Background: Although hippocampal atrophy is a well-known imaging biomarker of Alzheimer's disease (AD), this finding is not useful to differentiate AD from argyrophilic grain disease (AGD) which is a common AD mimicker presenting with similar amnestic symptoms and medial temporal atrophy. Instead, we propose use of the "sloping shoulders sign", defined as a distinct configuration of the bilateral hippocampal heads showing lateral and downward slopes on axial magnetic resonance imaging (MRI).
Objective: We investigated the diagnostic utility of the "sloping shoulders sign" as a simple radiological discriminator of AD from AGD.
Methods: Using axial and coronal three-dimensional MRI, our newly proposed "sloping shoulders sign", other quantitative indices including the axial hippocampal head angle (AHHA), and well-known medial temporal atrophy (MTA) score were evaluated in pathologically-proven 24 AD and 11 AGD patients.
Results: Detection rate of the "sloping shoulders sign" was significantly higher in all AD groups (83%; 20/24) and AD with Braak neurofibrillary tangle V/VI stage subgroup (88%; 15/17) than in AGD patients (18% - 2/11; p < 0.001 and p < 0.001, respectively). In contrast to the MTA score, this sign as well as AHHA demonstrated higher diagnostic performance and reproducibility, especially to differentiate all AD patients from AGD ones (accuracies of 71.4% , 82.9% and 82.9%; Cohen's kappa of 0.70 and 0.81, and intraclass correlation coefficient of 0.96, respectively).
Conclusion: The "sloping shoulders sign" is useful to differentiate advanced-stage AD from AGD. Its simplicity and reproducibility based on visual inspection using axial MRI make it suitable for routine clinical practice.
Keywords: Alzheimer’s disease; argyrophilic grain disease; hippocampus; magnetic resonance imaging; sloping shoulders sign.