Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

A multi-cohort study of longitudinal and cross-sectional Alzheimer's disease biomarkers in cognitively unimpaired older adults

Xie, Long ; Das, Sandhitsu R. ; Li, Yue ; Wisse, Laura E.M. LU orcid ; McGrew, Emily ; Lyu, Xueying ; DiCalogero, Michael ; Shah, Ujashi ; Ilesanmi, Ademola and Denning, Amanda E. , et al. (2025) In Alzheimer's and Dementia 21(2).
Abstract

INTRODUCTION: The generalizability of neuroimaging and cognitive biomarkers in their sensitivity to detect preclinical Alzheimer's disease (AD) and power to predict progression in large, multisite cohorts remains unclear. METHOD: Longitudinal demographics, T1-weighted magnetic resonance imaging (MRI), and cognitive scores of 3036 cognitively unimpaired (CU) older adults (amyloid beta [Aβ]-negative/positive [A–/A+]: 1270/1558) were included. Cross-sectional and longitudinal cognition and medial temporal lobe (MTL) structural measures were extracted. Cross-sectional MTL tau burden (T) was computed from tau positron emission tomography (N = 1095). RESULTS: We found cross-sectional tau and longitudinal structural biomarkers best separated... (More)

INTRODUCTION: The generalizability of neuroimaging and cognitive biomarkers in their sensitivity to detect preclinical Alzheimer's disease (AD) and power to predict progression in large, multisite cohorts remains unclear. METHOD: Longitudinal demographics, T1-weighted magnetic resonance imaging (MRI), and cognitive scores of 3036 cognitively unimpaired (CU) older adults (amyloid beta [Aβ]-negative/positive [A–/A+]: 1270/1558) were included. Cross-sectional and longitudinal cognition and medial temporal lobe (MTL) structural measures were extracted. Cross-sectional MTL tau burden (T) was computed from tau positron emission tomography (N = 1095). RESULTS: We found cross-sectional tau and longitudinal structural biomarkers best separated A+ CU from A– CU. A–T+ CU had significantly faster neurodegeneration rate compared to A–T– CU. MTL tau was significantly correlated with MRI and cognitive biomarkers regardless of Aβ status. MTL tau, MRI, and cognition provided complementary information about disease progression. DISCUSSION: This large multisite study replicates prior findings in CU older adults, supporting the utility of neuroimaging and cognitive biomarkers in preclinical AD clinical trials and normal aging studies. Highlights: We investigated neuroimaging and cognitive biomarkers in 3036 cognitively unimpaired (CU) participants. Medial temporal lobe (MTL) tau and longitudinal MTL atrophy best separate amyloid beta positive (A+) CU from amyloid beta negative (A–) CU. A– tau positive (T+) CU had a significantly faster neurodegeneration rate compared to A–T– CU. MTL tau correlated with structural magnetic resonance imaging (MRI) and cognition regardless of amyloid beta status. Combined baseline MTL tau, MRI, and cognition best predict Alzheimer's disease progression.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; and (Less)
author collaboration
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
amyloid, biomarkers, disease progression, magnetic resonance imaging, neurodegeneration, normal aging, preclinical Alzheimer's disease, prediction, tau
in
Alzheimer's and Dementia
volume
21
issue
2
article number
e14492
publisher
Wiley
external identifiers
  • pmid:39868491
  • scopus:85216832710
ISSN
1552-5260
DOI
10.1002/alz.14492
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2025 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
id
2699fbb2-6b14-4d16-ad30-54101bf0001e
date added to LUP
2025-04-10 11:28:11
date last changed
2025-05-08 12:18:15
@article{2699fbb2-6b14-4d16-ad30-54101bf0001e,
  abstract     = {{<p>INTRODUCTION: The generalizability of neuroimaging and cognitive biomarkers in their sensitivity to detect preclinical Alzheimer's disease (AD) and power to predict progression in large, multisite cohorts remains unclear. METHOD: Longitudinal demographics, T1-weighted magnetic resonance imaging (MRI), and cognitive scores of 3036 cognitively unimpaired (CU) older adults (amyloid beta [Aβ]-negative/positive [A–/A+]: 1270/1558) were included. Cross-sectional and longitudinal cognition and medial temporal lobe (MTL) structural measures were extracted. Cross-sectional MTL tau burden (T) was computed from tau positron emission tomography (N = 1095). RESULTS: We found cross-sectional tau and longitudinal structural biomarkers best separated A+ CU from A– CU. A–T+ CU had significantly faster neurodegeneration rate compared to A–T– CU. MTL tau was significantly correlated with MRI and cognitive biomarkers regardless of Aβ status. MTL tau, MRI, and cognition provided complementary information about disease progression. DISCUSSION: This large multisite study replicates prior findings in CU older adults, supporting the utility of neuroimaging and cognitive biomarkers in preclinical AD clinical trials and normal aging studies. Highlights: We investigated neuroimaging and cognitive biomarkers in 3036 cognitively unimpaired (CU) participants. Medial temporal lobe (MTL) tau and longitudinal MTL atrophy best separate amyloid beta positive (A+) CU from amyloid beta negative (A–) CU. A– tau positive (T+) CU had a significantly faster neurodegeneration rate compared to A–T– CU. MTL tau correlated with structural magnetic resonance imaging (MRI) and cognition regardless of amyloid beta status. Combined baseline MTL tau, MRI, and cognition best predict Alzheimer's disease progression.</p>}},
  author       = {{Xie, Long and Das, Sandhitsu R. and Li, Yue and Wisse, Laura E.M. and McGrew, Emily and Lyu, Xueying and DiCalogero, Michael and Shah, Ujashi and Ilesanmi, Ademola and Denning, Amanda E. and Brown, Chris A. and Cohen, Jesse and Sreepada, Lasya and Dong, Mengjin and Sadeghpour, Niyousha and Khandelwal, Pulkit and Ittyerah, Ranjit and Ravikumar, Sadhana and Sadaghiani, Shokufeh and Hrybouski, Stanislau and de Flores, Robin and Gibson, Eli and Yushkevich, Paul A. and Wolk, David A.}},
  issn         = {{1552-5260}},
  keywords     = {{amyloid; biomarkers; disease progression; magnetic resonance imaging; neurodegeneration; normal aging; preclinical Alzheimer's disease; prediction; tau}},
  language     = {{eng}},
  number       = {{2}},
  publisher    = {{Wiley}},
  series       = {{Alzheimer's and Dementia}},
  title        = {{A multi-cohort study of longitudinal and cross-sectional Alzheimer's disease biomarkers in cognitively unimpaired older adults}},
  url          = {{http://dx.doi.org/10.1002/alz.14492}},
  doi          = {{10.1002/alz.14492}},
  volume       = {{21}},
  year         = {{2025}},
}