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Disease stage-specific atrophy markers in Alzheimer's disease.

medRxiv : the preprint server for health sciences

Authors: Hannah Baumeister, Helena M Gellersen, Sarah E Polk, René Lattmann, Anika Wuestefeld, Laura E M Wisse, Trevor Glenn, Renat Yakupov, Melina Stark, Luca Kleineidam, Sandra Roeske, Barbara Marcos Morgado, Hermann Esselmann, Frederic Brosseron, Alfredo Ramirez, Falk Lüsebrink, Matthis Synofzik, Björn H Schott, Matthias C Schmid, Stefan Hetzer, Peter Dechent, Klaus Scheffler, Michael Ewers, Julian Hellmann-Regen, Ersin Ersözlü, Eike Spruth, Maria Gemenetzi, Klaus Fliessbach, Claudia Bartels, Ayda Rostamzadeh, Wenzel Glanz, Enise I Incesoy, Daniel Janowitz, Boris-Stephan Rauchmann, Ingo Kilimann, Sebastian Sodenkamp, Marie Coenjaerts, Annika Spottke, Oliver Peters, Josef Priller, Anja Schneider, Jens Wiltfang, Katharina Buerger, Robert Perneczky, Stefan Teipel, Christoph Laske, Michael Wagner, Gabriel Ziegler, Frank Jessen, Emrah Düzel, David Berron

INTRODUCTION: Structural 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 MRI readouts for different use cases.

METHODS: We included 363 older adults; healthy controls (HC) who were negative or positive for amyloidbeta (Aβ) and Aβ-positive patients with subjective cognitive decline (SCD), mild cognitive impairment, or dementia of the Alzheimer type. MRI and neuropsychological assessments were administered annually for up to three years.

RESULTS: Accelerated atrophy of distinct MTL subregions was evident already during preclinical AD. Symptomatic disease stages most notably differed in their hippocampal and parietal atrophy signatures. Associations of atrophy markers and cognitive inventories varied by intended use and disease stage.

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

PMID: 40162264

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