Shorter telomeres may mark early risk of dementia: preliminary analysis of 62 participants from the nurses' health study.
Shorter telomeres may mark early risk of dementia: preliminary analysis of 62 participants from the nurses' health study.
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DOI：
10.1371/journal.pone.0001590
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发表时间：
2008-02-13
期刊：
影响因子：
3.7
通讯作者：
De Vivo, Immaculata
中科院分区：
文献类型：
--
作者：
Grodstein, Francine;van Oijen, Marieke;Irizarry, Michael C.;Rosas, H. Diana;Hyman, Bradley T.;Growdon, John H.;De Vivo, Immaculata
痴呆症需要几十年的发展，有效的预防可能需要早期干预。因此，确定临床前疾病的生物标志物至关重要，从而可以针对高风险受试者进行预防工作。由于端粒随着年龄和氧化应激而缩短，这两者都是痴呆症发病的重要因素，因此端粒长度可能是一个有价值的生物标志物。在62名护士健康研究的参与者中，我们进行了神经系统评估，包括患者和护理人员的访谈，体格检查，神经系统检查和神经心理测试。我们还对其中29名妇女进行了磁共振成像（MRI）。在这些初步数据中，在调整了许多健康和生活方式因素后，我们发现外周血白细胞中截短的端粒与临床前痴呆状态分离，包括轻度认知障碍（MCI）;与端粒长度较长的人相比，端粒长度较短的人MCI的几率高12倍（比值比=12.00，95%置信区间1.24-116.5）。 此外，端粒长度的减少与海马体积的减少密切相关（p = 0.038）。 这些初步数据表明，端粒长度可能是痴呆风险的一个可能的早期标志物，值得在大型前瞻性研究中进一步研究。
Dementia takes decades to develop, and effective prevention will likely require early intervention. Thus, it is critical to identify biomarkers of preclinical disease, allowing targeting of high-risk subjects for preventive efforts. Since telomeres shorten with age and oxidative stress, both of which are important contributors to the onset of dementia, telomere length might be a valuable biomarker. Among 62 participants of the Nurses' Health Study, we conducted neurologic evaluations, including patient and caregiver interviews, physical exam, neurologic exam, and neuropsychologic testing. We also conducted magnetic resonance imaging (MRI) in a sample of 29 of these women. In these preliminary data, after adjustment for numerous health and lifestyle factors, we found that truncated telomeres in peripheral blood leukocytes segregate with preclinical dementia states, including mild cognitive impairment (MCI); the odds of MCI were 12-fold higher (odds ratio = 12.00, 95% confidence interval 1.24–116.5) for those with shorter telomere length compared to longer telomere length. In addition, decreasing telomere length was strongly related to decreasing hippocampal volume (p = 0.038). These preliminary data suggest that telomere length may be a possible early marker of dementia risk, and merits further study in large, prospective investigations.
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