Current Therapies and Drug Development Pipeline in Lewy Body Dementia: An Update

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.