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. 2021 Mar 31;13(1):e12174.
doi: 10.1002/dad2.12174. eCollection 2021.

Adding cognition to AT(N) models improves prediction of cognitive and functional decline

Deirdre M O'Shea  1 , Kelsey R Thomas  2   3 , Breton Asken  4 , Athene K W Lee  1 , Jennifer D Davis  1 , Paul F Malloy  1 , Stephen P Salloway  1 , Stephen Correia  1 ; Alzheimer's Disease Neuroimaging Initiative
Affiliations

Adding cognition to AT(N) models improves prediction of cognitive and functional decline

Deirdre M O'Shea et al. Alzheimers Dement (Amst). .

Abstract

Introduction: This study sought to determine whether adding cognition to a model with Alzheimer's disease biomarkers based on the amyloid, tau, and neurodegeneration/neuronal injury-AT(N)-biomarker framework predicts rates of cognitive and functional decline in older adults without dementia.

Methods: The study included 465 participants who completed amyloid positron emission tomography, cerebrospinal fluid phosphorylated tau, structural magnetic resonance imaging, and serial neuropsychological testing. Using the AT(N) framework and a newly validated cognitive metric as the independent variables, we used linear mixed effects models to examine a 4-year rate of change in cognitive and functional measures.

Results: The inclusion of baseline cognitive status improved model fit in predicting rate of decline in outcomes above and beyond biomarker variables. Specifically, those with worse cognitive functioning at baseline had faster rates of memory and functional decline over a 4-year period, even when accounting for AT(N).

Discussion: Including a newly validated measure of baseline cognition may improve clinical prognosis in non-demented older adults beyond the use of AT(N) biomarkers alone.

Keywords: AT(N); Alzheimer's disease; aging; cognitive decline; dementia; functional decline.

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Conflict of interest statement

There are no conflicts of interest to report.

Figures

FIGURE 1
FIGURE 1
Trajectories of cognitive and functional outcomes by DELTA score. The memory composite (A), executive composite (B), ADAS‐Cog (C), CDR‐SB (D), and FAQ (E) model predicted values displayed in z‐score metric. The DELTA score categories shown in the figure of DELTA = 0 (n = 251), DELTA = 1–3 (n = 133), and DELTA = 4+ (n = 81) were used for graphing purposes only. The continuous DELTA score was used in the models. Higher memory and executive composite scores are associated with better performance, while higher ADAS‐Cog, CDR‐SB, and FAQ scores are associated with worse functioning. ADAS‐Cog, Alzheimer's Disease Assessment Scale–Cognitive Subscale; CDR‐SB, Clinical Dementia Rating–Sum of Boxes; DELTA, Discrepancy‐Based Evidence for Loss of Thinking Abilities; FAQ, Functional Activities Questionnaire
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