Grodstein Francine, van Oijen Marieke, Irizarry Michael C, Rosas H Diana, Hyman Bradley T, Growdon John H, De Vivo Immaculata
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA.
PLoS One. 2008 Feb 13;3(2):e1590. doi: 10.1371/journal.pone.0001590.
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.
METHODOLOGY/PRINCIPAL FINDINGS: 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.
痴呆症的发展需要数十年时间，有效的预防可能需要早期干预。因此，识别临床前疾病的生物标志物至关重要，这有助于针对高危人群开展预防工作。由于端粒会随着年龄增长和氧化应激而缩短，而这两者都是导致痴呆症发病的重要因素，因此端粒长度可能是一种有价值的生物标志物。
方法/主要发现：在护士健康研究的62名参与者中，我们进行了神经学评估，包括对患者和照料者的访谈、体格检查、神经学检查和神经心理学测试。我们还对其中29名女性进行了磁共振成像（MRI）检查。在这些初步数据中，在对众多健康和生活方式因素进行调整后，我们发现外周血白细胞中端粒缩短与临床前痴呆状态相关，包括轻度认知障碍（MCI）；与端粒长度较长的人相比，端粒长度较短的人患MCI的几率高出12倍（优势比=12.00，95%置信区间1.24-116.5）。此外，端粒长度的缩短与海马体体积的减小密切相关（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潜在早期标志物，值得在大规模前瞻性研究中进一步探讨。
