Knapskog Anne-Brita, Eldholm Rannveig Sakshaug, Braekhus Anne, Engedal Knut, Saltvedt Ingvild
Department of Geriatric Medicine, The memory clinic, Oslo University Hospital, Ullevaal, Postboks 4956, Nydalen, 0424, Oslo, Norway.
Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
BMC Geriatr. 2017 Sep 11;17(1):210. doi: 10.1186/s12877-017-0611-4.
The cerebrospinal fluid (CSF) biomarkers amyloid β (Aβ), phospho tau (P-tau) and total tau (T-tau) are used increasingly to support a clinical diagnosis of Alzheimer's disease. The diagnostic power of these biomarkers has been reported to vary among different studies' results. The results are poorer when heterogeneous groups of patients have been included compared to studies where patients with Alzheimer's dementia (AD) and healthy controls have been studied. The aim of this study was to examine if age, APOE genotype and sex were associated with the levels of CSF biomarkers among patients referred to a memory clinic.
We included 257 patients from two memory clinics who had been assessed for dementia, including lumbar puncture.
The mean age of the patients was 68.1 (SD: 8.0) years; 50.2% were women and 66.5% were APOE ε4 positive. Of these patients, 80.5% were diagnosed with AD or amnestic MCI. Both APOE ε4 and increasing age were associated with decreasing levels of Aβ, but not the levels of the tau proteins. In multiple regression analyses, disease stage, defined as a MMSE ≥25 or <25, influenced factors associated with the CSF biomarkers. Among those with MMSE score ≥ 25, age, APOE ε4 genotype, and MMSE score, in addition to a diagnosis of AD, were associated with Aβ level, with an explained variance of 0.43. When using P-tau or T-tau as a dependent variable, the presence of one or two APOE ε4 alleles, and MMSE score influenced the results, in addition to the diagnosis of AD. The explained variance was lower for P-tau (0.26) and for T-tau (0.32). Among those with MMSE <25, these variables explained very little of the variance. There were no gender differences.
We found that factors in addition to a diagnosis of AD, were associated with the levels of CSF biomarkers. Among those with MMSE ≥25, lower levels of Aβ were associated with several factors including increasing age. This is not reflected in clinical practice, where age-specific cutoffs exist only for T-tau. In this study, age was not associated with the levels of tau proteins.
脑脊液（CSF）生物标志物β淀粉样蛋白（Aβ）、磷酸化tau蛋白（P-tau）和总tau蛋白（T-tau）越来越多地用于辅助阿尔茨海默病的临床诊断。据报道，这些生物标志物的诊断能力在不同研究结果中有所不同。与研究阿尔茨海默病痴呆（AD）患者和健康对照的研究相比，纳入异质性患者群体时结果更差。本研究的目的是检验年龄、APOE基因型和性别是否与转诊至记忆门诊的患者脑脊液生物标志物水平相关。
我们纳入了来自两家记忆门诊的257例接受过痴呆评估（包括腰椎穿刺）的患者。
患者的平均年龄为68.1（标准差：8.0）岁；50.2%为女性，66.5%为APOE ε4阳性。这些患者中，80.5%被诊断为AD或遗忘型轻度认知障碍（MCI）。APOE ε4和年龄增长均与Aβ水平降低相关，但与tau蛋白水平无关。在多元回归分析中，定义为简易精神状态检查表（MMSE）≥25或<25的疾病阶段影响与脑脊液生物标志物相关的因素。在MMSE评分≥25的患者中，年龄、APOE ε4基因型、MMSE评分以及AD诊断均与Aβ水平相关，解释方差为0.43。当使用P-tau或T-tau作为因变量时，除AD诊断外，一个或两个APOE ε4等位基因的存在以及MMSE评分影响结果。P-tau的解释方差较低（0.26），T-tau的解释方差为（0.32）。在MMSE<25的患者中，这些变量对方差的解释很少。不存在性别差异。
我们发现除AD诊断外，其他因素也与脑脊液生物标志物水平相关。在MMSE≥25的患者中，较低的Aβ水平与包括年龄增长在内的几个因素相关。这在临床实践中并未得到体现，临床实践中仅针对T-tau存在年龄特异性临界值。在本研究中，年龄与tau蛋白水平无关。
