyn Steinbach
Omair A. Khan
Dandan Liu
Julia O'Malley
Logan Dumitrescu
Amalia Peterson
Angela L. Jefferson
Timothy J. Hohman
Henrik Zetterberg
Katherine A. Gifford
for the Alzheimer's Disease Neuroimaging Initiative
author_sort Corey J. Bolton
collection DOAJ
description Abstract INTRODUCTION Plasma phosphorylated tau‐181 (p‐tau181) associations with global cognition and memory are clear, but the link between p‐tau181 with other cognitive domains and subjective cognitive decline (SCD) across the clinical spectrum of Alzheimer's disease (AD) and how this association changes based on genetic and demographic factors is poorly understood. METHODS Participants were drawn from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and included 1185 adults >55 years of age with plasma p‐tau181 and neuropsychological test data. Linear regression models related plasma p‐tau181 to neuropsychological composite and SCD scores with follow‐up models examining plasma p‐tau181 interactions with cognitive diagnosis, apolipoprotein E (APOE) ε4 carrier status, age, and sex on cognitive outcomes. RESULTS Higher plasma p‐tau181 level was associated with worse memory, executive functioning, and language abilities, and greater informant‐reported SCD. Visuospatial abilities and self‐report SCD were not associated with plasma p‐tau181. Associations were generally stronger in mild cognitive impairment (MCI) or dementia, APOE ε4 carriers, women, and younger participants. DISCUSSION Higher levels of plasma p‐tau181 are associated with worse neuropsychological test performance across multiple cognitive domains; however, these associations vary based on disease stage, genetic risk status, age, and sex. Highlights Greater plasma p‐tau181 was associated with lower cognition across most domains. Associations between p‐tau181 and cognition were modified by age and sex. Level of p‐tau181 was more strongly associated with cognition in people with mild cognitive impairment (MCI) and apolipoprotein E (APOE) ε4.
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spelling doaj-art-6dfb1e9f2a944de5a26684d9082acadc2025-08-20T02:50:51ZengWileyAlzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring2352-87292024-10-01164n/an/a10.1002/dad2.70047Clinical and demographic factors modify the association between plasma phosphorylated tau‐181 and cognitionCorey J. Bolton0Marilyn Steinbach1Omair A. Khan2Dandan Liu3Julia O'Malley4Logan Dumitrescu5Amalia Peterson6Angela L. Jefferson7Timothy J. Hohman8Henrik Zetterberg9Katherine A. Gifford10for the Alzheimer's Disease Neuroimaging InitiativeVanderbilt Memory and Alzheimer's Center Vanderbilt University Medical Center Nashville Tennessee USAVanderbilt Memory and Alzheimer's Center Vanderbilt University Medical Center Nashville Tennessee USAVanderbilt Memory and Alzheimer's Center Vanderbilt University Medical Center Nashville Tennessee USAVanderbilt Memory and Alzheimer's Center Vanderbilt University Medical Center Nashville Tennessee USAVanderbilt Memory and Alzheimer's Center Vanderbilt University Medical Center Nashville Tennessee USAVanderbilt Memory and Alzheimer's Center Vanderbilt University Medical Center Nashville Tennessee USAVanderbilt Memory and Alzheimer's Center Vanderbilt University Medical Center Nashville Tennessee USAVanderbilt Memory and Alzheimer's Center Vanderbilt University Medical Center Nashville Tennessee USAVanderbilt Memory and Alzheimer's Center Vanderbilt University Medical Center Nashville Tennessee USADepartment of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology The Sahlgrenska Academy at University of Gothenburg Mölndal SwedenVanderbilt Memory and Alzheimer's Center Vanderbilt University Medical Center Nashville Tennessee USAAbstract INTRODUCTION Plasma phosphorylated tau‐181 (p‐tau181) associations with global cognition and memory are clear, but the link between p‐tau181 with other cognitive domains and subjective cognitive decline (SCD) across the clinical spectrum of Alzheimer's disease (AD) and how this association changes based on genetic and demographic factors is poorly understood. METHODS Participants were drawn from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and included 1185 adults >55 years of age with plasma p‐tau181 and neuropsychological test data. Linear regression models related plasma p‐tau181 to neuropsychological composite and SCD scores with follow‐up models examining plasma p‐tau181 interactions with cognitive diagnosis, apolipoprotein E (APOE) ε4 carrier status, age, and sex on cognitive outcomes. RESULTS Higher plasma p‐tau181 level was associated with worse memory, executive functioning, and language abilities, and greater informant‐reported SCD. Visuospatial abilities and self‐report SCD were not associated with plasma p‐tau181. Associations were generally stronger in mild cognitive impairment (MCI) or dementia, APOE ε4 carriers, women, and younger participants. DISCUSSION Higher levels of plasma p‐tau181 are associated with worse neuropsychological test performance across multiple cognitive domains; however, these associations vary based on disease stage, genetic risk status, age, and sex. Highlights Greater plasma p‐tau181 was associated with lower cognition across most domains. Associations between p‐tau181 and cognition were modified by age and sex. Level of p‐tau181 was more strongly associated with cognition in people with mild cognitive impairment (MCI) and apolipoprotein E (APOE) ε4.https://doi.org/10.1002/dad2.70047ADNIAlzheimer's diseasedementiamild cognitive impairmentplasma p‐tau181
spellingShingle Corey J. Bolton
Marilyn Steinbach
Omair A. Khan
Dandan Liu
Julia O'Malley
Logan Dumitrescu
Amalia Peterson
Angela L. Jefferson
Timothy J. Hohman
Henrik Zetterberg
Katherine A. Gifford
for the Alzheimer's Disease Neuroimaging Initiative
Clinical and demographic factors modify the association between plasma phosphorylated tau‐181 and cognition
Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring
ADNI
Alzheimer's disease
dementia
mild cognitive impairment
plasma p‐tau181
title Clinical and demographic factors modify the association between plasma phosphorylated tau‐181 and cognition
title_full Clinical and demographic factors modify the association between plasma phosphorylated tau‐181 and cognition
title_fullStr Clinical and demographic factors modify the association between plasma phosphorylated tau‐181 and cognition
title_full_unstemmed Clinical and demographic factors modify the association between plasma phosphorylated tau‐181 and cognition
title_short Clinical and demographic factors modify the association between plasma phosphorylated tau‐181 and cognition
title_sort clinical and demographic factors modify the association between plasma phosphorylated tau 181 and cognition
topic ADNI
Alzheimer's disease
dementia
mild cognitive impairment
plasma p‐tau181
url https://doi.org/10.1002/dad2.70047
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