Alzheimer's & dementia : the journal of the Alzheimer's Association · 2021
Application of the ATN classification scheme in a population without dementia: Findings from the EPAD cohort.
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Ingala Silvia, De Boer Casper, Masselink Larissa A, Vergari Ilaria, Lorenzini Luigi, Blennow Kaj, Chételat Gaël, Di Perri Carol, Ewers Michael, van der Flier Wiesje M, Fox Nick C, Gispert Juan Domingo, Haller Sven, Molinuevo José Luís, Muniz-Terrera 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, EPAD consortium
Аннотация
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.
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.