Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, MD, USA; Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
Neuroimage. 2018 Jan 15;165:118-124. doi: 10.1016/j.neuroimage.2017.10.009. Epub 2017 Oct 7.
Altered function of the alpha7 nicotinic acetylcholine receptor (α7-nAChR) is implicated in several neuropsychiatric diseases. Nevertheless, studies of the human cerebral α7-nAChR even in healthy aging are limited in number and to postmortem tissue.
The distribution of the cerebral α7-nAChR was estimated in nine brain regions in 25 healthy volunteers (ages 21-86 years; median 57 years, interquartile range 52 years) using [F]ASEM with positron emission tomography (PET) imaging. Regional total distribution volume (V) measurements were calculated using the Logan method from each subject's 90 min dynamic PET data and their metabolite-corrected plasma input function. Spearman's rank or Pearson's correlation analysis was used depending on the normality of the data. Correlation between age and regional 1) volume relative to intracranial volume (volume ratio) and 2) [F]ASEM V was tested. Correlation between regional volume ratio and [F]ASEM V was also evaluated. Finally, the relationship between [F]ASEM V and neuropsychological measures was investigated in a subpopulation of 15 elderly healthy participants (those 50 years of age and older). Bonferroni correction for multiple comparisons was applied to statistical analyses.
A negative correlation between tissue volume ratio and age was observed in six of the nine brain regions including striatum and five cortical (temporal, occipital, cingulate, frontal, or parietal) regions. A positive correlation between [F]ASEM V and age was observed in all nine brain regions of interest (ROIs). There was no correlation between [F]ASEM V and volume ratio in any ROI after controlling for age. Regional [F]ASEM V and neuropsychological performance on each of eight representative subtests were not correlated among the well-performing subpopulation of elderly healthy participants.
Our results suggest an increase in cerebral α7-nAChR distribution over the course of healthy aging that should be tested in future longitudinal studies. The preservation of the α7-nAChR in the aging human brain supports the development of therapeutic agents that target this receptor for use in the elderly. Further study of the relationship between α7-nAChR availability and cognitive impairment over aging is needed.
使用正电子发射断层扫描（PET）成像的 [F]ASEM 研究 25 名健康志愿者（年龄 21-86 岁；中位数 57 岁，四分位距 52 岁）的 9 个脑区中大脑 α7-nAChR 的分布。使用每个受试者的 90 分钟动态 PET 数据及其代谢校正的血浆输入函数，通过 Logan 方法计算区域总分布容积（V）测量值。根据数据的正态性，使用 Spearman 秩或 Pearson 相关分析。测试年龄与 1）相对于颅内容积的区域体积（体积比）和 2）[F]ASEM V 之间的相关性。还评估了区域体积比与 [F]ASEM V 之间的相关性。最后，在 15 名老年健康参与者（年龄 50 岁及以上）的亚组中研究了 [F]ASEM V 与神经心理学测量之间的关系。对统计分析应用了 Bonferroni 多重比较校正。
在包括纹状体和五个皮质（颞叶、枕叶、扣带回、额叶或顶叶）区域在内的 9 个脑区中的 6 个脑区中观察到组织体积比与年龄呈负相关。在所有 9 个感兴趣的脑区（ROI）中都观察到 [F]ASEM V 与年龄呈正相关。在控制年龄后，任何 ROI 中都没有 [F]ASEM V 与体积比相关。在表现良好的老年健康参与者亚组中，8 个代表性子测试中的每个子测试的区域 [F]ASEM V 和神经心理学表现之间没有相关性。
我们的结果表明，在健康衰老过程中，大脑 α7-nAChR 的分布增加，这应在未来的纵向研究中进行测试。在衰老的人类大脑中保留 α7-nAChR 支持开发针对该受体的治疗剂，以便在老年人中使用。需要进一步研究随着年龄的增长，α7-nAChR 可用性与认知障碍之间的关系。
