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Open Access 01-12-2023 | Alzheimer's Disease | Research

Baseline structural MRI and plasma biomarkers predict longitudinal structural atrophy and cognitive decline in early Alzheimer’s disease

Authors: Long Xie, Sandhitsu R. Das, Laura E. M. Wisse, Ranjit Ittyerah, Robin de Flores, Leslie M. Shaw, Paul A. Yushkevich, David A. Wolk, for the Alzheimer’s Disease Neuroimaging Initiative

Published in: Alzheimer's Research & Therapy | Issue 1/2023

Abstract

Background

Crucial to the success of clinical trials targeting early Alzheimer’s disease (AD) is recruiting participants who are more likely to progress over the course of the trials. We hypothesize that a combination of plasma and structural MRI biomarkers, which are less costly and non-invasive, is predictive of longitudinal progression measured by atrophy and cognitive decline in early AD, providing a practical alternative to PET or cerebrospinal fluid biomarkers.

Methods

Longitudinal T1-weighted MRI, cognitive (memory-related test scores and clinical dementia rating scale), and plasma measurements of 245 cognitively normal (CN) and 361 mild cognitive impairment (MCI) patients from ADNI were included. Subjects were further divided into β-amyloid positive/negative (Aβ+/Aβ−)] subgroups. Baseline plasma (p-tau₁₈₁ and neurofilament light chain) and MRI-based structural medial temporal lobe subregional measurements and their association with longitudinal measures of atrophy and cognitive decline were tested using stepwise linear mixed effect modeling in CN and MCI, as well as separately in the Aβ+/Aβ− subgroups. Receiver operating characteristic (ROC) analyses were performed to investigate the discriminative power of each model in separating fast and slow progressors (first and last terciles) of each longitudinal measurement.

Results

A total of 245 CN (35.0% Aβ+) and 361 MCI (53.2% Aβ+) participants were included. In the CN and MCI groups, both baseline plasma and structural MRI biomarkers were included in most models. These relationships were maintained when limited to the Aβ+ and Aβ− subgroups, including Aβ− CN (normal aging). ROC analyses demonstrated reliable discriminative power in identifying fast from slow progressors in MCI [area under the curve (AUC): 0.78–0.93] and more modestly in CN (0.65–0.73).

Conclusions

The present data support the notion that plasma and MRI biomarkers, which are relatively easy to obtain, provide a prediction for the rate of future cognitive and neurodegenerative progression that may be particularly useful in clinical trial stratification and prognosis. Additionally, the effect in Aβ− CN indicates the potential use of these biomarkers in predicting a normal age-related decline.

Available only for authorised users

Full description of florbetapir PET can be found at this website: adni.bitbucket.io/reference/docs/UCBERKELEYAV45/ADNI_AV45_Methods_JagustLab_06.25.15.pdf

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Title: Baseline structural MRI and plasma biomarkers predict longitudinal structural atrophy and cognitive decline in early Alzheimer’s disease
Authors: Long Xie
Sandhitsu R. Das
Laura E. M. Wisse
Ranjit Ittyerah
Robin de Flores
Leslie M. Shaw
Paul A. Yushkevich
David A. Wolk
for the Alzheimer’s Disease Neuroimaging Initiative
Publication date: 01-12-2023
Publisher: BioMed Central
Keywords: Alzheimer's Disease
Alzheimer's Disease
Mild Neurocognitive Disorder
Biomarkers
Published in: Alzheimer's Research & Therapy / Issue 1/2023
Electronic ISSN: 1758-9193
DOI: https://doi.org/10.1186/s13195-023-01210-z

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Springer Medicine

Baseline structural MRI and plasma biomarkers predict longitudinal structural atrophy and cognitive decline in early Alzheimer’s disease

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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