Journal Article Voxel-Based Acetylcholinesterase PET Study in Early and Late Onset Alzheimer's Disease.

Hirano, Shigeki  ,  Shinoto, Hitoshi  ,  Shimada, Hitoshi  ,  Ota, Tsuneyoshi  ,  Sato, Koichi  ,  Tanaka, Noriko  ,  Ming-Rong, Zhang  ,  Higuchi, Makoto  ,  Fukushi, Kiyoshi  ,  Irie, Toshiaki  ,  Kuwabara, Satoshi  ,  Suhara, Tetsuya

Background: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by chronic progressive cognitivedecline and displays underlying brain cholinergic dysfunction, providing a rationale for treatment with cholinomimeticmedication. 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 analysisand 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 healthycontrols (HC) were enrolled. Voxel-based AChE activity estimation of [11C]MP4A PET images was conducted by arterialinput and unconstrained nonlinear least-squares method with subsequent parametrical analyses. Statistical threshold was setas 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 AChEdecrement in parietal, temporal, and occipital cortices, with wider and stringent cortical involvement in the EOAD group,most prominently demonstrated in the temporal region. Therewas no significant correlation between age and regional cerebralAChE 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 cholinomimeticdrug efficacy in AD.Keywords: Acetylcholinesterase, age, Alzheimer’s

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