Disease stage-specific atrophy markers in Alzheimer’s disease

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.