Gampawar Piyush, Schmidt Reinhold, Schmidt Helena
Research Unit-Genetic Epidemiology, Gottfried Schatz Research Centre for Cell Signalling, Metabolism and Aging, Molecular Biology and Biochemistry, Medical University Graz, Graz, Austria.
Department of Neurology, Clinical Division of Neurogeriatrics, Medical University Graz, Graz, Austria.
Front Psychiatry. 2020 Feb 28;11:100. doi: 10.3389/fpsyt.2020.00100. eCollection 2020.
There are controversial results if leukocyte telomere length (LTL) is related to structural brain changes and cognitive decline in aging. Here, we investigated the association between LTL and 1) global MRI correlates of brain aging such as brain parenchymal fraction (BPF) and white matter hyperintensities (WMH) load and Fazekas score as well as 2) global (g-factor) and domain-specific cognition such as attention/speed, conceptualization, memory, and visuopractical skills. In total, 909 participants of the Austrian Stroke Prevention Study with LTL, MRI, and cognitive tests were included. There were 388 (42.7%) men, and the mean age was 65.9 years. Longer LTL was significantly associated with larger BPF (β = 0.43, p < 0.001), larger WMH load (β = 0.03, p = 0.04), and score (β = 0.05, p = 0.04) after adjusting for age, sex, vascular risk factors, and ApoE4 carrier status. The effect on BPF was more significant in the subgroups of women (β = 0.51, p = 0.001), age >65 years (β = 0.58, p = 0.002), BMI ≥ 25 (β = 0.40, p = 0.004), education ≤10 years (β = 0.42, p = 0.002), hypertensives (β = 0.51, p = 0.001), cardiovascular disease (CVD) (β = 0.58, p = 0.005), non-diabetics (β = 0.42, p < 0.001), and Apoe4 non-carriers (β = 0.49, p < 0.001). The effect on WMH was significant within the hypertensives (load: β = 0.04, p = 0.02), non-diabetics (load:β = 0.03, p = 0.01; score: β = 0.06, p = 0.02), in those with education ≤10 years (load: β = 0.03, p = 0.04; score: β = 0.07, p = 0.02), in ApoE4 non-carriers (load: β = 0.03, p = 0.02; score: β = 0.07, p = 0.01) and in subjects without CVD (score: β = 0.06, p = 0.05). We only observed a significant association between LTL and the cognitive domain of attention/speed, which was confined to the subgroups of BMI ≥ 25 (β = 0.04, p = 0.05) and education ≤10 years (β = 0.04, p = 0.05). The effect of LTL on attention/speed was partly mediated in both subgroups by BPF (β = 0.02, 95% CI = 0.01:0.03) when tested by bootstrapping. Our results support a strong protective role of longer LTL on global brain volume which in turn may contribute to better cognitive functions, especially in the attention/speed domain in the elderly.
白细胞端粒长度(LTL)与衰老过程中的脑结构变化及认知衰退是否相关,目前存在争议性结果。在此,我们研究了LTL与以下两方面的关联:1)脑衰老的整体MRI相关指标,如脑实质分数(BPF)、白质高信号(WMH)负荷及 Fazekas 评分;2)整体(g 因子)及特定领域认知,如注意力/速度、概念化、记忆和视觉实践技能。奥地利卒中预防研究中共有909名参与者纳入研究,他们均接受了LTL、MRI及认知测试。其中男性388名(42.7%),平均年龄65.9岁。在调整年龄、性别、血管危险因素及 ApoE4携带者状态后,较长的LTL与更大的BPF(β = 0.43,p < 0.001)、更大的WMH负荷(β = 0.03,p = 0.04)及评分(β = 0.05,p = 0.04)显著相关。在女性亚组(β = 0.51,p = 0.001)、年龄>65岁亚组(β = 0.58,p = 0.002)、BMI≥25亚组(β = 0.40,p = 0.004)、教育年限≤10年亚组(β = 0.42,p = 0.002)、高血压患者亚组(β = 0.51,p = 0.001)、心血管疾病(CVD)患者亚组(β = 0.58,p = 0.005)、非糖尿病患者亚组(β = 0.42,p < 0.001)及Apoe4非携带者亚组(β = 0.49,p < 0.001)中,LTL对BPF的影响更为显著。在高血压患者亚组(负荷:β = 0.04,p = 0.02)、非糖尿病患者亚组(负荷:β = 0.03,p = 0.01;评分:β = 0.06,p = 0.02)、教育年限≤10年亚组(负荷:β = 0.03,p = 0.04;评分:β = 0.07,p = 0.02)、ApoE4非携带者亚组(负荷:β = 0.03,p = 0.02;评分:β = 0.07,p = 0.01)及无CVD受试者亚组(评分:β = 0.06,p = 0.05)中,LTL对WMH的影响显著。我们仅观察到LTL与注意力/速度这一认知领域存在显著关联,且仅限于BMI≥25亚组(β = 0.04,p = 0.05)和教育年限≤10年亚组(β = 0.04,p = 0.05)。通过自抽样检验发现,在这两个亚组中,LTL对注意力/速度的影响部分由BPF介导(β = 0.02,95%CI = 0.01:0.03)。我们的研究结果支持较长的LTL对全脑体积具有强大的保护作用,这反过来可能有助于改善认知功能,尤其是在老年人的注意力/速度领域。