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Clinical Manifestations.

David López-Martos1,2,3, Ibai Diez2,4,5,6,7, Oriol Grau-Rivera1,3,8

  • 1Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 25, 2025
PubMed
Summary
This summary is machine-generated.

Decreased awareness of cognitive function (ACF) in preclinical Alzheimer's disease (AD) is linked to higher amyloid burden and faster p-tau217 accumulation. This finding may aid early AD detection using plasma biomarkers.

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Area of Science:

  • Neurology
  • Biomarkers
  • Cognitive Science

Background:

  • Awareness of cognitive function (ACF) changes can signal preclinical Alzheimer's disease (AD).
  • Understanding these changes, especially decreased ACF (anosognosia), is crucial for predicting disease progression.
  • The relationship between ACF trajectories and AD pathophysiology needs further elucidation.

Purpose of the Study:

  • To identify distinct ACF trajectories in cognitively unimpaired (CU) individuals.
  • To examine the association of these ACF trajectories with amyloid PET and plasma p-tau217.
  • To explore ACF as a potential early marker for AD.

Main Methods:

  • Analysis of 1,643 CU individuals from A4 and LEARN cohorts.
  • Linear Mixed-Effects (LME) models to define increased, stable, and decreased ACF trajectories.
  • Assessment of cross-sectional amyloid PET and longitudinal plasma p-tau217 changes.

Main Results:

  • Decreased ACF trajectory showed significantly higher baseline amyloid burden.
  • Individuals with decreased ACF exhibited higher plasma p-tau217 levels and faster accumulation over time.
  • No significant associations were found for increased ACF trajectories.

Conclusions:

  • A decreasing ACF trajectory is strongly associated with underlying AD pathology.
  • Integrating plasma biomarkers with ACF measures offers a novel approach for early AD detection.
  • This strategy could improve understanding of preclinical AD dynamics and inform early intervention.