Disease stage–specific atrophy markers in Alzheimer's disease

  1. Hannah Baumeister
  2. Helena M. Gellersen
  3. Sarah E. Polk
  4. René Lattmann
  5. Anika Wuestefeld
  6. Laura E. M. Wisse
  7. Trevor Glenn
  8. Renat Yakupov
  9. Melina Stark
  10. Luca Kleineidam
  11. Sandra Roeske
  12. Barbara Marcos Morgado
  13. Hermann Esselmann
  14. Frederic Brosseron
  15. Alfredo Ramirez
  16. Falk Lüsebrink
  17. Matthis Synofzik
  18. Björn H. Schott
  19. Matthias C. Schmid
  20. Stefan Hetzer
  21. Peter Dechent
  22. Klaus Scheffler
  23. Michael Ewers
  24. Julian Hellmann‐Regen
  25. Ersin Ersözlü
  26. Eike Spruth
  27. Maria Gemenetzi
  28. Klaus Fliessbach
  29. Claudia Bartels
  30. Ayda Rostamzadeh
  31. Wenzel Glanz
  32. Enise I. Incesoy
  33. Daniel Janowitz
  34. Boris‐Stephan Rauchmann
  35. Ingo Kilimann
  36. Sebastian Sodenkamp
  37. Marie Coenjaerts
  38. Annika Spottke
  39. Oliver Peters
  40. Josef Priller
  41. Anja Schneider
  42. Jens Wiltfang
  43. Katharina Buerger
  44. Robert Perneczky
  45. Stefan Teipel
  46. Christoph Laske
  47. Michael Wagner
  48. Gabriel Ziegler
  49. Frank Jessen
  50. Emrah Düzel
  51. David Berron
  52. for the DELCODE study group
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Abstract

INTRODUCTION

Structural magnetic resonance imaging (MRI) often lacks diagnostic, prognostic, and monitoring value in Alzheimer's disease (AD), particularly in early disease stages. To improve its utility, we aimed to identify optimal atrophy markers for different intended uses.

METHODS

We included 363 older adults; cognitively unimpaired individuals who were negative or positive for amyloid beta (Aβ) and Aβ‐positive patients with subjective cognitive decline, mild cognitive impairment, or dementia of the Alzheimer type. MRI and neuropsychological assessments were administered annually for up to 3 years.

RESULTS

Accelerated atrophy of medial temporal lobe subregions was evident already during preclinical AD. Symptomatic disease stages most notably differed in their hippocampal and parietal atrophy signatures. Atrophy–cognition relationships varied by intended use and disease stage.

DISCUSSION

With the appropriate marker, MRI can detect abnormal atrophy already during preclinical AD. To optimize performance, atrophy markers should be tailored to the targeted disease stage and intended use.

Highlights

  • Subregional atrophy markers detect ongoing atrophy in preclinical Alzheimer's disease (AD).

  • Subjective cognitive decline in preclinical AD links to manifest atrophy.

  • Optimal atrophy markers differ by the disease stage and intended use.

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  1. Version published to 10.1002/alz.70482
  2. Version published to 10.1101/2025.03.13.25323904 on medRxiv