Utility of SPM8 plus DARTEL (VSRAD) Combined with Magnetic Resonance Spectroscopy as Adjunct Techniques for Screening and Predicting Dementia due to Alzheimer's Disease in Clinical Practice

Article type: Research Article

Authors: Waragai, Masaaki^{a; *} | Hata, Saori^b | Suzuki, Toshiharu^b | Ishii, Ryotaro^c | Fujii, Chihiro^c | Tokuda, Takahiko^c | Arai, Hiroyuki^d | Ohrui, Takashi^e | Higuchi, Susumu^f | Yoshida, Madoka^g | Igarashi, Kazuei^g | Moriya, Masaru^a | Iwai, Naomichi^a | Uemura, Kenichi^a

Affiliations: [a] Higashi Matsudo Municipal Hospital, Matsudo, Takatsuka shinden, Japan | [b] Laboratory of Neuroscience, Graduate School of Pharmaceutical Sciences, Hokkaido University, Hokkaido, Japan | [c] Department of Molecular Pathobiology of Brain Diseases (Department of Neurology), Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan | [d] Department of Geriatrics & Gerontology, Division of Brain Science Institute of Development, Aging and Cancer Tohoku University, Tohoku, Japan | [e] Division of Geriatric Pharmacotherapy, Institute of Development, Aging and Cancer, Tohoku University, Tohoku, Japan | [f] National Hospital Organization, Kurihama Medical and Addiction Center, Kanagawa, Japan | [g] Amine Pharma Research Institute, Innovation Plaza at Chiba University, Chiba, Japan

Correspondence: [*] Correspondence to: Masaaki Waragai, Higashi Matsudo Municipal Hospital, Matsudo, Takatsuka shinden, 270-2222, Japan. Tel.: +81 47 391 5500; Fax: +81 47 391 7556; E-mail: waragai@kk.iij4u.or.jp.

Abstract: We validated the utility of SPM8 plus DARTEL (VSRAD) combined with magnetic resonance spectroscopy (1H MRS) as an adjunct screening technique for dementia due to Alzheimer's disease (AD). We examined the posterior cingulate gyri of 228 subjects using VSRAD and 1H MRS in addition to conventional cerebrospinal fluid biomarkers at baseline. At the 3-year follow-up, the 228 subject were classified as follows: 93 healthy subjects, 42 MCI-non-converters (MCI-NC), 25 MCI-converters to AD (MCI-C), 44 AD, 8 dementia with Lewy bodies (DLB), 5 normal pressure hydrocephalus, and 11 patients with other neurological diseases. Our results demonstrated that subjects with increased medial temporal atrophy (MTA) severity on VSRAD, increased Cho/Cr, MI/Cr ratio, and decreased NAA/Cr and NAA/MI ratio on 1H MRS at baseline were at risk of dementia due to AD. Receiver operating characteristic analysis showed that severity of MTA and the NAA/MI ratio distinguished patients with AD and MCI-C from controls. Furthermore, the 118 subjects without dementia and MTA showing only a decreased NAA/MI ratio at baseline developed to MCI-C, AD, and DLB 3 years later. 1H MRS detected biochemical abnormalities preceding brain atrophy and cognitive decline. VSRAD combined with 1H MRS may be routinely applied to screen for MCI/AD and prodromal AD in clinical practice.

Keywords: Alzheimer's disease, magnetic resonance imaging, magnetic resonance spectroscopy (¹H MRS), screening, SPM8 plus DARTEL (VSRAD), surrogate marker

DOI: 10.3233/JAD-132786

Journal: Journal of Alzheimer's Disease, vol. 41, no. 4, pp. 1207-1222, 2014