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Pharmacological Management of Dementia with Lewy Bodies

机译：痴呆症的药理学管理

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摘要

Dementia with Lewy bodies (DLB) is a complex disease that involves a variety of cognitive, behavioral and neurological symptoms, including progressive memory loss, visual hallucinations, parkinsonism, cognitive fluctuations and rapid eye movement sleep behavior disorder (RBD). These symptoms may appear in varying combinations and levels of severity in each patient who is seen in the clinic, making diagnosis and treatment a challenge. DLB is the third most common of all the neurodegenerative diseases behind both Alzheimer's disease and Parkinson's disease (PD). The median age of onset for DLB (76.3years) is younger than that seen in PD dementia (81.4years). New pathological studies have shown that most DLB patients have variable amounts of Alzheimer's changes in their brains, explaining the wide variability in this disease's clinical presentation and clinical course. This review discusses the three cholinesterase inhibitors that have been shown to be effective in managing the cognitive and behavioral symptoms of DLB: rivastigmine, galantamine and donepezil. Memantine is able to improve clinical global impression of change in those with mild to moderate DLB. Levodopa can treat the parkinsonism of some DLB patients, but the dose is often limited due to the fact that it can cause agitation or worsening of visual hallucinations. A recent phase 2 clinical trial showed the benefit of zonisamide when it is added as an adjunct to levodopa for treating DLB parkinsonism. While atypical antipsychotic drugs may not always be helpful as monotherapy in managing the agitation associated with DLB, low doses of valproic acid can be effective when added as an adjunct to drugs like quetiapine. Pimavanserin may prove to be a useful treatment for psychosis in DLB patients, but like other antipsychotic drugs that are used in dementia patients, there is a small increased risk of mortality. RBD, which is a common core clinical feature of DLB, can be managed with either melatonin or clonazepam. Two agents targeting alpha-synuclein (NPT200-11 and ambroxol) currently hold promise as disease-modifying therapies for DLB, but they are yet to be tested in clinical trials. An agent(E2027) that offers hope of neuroprotection by increasing central cyclic guanosine monophosphate (cGMP) levels is currently being examined in clinical trials in DLB patients.
机译：具有Lewy Stodies（DLB）的痴呆症是一种复杂的疾病，包括各种认知，行为和神经症状，包括渐进记忆丧失，视觉幻觉，帕金森，认知波动和快速眼球运动睡眠行为障碍（RBD）。这些症状可能出现在诊所中观察到的每位患者的不同组合和严重程度，使诊断和治疗成为挑战。 DLB是Alzheimer疾病和帕金森病（PD）背后的所有神经退行性疾病中最常见的。 DLB（76.3年）发病的中位年龄小于PD痴呆（81.4年）中观察到的年轻。新的病理学研究表明，大多数DLB患者的大量阿尔茨米默患者的大脑变化，解释了该疾病的临床介绍和临床过程的广泛变化。本综述讨论了三种胆碱酯酶抑制剂，已被证明是有效地管理DLB的认知和行为症状：RIVASTIGMINE，GALANTAMINE和DENPEZIL。 Memantine能够改善临床全球变化的变化印象，以温和至中度DLB。 Levodopa可以治疗一些DLB患者的Parkinsonism，但由于它可能导致搅拌或恶化的视觉幻觉，剂量通常受限。最近的第2期临床试验显示Zonisamide的益处，当其作为左旋多巴的助剂进行治疗DLB Parkinsonism时。虽然非典型抗精神病药物在管理与DLB相关的搅拌方面可能并不总是有用的，但是当添加喹啉剂等药物添加时，低剂量的丙戊酸可以有效。 Pimavanserin可能被证明是在DLB患者中对精神病的一种有用的治疗方法，但与痴呆症患者使用的其他抗精神病药物一样，死亡率的风险较小。 RBD是DLB的常见核心临床特征，可以用褪黑激素或Clonazepam进行管理。靶向α-突触核蛋白（NPT200-11和Ambroxol）的两种药剂目前将希望作为DLB的疾病改性疗法，但尚未在临床试验中进行测试。目前在DLB患者的临床试验中检测通过增加中枢环状鸟苷一起的神经保护作用的代理（E2027）。

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  • 来源
    《Drugs and aging》 |2019年第4期|共11页
  • 作者

    Hershey Linda A.; Coleman-Jackson Rhonda;

  • 作者单位

    Univ Oklahoma Hlth Sci Ctr Dept Neurol 920 Stanton L Young Blvd Suite 2040 Oklahoma City OK;

    Univ Oklahoma Hlth Sci Ctr Dept Neurol 920 Stanton L Young Blvd Suite 2040 Oklahoma City OK;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 药学;
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