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

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.