Effects of age, BMI and sex on the glial cell marker TSPO - a multicentre [11C]PBR28 HRRT PET study

Effects of age, BMI and sex on the glial cell marker TSPO - a multicentre [11C]PBR28 HRRT PET study
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DOI:
10.1007/s00259-019-04403-7
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发表时间:
2019-10-01
影响因子:
9.1
通讯作者:
Cervenka, Simon
Cervenka, Simon
中科院分区:
医学1区
文献类型:
--
作者:
Tuisku, Jouni;Plaven-Sigray, Pontus;Cervenka, Simon

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目的本研究的目的是使用正电子发射断层扫描(PET)和放射性配体[C-11] PBR 28研究年龄、性别和体重指数(BMI)对健康受试者转运蛋白(TSPO)可用性的影响。方法收集140名健康志愿者的PBR 28数据(72名男性和68名女性; N = 78名HAB和N = 62名MAB基因型;年龄范围19-80岁; BMI范围17.6-36.9)在三个中心用高分辨率研究断层扫描仪采集:卡罗林斯卡研究所(N = 53)、图尔库PET中心(N = 62)和耶鲁大学PET中心(N = 25)。使用多线性分析1估计了整体灰质、额叶、颞叶、枕叶和顶叶皮质、海马和丘脑的总分布容积(V-T)。使用线性混合效应模型研究年龄、BMI和性别对TSPO可用性的影响,TSPO基因型和PET中心指定为随机截距。结果年龄与额叶、颞叶V-T呈显著正相关。各地区BMI与V-T呈显著负相关。此外,在所有区域都观察到男性和女性之间的显著差异,女性显示出较高的V-T。亚组分析显示,男性受试者所有区域的V-T与年龄呈正相关,而女性受试者的TSPO水平与年龄无关。结论TSPO结合率的高变异性可能与个体生物学特性有关,年龄、BMI和性别可能是临床研究中的混杂因素。
Purpose The purpose of this study was to investigate the effects of ageing, sex and body mass index (BMI) on translocator protein (TSPO) availability in healthy subjects using positron emission tomography (PET) and the radioligand [C-11]PBR28. Methods [C-11]PBR28 data from 140 healthy volunteers (72 males and 68 females; N = 78 with HAB and N = 62 MAB genotype; age range 19-80 years; BMI range 17.6-36.9) were acquired with High Resolution Research Tomograph at three centres: Karolinska Institutet (N = 53), Turku PET centre (N = 62) and Yale University PET Center (N = 25). The total volume of distribution (V-T) was estimated in global grey matter, frontal, temporal, occipital and parietal cortices, hippocampus and thalamus using multilinear analysis 1. The effects of age, BMI and sex on TSPO availability were investigated using linear mixed effects model, with TSPO genotype and PET centre specified as random intercepts. Results There were significant positive correlations between age and V-T in the frontal and temporal cortex. BMI showed a significant negative correlation with V-T in all regions. Additionally, significant differences between males and females were observed in all regions, with females showing higher V-T. A subgroup analysis revealed a positive correlation between V-T and age in all regions in male subjects, whereas age showed no effect on TSPO levels in female subjects. Conclusion These findings provide evidence that individual biological properties may contribute significantly to the high variation shown in TSPO binding estimates, and suggest that age, BMI and sex can be confounding factors in clinical studies.