Geneva University, Rehabilitation and Geriatrics Department, Thônex, Switzerland.
J Neurol Sci. 2010 Dec 15;299(1-2):108-11. doi: 10.1016/j.jns.2010.07.019. Epub 2010 Aug 14.
Clarifying the aetiology of dementia is of crucial importance in the management of patients as well as for research purposes but it is not always possible clinically. Therefore the identification of biological markers should complement clinical approaches. Telomere shortening is emerging as an important mechanism in vascular aging and the pathogenesis of hypertension and atherosclerosis. Thus, telomere length could be a potential candidate to accurately separate vascular from degenerative cognitive impairment.
To evaluate the usefulness of telomere length alone or combined with ApoE polymorphism in diagnosing mild cognitive impairment (MCI) and in differentiating Alzheimer's disease (AD) from vascular (VaD) and mixed dementia (MD).
Telomere length in peripheral blood lymphocytes was performed by flow cytometry in 439 patients (mean age, 85.1 years): 204 cognitively normal, 187 demented patients: 80 AD, 86 MD, and 21 with VaD; and 48 patients with MCI. Simple and multiple ordered logistic regressions were used to predict the risk of dementia from telomere length, ApoE polymorphism and age.
ApoEε4 was statistically associated with patients with dementia (p<0.001) compared to cognitively normal or MCI patients; but not with the aetiologies of dementia (AD, VaD and MD) (p=0.385). No significant differences in telomere length were found among patients with different aetiologies or severities of dementia. In the global model, the combination of telomere length and ApoE polymorphism did not confer a significantly higher dementia risk (OR=0.95, 95% CI=0.69-1.32; p=0.784) than APOEε4 alone (OR=2.12, 95% CI=1.15-3.9; p=0.016).
This longitudinal study in very old patients provided no evidence suggesting that telomere length alone could be used to distinguish between the different types of dementia or MCI, nor combined with the ApoE polymorphism.
阐明痴呆症的病因对于患者的治疗和研究都至关重要，但临床上并非总能做到这一点。因此，生物标志物的鉴定应该补充临床方法。端粒缩短正在成为血管老化以及高血压和动脉粥样硬化发病机制中的一个重要机制。因此，端粒长度可能是一种潜在的候选物，可以准确地区分血管性与退行性认知障碍。
评估端粒长度单独或与 ApoE 多态性结合用于诊断轻度认知障碍 (MCI) 以及区分阿尔茨海默病 (AD)、血管性痴呆 (VaD) 和混合性痴呆 (MD) 的有用性。
通过流式细胞术检测 439 例患者（平均年龄 85.1 岁）外周血淋巴细胞中的端粒长度：204 例认知正常，187 例痴呆患者：80 例 AD，86 例 MD，21 例 VaD；48 例 MCI。简单和多有序逻辑回归用于预测端粒长度、ApoE 多态性和年龄对痴呆的风险。
与认知正常或 MCI 患者相比，ApoEε4 与痴呆患者存在统计学关联（p<0.001）；但与痴呆的病因（AD、VaD 和 MD）无关（p=0.385）。不同病因或痴呆严重程度的患者之间端粒长度无显著差异。在整体模型中，端粒长度和 ApoE 多态性的组合并未显著增加痴呆风险（OR=0.95，95%CI=0.69-1.32；p=0.784），不如 APOEε4 单独（OR=2.12，95%CI=1.15-3.9；p=0.016）。
这项针对非常老年患者的纵向研究没有提供证据表明，端粒长度本身可用于区分不同类型的痴呆症或 MCI，也不能与 ApoE 多态性结合使用。
