Voxel-Based Acetylcholinesterase PET Study in Early and Late Onset Alzheimer's Disease
Voxel-Based Acetylcholinesterase PET Study in Early and Late Onset Alzheimer's Disease
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DOI：
10.3233/jad-170749
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发表时间：
2018-01-01
影响因子：
4
通讯作者：
Suhara, Tetsuya
中科院分区：
文献类型：
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作者：
Hirano, Shigeki;Shinotoh, Hitoshi;Suhara, Tetsuya
背景：阿尔茨海默病（AD）是一种神经退行性疾病，其特征是慢性进行性认知衰退，并表现出潜在的脑胆碱能功能障碍，这为使用拟胆碱药物治疗提供了依据。 AD 患者的临床表现和病程可能因发病年龄而异。 目的：本研究的目的是通过参数化全脑分析通过 N-[C-11] 甲基哌啶基-4-乙酸酯 ([C-11] MP4A) 和 PET 定量，说明脑乙酰胆碱酯酶 (AChE) 活性的区域差异，并阐明这些差异与年龄的关系。方法：22 岁早期 纳入发病年龄在65岁以下的发病AD（EOAD），其余26例为晚发AD（LOAD），以及16例健康对照（HC）。通过动脉输入和无约束非线性最小二乘法以及随后的参数分析，对 [C-11] MP4A PET 图像进行基于体素的 AChE 活性估计。统计阈值设置为家庭明智误差校正，簇水平上的 p 值 < 0.05，簇范围超过 30 个体素。结果：基于体素的组比较表明，与 HC 相比，EOAD 和 LOAD 均显示顶叶、颞叶和枕叶皮质的皮质 AChE 减少，EOAD 组的皮质受累范围更广、更严格，最显着地表现在颞叶皮质。 地区。除 AD 组中的一小部分左上颞区（布罗德曼面积 22，Z(max) = 5.13，396 体素）外，年龄和局部脑 AChE 活性之间没有显着相关性，而在 HC 组中没有发现显着的簇。结论：EOAD 和 LOAD 之间皮质胆碱能功能障碍的差异可能有助于了解拟胆碱药物在 AD 组中的疗效。 公元。
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-[C-11] methylpiperidinyl-4-acetate ([C-11] 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 [C-11] 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, Z(max) = 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.