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Catecholamine-Based Treatment in AD Patients: Expectations and Delusions

机译:AD患者以儿茶酚胺为基础的治疗:期望和妄想

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摘要

In Alzheimer disease, the gap between excellence of diagnostics and efficacy of therapy is wide. Despite sophisticated imaging and biochemical markers, the efficacy of available therapeutic options is limited. Here we examine the possibility that assessment of endogenous catecholamine levels in cerebrospinal fluid (CSF) may fuel new therapeutic strategies. In reviewing the available literature, we consider the effects of levodopa, monoamine oxidase inhibitors, and noradrenaline (NE) modulators, showing disparate results. We present a preliminary assessment of CSF concentrations of dopamine (DA) and NE, determined by HPLC, in a small dementia cohort of either Alzheimer’s disease (AD) or frontotemporal dementia patients, compared to control subjects. Our data reveal detectable levels of DA, NE in CSF, though we found no significant alterations in the dementia population as a whole. AD patients exhibit a small impairment of the DA axis and a larger increase of NE concentration, likely to represent a compensatory mechanism. While waiting for preventive strategies, a pragmatic approach to AD may re-evaluate catecholamine modulation, possibly stratified to dementia subtypes, as part of the therapeutic armamentarium.
机译:在阿尔茨海默氏病中,出色的诊断和治疗效果之间的差距很大。尽管有复杂的成像和生化标记物,但可用治疗选择的功效有限。在这里,我们检查了评估脑脊液(CSF)中内源性儿茶酚胺水平可能推动新的治疗策略的可能性。在回顾现有文献时,我们考虑了左旋多巴,单胺氧化酶抑制剂和去甲肾上腺素(NE)调节剂的作用,显示出不同的结果。与对照对象相比,我们对由阿尔茨海默氏病(AD)或额颞叶性痴呆患者组成的小型痴呆队列中的HPLC测定的脑脊液中多巴胺(DA)和NE的浓度进行了初步评估。我们的数据揭示了脑脊液中可检测到的DA,NE水平,尽管我们并未发现痴呆症总体上有明显改变。 AD患者的DA轴损伤较小,NE浓度升高较大,可能代表了一种补偿机制。在等待预防策略的同时,务实的治疗AD的方法可能会重新评估儿茶酚胺调节,可能将其分层为痴呆亚型,作为治疗性武器库的一部分。

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