Persson N, Ghisletta P, Dahle C L, Bender A R, Yang Y, Yuan P, Daugherty A M, Raz N
Department of Psychology, Stockholm University, Stockholm, Sweden; Stockholm Brain Institute, Stockholm, Sweden; Institute of Gerontology, Wayne State University, Detroit, MI 48202, USA.
Faculty of Psychology and Educational Sciences, University of Geneva, Sierre, Switzerland; Switzerland Distance Learning University, Sierre, Switzerland.
Neuroimage. 2014 Dec;103:334-348. doi: 10.1016/j.neuroimage.2014.09.042. Epub 2014 Sep 28.
We examined regional changes in brain volume in healthy adults (N=167, age 19-79years at baseline; N=90 at follow-up) over approximately two years. With latent change score models, we evaluated mean change and individual differences in rates of change in 10 anatomically-defined and manually-traced regions of interest (ROIs): lateral prefrontal cortex (LPFC), orbital frontal cortex (OF), prefrontal white matter (PFw), hippocampus (Hc), parahippocampal gyrus (PhG), caudate nucleus (Cd), putamen (Pt), insula (In), cerebellar hemispheres (CbH), and primary visual cortex (VC). Significant mean shrinkage was observed in the Hc, CbH, In, OF, and PhG, and individual differences in change were noted in all regions, except the OF. Pro-inflammatory genetic variants modified shrinkage in PhG and CbH. Carriers of two T alleles of interleukin-1β (IL-1β C-511T, rs16944) and a T allele of methylenetetrahydrofolate reductase (MTHFR C677T, rs1801133) polymorphisms showed increased PhG shrinkage. No effects of a pro-inflammatory polymorphism for C-reactive protein (CRP-286C>A>T, rs3091244) or apolipoprotein (APOE) ε4 allele were noted. These results replicate the pattern of brain shrinkage observed in previous studies, with a notable exception of the LPFC, thus casting doubt on the unique importance of prefrontal cortex in aging. Larger baseline volumes of CbH and In were associated with increased shrinkage, in conflict with the brain reserve hypothesis. Contrary to previous reports, we observed no significant linear effects of age and hypertension on regional brain shrinkage. Our findings warrant further investigation of the effects of neuroinflammation on structural brain change throughout the lifespan.
我们对健康成年人（基线时N = 167，年龄19 - 79岁；随访时N = 90）约两年间大脑体积的区域变化进行了研究。采用潜在变化分数模型，我们评估了10个通过解剖学定义并手动追踪的感兴趣区域（ROI）的平均变化及变化率的个体差异，这些区域包括：外侧前额叶皮质（LPFC）、眶额皮质（OF）、前额叶白质（PFw）、海马体（Hc）、海马旁回（PhG）、尾状核（Cd）、壳核（Pt）、脑岛（In）、小脑半球（CbH）和初级视觉皮质（VC）。在Hc、CbH、In、OF和PhG中观察到显著的平均萎缩，除OF外，所有区域均存在变化的个体差异。促炎基因变异改变了PhG和CbH的萎缩情况。白细胞介素 - 1β（IL - 1β C - 511T，rs16944）两个T等位基因和亚甲基四氢叶酸还原酶（MTHFR C677T，rs1801133）多态性的一个T等位基因携带者的PhG萎缩增加。未观察到促炎多态性对C反应蛋白（CRP - 286C>A>T，rs3091244）或载脂蛋白（APOE）ε4等位基因的影响。这些结果重复了先前研究中观察到的大脑萎缩模式，但LPFC是一个显著例外，因此对前额叶皮质在衰老过程中的独特重要性提出了质疑。CbH和In较大的基线体积与萎缩增加相关，这与脑储备假说相矛盾。与先前报道相反，我们未观察到年龄和高血压对区域脑萎缩有显著的线性影响。我们的研究结果值得进一步探讨神经炎症对整个生命周期大脑结构变化的影响。
