05 Apr 21. Featured Paper

Application of the ATN classification scheme in a population without dementia: Findings from the EPAD cohort.

Link to paper on Alzheimer's & Dementia

Authors

Silvia Ingala, Casper De Boer, Larissa A Masselink, Ilaria Vergari, Luigi Lorenzini, Kaj Blennow, Gaël Chételat, Carol Di Perri, Michael Ewers, Wiesje M van der Flier, Nick C Fox, Juan Domingo Gispert, Sven Haller, José Luís Molinuevo, Graciela Muniz‐Terrera, Henri JMM Mutsaerts, Craig W Ritchie, Karen Ritchie, Mark Schmidt, Adam J Schwarz, Lisa Vermunt, Adam D Waldman, Joanna Wardlaw, Alle Meije Wink, Robin Wolz, Viktor Wottschel, Philip Scheltens, Pieter Jelle Visser, Frederik Barkhof, the EPAD consortium

Abstract

Background: We classified non‐demented European Prevention of Alzheimer's Dementia (EPAD) participants through the amyloid/tau/neurodegeneration (ATN) scheme & assessed their neuropsychological & imaging profiles.

Materials & methods: From 1500 EPAD participants, 312 were excluded.

Cerebrospinal fluid cut‐offs of 1000 pg/mL for amyloid beta (Aß)1‐42 & 27 pg/mL for p‐tau181 were validated using Gaussian mixture models.

Given strong correlation of p‐tau & 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 & regional brain volumes could distinguish ATN stages.

Results: Age was 65 ± 7 years, with 58% females & 38% apolipoprotein E (APOE) ε4 carriers; 57.1% were A–T–N–, 32.5% were in the Alzheimer's disease (AD) continuum, & 10.4% suspected non‐Alzheimer's pathology.

Age & 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 & language domains are affected in the earliest stages.

Keywords

• Alzheimer's disease (AD)
• Amyloid beta
• Amyloid/tau/neurodegeneration (ATN) staging
• Cognition
• European Prevention of Alzheimer's Dementia (EPAD)
• Magnetic resonance imaging (MRI)
• Neurodegeneration
• Neuroimaging
• Tau