Simple Quantitative Indices for the Differentiation of Advanced-Stage Alzheimer’s Disease and Other Limbic Tauopathies

Article type: Research Article

Authors: Sakurai, Keita^{a; *} | Kaneda, Daita^b | Inui, Shohei^c | Uchida, Yuto^d | Morimoto, Satoru^e | Nihashi, Takashi^a | Kato, Takashi^a | Ito, Kengo^a | Hashizume, Yoshio^b

Affiliations: [a] Department of Radiology, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan | [b] Choju Medical Institute, Fukushimura Hospital, Toyohashi, Japan | [c] Department of Radiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan | [d] Department of Neurology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan | [e] Department of Physiology, School of Medicine, Keio University, Tokyo, Japan

Correspondence: [*] Correspondence to: Keita Sakurai, MD, PhD, Department of Radiology, National Center for Geriatrics and Gerontology, 7-430 Morioka-cho, Obu, 474-8511, Aichi, Japan. Tel.: +81 52 46 2311; E-mail: ksak666@yahoo.co.jp.; ORCID ID: 0000-0002-8849-7335

Abstract: Background:The differentiation of Alzheimer’s disease (AD) from age-related limbic tauopathies (LT), including argyrophilic grain disease (AGD) and senile dementia of the neurofibrillary tangle type (SD-NFT), is often challenging because specific clinical diagnostic criteria have not yet been established. Despite the utility of specific biomarkers evaluating amyloid and tau to detect the AD-related pathophysiological changes, the expense and associated invasiveness preclude their use as first-line diagnostic tools for all demented patients. Therefore, less invasive and costly biomarkers would be valuable in routine clinical practice for the differentiation of AD and LT. Objective:The purpose of this study is to develop a simple reproducible method on magnetic resonance imaging (MRI) that could be adopted in daily clinical practice for the differentiation of AD and other forms of LT. Methods:Our newly proposed three quantitative indices and well-known medial temporal atrophy (MTA) score were evaluated using MRI of pathologically-proven advanced-stage 21 AD, 10 AGD, and 2 SD-NFT patients. Results:Contrary to MTA score, hippocampal angle (HPA), inferior horn area (IHA), and ratio between HPA and IHA (i.e., IHPA index) demonstrated higher diagnostic performance and reproducibility, especially to differentiate advanced-stage AD patients with Braak neurofibrillary tangle stage V/VI from LT patients (the area under the receiver-operating-characteristic curve of 0.83, 089, and 0.91; intraclass correlation coefficients of 0.930, 0.998, and 0.995, respectively). Conclusion:Quantitative indices reflecting hippocampal deformation with ventricular enlargement are useful to differentiate advanced-stage AD from LT. This simple and convenient method could be useful in daily clinical practice.

Keywords: Alzheimer’s disease, argyrophilic grain disease, hippocampal angle, limbic tauopathy, magnetic resonance imaging, senile dementia of the neurofibrillary tangle type, ventricular enlargement

DOI: 10.3233/JAD-210043

Journal: Journal of Alzheimer's Disease, vol. 81, no. 3, pp. 1093-1102, 2021