Single-value brain activity scores reflect both severity and risk across the Alzheimer’s continuum

Joram Soch, Anni Richter, Jasmin M. Kizilirmak, Hartmut Schütze, Gabriel Ziegler, Slawek Altenstein, Frederic Brosseron, Peter Dechent, Klaus Fliessbach, Silka Dawn Freiesleben, Wenzel Glanz, Daria Gref, Michael T. Heneka, Stefan Hetzer, Enise I. Incesoy, Ingo Kilimann, Okka Kimmich, Luca Kleineidam, Elizabeth Kuhn, Christoph LaskeAndrea Lohse, Falk Lüsebrink, Matthias H. Munk, Oliver Peters, Lukas Preis, Josef Priller, Alfredo Ramirez, Sandra Roeske, Ayda Rostamzadeh, Nina Roy-Kluth, Klaus Scheffler, Matthias Schmid, Anja Schneider, Annika Spottke, Eike Jakob Spruth, Stefan Teipel, Jens Wiltfang, Frank Jessen, Michael Wagner, Emrah Düzel, Björn H. Schott

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Single-value scores reflecting the deviation from (FADE score) or similarity with (SAME score) prototypical novelty-related and memory-related functional MRI activation patterns in young adults have been proposed as imaging biomarkers of healthy neurocognitive ageing. Here, we tested the utility of these scores as potential diagnostic and prognostic markers in Alzheimer’s disease (AD) and risk states like mild cognitive impairment (MCI) or subjective cognitive decline (SCD). To this end, we analysed subsequent memory functional MRI data from individuals with SCD, MCI and AD dementia as well as healthy controls and first-degree relatives of AD dementia patients (AD-rel) who participated in the multi-centre DELCODE study (n = 468). Based on the individual participants’ whole-brain functional MRI novelty and subsequent memory responses, we calculated the FADE and SAME scores and assessed their association with AD risk stage, neuropsychological test scores, CSF amyloid positivity and APOE genotype. Memory-based FADE and SAME scores showed a considerably larger deviation from a reference sample of young adults in the MCI and AD dementia groups compared to healthy controls, SCD and AD-rel. In addition, novelty-based scores significantly differed between the MCI and AD dementia groups. Across the entire sample, single-value scores correlated with neuropsychological test performance. The novelty-based SAME score further differed between Aβpositive and Aβ-negative individuals in SCD and AD-rel, and between ApoE Ɛ4 carriers and non-carriers in AD-rel. Hence, FADE and SAME scores are associated with both cognitive performance and individual risk factors for AD. Their potential utility as diagnostic and prognostic biomarkers warrants further exploration, particularly in individuals with SCD and healthy relatives of AD dementia patients.

Original languageEnglish
Pages (from-to)3789-3803
Number of pages15
JournalBrain
Volume147
Issue number11
DOIs
StatePublished - 1 Nov 2024
Externally publishedYes

Keywords

  • Alzheimer’s disease
  • dementia risk
  • fMRI scores
  • mild cognitive impairment
  • novelty processing
  • subsequent memory

Fingerprint

Dive into the research topics of 'Single-value brain activity scores reflect both severity and risk across the Alzheimer’s continuum'. Together they form a unique fingerprint.

Cite this