Data from: ATN profiles among cognitively normal individuals and longitudinal cognitive outcomes

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.