Amnestic Transitional Cognitive Decline in Aging and Preclinical Alzheimer’s Disease

  1. David López-Martos
  2. Raffaele Cacciaglia
  3. Marc Suárez-Calvet
  4. Gemma Salvadó
  5. Mahnaz Shekari
  6. Armand González-Escalante
  7. Marta Milà-Alomà
  8. Anna Brugulat-Serrat
  9. Carolina Minguillon
  10. Matteo Tonietto
  11. Edilio Borroni
  12. Gregory Klein
  13. Clara Quijano-Rubio
  14. Gwendlyn Kollmorgen
  15. Henrik Zetterberg
  16. Kaj Blennow
  17. Juan Domingo Gispert
  18. Oriol Grau-Rivera
  19. Gonzalo Sánchez-Benavides
  20. the ALFA study
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Abstract

INTRODUCTION

This study proposes objective, standardized criteria for defining amnestic transitional cognitive decline (aTCD) in aging and preclinical Alzheimer’s disease (AD), supported by a comprehensive multimodal biomarker characterization.

METHODS

This prospective observational study analyzed 3-year longitudinal data from the Alzheimer’s and Families+ cohort, including 350 cognitively unimpaired participants. The presence of aTCD was defined using robust longitudinal neuropsychological references with a multivariate base rate threshold of significant cognitive decline; its association with fluid (plasma and CSF) and neuroimaging biomarkers (PET and MRI) was evaluated using mixed-effects and voxel-wise regression models, respectively.

RESULTS

Applying the defined criteria, aTCD was identified in 35 individuals (10%), demonstrating significant associations with Core AD biomarkers (Aβ and tau) and biomarkers of non-specific processes involved in AD pathophysiology (neurodegeneration and inflammation).

DISCUSSION

These findings underscore the need for standardized clinical staging criteria to improve early detection and risk stratification in aging and preclinical AD.

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