Del Campo Natalia, Cesari Matteo, Canevelli Marco, Hoogendijk Emiel O, Lilamand Matthieu, Kelaiditi Eirini, Soto Maria E, Ousset Pierre-Jean, Weiner Michael W, Andrieu Sandrine, Vellas Bruno
Gérontopôle, Institute of Ageing, Toulouse University Hospital, Toulouse, France; "NeuroToul" Center of Excellence in Neurodegeneration of Toulouse, Toulouse, France; Department of Psychiatry, University of Cambridge, Cambridge, England.
Gérontopôle, Institute of Ageing, Toulouse University Hospital, Toulouse, France; INSERM UMR 1027, Paul Sabatier University of Toulouse, Toulouse, France.
J Am Med Dir Assoc. 2016 Oct 1;17(10):913-20. doi: 10.1016/j.jamda.2016.06.005.
Recent evidence suggests that a substantial minority of people clinically diagnosed with probable Alzheimer disease (AD) in fact do not fulfill the neuropathological criteria for the disease. A clinical hallmark of these phenocopies of AD is that these individuals tend to remain cognitively stable for extended periods of time, in contrast to their peers with confirmed AD who show a progressive decline. We aimed to examine the prevalence of patients clinically diagnosed with mild-to-moderate AD who do not experience the expected clinically significant cognitive decline and identify markers easily available in routine medical practice predictive of a stable cognitive prognosis in this population.
Data were obtained from two independent, longitudinal, observational multicenter studies in patients with mild-to-moderate AD.
The two studies were the European "Impact of Cholinergic Treatment Use" (ICTUS) and the French "REseau sur la maladie d'Alzheimer FRançais" (REAL.FR).
We used prospective data of 756 patients enrolled in ICTUS and 340 enrolled in REAL.FR.
A prediction rule of cognitive decline was derived on ICTUS using classification and regression tree analysis and then cross-validated on REAL.FR. A range of demographic, clinical and cognitive variables were tested as predictor variables.
Overall, 27.9% of patients in ICTUS and 20.9% in REAL.FR did not decline over 2 years. We identified optimized cut-points on the verbal memory items of the Alzheimer Disease Assessment Scale-Cognitive Subscale capable of classifying patients at baseline into those who went on to decline and those who remained stable or improved over the duration of the trial.
The application of this simple rule would allow the identification of dementia cases where a more detailed differential diagnostic examination (eg, with biomarkers) is warranted. These findings are promising toward the refinement of AD screening in the clinic. For a further optimization of our classification rule, we encourage others to use our methodological approach on other episodic memory assessment tools designed to detect even small cognitive changes in patients with AD.
最近有证据表明，临床上被诊断为可能患有阿尔茨海默病（AD）的人群中，有相当一部分实际上并不符合该疾病的神经病理学标准。这些AD临床拟态的一个临床特征是，与确诊为AD且认知功能呈进行性下降的同龄人相比，这些个体往往在较长时间内保持认知稳定。我们旨在研究临床诊断为轻度至中度AD但未出现预期的临床显著认知下降的患者的患病率，并确定在常规医疗实践中易于获得的、可预测该人群认知预后稳定的标志物。
数据来自两项针对轻度至中度AD患者的独立、纵向、观察性多中心研究。
这两项研究分别是欧洲的“胆碱能治疗使用的影响”（ICTUS）研究和法国的“法国阿尔茨海默病研究网络”（REAL.FR）研究。
我们使用了ICTUS研究中756名患者和REAL.FR研究中340名患者的前瞻性数据。
在ICTUS研究中，使用分类与回归树分析得出认知下降的预测规则，然后在REAL.FR研究中进行交叉验证。对一系列人口统计学、临床和认知变量作为预测变量进行了测试。
总体而言，ICTUS研究中27.9%的患者和REAL.FR研究中20.9%的患者在2年内认知功能未下降。我们在阿尔茨海默病评估量表 - 认知分量表的言语记忆项目上确定了优化的切点，能够在基线时将患者分为在试验期间认知功能下降的患者和保持稳定或改善的患者。
应用这个简单规则将有助于识别那些需要进行更详细鉴别诊断检查（如使用生物标志物）的痴呆病例。这些发现对于优化临床AD筛查很有前景。为了进一步优化我们的分类规则，我们鼓励其他人在其他旨在检测AD患者即使微小认知变化的情景记忆评估工具上使用我们的方法。
