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Application of the ATN classification scheme in a population without dementia: Findings from the EPAD cohort
Author(s) -
Ingala Silvia,
De Boer Casper,
Masselink Larissa A,
Vergari Ilaria,
Lorenzini Luigi,
Blennow Kaj,
Chételat Gaël,
Di Perri Carol,
Ewers Michael,
Flier Wiesje M,
Fox Nick C,
Gispert Juan Domingo,
Haller Sven,
Molinuevo José Luís,
MunizTerrera Graciela,
Mutsaerts Henri JMM,
Ritchie Craig W,
Ritchie Karen,
Schmidt Mark,
Schwarz Adam J,
Vermunt Lisa,
Waldman Adam D,
Wardlaw Joanna,
Wink Alle Meije,
Wolz Robin,
Wottschel Viktor,
Scheltens Philip,
Visser Pieter Jelle,
Barkhof Frederik
Publication year - 2021
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.12292
Subject(s) - dementia , neuropsychology , neurodegeneration , cohort , biomarker , medicine , population , alzheimer's disease , psychology , apolipoprotein e , cognition , oncology , disease , psychiatry , chemistry , environmental health , biochemistry
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 (R 2 = 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.