Voxel-Based Acetylcholinesterase PET Study in Early and Late Onset Alzheimer’s Disease

Article type: Research Article

Authors: Hirano, Shigeki^{a; b} | Shinotoh, Hitoshi^{a; c} | Shimada, Hitoshi^a | Ota, Tsuneyoshi^d | Sato, Koichi^e | Tanaka, Noriko^f | Zhang, Ming-Rong^g | Higuchi, Makoto^a | Fukushi, Kiyoshi^g | Irie, Toshiaki^g | Kuwabara, Satoshi^b | Suhara, Tetsuya^a

Affiliations: [a] Department of Functional Brain Imaging Research, Clinical Research Cluster, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan | [b] Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan | [c] Neurology Clinic Chiba, Chiba, Japan | [d] Department of Psychiatry, Juntendo University School of Medicine, Tokyo, Japan | [e] Department of Psychiatry, Teikyo University Chiba Medical Center, Chiba, Japan | [f] Bureau of Social Welfare and Public Health, Tokyo Metropolitan Government, Tokyo, Japan | [g] Department of Radiopharmaceuticals Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan

Correspondence: [*] Correspondence to: Shigeki Hirano, MD, PhD, Department of Functional Brain Imaging Research, Clinical Research Cluster, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba-shi, Chiba, 263-8555, Japan. Tel.: +81 43 206 3025; Fax: +81 43 206 4061; E-mail: s_hirano@chiba-u.jp.

Abstract: Background:Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by chronic progressive cognitive decline and displays underlying brain cholinergic dysfunction, providing a rationale for treatment with cholinomimetic medication. The clinical presentations and courses of AD patients may differ by age of onset. Objective:The objective of the present study was to illustrate the regional differences of brain acetylcholinesterase (AChE) activity as quantified by N-[11C]methylpiperidinyl-4-acetate ([11C]MP4A) and PET using parametric whole brain analysis and clarify those differences as a function of age. Methods:22 early onset AD (EOAD) with age at onset under 65, the remaining 26 as late onset AD (LOAD), and 16 healthy controls (HC) were enrolled. Voxel-based AChE activity estimation of [11C]MP4A PET images was conducted by arterial input and unconstrained nonlinear least-squares method with subsequent parametrical analyses. Statistical threshold was set as Family Wise Error corrected, p-value <0.05 on cluster-level and cluster extent over 30 voxels. Results:Voxel-based group comparison showed that, compared to HC, both EOAD and LOAD showed cortical AChE decrement in parietal, temporal, and occipital cortices, with wider and stringent cortical involvement in the EOAD group, most prominently demonstrated in the temporal region. There was no significant correlation between age and regional cerebral AChE activity except for a small left superior temporal region in the AD group (Brodmann’s area 22, Zmax = 5.13, 396 voxels), whereas no significant cluster was found in the HC counterpart. Conclusion:Difference in cortical cholinergic dysfunction between EOAD and LOAD may shed some light on the cholinomimetic drug efficacy in AD.

Keywords: Acetylcholinesterase, age, Alzheimer’s disease, parametric analysis, positron emission tomography

DOI: 10.3233/JAD-170749

Journal: Journal of Alzheimer's Disease, vol. 62, no. 4, pp. 1539-1548, 2018