Cleveland Clinic Lou Ruvo Center for Brain Health, Cleveland, OH, USA.
Case Western Reserve University, Cleveland, OH, USA.
Drugs Aging. 2022 Jul;39(7):505-522. doi: 10.1007/s40266-022-00939-w. Epub 2022 May 27.
The term Lewy body dementia refers to either of two related diagnoses: dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). Clinical management of Lewy body dementia is challenging. The current treatment options focus on relieving symptoms; no disease-modifying therapies are available. There are currently no US Food and Drug Administration (FDA) approved drugs for the treatment of DLB, and there are only a few for PDD. Cholinesterase inhibitors are shown to be beneficial in improving cognitive symptoms in Lewy body dementia. Rivastigmine was approved by the FDA to treat PDD. Donepezil was approved in Japan as a treatment for DLB. Levodopa may provide modest benefit in treating motor symptoms and zonisamide in adjunct to low-dose levodopa helps with parkinsonism. Treatment of autonomic symptoms are based on symptomatic treatment with off-label agents. Our main objective in this article is to present an overview of the current pharmacological options available to treat the clinical features of DLB and PDD. When evaluating the existing management options for Lewy body dementia, it is difficult to fully separate PDD from DLB. However, we have attempted to identify whether the cited studies include patients with PDD and/or DLB. Moreover, we have provided an overview of the current drug pipeline in Lewy body dementia. All currently active trials are in phase I or II and most are focused on disease modification rather than symptomatic treatment. Phase II trial results for neflamapimod show promising results. Due to heterogeneity of symptoms and underlying pathophysiology, there is a need for new biomarker strategies and improved definitions of outcome measures for Lewy body dementia drug trials.
路易体痴呆（DLB）和帕金森病痴呆（PDD）。路易体痴呆的临床管理具有挑战性。目前的治疗选择侧重于缓解症状；没有可用的疾病修饰疗法。目前，没有美国食品和药物管理局（FDA）批准的药物用于治疗 DLB，只有少数用于 PDD。胆碱酯酶抑制剂已被证明可改善路易体痴呆的认知症状。加兰他敏被 FDA 批准用于治疗 PDD。多奈哌齐在日本被批准用于治疗 DLB。左旋多巴可能对治疗运动症状有一定益处，而佐尼沙胺与低剂量左旋多巴联合使用有助于治疗帕金森病。自主症状的治疗基于对症治疗，使用非标签药物。我们在本文中的主要目标是介绍目前可用于治疗 DLB 和 PDD 临床特征的药理学选择概述。在评估路易体痴呆现有的管理选择时，很难将 PDD 与 DLB 完全分开。然而，我们试图确定所引用的研究是否包括 PDD 和/或 DLB 患者。此外，我们还概述了目前在路易体痴呆中的药物研发管道。所有目前正在进行的试验均处于 I 期或 II 期，大多数都专注于疾病修饰而非症状治疗。尼氟拉明的 II 期试验结果显示出有希望的结果。由于症状和潜在病理生理学的异质性，需要新的生物标志物策略和改进的路易体痴呆药物试验的结果衡量标准。
