Disease stage–specific atrophy markers in Alzheimer's disease
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 Ramı́rez, Falk Lüsebrink, Matthis Synofzik, Björn H. Schott, Matthias Schmid, Stefan Hetzer, Peter Dechent, Klaus Scheffler, Michael Ewers, Julian Hellmann‐Regen, Ersin Ersözlü, Eike Jakob 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 Büerger, Robert Perneczky, Stefan Teipel, Christoph Laske, Michael Wagner, Gabriel Ziegler, Frank Jessen, Emrah Düzel, David Berron, for the DELCODE study group
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.