ATN profiles among cognitively normal individuals and longitudinal cognitive outcomes.

Abstract:

OBJECTIVE:To examine the long-term cognitive trajectories of individuals with normal cognition at baseline and distinct amyloid/tau/neurodegeneration (ATN) profiles. METHODS:Pooling data across 4 cohort studies, 814 cognitively normal participants (mean baseline age = 59.6 years) were classified into 8 ATN groups using baseline CSF levels of β-amyloid 1-42 as a measure of amyloid (A), phosphorylated tau 181 as a measure of tau (T), and total 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. We compared 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 National Institute on Aging-Alzheimer's Association/suspected non-Alzheimer disease pathophysiology schema, only individuals with abnormal levels of both amyloid and phosphorylated tau 181 or total tau (stage 2) showed greater cognitive decline than those with normal biomarker levels (stage 0). CONCLUSION: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.

journal_name

Neurology

journal_title

Neurology

authors

Soldan A,Pettigrew C,Fagan AM,Schindler SE,Moghekar A,Fowler C,Li QX,Collins SJ,Carlsson C,Asthana S,Masters CL,Johnson S,Morris JC,Albert M,Gross AL

doi

10.1212/WNL.0000000000007248

subject

Has Abstract

pub_date

2019-04-02 00:00:00

pages

e1567-e1579

issue

14

eissn

0028-3878

issn

1526-632X

pii

WNL.0000000000007248

journal_volume

92

pub_type

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