Effect of leukocyte telomere length on total and regional brain volumes in a large population-based cohort.
Effect of leukocyte telomere length on total and regional brain volumes in a large population-based cohort.
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DOI：
10.1001/jamaneurol.2014.1926
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发表时间：
2014-10
期刊：
影响因子：
29
通讯作者：
Garcia CK
中科院分区：
文献类型：
--
作者：
King KS;Kozlitina J;Rosenberg RN;Peshock RM;McColl RW;Garcia CK
端粒长度与痴呆和心理压力有关，但其与人脑大小的关系尚不清楚。确定外周血端粒长度是否与脑容量相关。在达拉斯心脏研究中，测量了1960名个体的外周血白细胞端粒长度和脑体积，该研究是德克萨斯州达拉斯县居民的基于人群的概率样本，中位数（第25 - 75百分位数）年龄为50（42-58）岁。根据磁共振成像的自动分析评估了全球和48个区域脑体积。端粒长度与全脑和局部脑容量。白细胞端粒长度与总脑体积相关（β [SE]，0.06 [0.01]，P <0.001），包括白色和皮质灰质体积（分别为β [SE]，0.04 [0.01]，P = 0.002; β [SE]，0.07 [0.02]，P <0.001），与年龄、性别、种族和总颅内体积无关。虽然年龄与大脑皮层大多数亚段区域的大小有关，但端粒长度与某些亚段区域有关。与年龄相比，端粒长度（TL）解释了海马、杏仁核和下颞区体积变化的相当大的比例（海马：βTL [SE]，0.08 [0.02]，R2，0.91% vs βage [SE]，-0.16 [0.02]，R2，3.80%;杏仁核：βTL [SE]，0.08 [0.02]，R2，0.78% vs βage [SE]，−0.19 [0.02]，R2，4.63%;下颞侧：βTL [SE]，0.07 [0.02]，R2，0.92% vs βage [SE]，−0.14 [0.02]，R2，3.98%）（所有P <0.001）。年龄大于50岁的个体端粒长度与顶叶下部和上级、海马和梭状区的大小之间的关联性比年轻个体更强（下顶骨：β>50 [SE]，0.13 [0.03]，P <.001 vs β≤50 [SE]，0.02 [0.02]，P = .51，相互作用P = .001;上级顶骨：β>50 [SE]，0.11 [0.03]，P <.001 vs β≤50 [SE]，0.01 [0.02]，P = .71，相互作用P = .004;海马：β>50 [SE]，0.10 [0.03]，P = .004 vs β≤50 [SE]，0.05 [0.02]，P = .07，相互作用P = .04;梭形：β>50 [SE]，0.09 [0.03]，P = .002，β≤50 [SE]，0.03 [0.02]，P = .31，相互作用P = .03）。在调整所有协变量（年龄、性别、种族、颅内总体积、体重指数、血压、糖尿病、吸烟状况和APOE基因型）后，海马、杏仁核、颞叶上级和颞叶下、楔前叶、眶额外侧、扣带回后部、丘脑和间脑腹侧的体积与端粒长度独立相关。据我们所知，这是迄今为止第一项基于人群的研究，评估端粒长度作为全球和局部大脑大小的独立预测因素。未来的研究需要确定端粒长度和解剖结构的变化如何与认知功能，痴呆症和心理疾病相关。
Telomere length has been associated with dementia and psychological stress, but its relationship with human brain size is unknown. To determine if peripheral blood telomere length is associated with brain volume. Peripheral blood leukocyte telomere length and brain volumes were measured for 1960 individuals in the Dallas Heart Study, a population-based, probability sample of Dallas County, Texas, residents, with a median (25th-75th percentile) age of 50 (42-58) years. Global and 48 regional brain volumes were assessed from the automated analysis of magnetic resonance imaging. Telomere length and global and regional brain volumes. Leukocyte telomere length was associated with total cerebral volume (β [SE], 0.06 [0.01], P <.001) including white and cortical gray matter volume (β [SE], 0.04 [0.01], P = .002; β [SE], 0.07 [0.02], P <.001, respectively), independent of age, sex, ethnicity, and total intracranial volume. While age was associated with the size of most subsegmental regions of the cerebral cortex, telomere length was associated with certain subsegmental regions. Compared with age, telomere length (TL) explained a sizeable proportion of the variance in volume of the hippocampus, amygdala, and inferior temporal region (hippocampus: βTL [SE], 0.08 [0.02], R2, 0.91% vs βage [SE], −0.16 [0.02], R2, 3.80%; amygdala: βTL [SE], 0.08 [0.02], R2, 0.78% vs βage [SE], −0.19 [0.02], R2,4.63%; inferior temporal: βTL [SE], 0.07 [0.02], R2, 0.92% vs βage [SE], −0.14 [0.02], R2, 3.98%) (P <.001 for all). The association of telomere length and the size of the inferior and superior parietal, hippocampus, and fusiform regions was stronger in individuals older than 50 years than younger individuals (inferior parietal: β>50 [SE], 0.13 [0.03], P <.001 vs β≤50 [SE], 0.02 [0.02], P = .51, P for interaction = .001; superior parietal: β>50 [SE], 0.11 [0.03], P <.001 vs β≤50 [SE], 0.01 [0.02], P = .71, P for interaction = .004; hippocampus: β>50 [SE], 0.10 [0.03], P = .004 vs β≤50 [SE], 0.05 [0.02], P = .07, P for interaction = .04; fusiform: β>50 [SE], 0.09 [0.03], P = .002, β≤50 [SE], 0.03 [0.02], P = .31, P for interaction = .03). The volume of the hippocampus, amygdala, superior and inferior temporal, precuneus, lateral orbitofrontal, posterior cingulate, thalamus and ventral diencephalon were independently associated with telomere length after adjustment for all covariates (age, gender, ethnicity, total intracranial volume, body mass index, blood pressure, diabetes, smoking status, and APOE genotype). To our knowledge, this is the first population-based study to date to evaluate telomere length as an independent predictor of global and regional brain size. Future studies are needed to determine how telomere length and anatomic structural changes are related to cognitive function, dementia, and psychological disease.