Oliver Peters, Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany, Tel.: +49-30-450-517628, Fax.: +49-30-450-517942, Email:
J Prev Alzheimers Dis. 2018;5(3):202-206. doi: 10.14283/jpad.2018.5.
In several randomized controlled trials (RCT) acetylcholinesterase-inhibitors (AChE-I) were tested in patients with mild cognitive impairment (MCI) but were ineffective in delaying disease progression as determined by neuropsychological testing only. Here we present data from an open label observational extension of a multicenter RCT in order to assess if biomarkers are providing useful additional information about a drug's efficacy. We followed 83 amnestic MCI patients and performed correlational analyses of Aβ 1-42 and total-Tau in the cerebrospinal fluid (CSF), hippocampal and amygdala volume at baseline, the total duration of blinded and open label AChE-I treatment and the outcome 24 months after inclusion into the RCT. Twelve out of 83 amnestic MCI (14%) had progressed to Alzheimer's disease (AD). Overall, worsening and disease progression as measured by the Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-cog), Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) and Clinical Dementia Rating (CDR) did not correlate with the duration of AChE-I treatment. However, a specific multidimensional biomarker profile at baseline indicated more reliably than cognitive testing alone progression to AD. We conclude that pharmacological RCTs testing symptomatic treatment effects in MCI should include biomarker assessment.
在几项随机对照试验（RCT）中，乙酰胆碱酯酶抑制剂（AChE-I）在轻度认知障碍（MCI）患者中进行了测试，但仅通过神经心理学测试，发现它们无法延缓疾病进展。在这里，我们呈现了一项多中心 RCT 的开放标签观察性扩展的数据，以评估生物标志物是否为药物疗效提供了有用的额外信息。我们随访了 83 名遗忘型 MCI 患者，并对基线时脑脊液（CSF）中的 Aβ 1-42 和总 Tau、海马和杏仁核体积、盲法和开放标签 AChE-I 治疗的总持续时间以及 RCT 纳入后 24 个月的结果进行了相关性分析。83 名遗忘型 MCI 患者中有 12 名（14%）进展为阿尔茨海默病（AD）。总的来说，阿尔茨海默病评估量表-认知子量表（ADAS-cog）、阿尔茨海默病合作研究-日常生活活动（ADCS-ADL）和临床痴呆评定量表（CDR）测量的病情恶化和疾病进展与 AChE-I 治疗的持续时间无关。然而，基线时的特定多维生物标志物特征比认知测试单独更可靠地表明向 AD 的进展。我们得出结论，在 MCI 中测试症状治疗效果的药理学 RCT 应包括生物标志物评估。
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