Ingala, S;
De Boer, C;
Masselink, LA;
Vergari, I;
Lorenzini, L;
Blennow, K;
Chételat, G;
... EPAD consortium; + view all
(2021)
Application of the ATN classification scheme in a population without dementia: Findings from the EPAD cohort.
Alzheimer's & Dementia
, 17
(7)
pp. 1189-1204.
10.1002/alz.12292.
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Abstract
BACKGROUND: We classified non-demented European Prevention of Alzheimer's Dementia (EPAD) participants through the amyloid/tau/neurodegeneration (ATN) scheme and assessed their neuropsychological and imaging profiles. MATERIALS AND METHODS: From 1500 EPAD participants, 312 were excluded. Cerebrospinal fluid cut-offs of 1000 pg/mL for amyloid beta (Aß)1-42 and 27 pg/mL for p-tau181 were validated using Gaussian mixture models. Given strong correlation of p-tau and t-tau (R2 = 0.98, P < 0.001), neurodegeneration was defined by age-adjusted hippocampal volume. Multinomial regressions were used to test whether neuropsychological tests and regional brain volumes could distinguish ATN stages. RESULTS: Age was 65 ± 7 years, with 58% females and 38% apolipoprotein E (APOE) ε4 carriers; 57.1% were A-T-N-, 32.5% were in the Alzheimer's disease (AD) continuum, and 10.4% suspected non-Alzheimer's pathology. Age and cerebrovascular burden progressed with biomarker positivity (P < 0.001). Cognitive dysfunction appeared with T+. Paradoxically higher regional gray matter volumes were observed in A+T-N- compared to A-T-N- (P < 0.001). DISCUSSION: In non-demented individuals along the AD continuum, p-tau drives cognitive dysfunction. Memory and language domains are affected in the earliest stages.
| Type: | Article |
|---|---|
| Title: | Application of the ATN classification scheme in a population without dementia: Findings from the EPAD cohort |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/alz.12292 |
| Publisher version: | http://dx.doi.org/10.1002/alz.12292 |
| Language: | English |
| Additional information: | © 2021 The Authors. Alzheimer's & Dementia published by Wiley Periodicals, LLC on behalf of Alzheimer's Association This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
| Keywords: | Alzheimer's disease (AD), European Prevention of Alzheimer's Dementia (EPAD), amyloid beta, amyloid/tau/neurodegeneration (ATN) staging, cognition, magnetic resonance imaging (MRI), neurodegeneration, neuroimaging, tau |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Brain Repair and Rehabilitation UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10126260 |
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