DOI: 10.5061/dryad.88br3tn
title: Data from: ATN profiles among cognitively normal individuals and longitudinal cognitive outcomes

description: Objective. The amyloid/tau/neurodegeneration (ATN) research framework for
 Alzheimer’s disease (AD) was proposed to organize AD biomarkers and to
 stage AD across its preclinical and symptomatic phases. Applying this
 framework requires a large number of participants since the framework
 envisions eight biomarker profiles. This study examined the long-term
 cognitive trajectories of individuals with normal cognition at baseline
 and distinct ATN profiles. Methods. Pooling data across four cohort
 studies, 814 cognitively normal participants (mean baseline age=59·6
 years) were classified into eight ATN groups using baseline CSF levels of
 Aβ1-42 as a measure of amyloid (A), phosphorylated tau 181 (p-tau181) as a
 measure of tau (T), and total tau (t-tau) as a measure of
 neurodegeneration (N). Cognitive performance was measured using a
 previously validated global factor score and with the Mini-Mental State
 Examination (MMSE). We compare the cognitive trajectories across groups
 using growth curve models (mean follow-up time = 7 years). Results. Using
 different model formulations and cut-points for determining biomarker
 abnormality, only the group with abnormal levels of amyloid, tau, and
 neurodegeneration (A+T+N+) showed consistently greater cognitive decline
 than the group with normal levels of all biomarkers (A-T-N-). Replicating
 prior findings using the 2011 NIA-AA/SNAP schema, only individuals with
 abnormal levels of both amyloid and p-tau181 or t-tau (Stage 2) showed
 greater cognitive decline than those with normal biomarker levels (Stage
 0). Conclusions. The results are consistent with the hypothesis that both
 elevated brain amyloid and neurofibrillary tangles are necessary to
 observe accelerated neurodegeneration, which in turn leads to cognitive
 decline.
description: Dryad supplementary
 materials (Tables 1-6, Figures 1-2)Table of Contents: Pg.
 2: Supplementary table 1: List of cognitive tests used to compute the
 global cognitive factor score by cohort. Supplementary table 2:
 Correlations between CSF biomarkers by cohort. Pg. 3: Supplementary table
 3: Results of linear growth curve models assessing level and change of
 cognitive trajectories using quartile cut-points for CSF abeta, p-tau, and
 t-tau to define the NIA-AA/SNAP groups. Pg. 4: Supplementary figure 1:
 Estimates of longitudinal change in cognition for the NIA-AA/SNAP groups
 as defined by quartile cut-points for abeta, p-tau, and t-tau. Pg. 5:
 Supplementary table 4: Results of linear growth curve models assessing
 level and change of cognitive trajectories using tertile cut-points for
 CSF abeta, and quartile cut-points for CSF p-tau and t-tau to define the
 NIA-AA/SNAP groups. Pg. 6: Supplementary table 5: Results of linear growth
 curve models assessing level and change of cognitive trajectories of the
 eight ATN profile groups defined using quartile cut-points for CSF abeta,
 p-tau, and t-tau. Pg. 7: Supplementary figure 2: Estimates of longitudinal
 change in cognition for the eight ATN profile groups using quartiles to
 define the groups. Pg. 8: Supplementary table 6: Results of linear growth
 curve models assessing level and change of cognitive trajectories of the
 eight ATN profile groups defined using tertile cut-points for CSF abeta
 and quartile cut-points for CSF p-tau, and t-tau.ATN_supplementaryMaterials.R1_15.11.2018.docx