Discordant Alzheimer's neurodegenerative biomarkers and their clinical outcomes

© 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association..

OBJECTIVE: In the 2018 ATN framework, Alzheimer's neurodegenerative biomarkers comprised cerebrospinal fluid (CSF) total tau, 18 F-fluorodeoxyglucose-positron emission tomography, and brain atrophy. We aimed to assess the clinical outcomes of having discordant Alzheimer's neurodegenerative biomarkers.

METHODS: A total of 721 non-demented individuals from the Alzheimer's Disease Neuroimaging Initiative database were included and then further categorized into concordant-negative, discordant, and concordant-positive groups. Demographic distributions of the groups were compared. Longitudinal changes in clinical outcomes and risk of conversion were assessed using linear mixed-effects models and multivariate Cox proportional hazard models, respectively.

RESULTS: Discordant group was intermediate to concordant-negative and concordant-positive groups in terms of APOE ε4 positivity, CSF amyloid-beta, and phosphorylated tau. Compared with concordant-negative group, discordant group deteriorated faster in cognitive scores (Mini-Mental State Examination, the Clinical Dementia Rating Scale-Sum of Boxes, and the Functional Activities Questionnaire) and demonstrated greater rates of atrophy in brain structures (hippocampus, entorhinal cortex, and whole brain), and concordant-positive group performed worse over time than discordant group. Moreover, the risk of cognitive decline increased from concordant-negative to discordant to concordant-positive. The results from longitudinal analyses were validated in A+T+, cognitively normal, and mild cognitive impairment individuals, and were also validated by applying different cutoffs and neurodegenerative biomarkers.

INTERPRETATION: Discordant neurodegenerative status denotes a stage of cognitive function which is intermediate between concordant-negative and concordant-positive. Identification of discordant cases would provide insights into intervention and new therapy approaches, particularly in A+T+ individuals. Moreover, this work may be a complement to the ATN scheme.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:7

Enthalten in:

Annals of clinical and translational neurology - 7(2020), 10 vom: 03. Okt., Seite 1996-2009

Sprache:

Englisch

Beteiligte Personen:

Guo, Yu [VerfasserIn]
Li, Hong-Qi [VerfasserIn]
Tan, Lin [VerfasserIn]
Chen, Shi-Dong [VerfasserIn]
Yang, Yu-Xiang [VerfasserIn]
Ma, Ya-Hui [VerfasserIn]
Zuo, Chuan-Tao [VerfasserIn]
Dong, Qiang [VerfasserIn]
Tan, Lan [VerfasserIn]
Yu, Jin-Tai [VerfasserIn]
Alzheimer's Disease Neuroimaging Initiative [VerfasserIn]

Links:

Volltext

Themen:

Amyloid beta-Peptides
Biomarkers
Journal Article
Peptide Fragments
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Tau Proteins

Anmerkungen:

Date Completed 17.08.2021

Date Revised 14.02.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1002/acn3.51196

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM315205687